Essentials of Palliative Care

Essentials of Palliative Care
Nalini Vadivelu ●
Alan David Kaye
Jack M. Berger
Editors
Essentials of Palliative Care

Editors
Nalini Vadivelu, MD Alan David Kaye, MD, PhD
Department of Anesthesiology Departments Anesthesiology
Yale University School of Medicine Louisiana State University School
New Haven, CT, USA of Medicine,
New Orleans, LA, USA
Jack M. Berger, MS, MD, PhD
Department of Anesthesiology
Pain Medicine, and Critical Care
Keck School of Medicine of the
University of Southern California
Los Angeles, CA, USA
ISBN 978-1-4614-5163-1 ISBN 978-1-4614-5164-8 (eBook)

DOI 10.1007/978-1-4614-5164-8
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2012951667
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I wish to thank my parents, Major General
Vadivelu and Gnanambigai Vadivelu, my
husband, Thangamuthu Kodumudi, and my
sons, Gopal and Vijay, for their steadfast
support. I would also wish to thank my
brother, Dr. Amarender Vadivelu, and sister,
Suguna Vadivelu, for their inspiration, and
my innumerable friends, colleagues, and
students who encourage me to reach for
heights higher than the day before.
–NV
I want to thank my wife, Dr. Kim Kaye, for

her dedication and love over many decades;
my brother, Dr. Adam Kaye, for a lifetime of
friendship and support; and my mother-in-
law, Dr. Patricia B. Sutker, for the thousands
of loving and helpful things she has done for
me over the past 25 years. Finally, I want to
thank my mother, Florence Feldman, for
inspiring me to be a doctor many years ago
and for her love and support during my life.
–AK
I would like to thank my wife, Ethel, and my
family for all their support, love, and
understanding over the years of having to
miss family functions because I became a
doctor and my parents, Sol and Gertrude
Berger, for all their support and
encouragement to pursue my dreams. Special
thanks to Angèle Ryan, MD, Jackie Carter,
RN, MNS, and Janet Lucas, MSW, for
teaching me about compassionate care and
what it really means to be a doctor.
–JB
Foreword
When my mother turned 90 years old, she had moderately advanced Parkinson’s
disease, but no other major ailments. Her function was declining gradually, and she
began to fall and become a bit forgetful. Her ability to live independently was
waning. But her need for palliative care was clear and rapidly growing. It began
with a general consideration of her medical goals—she did not want any big medi-
cal adventures, so resuscitation and intubation were easily taken off the table. But
she still had a lot of things to enjoy in life, so she was willing to have her doctors
try to fix easily treatable problems as long as she had a good chance of returning to
an acceptable level of independence. But the ground rules of this approach were
not clear, because her condition was fragile and her ability to live alone in her
beloved house was becoming more and more difficult because of the ravages of her
Parkinson’s disease.
The next big event in her life was a fall where she sustained a broken hip.
Surgically repairing the hip made sense given her goals (and the absence of good
alternatives), but her recovery was complicated by pain, postoperative delirium, de-
conditioning, and worsening of her Parkinson’s disease. The need for palliative care
expertise to address the growing complexity of her symptoms and her condition was
clearly growing, as her goals were now shifting more toward purely comfort-ori-
ented approach. She had no definable terminal illness, so she did not qualify for a
formal hospice program (even though that was the philosophy of treatment both she
and we wanted), and no one could say with honesty that she was more likely than
not to die in the next 6 months. With excellent palliation, she eventually made it to
a rehabilitation program in a skilled nursing facility. Although her function improved
modestly, she did not return to her former baseline. She hated living there, and her
inability to safely walk without someone with her at all times was a real challenge
to her sense of identity and personhood. Palliation now required multidimensional
interventions that included orthopedic guidance, pain management, physical ther-
apy, neurologic management of her Parkinson’s disease, and psychological treat-
ment of her grief.
My mother was adamant in her desire to return to her home, yet we as a family
knew it was unsafe without 24-hour supervision, which she flatly refused. As we
vii
viii Foreword
were struggling with next steps, she suddenly became jaundiced. Her doctor fortu-
nately was skilled in palliative care and knowledgeable about hospice care. He
helped us think through her limited options. My mother was painfully aware that her
quality of life was waning rapidly, as was her ability to live independently, and that
more medical intervention was the last thing she wanted unless it had a high likeli-
hood of returning her to full independence. A biopsy or a biliary drainage procedure
would not help her achieve these goals, and therefore would not be in her best inter-
est. It was time to shift gears toward pure, noninvasive palliation, and a hospice
referral was made without any biopsies or interventions. With her new found termi-
nal illness, she now qualified for hospice medically as well as philosophically, and
we began to think through where she would spend her final time. Although our
extended family lived on the North Shore of Boston where my mother was living,
she agreed to a move to Rochester to be near us so that we could help care for her
over her final weeks or months. She put on my Red Sox cap for her final road trip,
and my brother and I brought her to Rochester where she lived in a comfort care
home for her final weeks. With the help of a skilled hospice team, we were able to
keep her very comfortable. There were symptoms that required intensive manage-
ment, including pruritis, pain, and delirium, but there were also wonder times of
storytelling and family members coming together. She died very peacefully in our
presence 3 weeks after her move to Rochester.
There ought not to be very much special or unique about this story, but in fact in
the current environment it is probably the exception rather than the rule. Part of the
reason it is exceptional is that many physicians do not have the knowledge and skill
about palliative care and hospice that her physician and our family had. Such knowl-
edge, skill, and advice is thoughtfully and accessibly presented in Essentials of
Palliative Care, co-edited by three highly skilled and respected palliative care phy-
sicians, Drs. Vadivelu, Kaye, and Berger. The physicians caring for my mother were
not specialists in palliative care or hospice, but they knew enough about palliative
treatments to be able to help us think through a broad range of options at each clini-
cal curve in the road. Although they did not always have all the palliative care treat-
ment options at their fingertips, they knew how to find them and how to adapt the
treatment plan to my mother’s preferences and changing clinical circumstances.
Many of the chapters in this book would have been relevant to my mother’s care,
including the chapters on pain management, on physical and occupational therapy,
and psychological distress, as well as the chapter covering the transition to hospice.
There are other chapters that provide guidance about vascular access, ostomy care,
and palliative use of interventional radiology that might not be within the knowl-
edge base of all clinicians, but would increase awareness of potential palliative
options to address difficult symptom-related problems.
Not everyone providing palliative care needs to be a subspecialist (there is far too
much work and too few fully trained and certified clinicians), but all clinicians who
care for seriously ill patients should have solid basic palliative care skills both in
terms of pain and symptom management, and in terms of helping patients negotiate
the medical system in light of a full understanding of their patients’ goals and
clinical options. Essentials of Palliative Care should be a part of that toolkit, and we
Foreword ix
are indebted to Drs. Vadivelu, Kaye, Berger, and their other chapter authors for
providing such an accessible, useful resource.
Rochester, NY, USA Timothy E. Quill Rochester

Preface
Palliative Medicine has become a familiar term in recent years and is becoming
established as a key component in modern health care, and many institutions pro-
mote Palliative Care teams. Although this is a term relatively new to many practitio-
ners, palliative care was coined several decades ago by Dr. Balfour Mount, a
Canadian physician. After training in Dame Cicely Saunders’ St. Christopher’s
Hospice in London, he was so impressed that he was inspired to bring this type of
care to mainstream curative medicine. As a result, he founded the Royal Victoria
Hospital Palliative Care Service in 1974 and is credited with establishing the first
in-patient palliative care unit in North America. Having emerged from the nurse
driven hospice movement, the care of the dying has evolved to a formal hospice
benefit and development of a recognized subspecialty.
This specialty of Hospice and Palliative Medicine (HPM) is dedicated to promot-
ing quality end of life care to patients and families struggling with advanced dis-
ease. In recent years, palliative care has become increasingly common in the medical
literature as well as in public media. Although the delivery of palliative care is
influenced by the hospice model, the composition of a hospital-based palliative care
team varies significantly from one institution to another, but fundamental roles are
generally identified as the provision of physical, emotional, social, and spiritual
comfort. The requirements for a “home” based palliative care team service is similar
to those of the hospital-based service.
In developing an education program for symptom management and palliative
care, physicians and other healthcare providers will need to learn how to make the
difficult decisions with respect to recommending or initiating therapeutic interven-
tions or recommending and discontinuing interventions. Examples of symptoms
which would have to be considered can be grouped as follows:
• Pain of any etiology, tumor metastasis, spinal cord or nerve root compression,
lymphedema, bowel obstruction, electrolyte abnormalities.
• Dehydration, malnutrition, anorexia–cachexia syndrome, radiation enteritis,
diarrhea, nausea, vomiting.
• Asthenia, fatigue, weakness.
xi
xii Preface
• Dyspnea, respiratory failure, respiratory tract infections, pleural effusions, lymp-

hangitis carcinomatosis.
• Anemia, wound breakdown, ulcerations, decubitus ulcers, ostomies.
• Anxiety, confusion, sleep disorders, depression, sadness, anger.
• Hiccoughs, cough, bloating, belching, mucositis, foul body ordors, wheezing.
It is necessary to develop systems for evaluating the necessity or futility of inter-
vening based upon an understanding of the pathophysiology of the above symptoms
in the terminally ill patient. The costs both economic and psychosocial of interven-
ing or not intervening or cessation of ongoing interventions must be better defined.
Only through facing these difficult problems critically can we learn how best to deal
with them.
The Physician
The American Board of Medical Specialties is a self-policing organization that sets

standards and grants certification for medical practice beyond the minimum require-
ments for licensure. In a given field of medical practice, a physician seeks recognition
for expertise. When Palliative Medicine became part of modern medical practice, the
logical result was the pursuit of formal certification. As a result, the American Board of
Hospice and Palliative Medicine was formed, an independent certifying organization.
From 1996 to 2006, the available certification for physicians practicing palliative
medicine was through the independent American Board of Hospice and Palliative
Medicine. This entity provided recognition of expertise for practitioners caring for
the dying, while promoting the importance of the specialty and working toward
transition to formal recognition by the American Board of Medical Specialties, the
official body that is recognized by healthcare systems as the stamp of approval of
medical specialties. Currently, there are ten co-sponsoring boards that offer subspe-
cialty certification in Hospice and Palliative Medicine (HPM), including the
American Boards of Anesthesiology, Emergency Medicine, Family Medicine,
Internal Medicine, Obstetrics and Gynecology, Pediatrics, Physical Medicine and
Rehabilitation, Psychiatry and Neurology, Radiology, and Surgery.
Competencies of subspecialist-level hospice and palliative medicine include
skills in symptom management, relief of suffering and improving the quality of life
for patients and families living with life-threatening illness, provision of assistance
for patients and families coping with loss, and management of challenging prob-
lems associated with end-of-life care.
Nursing
The nursing profession has been in the forefront of the hospice movement and plays
a pivotal role in modern palliative medicine. The National Board for Certification of
Hospice and Palliative Nurses (NBCHPN), established in 1993, provides nursing
Preface xiii
certification for hospice and palliative medicine for several categories of nursing
positions. The classifications of expertise include Advanced Certified Hospice and
Palliative Nurse (ACHPN), Certified Hospice and Palliative Nurse (CHPN), Certified
Hospice and Palliative Pediatric Nurse (CHPPN), Certified Hospice and Palliative
Licensed Nurse (CHPLN), Certified Hospice and Palliative Nursing Assistant
(CHPNA), Certified Hospice and Palliative Care Administrator (CHPCA). Each
certification period is valid for 4 years and is renewable.
Advanced practice nursing certification is granted for nursing professionals who
either hold a Clinical Nurse Specialist or Nurse Practitioner license, and have gradu-
ated from an accredited education program specializing in palliative care that
includes a minimum of 500 hours of palliative care training, or have post master’s
graduate practice experience of 500 hours in providing palliative care in the year
prior to examination. Successful completion of the examination establishes excel-
lence in the area of clinical judgment, advocacy and ethics and systems thinking,
professionalism and research, collaboration, facilitation of learning and communi-
cation, and cultural and spiritual competence.
For a registered nurse to test for CHPN status, the candidate must hold a valid
registered nurse license. It is recommended that the individual also have at least
2 years of practice in end-of-life care prior to testing. Successful completion of
the examination demonstrates ability in recognition of life-limiting conditions in
adult patients, pain and symptom management, care of patient and family, educa-
tion and advocacy, interdisciplinary/collaborative practice, and professional
issues.
A nursing professional seeking certification for NBCHPN is required to hold a
valid registered nurse license and is encouraged to have a minimum of 2 years expe-
rience in the care of terminally ill children. This encompasses the care of patients
ranging in age from perinatal to young adulthood. As a result of certification, the
pediatric nurse establishes competencies in recognition of life-threatening condi-
tions in children, pain and symptom management, treatments and procedures, fam-
ily centered care, education and advocacy, care at end of life, grief and bereavement,
and professional issues.
The certification exam for licensed practical nurses (LPN) and licensed voca-
tional nurses (LVN) has been offered since 2004. Successful candidates achieve the
CHPLN credential, which is valid for 4 years. Candidates holding a valid LPN or
LVN are eligible to take the exam. Two years experience in the hospice or palliative
care setting is recommended. Clinical areas of expertise include various aspects of
patient care such as end-stage disease process in adult patients, pain, symptom, and
comfort management, treatments and procedures, care of patient, family, and other
caregivers, patient and family education and advocacy, and interdisciplinary and
collaborative practice issues.
Nursing assistants are eligible to test for the CHPNA credential if the candidate
can provide documentation of 2000 practice hours under the supervision of a regis-
tered nurse in the previous 2 years. It is also recommended that the candidates have
2 years of experience specifically in the field of hospice or palliative care.
xiv Preface
Examination for the CHPCA credential is offered for any individual with 2 years
experience in an administrative role, verified by a supervisor, that involves hospice
or palliative care. The NBCHPN administrator examination tests for competency in
leadership, planning, operations, fiscal and human resource management, quality
management, marketing, public relations, and ethics.
Social Work
The advanced certified hospice and palliative social worker (ACHP-SW) credential
was added in 2009, adapted for the specialized skills and expertise of social work
professionals who provide care in the hospice and palliative care setting . The eligi-
bility requirements include a master’s degree in social work from an accredited
university, 20 or more continuing education credits specific to hospice and palliative
care, documentation of at least 2 years of supervised social work experience in hos-
pice or palliative care setting, and a current license to practice as a professional
social worker.
Program Certification
With the ambitious credentialing process for all members of the palliative care team,
it is logical to expect progression to program certification. The Joint Commission on
Accreditation of Healthcare Organizations has developed an Advanced Certification
Program for Palliative Care. Expertise and commitment of dedicated individuals
representing the credentialed disciplines is greatly enhanced in the setting of insti-
tutional support. Standards set forth by the Joint Commission certification program
emphasize this need to consign resources and support for palliative care teams.
Eligibility requirements for palliative care program certification include: be a joint
commission accredited hospital or facility, have full time coverage for palliative
care services, have served a minimum of ten patients and have at least one active
patient at the time of the initial joint commission review, provide care based on
clinical practice guidelines and/or evidence-based practice, have control in the clini-
cal management of patients and coordination of care, follow an organized approach
supported by an interdisciplinary team of health professionals, and use performance
measurement to improve its performance over time.
These standards are based on The National Consensus Project’s Clinical Practice
Guidelines for Quality Palliative Care and the National Quality Forum’s National
Framework and Preferred Practices for Palliative and Hospice Care Quality.
The common goals and standards of all the credentialing disciplines and organi-
zations reflect the scope and complexity of palliative care. All entities strive for
complete care of the dying patient and family, including the physical, spiritual,
emotional, cultural, legal, and ethical components treatments. Features that are
Preface xv
shared by all programs stress the importance of the interdisciplinary approach for
alleviation of suffering, care in multiple settings, education, quality improvement,
and attention to family and caregivers.
The monumental efforts that have led to the entry of palliative care into the main-
stream of medical practice provide a sound foundation for individual institutions to
incorporate this practice into the network of customary hospital services . Although
the number of institutions that provide a palliative care team continues to grow,
there is a lack of standardization regarding the composition and role of such a team.
There is opportunity for institutions to support the excellence and standards of spe-
cialized professionals, and offer customized service that is focused on the unique
patient populations that they serve. Each hospital has tools available developing its
own unique approach for delivery of palliative care.
Education, of course, should be a major component of any symptom manage-
ment and palliative care program. Mark Lema, MD, PhD commented in the ASA
Newsletter, July 1998, that “The AMA is concerned that physician assisted suicide
is a symptom of a much bigger problem, that physicians are not prepared to properly
care for dying patients” [6]. Changing one’s focus from cure to comfort care is not
in the traditional medical curriculum or philosophy. Attendings, fellows, residents,
interns, and medical students as well as nursing staff and all other ancillary person-
nel of the team have to be taught this reorientated mind-set. How to approach the
patient and/or significant others with the diagnosis of terminal illness, the presenta-
tion of options for end-of-life care, the emphasis that palliative care does not mean
“nothing else can be done,” or that no care will be offered, but rather that the goal of
therapy will be comfort and dignity is something that must be taught and practiced.
How one obtains a “true informed consent” for do not resuscitate (DNR), and how
one approaches the completion of an advanced directive needs to be taught and
needs to be learned.
In summary, true palliative care involves a paradigm shift. A patient used to
receive a diagnosis of a life-threatening disease and a treatment plan was laid out
with little attention paid to the consequences of the treatment or what will be done
if the treatment fails to arrest the disease. And it was only in the last few days or
weeks of life that a patient was offered comfort care measures. Today, as compas-
sionate healthcare providers it is incumbent upon us to introduce comfort care early
in the process. Comfort measures (palliative care) will intensify as curative mea-
sures are exhausted. Thus, the needs of the patient and his/her family can be met at
all stages of the disease process. We hope that our book, Essentials of Palliative
Care, is useful for clinicians of all disciplines as we move forward in this ever
changing and complex world.
New Haven, CT, USA Nalini Vadivelu

New Orleans, LA, USA Alan David Kaye
Los Angeles, CA, USA Jack M. Berger
xvi Preface
References
1. Portenoy RK, Lupu DE, Arnold RM, Cordes A, Storey P. Formal ABMS and ACGME recogni-
tion of hospice and palliative medicine expected in 2006. J Palliat Med. 2006;9(1):21–3.
2. Berzoff J, Lucas G, Deluca D, Gerbino S, Browning D, Foster Z, Chatchkes E. Clinical social
work education in palliative and end-of-life care: relational approaches for advanced practitio-
ners. J Soc Work End Life Palliat Care. 2006;2(2):45–63.
3. Von Gunten CF. Set an example. J Palliat Med. 2009;12(5):409.
4. Weissman DE, Meier DE. Identifying patients in need of a palliative care assessment in the
hospital setting, a consensus report from the Center to Advance Palliative Care. J Palliat Med.
2011;14(1):17–22.
5. Weissman DE, Meier DE. Operational features for hospital palliative care programs: consensus
recommendations. J Palliat Med. 2008;11(9):1189–94.
6. Lema M. Comments in the ASA Newsletter, July 1998.
Contents
1 Introduction and Education .................................................................. 1

Angèle Ryan and Jack M. Berger
2 Multidisciplinary Approach and Coordination of Care ..................... 7
Sukanya Mitra and Nalini Vadivelu
3 Psychological Distress and Psychiatric Comorbidities
in Palliative Care .................................................................................... 23
Raphael J. Leo and Maria Theresa Mariano
4 Hospice for the Terminally Ill and End-of-Life Care ......................... 49
Jamie Capasso, Robert Byron Kim, and Danielle Perret
5 Communication in Palliative Care ....................................................... 73
Dominique Anwar, Sean Ransom, and Roy S. Weiner
6 Guidance with Complex Treatment Choices ....................................... 89
7 Symptom Management.......................................................................... 107
Angèle Ryan
8 Nutrition in Palliative Care ................................................................... 137
M. Khurram Ghori and Susan Dabu-Bondoc
9 Nursing Perspective and Considerations ............................................. 163
Ena M. Williams and Tong Ying Ge
10 Physical and Occupational Therapy in Palliative Care ...................... 177
Kais Alsharif and Justin Hata
11 Social Work in Palliative Care .............................................................. 189
Janet Lucas, Bill Mejia, and Anne Riffenburgh
12 The Healthcare System: More Questions than Answers .................... 209
Jackie D.D. Carter
xvii
xviii Contents
13 Vascular Access: Ostomies and Drains Care

in Palliative Medicine............................................................................. 217
Patricia L. Devaney
14 Drug Formulary ..................................................................................... 229
Angèle Ryan
15 Interventional Radiology in Palliative Care ........................................ 253
Oliver Hulson, Neal Larkman, and S. Kunnumpurath
16 Stroke, Epilepsy, and Neurological Diseases ....................................... 279
María Gudín
17 Interventional Techniques in Palliative Care ...................................... 299
Rinoo V. Shah, Alan David Kaye,
Christopher K. Merritt, and Lien B. Tran
18 Headache in Palliative Care .................................................................. 315
Nicholas Connolly, Matthew Peña, and Tara M. Sheridan
19 Endoscopic Therapies for Palliation of Gastrointestinal
Malignancies ........................................................................................... 349
Henry C. Ho and Uzma D. Siddiqui
20 The Role of Palliative Care in Cardiothoracic Surgery ..................... 369
Amit Banerjee
21 Management of Advanced Heart Failure Patients .............................. 375
Dominique Anwar and Asif Anwar
22 Palliative Care in Cardiac Electrophysiology...................................... 385
Eric Grubman
23 Palliation in Respiratory Disease .......................................................... 395
David R. Meek, Martin D. Knolle, and Thomas B. Pulimood
24 Palliative Care in Critical Care Units .................................................. 417
Rita Agarwala, Ben Singer, and Sreekumar Kunnumpurath
25 Pediatric Palliative Care ........................................................................ 441
Shu-Ming Wang, Paul B. Yost, and Leonard Sender
26 New Pain Management Vistas in Palliative Care ................................ 457
Christopher K. Merritt, Lien B. Tran, Rinoo V. Shah,
and Alan David Kaye
27 Ethics in Palliative and End-of-Life Care ............................................ 483
Jack M. Berger
28 Physician Coding, Billing, and Reimbursement
for Palliative Care .................................................................................. 501
Rene R. Rigal
Index ................................................................................................................ 505

Contributors
Rita Agarwala, B.M., B.Sc. Department of Anesthetics, Epsom and St Helier

University Hospitals NHS Trust, Carshalton, Surrey, UK
Kais Alsharif, M.D. Department of Anesthesiology and Perioperative Care,
University of California, Irvine School of Medicine, Irvine, CA, USA
Asif Anwar, M.D. Heart and Vascular Institute, Department of Medicine, Tulane
University School of Medicine, New Orleans, LA, USA
Dominique Anwar, M.D. Section of General Internal Medicine and Geriatrics,
Tulane University School of Medicine, New Orleans, LA, USA
Amit Banerjee, M.S., M.Ch. Department of Cardiothoracic Surgery, Maulana
Azad Medical College, New Delhi, India
Govind Ballabh Pant Hospital, University of Delhi, New Delhi, India
Jack M. Berger, M.S., M.D., Ph.D. Department of Anesthesiology, Keck School
of Medicine, University of Southern California, Los Angeles, CA, USA
Jamie Capasso, D.O. Department of Medicine, University of California, Irvine
School of Medicine, Irvine, CA, USA
Jackie D.D. Carter, R.N., M.S.N., C.N.S. Department of Nursing, LAC+USC
Medical Center, Los Angeles, CA, USA
Nicholas Connolly, M.D. Department of Anesthesiology, Naval Medical Center
San Diego, San Diego, CA, USA
Susan Dabu-Bondoc, M.D. Department of Anesthesiology, Yale University
School of Medicine, New Haven, CT, USA
Patricia L. Devaney, R.N., B.S., M.S. Department of Diagnostic Radiology,
Yale-New Haven Hospital, New Haven, CT, USA
Tong Ying Ge, R.N., M.S.N. (Master Degree of Nursing) Pain Advanced
practice nurse, Sir Run Run Shaw Hospital, Hangzhou, China
xix
xx Contributors
M. Khurram Ghori, M.D. Department of Anesthesiology, Yale University School

of Medicine, New Haven, CT, USA
Eric Grubman, M.D. Department of Internal Medicine, Yale University School
of Medicine, New Haven, CT, USA
María Gudín, Ph.D. Neurology Department, Ciudad Real General University
Hospital, Ciudad Real, Castilla–La Mancha, Spain
Justin Hata, M.D. Department of Anesthesiology and Perioperative Care,
Henry C. Ho, M.D. Section of Digestive Diseases, Department of Internal
Medicine, Yale University School of Medicine, New Haven, CT, USA
Oliver Hulson, M.B.Ch.B. (Hons.) Leeds and Bradford Radiology Training
Scheme, Leeds General Infirmary, Leeds, UK
Alan David Kaye, M.D., Ph.D. Department of Anesthesiology, Louisiana State
Robert Byron Kim, M.D. Department of Anesthesiology & Perioperative Care,
Martin D. Knolle, M.B., B.Chir., M.R.C.P. Department of Respiratory Medicine,
Lister Hospital, Stevenage, UK
Sreekumar Kunnumpurath, M.B.B.S., M.D. Department of Anaesthetics,
Epsom and St Helier University Hospitals NHS Trust, Carshalton, Surrey, UK
Neal Larkman, M.B.B.S. M.P.H., Leeds and Bradford Radiology Training
Scheme, Leeds General Infirmary, Leeds, UK
Raphael J. Leo, M.A., M.D. Department of Psychiatry, School of Medicine and
Biomedical Sciences, State University of New York, Buffalo, NY, USA
Janet Lucas, L.C.S.W., B.S., M.S.W. Family Practice Residency Program,
Glendale Adventist Medical Center, Glendale, CA, USA
Maria Theresa Mariano, M.D. Department of Psychiatry, School of Medicine
and Biomedical Sciences, State University of New York, Buffalo, NY, USA
David R. Meek, M.R.C.P. Department of Respiratory and General Internal
Medicine, West Suffolk Hospital, University of Cambridge Teaching Hospital, Bury
St Edmunds, Suffolk, UK
Bill Mejia, L.C.S.W., B.S., M.S.W. Palliate Care Consult Service, Huntington
Hospital, Pasadena, CA, USA
Christopher K. Merritt, M.D. Department of Anesthesiology, Louisiana State
Sukanya Mitra, M.D. Department of Anaesthesia and Intensive Care, Government
Medical College and Hospital, Chandigarh, India
Contributors xxi
Matthew Peña, M.D. Department of Anesthesiology, Naval Medical Center San

Diego, San Diego, CA, USA
Danielle Perret, M.D. Department of Anesthesiology & Perioperative Care,
Thomas B. Pulimood, M.B.B.S., F.R.C.P. Department of Respiratory and General
Internal Medicine, West Suffolk Hospital, University of Cambridge Teaching
Hospital, Bury St Edmunds, Suffolk, UK
Sean Ransom, Ph.D. Department of Psychiatry and Behavioral Sciences, Tulane
Anne Riffenburgh, L.C.S.W., B.S., M.S.W. Huntington Cancer Center,
Huntington Hospital, Pasadena, CA, USA
Rene R. Rigal, M.D. Pain Management Center, Divine Providence Hospital,
Williamsport, PA, USA
Angèle Ryan, M.D. Department of Anesthesiology, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA
Leonard Sender, M.D. Department of Medicine, University of California, Irvine
School of Medicine, Irvine, CA, USA
Rinoo V. Shah, M.D., M.B.A. Department of Anesthesiology, Guthrie Clinic-Big
Flats, Horseheads, NY, USA
Tara M. Sheridan, M.D. Department of Anesthesiology, Naval Medical Center
San Diego, Bethesda, MD, USA
Uzma D. Siddiqui, M.D. Department of Medicine, University of Chicago Pritzker
School of Medicine, Chicago, IL, USA
Ben Singer, M.B.B.S., F.R.C.A. Department of Anaesthetics, Epsom and St Helier
University Hospitals NHS Trust, Carshalton, Surrey, UK
Lien B. Tran, M.D. Department of Anesthesiology, Louisiana State University
School of Medicine, New Orleans, LA, USA
Nalini Vadivelu, M.D. Department of Anesthesiology, Yale University School of
Medicine, New Haven, CT, USA
Shu-Ming Wang, M.D. Department of Anesthesiology and Perioperative Care,
Roy S. Weiner, M.D. Tulane Cancer Center, Tulane University School of Medicine,
Ena M. Williams, R.N., M.S.M., M.B.A. Department of Perioperative Services,
Yale-New Haven Hospital, New Haven, CT, USA
Paul B. Yost, M.D., F.A.A.P. Department of Anesthesiology, St. Joseph’s of
Orange, Orange, CA, USA
Chapter 1
Introduction and Education
Angèle Ryan and Jack M. Berger
Palliative Medicine has become a familiar term in recent years and is becoming
established as a key component in modern health care, and many institutions pro-
mote Palliative Care teams. Although this is a term relatively new to many practitio-
ners, palliative care was coined several decades ago by Dr. Balfour Mount, a
Canadian physician. After training in Dame Cicely Saunders’ St. Christopher’s
Hospice in London, he was so impressed that he was inspired to bring this type of
care to mainstream curative medicine. As a result, he founded the Royal Victoria
Hospital Palliative Care Service in 1974 and is credited with establishing the first
in-patient palliative care unit in North America. Having emerged from the nurse
driven hospice movement, the care of the dying has evolved to a formal hospice
benefit and development of a recognized subspecialty.
This specialty of Hospice and Palliative Medicine (HPM) is dedicated to the
promotion of quality end of life care to patients and to families struggling with
advanced disease. In recent years, palliative care has become increasingly common
in the medical literature as well as in the public media. Although the delivery of
palliative care is influenced by the hospice model, the composition of a hospital-
based palliative care team varies significantly from one institution to another, but
fundamental roles are generally identified for the provision of physical, emotional,
social, and spiritual comfort. The requirements for a “home” based palliative care
team service are similar to those of the hospital-based service.
In developing an educational program for symptom management and palliative
care, physicians and other healthcare providers need to learn how to make difficult
decisions with respect to recommending or initiating therapeutic interventions or
recommending and discontinuing interventions. Examples of symptoms which have
to be considered can be grouped as follows:
A. Ryan, M.D. (*) • J.M. Berger, M.S., M.D., Ph.D.

Department of Anesthesiology, Keck School of Medicine, University of Southern California,
e-mail: angel@ix.netcom.com; jmberger@usc.edu
N. Vadivelu et al. (eds.), Essentials of Palliative Care, 1

DOI 10.1007/978-1-4614-5164-8_1,
2 A. Ryan and J.M. Berger
• Pain of any etiology, tumor metastasis, spinal cord or nerve root compression,
lymphedema, bowel obstruction, electrolyte abnormalities.
• Dehydration, malnutrition, anorexia–cachexia syndrome, radiation enteritis,
diarrhea, nausea, vomiting.
• Asthenia, fatigue, weakness.
• Dyspnea, respiratory failure, respiratory tract infections, pleural effusions,
lymphangitis carcinomatosis.
• Anemia, wound breakdown, ulcerations, decubitus ulcers, ostomies.
• Anxiety, confusion, sleep disorders, depression, sadness, anger.
• Hiccoughs, cough, bloating, belching, mucositis, foul body odors, wheezing.
It is necessary to develop systems for evaluating the necessity or futility of inter-
vening based upon an understanding of the pathophysiology of the above symptoms
in the face of the terminally ill patient. The costs both economic and psychosocial
of intervening or not intervening or cessation of ongoing interventions must be bet-
ter defined. Only through facing these difficult problems critically can we learn how
best to deal with them.
The Physician
The American Board of Medical Specialties is a self-policing organization that sets

standards and grants certification for medical practice beyond the minimum requirements
for licensure. In a given field of medical practice, a physician seeks recognition for
expertise. When Palliative Medicine became part of modern medical practice, the
logical result was the pursuit of formal certification. As a result, the American Board
of Hospice and Palliative Medicine was formed, an independent certifying
organization.
From 1996 to 2006, the available certification for physicians practicing palliative
medicine was through the independent American Board of Hospice and Palliative
Medicine. This entity provides recognition of expertise for practitioners caring for
the dying, while promoting the importance of the specialty and working toward
transition to formal recognition by the American Board of Medical Specialties, the
official body that is recognized by healthcare systems as the stamp of approval of
medical specialties [1]. Currently, there are ten cosponsoring boards that offer sub-
specialty certification in Hospice and Palliative Medicine (HPM), including the
American Boards of Anesthesiology, Emergency Medicine, Family Medicine,
Internal Medicine, Obstetrics and Gynecology, Pediatrics, Physical Medicine and
Rehabilitation, Psychiatry and Neurology, Radiology, and Surgery.
Competencies of subspecialist-level hospice and palliative medicine include
skills in symptom management, relief of suffering and improving the quality of life
for patients and families living with life-threatening illness, provision of assistance
for patients and families coping with loss, and management of challenging
problems associated with end-of-life care.
1 Introduction and Education 3
Nursing
The nursing profession has been at the forefront of the hospice movement and plays
a pivotal role in modern palliative medicine. The National Board for Certification of
Hospice and Palliative Nurses (NBCHPN), established in 1993, provides nursing
certification for hospice and palliative medicine for several categories of nursing
positions. The classifications of expertise include: Advanced Certified Hospice and
Palliative Nurse (ACHPN), Certified Hospice and Palliative Nurse (CHPN), Certified
Hospice and Palliative Pediatric Nurse (CHPPN), Certified Hospice and Palliative
Licensed Nurse (CHPLN), Certified Hospice and Palliative Nursing Assistant
(CHPNA), and Certified Hospice and Palliative Care Administrator (CHPCA). Each
certification period is valid for 4 years and is renewable.
Advanced practice nursing certification is granted for nursing professionals who
hold a Clinical Nurse Specialist or Nurse Practitioner license and have graduated
from an accredited education program specializing in palliative care. The program
must include a minimum of 500 hours of palliative care training or have post mas-
ter’s graduate practice experience of 500 hours in providing palliative care in the
year prior to examination. Successful completion of the examination establishes
excellence in the area of clinical judgment, advocacy and ethics and systems think-
ing, professionalism and research, collaboration, facilitation of learning and com-
munication, and cultural and spiritual competence.
The eligibility requirements for a registered nurse to test for CHPN status, the
candidate must hold a valid registered nurse license. It is recommended that the
individual also have at least 2 years of practice in end-of-life care prior to testing.
Successful completion of the examination demonstrates abilities in recognition of
life-limiting conditions in adult patients, pain and symptom management, care of
patient and family, education and advocacy, interdisciplinary/collaborative practice,
A nursing professional seeking certification for NBCHPN is required to hold a
valid registered nurse license and is encouraged to have a minimum of 2 years expe-
rience in the care of terminally ill children. This encompasses the care of patients
ranging in age from prenatal to young adulthood. As a result of certification, the
pediatric nurse establishes competencies in recognition of life-threatening condi-
tions in children, pain and symptom management, treatments and procedures, fam-
ily centered care, education and advocacy, care at end of life, grief and bereavement,
The certification exam for licensed practical nurses (LPN) and licensed vocational
nurses (LVN) has been offered since 2004. Successful candidates achieve the CHPLN
credential, which is valid for 4 years. Candidates holding a valid LPN or LVN are eli-
gible to take the exam. Two years experience in the hospice or palliative care setting is
recommended. Clinical areas of expertise include: various aspects of patient care, such
as end-stage disease process in adult patients, pain, symptom, and comfort
management, treatments and procedures, care of patient, family, and other caregivers,
patient and family education and advocacy, and interdisciplinary and collaborative
practice issues.
Nursing assistants are eligible to test for the CHPNA credential if the candidate
can provide documentation of 2000 practice hours under the supervision of a registered
nurse in the previous 2 years. It is also recommended that the candidates have 2
years of experience specifically in the field of hospice or palliative care.
Examination for the CHPCA credential is offered for any individual with 2 years
experience in an administrative role, verified by a supervisor which involves hos-
pice or palliative care. The NBCHPN administrator examination tests for compe-
tency in leadership, planning, operations, fiscal and human resource management,
quality management, marketing, public relations, and ethics.
Social Work
The advanced certified hospice and palliative social worker (ACHP-SW) credential
was added in 2009. It was adapted for the specialized skills and expertise of social
work professionals who provide care in the hospice and palliative care setting [2].
The eligibility requirements include a master’s degree in social work from an
accredited university, 20 or more continuing education credits specific to hospice
and palliative care, documentation of at least 2 years of supervised social work
experience in hospice or palliative care setting, and current license to practice as a
professional social worker.
Program Certification
With the ambitious credentialing process for all members of the palliative care team, it
is logical to expect progression to program certification. The Joint Commission on
Accreditation of Healthcare Organizations has developed an Advanced Certification
Program for Palliative Care. Expertise and commitment of dedicated individuals repre-
senting the credentialed disciplines is greatly enhanced in the setting of institutional
support. Standards set forth by the Joint Commission certification program emphasize
this need to consign resources and support for palliative care teams.
Eligibility requirements for palliative care program certification include joint
commission accredited hospital or facility, full-time coverage for palliative care ser-
vices, have served a minimum of ten patients and have at least one active patient at
the time of the initial joint commission review, provide care based on clinical
practice guidelines and/or evidence-based practice, have control in the clinical man-
agement of patients and coordination of care, follow an organized approach supported
by an interdisciplinary team of health professionals, and use performance measure-
ment to improve its performance over time. These standards are based on The
National Consensus Project’s Clinical Practice Guidelines for Quality Palliative
1 Introduction and Education 5
Care and the National Quality Forum’s National Framework and Preferred Practices
for Palliative and Hospice Care Quality.
The common goals and standards of all the credentialing disciplines and organizations
reflect the scope and complexity of palliative care. All entities strive for complete
care of the dying patient and family, including the physical, spiritual, emotional,
cultural, legal, and ethical components treatments. Features that are shared by all
programs stress the importance of the interdisciplinary approach for alleviation of
suffering, care in multiple settings, education, quality improvement, attention to
family and caregivers.
The monumental efforts that have led to the entry of palliative care into the
mainstream of medical practice provide a sound foundation for individual institu-
tions to incorporate this practice into the network of customary hospital services
[3]. Although the number of institutions that provide a palliative care team contin-
ues to grow, there is a lack of standardization regarding the composition and role
of such a team. There is opportunity for institutions to support the excellence and
standards of specialized professionals, and offer customized service that is focused
on the unique patient populations that they serve [4, 5]. Each hospital has tools
available for development of its own unique approach for delivery of palliative
care.
Education of course should be a major component of any symptom manage-
ment and palliative care program. Mark Lema M.D., Ph.D. commented in the
American Society of Anesthesiologists Newsletter, July 1998, that “The American
Medical Association is concerned that physician assisted suicide is a symptom of
a much bigger problem, that physicians are not prepared to properly care for dying
patients” [6].
Changing one’s focus from cure to comfort care is not in the traditional medi-
cal curriculum or philosophy. Attendings, fellows, residents, interns, and medical
students as well as nursing staff and all other ancillary personnel of the team have
to be taught this reorientation of mind-set. How to approach the patient and/or
significant others with the diagnosis of terminal illness, the presentation of options
for end of life care, the emphasis that palliative care does not mean “nothing else
can be done,” or that no care will be offered, but rather that the goal of therapy
will be comfort and dignity is something that must be taught and practiced. How
one obtains a “true informed consent” for do not resuscitate (DNR), and how one
approaches the completion of an advanced directive needs to be taught and needs
to be learned.
In summary, true palliative care involves a paradigm shift. A patient used to
receive a diagnosis of a life-threatening disease and a treatment plan was laid out
with little attention paid to the consequences of the treatment or what will be done
if the treatment fails to arrest the disease. And it was only in the last few days or
weeks of life that a patient was offered comfort care measures. Today, as
compassionate healthcare providers it is incumbent upon us to introduce comfort
care early in the process. Comfort measures (palliative care) will intensify as cura-
tive measures are exhausted. Thus, the needs of the patient and his/her family can be
met at all stages of the disease process.
References
1. Portenoy RK, Lupu DE, Arnold RM, Cordes A, Storey P. Formal ABMS and ACGME recog-
nition of hospice and palliative medicine expected in 2006. J Palliat Med. 2006;9(1):21–3.
2. Berzoff J, Lucas G, Deluca D, Gerbino S, Browning D, Foster Z, Chatchkes E. Clinical social
work education in palliative and end-of-life care: relational approaches for advanced practitio-
ners. J Soc Work End Life Palliat Care. 2006;2(2):45–63.
3. Von Gunten CF. Set an example. J Palliat Med. 2009;12(5):409.
hospital setting, a consensus report from the Center to Advance Palliative Care. J Palliat Med.
2011;14(1):17–22.
5. Weissman DE, Meier DE. Operational features for hospital palliative care programs: consen-
sus recommendations. J Palliat Med. 2008;11(9):1189–94.
6. Lema M. Comments in the ASA Newsletter, July 1998.
Chapter 2
Multidisciplinary Approach and Coordination
of Care
Introduction and Basic Concepts
On September 1, 2011, The Joint Commission (formerly the Joint Commission on

Accreditation of Healthcare Organizations) announced the Advanced Certification
Program for Palliative Care, “designed to recognize hospital inpatient programs that
demonstrate exceptional patient and family-centered care in order to optimize the qual-
ity of life for patients with serious illness” [1]. This development represents the latest
important milestone marked on a long and arduous journey that began in the hospice
movement in the 1960s and then the related palliative care movement in the 1980s.
The word “palliative” or “palliation” is derived from Latin “palliare,” which
means “to cloak,” or in other words, to mask, to cover up, or to mitigate. Traditional
medicine has generally been curative, i.e., focused on cure of the underlying cause
of a disease. Symptom removal (or “symptomatic treatment”) has often been
perceived as incomplete and facile. In a similar vein, traditional medicine has usually
regarded issues such as distress reduction and improvement in quality of life as
secondary to the primary aim of treating the actual disease. Understandably, such an
approach immediately faces an obvious roadblock when dealing with diseases that
are remotely curable or incurable (e.g., some cancers, cancers with widespread
metastasis, advanced HIV disease, some neurological, renal, and pulmonary
diseases, etc.). In these unfortunate progressive and life-threatening illnesses, where
S. Mitra, M.D. (*)

Department of Anaesthesia and Intensive Care,
Government Medical College and Hospital,
Chandigarh, India
e-mail: Drsmitra12@yahoo.com
N. Vadivelu, M.D.
Department of Anesthesiology,
Yale University School of Medicine,
New Haven, CT, USA

DOI 10.1007/978-1-4614-5164-8_2,
8 S. Mitra and N. Vadivelu
the prospect of a “cure” is largely nonexistent, one is forced to “shift gear” and
adopt a modified perspective. The focus then changes to one of symptom reduction,
distress management, and eventually, improving the quality of life under the
circumstances. This, in essence, is the palliative care approach.
The World Health Organization (WHO) has defined palliative care as:
Palliative care is an approach that improves the quality of life of patients and their families
facing the problems associated with life-threatening illness, through the prevention and
relief of suffering by means of early identification and impeccable assessment and treat-
ment of pain and other problems, physical, psychosocial and spiritual [2].
It goes on further to clarify that palliative care:
• Provides relief from pain and other distressing symptoms.

• Affirms life and regards dying as a normal process.
• Intends neither to hasten nor postpone death.
• Integrates the psychological and spiritual aspects of patient care.
• Offers a support system to help patients live as actively as possible until death.
• Offers a support system to help the family cope during the patient’s illness and in
their own bereavement.
• Uses a team approach to address the needs of patients and their families, including
bereavement counseling, if indicated.
• Will enhance quality of life, and may also positively influence the course of
illness.
• Is applicable early in the course of illness, in conjunction with other therapies
that are intended to prolong life, such as chemotherapy or radiation therapy, and
includes those investigations needed to better understand and manage distressing
clinical complications [2].
Similar definitions of palliative care are found elsewhere. For example, The
National Consensus Project (NCP) has given a comprehensive definition and
characterization of palliative care as follows:
The goal of palliative care is to prevent and relieve suffering and to support the best possible
quality of life for patients and their families, regardless of the stage of the disease or the
need for other therapies. Palliative care is both a philosophy of care and an organized,
highly structured system for delivering care. Palliative care expands traditional disease-
model medical treatments to include the goals of enhancing quality of life for patient and
family, optimizing function, helping with decision making, and providing opportunities for
personal growth. As such, it can be delivered concurrently with life-prolonging care or as
the main focus of care. Palliative care is operationalized through effective management of
pain and other distressing symptoms, while incorporating psychosocial and spiritual care
with consideration of patient/family needs, preferences, values, beliefs, and culture.
Evaluation and treatment should be comprehensive and patient-centered with a focus on the
central role of the family unit in decision making. Palliative care affirms life by supporting
the patient and family’s goals for the future, including their hopes for cure or life-prolonga-
tion, as well as their hopes for peace and dignity throughout the course of illness, the dying
process, and death. Palliative care aims to guide and assist the patient and family in making
decisions that enable them to work toward their goals during whatever time they have
remaining. Comprehensive palliative care services often require the expertise of various
2 Multidisciplinary Approach and Coordination of Care 9
providers to adequately assess and treat the complex needs of seriously ill patients and their
families. Leadership, collaboration, coordination, and communication are key elements for
effective integration of these disciplines and services [3].
Finally, the National Quality Forum (NQF) has provided this rather concise
definition:
Palliative care refers to patient- and family-centered care that optimizes quality of life by
anticipating, preventing, and treating suffering. Palliative care throughout the continuum of
illness involves addressing physical, intellectual, emotional, social, and spiritual needs and
facilitating patient autonomy, access to information, and choice [4].
The NCP and the NQF both espoused eight domains of palliative care as
follows:
1. Structure and processes of care
2. Physical aspects of care
3. Psychosocial and psychiatric aspects of care
4. Social aspects of care
5. Spiritual, religious, and existential aspects of care
6. Cultural aspects of care
7. Care of the imminently dying patient
8. Ethical and legal aspects of care
Multidisciplinary Approach in Palliative Care
From all the above definitions and characterizations of palliative care, one key element
of palliative care that stands out is the element of multidisciplinary (also termed
interdisciplinary; but see later) approach. All the definitions either directly or
indirectly include this element as a defining component of palliative care. The basic
logic behind this approach is simple: the needs to be addressed in palliative care are
diverse, complex, multidimensional, and dynamic. These needs transgress the narrow
bounds of disease-governed dimensions (e.g., metastasis, CD4 cell counts) and
extend to several symptom and syndromal domains (e.g., pain, dyspnea, delirium,
depression, nausea, weight loss, and many others). More importantly, as repeatedly
emphasized in all the definitions of palliative care, these needs transverse multiple
overlapping dimensions: physical, emotional, intellectual, familial and other
interpersonal, financial and other practical, social and cultural, and, finally, spiritual
or existential. It naturally follows that so many aspects of palliative care (see the
domains of care mentioned by both NCP and NQF) cannot be addressed by one
person or even one team from a particular discipline. Hence the essential need for a
multidisciplinary approach in palliative care. The NCP, for example, has explicitly
stated this as the fifth of their 11 “key elements of palliative care”:
Interdisciplinary team: Palliative care presupposes indications for, and provision of, inter-
disciplinary team evaluation and treatment in selected cases. The palliative-care team must
be skilled in care of the patient population to be served. Palliative-care teams may be

expanded to include a range of professionals based on the services needed. They include a
core group of professionals from medicine, nursing and social work, and may include some
combination of volunteer coordinators, bereavement coordinators, chaplains, psycholo-
gists, pharmacists, nursing assistants and home attendants, dietitians, speech and language
pathologists, physical, occupational, art, play, music, and child-life therapists, case manag-
ers, and trained volunteers [3].
As an aside, it is to be noted that although the terms multidisciplinary and

interdisciplinary are used interchangeably in this chapter, these two are not exactly
synonymous. Both the terms refer to inputs from different disciplines regarding
individual patient care. In multidisciplinary model, however, each member of a
particular discipline provides an expert consultation in his or her area of expertise,
clearly maintains one’s own disciplinary identity, and works in relative isolation where
team membership, while important, is secondary. There is usually a clearly defined
hierarchy in the multidisciplinary team. The identified “leader” of the multidisciplinary
team (MDT) integrates the inputs from different disciplines and takes the final decision.
In interdisciplinary model, however, the approach is more of sharing and integration
from the beginning, less clear role distinction and hierarchy, and leadership is task
dependent rather than hierarchy dependent. Also, the patient is kept at the center of an
interdisciplinary approach and he or she takes an active part in the consultative and
decision-making process [5, 6]. Many of the current documents (NCP, NQF) use the
term interdisciplinary rather than multidisciplinary. Research literature and general
clinical practice, however, maintain the term multidisciplinary. Further, the differences
between these two terms are subtle and graded. In keeping with the title of this
chapter, the term multidisciplinary will be consistently used here.
Models of Palliative Care and Multidisciplinary Approach
Palliative care can be provided at various levels. Because the current expanded
concept of palliative care encompasses this care of the patient to start ideally right
from the diagnosis of a potentially life-threatening illness, the first level of pallia-
tive care can start at the primary care level itself. Depending upon the stage of
progression of disease, its complications and newly emergent needs of the patient
and the family, the level of such care then moves through secondary care and
finally specialist tertiary care. Understandably, the composition and activities
(structure and process) of the multidisciplinary team will also vary according to
these levels of care.
There are different models of palliative care depending upon the different levels.
These may be:
(a) Outpatient Palliative Care Programs—these occur in ambulatory care settings to
provide continuity of care for patients with serious or life-threatening illnesses.
(b) Community Palliative Care Programs—these occur in communities as consultative
teams who collaborate with hospices or home health agencies to support
seriously ill patients who have not yet accessed hospice.
(c) Institutional Palliative Care Programs—these are institutional-based programs in

the hospital or nursing home to serve patients with life-threatening or life-limiting
illnesses. They occur in hospital settings (academic, community, rehabilitation)
and skilled nursing facilities. These provide services to patients anywhere along
the disease continuum between initial diagnosis and death.
(d) Hospice Care—this is a well-established program to provide patients with a
prognosis of 6 months or less. As delineated within the Medicare Hospice
Benefit, these services can be provided in the home, nursing home, residential
facility, or on an inpatient unit.
Role Played by the Multidisciplinary Team in Palliative Care
The MDT plays an essential role in virtually every stage of the palliative care process,
starting from the comprehensive assessment of the patient in the beginning till the
final days of end-of-life care.
Under the first domain of palliative care (structure and processes of care), the very
first guideline (1.1) of NCP stresses this fact: The timely plan of care is based on
a comprehensive interdisciplinary assessment of the patient and family. It elabo-
rates that “Assessment includes documentation of disease status, including diag-
noses and prognosis; comorbid medical and psychiatric disorders; physical and
psychological symptoms; functional status; social, cultural, spiritual, and advance
care planning concerns and preferences, including appropriateness of referral to
hospice.”
The guideline 1.2 (care plan) too emphasizes the role of the MDT: “The
interdisciplinary team coordinates and shares the information, provides support
for decision making, develops and carries out the care plan, and communicates
the palliative care plan to patient and family, to all involved health professionals,
and to the responsible providers when patients transfer to different care
settings.”
Guideline 1.3 most clearly espouses the role of the MDT in palliative care and is
worth quoting in full:
Guideline 1.3 An interdisciplinary team provides services to the patient and family
consistent with the care plan. In addition to nursing, medicine, and social work, other therapeu-
tic disciplines with important assessment of patients and families include physical thera-
pists, occupational therapists, speech and language pathologists, nutritionists, psychologists,
chaplains, and nursing assistants. For pediatrics, this should include child-life specialists.
Complementary and alternative therapies may be included.
Criteria:
• Specialist-level palliative care is delivered by an interdisciplinary team.

• The team includes palliative care professionals with the appropriate patient-
population-specific education, credentialing, and experience and the ability
to meet the physical, psychological, social, and spiritual needs of both patient
and family. Of particular importance is hiring physicians, nurses, and social

workers “appropriately trained” and ultimately certified in hospice and pallia-
tive care. Education should include a fundamental understanding of the
domains of palliative care and the goals of the Medicare Hospice Benefit, in
addition to pain, symptoms, grief, bereavement, and communication. Ideally
this occurs in preceptorships, fellowships, or in baccalaureate and graduate
specific programs. Continuing education is an essential for professionals cur-
rently in practice.
• The interdisciplinary palliative care team involved in the care of children, either
as patients or as the children of adult patients, has expertise in the delivery of
services for such children.
• The patient and family have access to palliative care expertise and staff 24 hours
a day, seven days a week. Respite services are available for the families and care-
givers of children or adults with life-threatening illnesses.
• The interdisciplinary team communicates regularly (at least weekly or more
often as required by the clinical situation) to plan, review, and evaluate the care
plan, with input from both the patient and family.
• The team meets regularly to discuss provision of quality care, including staffing,
policies, and clinical practices.
• Team leadership has appropriate training, qualifications, and experience.
• Policies for prioritizing and responding to referrals in a timely manner are docu-
mented [3].
Specific instances of the roles of the MDT in other domains of palliative care
are mentioned as well. For example, under domain 2 (Physical aspects of care),
Guideline 2.1 mentions as its first criterion: “The interdisciplinary team includes
professionals with specialist-level skill in symptom control for all types of
life-threatening illnesses, including physicians, nurses, social workers, rehabili-
tation specialists, physical therapists, occupational therapists, speech and lan-
guage pathologists, psychologists, child-life specialists (and other appropriate
therapists for children), and chaplains” [3]. Similarly, under domain 3
(Psychological and psychiatric aspects of care), Guideline 3.1 mentions as its
first criterion: “The interdisciplinary team includes professionals with patient-
specific skills and training in the psychological consequences and psychiatric
comorbidities of serious illness for both patient and family, including depression,
anxiety, delirium, and cognitive impairment” [3]. Under the same domain, the
first criterion of Guideline 3.2 mentions: “The interdisciplinary team includes
professionals with patient-population-appropriate education and skill in the care
of patients, families, and care staff experiencing loss, grief, and bereavement”
[3].
Domain 4 (Social aspects of care) again heavily stresses the role of the MDT in
case assessment and care plan formulation, and is quoted below:
Guideline 4.1 Comprehensive interdisciplinary assessment identifies the social needs
of patients and their families, and a care plan is developed to respond to these needs as
effectively as possible.
Criteria:
• The interdisciplinary team includes professionals with patient-population-specific

skills in the assessment and management of social and practical needs during a
life-threatening or chronic debilitating illness
• It is essential that practitioners skilled in the assessment and management of the
developmental needs of children are available for pediatric patients and the chil-
dren of adult patients, as appropriate.
• A comprehensive interdisciplinary social assessment is completed and docu-
mented to include: family structure and geographic location; relationships; lines
of communication; existing social and cultural networks; perceived social sup-
port; medical decision making; work and school settings; finances; sexuality;
intimacy; living arrangements; caregiver availability; access to transportation;
access to prescription and over-the-counter medicines and nutritional products;
access to needed equipment; community resources, including school and work
settings; and legal issues
• Routine patient and family meetings are conducted with appropriate members of
the interdisciplinary team to assess understanding and address questions; provide
information and help with decision making, discuss goals of care and advance
care planning; determine wishes, preferences, hopes and fears; provide emo-
tional and social support; and enhance communication.
• The social care plan is formulated from a comprehensive social and cultural
assessment and reassessment and reflects and documents values, goals, and pref-
erences as set by the patient and family over time. Interventions are planned to
minimize the adverse impact of caregiving on the family and to promote care-
giver and family goals and well-being.
• Referrals to appropriate services are made that meet identified social needs
and promote access to care, help in the home, school or work, transportation,
rehabilitation, medications, counseling, community resources, and equip-
ment [3].
Indeed, the roles of the MDT have been mentioned for all the other domains of
palliative care (Spiritual, religious, and existential aspects of care; Cultural aspects
of care; Care of the imminently dying patient; Ethical and legal aspects of care). It
is especially worthwhile to note that the MDT has an important role to play after
death of the patient as well: (“Guideline 7.3 A post-death bereavement plan is acti-
vated. An interdisciplinary team member is assigned to the family in the post-death
period to help with religious practices, funeral arrangements, and burial planning”
[3]).
The NQF too echoes this general emphasis as reflected in many of its “Preferred
Practices” starting, for example, from its Preferred Practice number 1: “Provide
palliative and hospice care by an interdisciplinary team of skilled palliative care
professionals, including, for example, physicians, nurses, social workers, pharmacists,
spiritual care counselors, and others who collaborate with primary healthcare
professional(s)” [4].
Advantages and Effectiveness and of MDT Approach
The most obvious advantage of MDT is that more heads put together may work
better than one head. In other words, MDT approach may generate new options and
yield creative solutions to complex and multidimensional problems. The other
advantages include:
• Decrease the time from presentation to treatment.
• Decrease fragmentation, with better communication, decreased errors and
duplicate tests, and clarified treatment plan.
• Decrease variability between physicians, ensuring application of good clinical
practice.
• Increase patient satisfaction through fewer visits and consistent
communication.
• Enable doctors to focus on multiple aspects of a patient’s care (socio-emotional,
nutrition, etc).
• Decrease medico-legal risk.
• Improve quality of life.
• Foster the setting wherein complex treatment plans can be created and
sustained.
• Increase enrollment in research studies.
• Improve the education and support of family members.
• Provide a marketable service for an institution.
• Create a unique experience for graduate medical education.
• Decrease the number of procedures needed to make a diagnosis.
• Align programs.
• Improve survival [7].
The benefits of MDT approach, supported by data, include: increased patient
satisfaction; enhanced quality of life; increased accuracy of care; decreased time to
treatment; decreased variability of care; and even some data to show a modest
increase in survival in cancer patients [7–13]. There is, however, a need to conduct
more methodologically rigorous controlled trials in this area [14].
Barriers and Challenges
Theoretically and conceptually, the MDT approach lies at the heart of the palliative
care. However, there are a number of practical challenges in setting up and running
a successful MDT [15–17]. Like any other program, setting up a MDT in a busy and
resource-competitive hospital can be a daunting task. It requires, among other
things, political will and administrative support, institutional back-up, adequate and
sustainable funding, identifying specific team members and securing professional
support from the identified team members in terms of time, effort, and commitment.
All these can prove quite an uphill task!
After these barriers have been overcome, other issues remain. These involve practi-
cal logistic issues such as the format, location, frequency, duration, and order of pri-
oritization of the MDT meetings. During the meetings, certain professionals may view
it as a duplication of their efforts (and hence waste of their time, especially if there is
no reimbursement for the same) because of repetition of parts of information from dif-
ferent sources. On the other hand, at times, professionals from widely diverse disci-
plines (neurosurgeon, radiation oncologist, nursing staff, psychologist, social worker,
counselor, chaplain) speak different “languages” and may find it difficult understand-
ing one another’s perspectives and priorities. Communication barriers may ensue,
which may further complicate matters and perhaps foster a sense of alienation and
futility. Leadership issues may arise, either directly or covertly. Finally, the sheer
arrangement of such meetings can prove an arduous task given the busy schedules and
prior commitments of the individual members of the MDT.
Even when a MDT is put in place and has been running its services for a while,
barriers and challenges continue to haunt these services. As recently found in a
survey conducted in Australia, these barriers are of six thematic types [17]:
1. Confusion about the roles and responsibilities of the different members of the
MDT involved in care (e.g., perceived lack of recognition of the identified care
coordinator as a professional in her own right, role tensions between the primary
care providers and MDT members, confusion in the patient’s mind as to what a
“care coordinator” means and who is that—the primary referring doctor, the
surgeon, the oncologist(s), or the named care coordinator, etc.)
2. Problems in implementing comprehensive multidisciplinary team meetings (e.g.,
time constraints, lack of support for meetings, logistical issues in trying to get all
members of the MDT together at the onetime, large geographical distances
between team members, staff shortages in key disciplines such as oncology,
alack of administrative support for these meetings and dominant personalities
limiting open discussion
3. Transitioning of care: “Falling through the cracks” (e.g., lack of communica-
tion and effective referral between these centers, particularly from large urban
centers of expertise back to the local services from which patients sought sup-
port, lack of communication and coordination between the public and private
sectors)
4. Inadequate communication between specialist and primary care (inconsistent,
delayed and incomplete communication among the health care team, particularly
between family physicians and specialists which inhibited the delivery of
coordinated patient care)
5. Inequitable access to health services (rural or regional disadvantages, public/
private care differences)
6. Managing scarce resources and personnel (in terms of primary care physicians,
specialists, care coordinators, and other members of the MDT)
Coordination of Care
Many of these barriers and challenges may be overcome by an effective and

continuous coordination of care. Coordination of care, in fact, is one of the central
tenets of the MDT approach. Coordination of care is vitally important:
(a) For the patient: for ensuring proper continuity of care of the individual patient
through different stages of the disease and emergent needs
(b) For the MDT: for ensuring its smooth operation and overcoming many of the
barriers mentioned above
(c) For the healthcare system: for enhancing its efficiency and minimizing fragmentation
of the system involved in palliative care as a whole
Lack of coordinated care can lead to fragmented care, patients getting “lost” in the
system and failing to access appropriate services, as well as more unplanned health
utilization [17]. On the other hand, a proper system of care coordination has multiple
benefits, both over short and long term.
Coordination of palliative care can:
• Improve patient outcomes (when patients receive the appropriate care at the right
time)
• Improve use of recommended treatments, including increased referral to
appropriate services and patient compliance (when system processes are known
and used)
• Improve communication between providers (when reliable and trusting relation-
ships are built over time)
• Streamline services, decrease duplication, and reduce costs (when processes and
communication are efficient and monitored or reviewed over time) [18, 19]
Care coordination is a comprehensive approach to achieving continuity of care

for patients.
This approach aims to ensure that care is delivered in a logical, connected, and
timely manner so that the medical and personal needs of patients are met.
Coordinated care is an important part of management for all patients who require
a variety of treatments and care, particularly when care is provided over time and
between settings. This is often the case for people with chronic and progressive
diseases in need of palliative care.
Effective care coordination provides the necessary interface between patients and
healthcare providers, between the providers themselves, between the providers and the
healthcare system, and, importantly, between different healthcare settings as the patient
“transitions” from the primary care to various levels of specialist care during the phases
of the illness, in order to prevent the patient “falling through the cracks.” For cancer
patients, for example, it is well known that the treatment journey is complex and chal-
lenging. It is not uncommon for these patients to be seen by many health professionals
within and across multiple health services and across different health sectors including
public, private, and community health in both metropolitan and rural regions.
The Victorian Government Department of Human Services, Melbourne, Victoria,

Australia, in their important document “Linking cancer care: A guide for implementing
coordinated cancer care” has identified the following as the key principles of care
coordination in the context of cancer care (which are easily applicable for palliative
care in general) [19]:
• Patients, their families and carers affected by cancer are at the center of care
• Care coordination initiatives should take into consideration the continuum of
care including the various health sectors involved in delivering care across tumor
streams
• Care coordination initiatives should take into consideration rural/regional and
metropolitan contexts of care
• Enhancing continuity of care across the health sector requires a whole-of-system
response, that is, initiatives developed to address continuity of care need to occur
across a number of key levels—that of the health system, health service, team,
and individual
• Improving care coordination is the responsibility of all health professionals
involved in the care of individual patients and should therefore be considered in
their practice
Conclusion
Palliative care aims to reduce distress, enhance functioning, and improve the quality
of life of people and their families facing life-threatening diseases, rather than
directly aiming at cure or disease modification. Palliative care should start early and
alongside disease-modifying treatment, and become the predominant mode of care
with more advanced stages of disease, finally ending in bereavement care. Palliative
care thus is a continuum. During this continuum, palliative care addresses the mul-
tiple domains of needs and concerns of the patient and the family—physical, psy-
chological, social, and spiritual. These needs cannot be addressed by one single
person or agency without causing fragmentation of care. Hence a multidisciplinary
approach is the backbone of palliative care. In this approach, inputs are obtained and
integrated from multiple sources depending upon, among other factors, stage of
disease progression, pain and other symptoms, patient’s and family’s psychological
state, social and practical requirements, and available resources. The doctors (both
primary care and specialists), nursing staff, social worker, and many others involved
in the multifaceted care of the patient form the multidisciplinary team, which pro-
vides this care in a coordinated manner so as to provide continuity of care. There are
many obvious advantages of the multidisciplinary approach, and its efficacy has
been demonstrated convincingly in increasing satisfaction of the patient and family,
improving quality of life, and even a modest increase in survival for some patients.
However, the multidisciplinary approach has its own barriers and challenges. Some of
these can be at least partly overcome with an effective coordination of care between
different locations (primary, secondary), personnel (both between the patient and the
healthcare providers, and between different categories of the providers themselves),

and time points of care. With proper coordination of care, people living with life-
threatening diseases can look forward to receiving palliative care.
References
1. jointcommission.org. Washington, DC: The Joint Commission. Advanced certification for

palliative care programs. http://www.jointcommission.org/certification/palliative_care.aspx.
Updated 24 Oct 2011; cited 25 Oct 2011.
2. who.int. Geneva, Switzerland: World Health Organization. WHO definition of palliative care.
http://www.who.int/cancer/palliative/definition/en/. Updated 24 Oct 2011; cited 25 Oct 2011.
3. National Consensus Project for Palliative Care. Clinical practice guidelines for quality palliative
care. 2nd ed. Pittsburgh: National Consensus Project for Palliative Care; 2009.
4. National Quality Forum. A national framework and preferred practices for palliative and
hospice care quality. Washington, DC: National Quality Forum; 2006.
5. Crawford GB, Price SD. Team working: palliative care as a model of interdisciplinary practice.
Med J Aust. 2003;179:S32–4.
6. Jessup RL. Interdisciplinary versus multidisciplinary care teams: do we understand the difference?
Aust Health Rev. 2007;31:330–1.
7. Horvath LE, Yordan E, Malhotra D, Leyva I, Bortel K, Schalk D, et al. Multidisciplinary care
in the oncology setting: historical perspective and data from lung and gynecology
multidisciplinary clinics. J Oncol Pract. 2010;6:e21–6.
8. Rummans TA, Clark MM, Sloan JA, et al. Impacting quality of life for patientswith advanced
cancer with a structured multidisciplinary intervention: a randomized controlled trial. J Clin
Oncol. 2006;24:635–42.
9. Walker MS, Ristvedt SL, Haughey BH, et al. Patient care in multidisciplinary cancer clinics:
does attention to psychosocial needs predict patient satisfaction? Psychooncology.
2003;12:291–300.
10. Newman EA, Guest AB, Helvie MA, et al. Changes in surgical management resulting from
case review at a breast cancer multidisciplinary tumor board. Cancer. 2006;107:2346–51.
11. Bakitas M, Lyons KD, Hegel MT, et al. Effects of a palliative care intervention on clinical
outcomes in patients with advanced cancer: the Project ENABLE II randomized controlled
trial. JAMA. 2009;302:741–9.
12. Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patientswith metastatic
non-small-cell lung cancer. N Engl J Med. 2010;363:733–42.
13. Meier DE, Brawley OW. Palliative care and the quality of life. J Clin Oncol.
2011;29:2750–2.
14. Carey M, Sanson-Fisher R, Lotfi-Jam K, Schofield P, Aranda S. Multidisciplinary care in
cancer: do the current research outputs help? Eur J Cancer Care. 2010;19:434–41.
15. Hammond DB. Multidisciplinary cancer care in a hospital setting: challenges and rewards.
J Oncol Pract. 2010;6:281–3.
16. Look Hong NJ, Gagliardi AR, Bronskill SE, Paszat LF, Wright FC. Multidisciplinary cancer
conferences: exploring obstacles and facilitators to their implementation. J Oncol Pract.
2010;6:61–8.
17. Walsh J, Harrison JD, Young JM, Butow PN, Solomon MJ, Masya L. What are the current
barriers to effective cancer care coordination? A qualitative study. BMC Health Serv Res.
2010;10:132.
18. Morrison RS, Meier DE. Palliative care. N Engl J Med. 2004;350:2582–90.
19. Victorian Government Department of Human Services. Linking cancer care: a guide for
implementing coordinated cancer care. Melbourne: Victorian Government Department of
Human Services; 2007.
Review Questions
1. According to the World Health Organization definition of palliative care, the

essential aim of palliative care is to:
(a) Correct the underlying metabolic derangements in life-threatening disease
(b) Focus on disease modification
(c) Improve the quality of life
(d) Provide symptomatic and psychosocial support exclusively for the patient
2. Palliative care is:
(a) Disease centered
(b) Patient centered
(c) Family centered
(d) Patient- and family centered
3. The needs addressed by palliative care does not include:
(a) Spiritual
(b) Curative
(c) Psychosocial
(d) Physical
4. The number of domains of palliative care endorsed by both National Consensus
Project (NCP) and National Quality Forum (NQF) is:
(a) 4
(b) 6
(c) 8
(d) 10
5. According to NCP Clinical Practice Guidelines 2009, the core group in an inter-
disciplinary (multidisciplinary) palliative care team should have professionals
from all the following disciplines except:
(a) Psychology
(b) Social work
(c) Nursing
(d) Medicine
6. According to expanded model and scope of palliative care, such care can start at
the level of :
(a) Primary care
(b) Secondary care
(c) Tertiary care
(d) Any of the above levels
7. The following statement is true regarding research-evidenced benefits of a

multidisciplinary team (MDT) in palliative care:
(a) Modest increase in survival of certain cancer patients
(b No effect on patient satisfaction
(c) No effect on quality of life
(d) Time delay in reaching consensus opinions
8. Coordination of care is important for:
(a) The patient
(b) The MDT
(c) The healthcare system
(d) All of the above
9. For patients in palliative care, the overall aim of coordination of care is to
provide:
(a) Consultations from various doctors
(b) Arrangement of MDT meetings
(c) Continuity of care over time and across settings
(d) Bereavement counseling
10. The Advanced Certification Program for Palliative Care announced by the Joint
Commission is designed for the following type of palliative care program
(as of September 2011):
(a) Outpatient based
(b) Inpatient based
(c) Community based
(d) Hospice based
Answers
1. (c)
2. (d)
3. (b)
4. (c)
5. (a)
6. (d)
7. (a)
8. (d)
9. (c)
10. (b)
Chapter 3
Psychological Distress and Psychiatric
Comorbidities in Palliative Care
Raphael J. Leo and Maria Theresa Mariano
Introduction
Palliative care medicine has expanded awareness of, and the refinement of treat-
ment efforts directed at, alleviating physical symptoms of patients with terminal
conditions. Over the years, medical and psychological discourse on end-of-life care
has increasingly drawn attention to many of the distinct psychosocial challenges
that patients confront, emphasizing the importance of integrating the physical and
psychological aspects of care essential to improving quality of life. Addressing the
multiplicity of psychological issues faced by patients can be daunting, especially
when considered in the context of the limited time available before death ensues.
This chapter highlights the psychological needs of the terminal patient. An empha-
sis will be placed on subsyndromal, but nonetheless distressing, psychological
states, as well as the assessment and management of psychiatric disorders frequently
encountered within the context of palliative care. Although much of the data come
from studies of patients with terminal cancer, many of the principles outlined herein
are likely to apply to a broad spectrum of patients requiring end-of-life care.
Psychosocial Demands at the End of Life
Having a terminal prognosis alters, and often disrupts, one’s view of the world,
one’s self and the future. Several, perhaps all, aspects of one’s life may be sus-
pended because of prevailing physical needs, e.g., one’s life may become centered
on pain and/or other physical symptoms and the securing of basic bodily needs.
R.J. Leo, M.A., M.D. (*) • M.T. Mariano, M.D.

Department of Psychiatry, School of Medicine and Biomedical Sciences,
State University of New York,
Buffalo, NY, USA
e-mail: rleomd@aol.com

DOI 10.1007/978-1-4614-5164-8_3,
24 R.J. Leo and M.T. Mariano
The patient may be thrust into positions of marked dependency on others. Progressive
physical deconditioning may interfere with one’s capacity to engage in customary
activities and interests, and may restrict access to customary social support networks.
There may be limited emotional reserve to invest in others or to maintain relationships.
The patient may experience a loss of hope for goals and aspirations. Concerns may
arise about one’s transcendence and generativity, i.e., leaving a legacy, and how one
is remembered by those who are left behind.
Any of these factors, in isolation or combined, can trigger, and amplify, psycho-
logical reactions that present significant sources of distress and suffering for the
terminal patient as well as caregivers. Acknowledgement of the finite nature of
one’s future requires coping with grief and highlights one’s concerns about life
meaning. These issues will be briefly discussed below.
Grief, Life Meaning, and Spiritual Distress
Grief is the emotional and psychological reaction to a loss, not necessarily limited
to death. Many patients with medical illness, especially those confronting terminal
illness, suffer grief reactions related to losses arising from the illness, e.g., loss of a
sense of future, self-image, self-esteem and self-efficacy, and material losses. The
process of mourning allows for the expression of loss, facilitates acceptance of
prevailing life circumstances, and enables the individual to begin to channel energy
into maintaining relationships, resolving interpersonal conflicts, and managing the
challenges faced as death approaches [1].
For family and loved ones too, there can be sadness in anticipation of the impending
death. Anticipatory grief, therefore, has the potential for drawing families and loved
ones closer to the patient, as well as to one another. Effective and open communication
during this time between the patient and loved ones, engendered by exchanging
gratitude, story-telling and reminiscing, and celebrating the life and contributions of
the dying person, may facilitate the mourning process, providing opportunities for
“saying goodbye” and sharing in the completion of “unfinished business” [1, 2].
Symptoms of grief include profound sadness, which can sometimes be expressed
as a focus on physical symptoms, withdrawal from others, and even fleeting thoughts
of despair. However, there can be variability in mood during mourning that serves
to distinguish it from depression [3]. Impediments to mourning can arise from
denial, avoidance of the inevitability of death, and unaddressed anger, triggering
persisting, i.e., less variability in, symptoms. Persistent and unremitting dysphoria,
hopelessness, helplessness, preoccupations with guilt and/or worthlessness, anhe-
donia, and death preoccupation, by contrast, may signal an underlying depressive
disorder, and should not be dismissed as an expected grief-related reaction. If present,
these symptoms should prompt efforts to secure treatment.
Dying patients may experience existential distress, i.e., despair engendered by
threats to one’s perception of the meaningfulness of life and a sense of disconnection
from one’s sense of purpose. Such distress can present with an admixture of emotional
3 Psychological Distress and Psychiatric Comorbidities in Palliative Care 25
and psychological reactions including fear, shock, anger, vulnerability, uncertainty,

isolation, hopelessness, and desires for hastening death. Having an opportunity to
express concerns related to the meaningfulness of one’s life and to pursue goals and
responsibilities towards others may assist patients to alter their attitudes and begin
to view their lives as worthwhile despite the severe illness.
Closely related to existential distress is a perceived disruption from one’s
spirituality. For some persons, the experience of spirituality will guide one’s ability
to derive meaning from life experiences, e.g., lending a framework within which to
understand suffering and impart a means for understanding existential issues and
one’s imminent death [4].
Research has demonstrated that spirituality can serve to buffer against depression
[5, 6] and hopelessness [7, 8], and fosters coping [6, 9]. Thus, spirituality and one’s
ability to cultivate and sustain life meaning and purpose may be particularly predictive
of psychological well-being and quality of life among patients with terminal illness
[10]. However, facing a life-threatening illness can pose challenges to one’s spiritual
framework, e.g., causing one to question fundamental belief systems such as beliefs
in the afterlife, or to face issues related to the meaningfulness of one’s life and exis-
tential issues, and thereby trigger distress [11].
A broad range of psychological and emotional reactions are therefore possible in
the context of terminal illness. The challenge for treatment providers is to effec-
tively identify those patients for whom such emotional and psychological reactions
constitute pathologic states warranting treatment measures and referral to other
sources of support, e.g., pastoral and/or mental health services.
Patient–Provider Communication: When Is Distress

Pathological?
It is common for terminal patients to experience transient feelings of sadness,

apprehension, worry (e.g., about aspects of the illness or treatment), or manifest
preoccupations with life meaning, futility or pessimism often contingent upon, and
in response to, clinical developments. Patients may, nonetheless, successfully navigate
the adaptational challenges posed at advanced stages of illness without significant
and enduring suffering and distress, depending upon whether they have psychological
resources (influenced by intrinsic emotional reserves, cognitive attributions, and
problem-solving strategies) [12]. The meanings ascribed to, and expectations related
to, the illness, the beliefs and assumptions one has about one’s life and self-perceptions,
one’s coping strategies, and the perception one has about his/her competence with
which to manage the illness can be significant determinants influencing the extent
to which distress is experienced [13–16]. Distress incurred by ineffective coping
strategies and beliefs about the illness or its effects can, however, be buffered by
strong and supportive relationships, e.g., the accessibility of physical, psychological,
spiritual, and emotional support from family, friends, caregivers, and treatment
providers. For example, the degree to which family and other social supports are
perceived as accessible and supportive can influence the extent to which psychological
distress is experienced [17].
However, in some circumstances, the distress incurred may be overwhelming,
leading to impairments in adaptation. Thus, for example, an individual perceiving
the illness as uncontrollable and unpredictable and perceiving minimal social
support is likely to experience significant distress as compared with another who is
apt to appraise herself as capable of exerting control over at least some aspects of
the illness or her life and/or perceiving greater social support.
Given the magnitude of psychological issues encountered in the advanced stages
of illness, competence in the skills in providing grief/bereavement and spiritual support
are critical and central components for the palliative care team [18]. The relationship
with primary medical caregiver(s) may be the safest and the main source of support
for exploration of psychological distress. Ongoing clinician–patient communication
is essential to the assessment of the patient’s psychological well-being. Being aware
of the critical psychological tasks encountered at the end of life can influence the
tenor of care offered by palliative care providers, potentially humanizing it and
infusing it with a respect for the patient. Patients may find openness to discussions
about matters pertaining to loss, grief, life meaning, and spirituality to be reassuring,
conveying that such deeply personal experiences are esteemed and respected, and
that their values will be honored in the context of the patient–clinician relationship.
Typically, approaches that are advocated involve making time to foster a connection
with the patient, respecting the unique aspects of the individual’s experiences and
spirituality, enabling the sharing of the patient’s perspectives and conveying that s/
he is heard [19]. Furthermore, ongoing communication between treatment provider
and patient may unveil signs that psychological distress related to grief, existential
matters, and spirituality are incapacitating, burdensome, and/or may be harbingers
of more significant psychiatric disturbance that warrant treatment.
It is often difficult to determine when one’s emotional and psychological reactions
constitute appropriate and expected responses to life-altering experiences and when
the patient’s reactions signal a clinicopathological state; the benchmark for making
this determination is defined in terms of the duration, flexibility, and consequences
of symptoms. Thus, when negative emotions persist and/or when problematic
cognitive appraisals remain inflexible, and thereby significantly disrupt function-
ing, hinder treatment, or impede one’s capacity to take in pleasure or comfort, these
psychological reactions are thought to reflect more of a pathological state. Under
such circumstances, having access to psychiatrists, other mental health practitioners
and pastoral care services can be particularly helpful, serving to bolster psychological
and physical well-being, and foster life meaning.
Unfortunately, recognition of psychological distress and comorbid psychiatric
conditions often goes unrecognized by palliative care clinicians [20–22]. Common
impediments to open communication about the patient’s emotional/psychological
needs in palliative care are summarized in Table 3.1. For example, very brief clinical
encounters, embarrassment, and the perception that one’s care providers would be
disinterested in such matters may prevent patients from disclosing information
about their level of emotional distress. On the other hand, clinicians often are prone
Table 3.1 Patient–clinician factors impeding communication about psychological distress

Patient-related factors Clinician-related factors
Embarrassment precluding open discussion The perception that it is not one’s role to
about psychological distress address psychosocial concerns
Stigma associated with being labeled with a Insufficient skills or training to address
psychological disorder psychosocial concerns
Perception that doctors are too busy or Clinician discomfort with emotionally-laden
disinterested topics
Believing that psychological distress is expected Lack of awareness of psychological stressors
A tendency to somatize as a means of conveying confronting patients at end of life
psychological distress instead of directly Misattributions that emotional distress is
expressing distress openly expected and “normal” response to
confronting terminal illness
Greater weight given to physical ailments
rather than psychological distress
Under-recognition of psychiatric comorbidi-
ties potentially affecting patients at
end-of-life
[23–25]
to prioritize medical diagnostic and treatment concerns and overlook emotional dis-
tress [23, 24]. This tendency may be fueled by the assumptions that dysphoria and
depression are understandable reactions to being afflicted with an unremitting and
terminal condition. In addition, clinicians may be reluctant to explore emotionally-
laden issues with their patients because they fear that such discussion will be insulting
or stigmatizing. However, failure to explore the presence of clinically significant
emotional distress may leave potentially treatable conditions unidentified and
unaddressed, further compromising quality of life in advanced stages of illness.
To bypass some of these impediments, palliative care practice guidelines strongly
advocate for constant monitoring for, and use of screening assessments to assist in
the identification of, psychological distress [18]. Although the utility of many of
these screening instruments, e.g., the Distress Thermometer [26], the Functional
Assessment of Chronic Illness Therapy Spiritual Well-Being Scale [10], among oth-
ers, have not been empirically established [27], their use facilitates dialogue and can
be the basis for the exploration of treatment options that can be potentially
implemented to enhance patient comfort.
Psychiatric Disorders Encountered in the Palliative Care Setting
There is an extensive epidemiological literature that supports the high prevalence of

primary psychiatric disorders among persons in the terminal phases of illness (e.g.,
[28, 29]). Several meta-analyses and systematic reviews of the literature revealed
that adjustment disorders, depression, anxiety disorders, and delirium are among the
most common psychiatric conditions encountered in palliative care settings [30–34].

(More specific features of each of these conditions and their management are dis-
cussed in the next section.)
It is noteworthy that prevalence estimates of psychiatric disorders vary across
studies included in the aforementioned reviews depending upon the assessment
methodologies employed, sampling heterogeneity and selection bias, and the ranges
of symptoms upon which diagnoses were based. Thus, the types of assessments
employed, e.g., clinical diagnostic interview versus self-rated questionnaire, can
account for some of the variability in prevalence rates observed [35, 36]. Brief rat-
ing instruments customarily applied to, and standardized based upon, non-terminal
patients may not be appropriate for terminal patients and thus results reported by
investigations based on such self-report measures should be interpreted with caution
[37]. Additionally, selection bias may have had a bearing on outcomes, e.g., severely
ill patients who may ostensibly have comparatively high rates of psychiatric illness,
may have been excluded from such investigations due to poor health limiting
participation in assessments [38]. Lastly, the inclusiveness, or exclusiveness, in the
range of symptoms upon which the diagnosis of various psychiatric disorders was
based may have been inconsistent across studies influencing the reported preva-
lence rates. For example, many symptoms, e.g., sleep disturbances, fatigue, or
anorexia, occurring as a direct result of medical illness may mimic neurovegetative
symptoms of major mood and anxiety disorders. Reliance on these symptoms may
yield false positives, and therefore, inflate reported rates of psychiatric comorbidi-
ties. On the other hand, studies utilizing stringent criteria, i.e., excluding symptoms
with ambiguous etiologies, may have potentially led to missed cases and lower
reported prevalence rates.
Despite the aforementioned methodological issues in the extant literature, it
nonetheless appears that palliative care practitioners should prudently and judi-
ciously consider an extensive array of psychiatric comorbidities among terminal
patients and that psychiatric treatment be secured whenever appropriate. Generally,
a multimodal approach to treatment, i.e., employing psychotherapeutic and psy-
chopharmacologic interventions, may be necessary. Although it is not feasible to
provide an exhaustive overview of available psychotherapeutic approaches useful in
palliative care here, the reader should recognize that there are several approaches
available. A summary of the possible uses of various psychotherapeutic and phar-
macologic treatment approaches employed in palliative care settings is provided in
Tables 3.2 and 3.3, respectively. Briefly, the goals of treatment include alleviation
of subjectively perceived distress, facilitating comfort and hope, and, in as much as
it is feasible given the severity of prevailing medical conditions, improvement of
symptoms and the patient’s functional capabilities. The implementation of psycho-
therapeutic interventions outlined herein can also be useful in assisting patients con-
tending with subsyndromal psychological distress related to existential distress,
grief, etc. The selection of a particular modality or combination of modalities would
depend on the particular patient’s needs, the commitment to pursue psychotherapy
and the training/skills of the psychiatrist, and other available mental health practi-
tioners, enlisted in the care of the terminal patient.
Table 3.2 Psychotherapeutic interventions that may be useful in addressing psychological

distress and psychiatric comorbidities in the palliative care setting
Modality Technique Uses
Supportive Active listening, problem-solving Reduce distressing emotions;
psychotherapy strategies; allowing the expression of emotions in a
expression of distressing safe environment; enhance
emotions; enhance availabil- focused problem-solving;
ity and accessibility of social enhancement of social
support networks supports to sustain patient
through difficulties
Cognitive-behavioral Collaborative process identifying Reduce depression and anxiety;
therapy cognitive appraisals; reduce problematic cognitive
cognitive restructuring and styles and faulty attributions;
coping skills training develop effective coping
strategies
Interpersonal Role-playing, analysis of and Address role transitions due to
psychotherapy modification of problematic illness, relationship
communication patterns difficulties, and interpersonal
conflicts
Existential therapy Life narrative and life review, i.e., Fostering a sense of meaningful-
identifying and highlighting ness; placing current
one’s significant life experiences within the
experiences and achievements context of coping with illness
Grief therapy Exploration of perceived losses, Fostering mourning, acceptance;
facilitating mourning, fostering a sense of
encouraging restoration of meaningfulness; and leaving
function and delineation of a legacy/generativity
remaining goals, re-engage-
ment with others
Dignity-preserving Preserving self-care and Maintaining pride, and sense of
therapy customary roles; ensuring self-efficacy and autonomy;
appropriate privacy boundar- reducing perceived burden to
ies, preserving autonomy and others
control in life matters and
decision-making whenever
feasible
Relaxation training Deep breathing exercises; Relaxation; distraction from
progressive muscle relax- physical discomfort, e.g.,
ation; guided imagery pain; fosters a sense of
mastery and empowerment
Self-hypnosis Focused attention and dissocia- Relaxation; distraction; pain
tion is directed at alleviating relief
physical discomfort and
anxiety/distress
[38–40]
A few caveats are worth noting, however. First, recommendations for many of
the treatment approaches delineated in the section below are not based upon a solid
foundation of empirical work. For some of these, the proposed benefit is extrapo-
lated from studies demonstrating the benefits obtained from employing these
Table 3.3 Uses of various classes of psychopharmacologic agents in

palliative care
Antidepressants Neuroleptics
Depression Antiemetic
Anxiety Delirium
Co-analgesic agents in pain Psychosis
Severe agitation/violent behavior
Benzodiazepines Psychostimulants
Anxiety Depressive disorders
Insomnia Opioid-induced sedation
Neuroleptic-induced akathisia Fatigue
Alcohol withdrawal Narcolepsy
Muscle spasm
Conscious sedation
[12, 28, 40, 41]
interventions in nonterminal patients. There are limited prospective, randomized tri-

als or systematic meta-analytic reviews to draw upon to guide or direct selection of
optimal treatment strategies in the palliative care setting. Often, the evidence for
the utility of many of the psychotherapeutic and psychopharmacologic approaches
discussed herein has largely been anecdotal, or based upon few randomized con-
trolled trials or investigations employing small sample sizes. Additionally, there
has been little investigation comparing the efficacy of one approach versus another,
or determining the efficacy of combined endeavors versus those administered in
isolation. It is imperative, however, to point out that the dearth of empirical research
does not constitute evidence of a lack of efficacy in these conditions [42, 43].
Second, the logistics of some of the treatment approaches outlined herein can some-
times be impractical. Prognostic factors, e.g., life expectancy and the time frame avail-
able for treatment, are significant determinants influencing selection of the types of
psychopharmacologic and psychotherapeutic measures undertaken. The terminal
patient expected to live several months may be able to afford the time it takes to undergo
certain psychotherapeutic modalities and/or the time requirements to appreciate the
clinical efficacy of certain psychopharmacologic interventions, e.g., antidepressant
effects. By contrast, patients with extremely restricted life expectancies, e.g., a few
weeks, may not be able to yield much benefit from such interventions, requiring more
expedient palliative measures to allay distress and provide comfort. In addition, the
limited stamina of the patient and/or diminished cognitive acuity may impede the abil-
ity to successfully engage a patient in psychotherapy. Under such circumstances, there
may be a need to rely predominantly on psychopharmacologic approaches instead.
Adjustment Disorders
The literature has suggested high, albeit variable, prevalence rates for adjustment
disorders among patients in palliative care settings, ranging from 10 to 22% [32].
Risk factors associated with the development of adjustment disorders have been
suggested to include physical limitations, problems related to social supports, and

existential issues [44].
As a cluster, adjustment disorders refer to subthreshold conditions, possessing
features of other conditions, e.g., anxiety and depression. According to the
Diagnostic and Statistical Manual of Mental Disorders (DSM), the diagnosis rests
on an assessment of one’s emotional and behavioral responses to a stressor, and
determining whether those responses appear to be in excess of normative standards,
i.e., what would be expected by most persons facing comparable circumstances
[45]. The potential pitfall to this diagnostic scheme is that it is subjective. Often, it
is unclear how one knows what the normative response to a stressor might be; this
issue is likely to become particularly onerous given the complexities of the stressors
confronting patients at the end of life. The parameters for what constitutes maladap-
tive responses to stress can vary depending on one’s gender, as well as societal and
cultural influences further obscuring diagnosis. Unfortunately, adjustment disor-
ders, unlike depressive and anxiety disorders, possess indefinite symptoms and lack
an objective checklist of diagnostic criteria upon which to rely.
The confusion around diagnosis of adjustment disorders is paralleled by the
numerous attempts within the literature to characterize psychological and emotional
distress among palliative care patients, encapsulated in terms such as emotional
suffering [46, 47], psychological distress [48], existential distress [49], and demor-
alization [50, 51]. Many of these terms reflect unpleasant and aversive emotions and
behaviors, possessing features overlapping with, although not quite meeting, diag-
nostic criteria for major mood or anxiety disorders as outlined in DSM phenome-
nology. For example, demoralization has been described as a state encompassing
isolation, hopelessness, dysphoria, apprehension, and an inability to cope [52]. It
would be an oversimplification to merely suggest that demoralization, or any of the
other aforementioned terms, be cast under the general rubric of adjustment disor-
ders. It is plausible that the distress encapsulated by some of these terms might exist
along a continuum, ranging from normal or appropriate responses to the challenges
faced at the end of life to more extreme forms representing adjustment disorders and
perhaps a more pernicious depressive or anxiety disorder [51]. However, as alluded
to previously, distinguishing between a normal variant and psychiatric disorder can
be difficult. When distress diminishes one’s capacity for pleasure or to maintain
connections with others or detracts from one’s sense of meaning, clinicians ought to
consider the possibility of an underlying psychiatric disorder [26].
Because of a lack of operationalized diagnostic criteria, there are no screening
instruments that can be implemented to unearth the presence of adjustment disorders.
Other screening instruments, e.g., the Distress Thermometer among others, may be
considered surrogate assessments of subjective distress that can be incorporated rou-
tinely to unveil whether a condition exists that may be responsive to treatment [26].
Treatment approaches for adjustment disorders primarily rest upon psychothera-
peutic measures that foster coping, reduce the impact of stress, and enhance social
support systems to bolster and sustain the patient so as to enhance adaptation (see
Table 3.2). Essentially, the goals of psychotherapy include the provision of a nurturing
environment and support, cultivation of patient empowerment over psychological
distress, the fostering of problem-solving and coping strategies with which to
effectively deal with adversity, and to mitigate psychological distress that can
potentially exacerbate, perpetuate, or maintain physical discomfort, e.g., pain.
In some cases, short-term courses of pharmacotherapy may be indicated to mitigate
distress. For example, anxiolytics and sedative-hypnotics may be useful in reducing
the impact of incapacitating symptoms that otherwise compromise functioning and
impede one’s ability to participate in short-term psychotherapy.
Depression
The experience of sadness is a natural and expected reaction to the multiple

adversities encountered when one is confronted with advanced stages of illness,
e.g., alteration of one’s life trajectory, changes in body image, disability and
dependency, etc. The inability to mourn loss or adapt to new challenges may man-
ifest with signs and symptoms of clinical depression. Individuals who possess a
prior history of depression, a family history of depression, or who have limited
social supports may be more likely to develop clinical depression in the context of
medical illnesses [53, 54]. Among patients with cancer, the severity of cancer-
related symptoms and decrements in functioning that they produce may be fac-
tors predisposing patients to depression [55]. Prevalence rates of depression
among patients in palliative care settings are substantially higher than those in
the general population; a recent meta-analysis reported prevalence rates ranging
from 13 to 20% [32].
Symptoms of depression can manifest with psychological symptoms, i.e., perva-
sive sadness, loss of interests in customarily pleasurable activities, preoccupations
with guilt, worthlessness, death, dying and/or suicide, social withdrawal, indeci-
siveness and concentration deficits, as well as vegetative symptoms, i.e., appetite
changes, sleep disturbances [45]. Depression is a significant cause of suffering and
distress, resulting in the intensification and perpetuation of significant physical
symptoms, e.g., pain and fatigue, and is associated with increased mortality among
patients with cancer [7, 24, 56–61].
Depression can play a pivotal role in the expressed desires of patients for has-
tened death. Although fleeting thoughts of a desire to hasten death are relatively
commonly encountered among terminal patients [62, 63], those patients with per-
sisting desires for hastened death were most apt to be clinically depressed.
Conversely, depressed terminally ill cancer patients were more likely than those
who were not to endorse a desire for hastened death [7]. However, one should be
aware that a desire for hastened death is not invariably associated with depression
[64], for some, such passive desires for hastened death may be linked with inade-
quate pain treatment and other physical symptoms, and that, once appropriately
managed, such desires for death may abate [65, 66].
Transient and intermittent suicidal ideas are reportedly experienced by patients
with advanced phases of illness [67], however, persistent suicidal ideation is likely
to signal severe psychiatric illness, including depression, adjustment disorder, or
delirium [68, 69]. Vulnerability to enduring suicidal ideation is related to inadequately

treated pain, the perception that one is helpless or that one is inefficacious in exert-
ing control over aspects of one’s illness/life [70, 71]. Hopelessness is a significant
predictor of completed suicide in the general population [72, 73] and is a clinical
predictor of suicidal ideation among the terminally ill [57]. Sensitive inquiry into
the patient’s harboring of suicidal ideas, intent, and/or plans is imperative so as to
effectively develop, in conjunction with psychiatric consultation, appropriate
measures to ensure the patient’s safety, mitigate risk, and more effectively manage
pain, mood disorders, and/or delirium.
According to the DSM, the diagnosis of a depressive disorder is restricted to
situations in which patients manifest prototypic signs and symptoms that would not
otherwise be accounted for by another medical/psychiatric condition or their treat-
ment [45]. As alluded to previously, this exclusionary approach to assessment can
present a diagnostic dilemma particularly in the palliative care setting. Uncertainties
may arise as to whether symptoms that are commonly included among the diagnos-
tic criteria for depression should be excluded if these can be otherwise ascribed to
the medical illness. Thus, for example, many symptoms of medical illnesses, e.g.,
fatigue, anorexia, diminished concentration, and sleep disturbances, among others,
can resemble the somatic symptoms of depression. Similarly, reductions in endur-
ance and physical deconditioning can compromise one’s capacity for engaging in
pleasurable activities, resembling anhedonia. Exclusion of such symptoms when
evaluating patients may reduce ambiguities, but conversely, potentially incurs the
risk of missing a potentially treatable depressive disorder.
It is generally agreed that screening methods for depression should be accurate
and easily administered, so as to facilitate development of timely and effective treat-
ment approaches and resource planning, e.g., psychological and/or psychiatric
referral. The Center for Epidemiologic Studies Depression Scale (CES-D) [74], the
Hospital Anxiety and Depression Scale (HADS) [75], and the Beck-Depression
Inventory-II (BDI-II) [76] have been demonstrated to be effective depression screen-
ing instruments employed among the medically ill. Part of the confusion surrounding
the use of these measures has to do with decisions regarding the selection of
appropriate cutoff scores. Certainly, if the intent is to avoid missing patients with
depression who could, therefore, benefit from treatment, less stringent cutoff scores
should be employed. The HADS is perhaps the most frequently used screening
instrument employed in palliative care settings, partly attributable to its brevity and
ease of administration and the fact that it places less emphasis on somatic symptoms
[77, 78]. However, controversy attends whether the HADS is a particularly useful
measure, i.e., having demonstrated unacceptably low sensitivity and specificity val-
ues [79]. Recently, there has been increased interest in the use of a single item
screen asking the question “Are you depressed?” [80]. Although there has been
some evidence to suggest the utility of straightforward inquiry in medical settings,
the low sensitivity and specificity values of affirmative replies in assessing major
depression in palliative care settings raise questions about their utility [81].
Regardless of the screening instrument employed, diagnosis requires a thorough
clinical interview based upon clinical criteria as specified in the DSM; when
uncertainties arise, consultation with mental health providers may clarify diagnosis
and guide treatment approaches [82].
In evaluating a terminal patient with symptoms of depression, it is essential to
consider the full range of potential causes as these may have implications for how
treatment is contoured. It would be presumptuous to assume that depression is
ascribable to the patient’s reactions to having a terminal diagnosis, to a primary
(functional) depressive disorder, or to the social sequelae of grave illness, e.g., isolation
from customary supports. Thus, medical conditions (hypothyroidism and other
metabolic abnormalities, HIV, cerebral metastasis, etc.) and medication use (corti-
costeroids, several chemotherapeutic agents, narcotics, anticonvulsants, antibiotics,
digitalis, beta adrenergic blockers, among others) may need to be considered among
the possibilities to unearth potential causes of depression [40]. It should be noted
that for a particular patient, multiple factors can contribute to or exacerbate depres-
sion symptoms concurrently and that these factors can often have reciprocal
influences. For example, chemotherapy may have direct depressogenic effects while
concomitantly triggering marked dysphoria related to changes in body image.
Therefore, consideration of multiple factors can inform treatment approaches that
are individualized to the unique needs of the patient. In some cases, addressing
remediable medical illnesses and/or modifications in medication selection or doses
whenever possible or reasonable, may be helpful, and possibly sufficient, measures
undertaken to mitigate depressive symptoms.
As a general class, antidepressants have established efficacy in the management
of major depression in the context of palliative care [83]. Among the various classes
of antidepressants available, tricyclic antidepressants (TCAs), serotonin-selective
reuptake inhibitors (SSRIs), and mirtazapine have demonstrated clinical efficacy as
compared to placebo conditions [84]. Although, the clinical benefits of TCAs may
be apparent sooner than those acquired from SSRIs, the extant literature has not
demonstrated greater efficacy of any particular antidepressant class over another
[82, 85]. Evaluation of the utility of alternate antidepressant classes, e.g., serotonin–
norepinephrine reuptake inhibitors (SNRIs) and bupropion has not been extensively
investigated in the palliative care setting.
Selection of an antidepressant is predicated on several factors, i.e., the side effect
profile of the drug, drug tolerability, safety concerns in light of prevailing medical
conditions, and a history of the patient’s personal or familial successful use of a
particular agent or class of agent. For example, so as to minimize the encumbrance
of, and potential risks associated with, polypharmacy, it may be prudent to select an
agent which has demonstrated efficacy in addressing two or more conditions con-
currently, e.g., depression and pain,. In such circumstances, use of a TCA or per-
haps an SNRI, may be preferable. The side effects of a particular medication might
be used to the patient’s advantage as well. Thus, individuals experiencing insomnia
and/or diminished appetite as part of their symptom complex may benefit from
agents that can simultaneously yield these benefits, e.g., mirtazapine or TCAs;
whereas persons who experience marked and incapacitating fatigue may benefit
from the addition of antidepressants with less sedating side effects, e.g., an SNRI or
bupropion.
Similarly, the adverse effects of antidepressants can be prohibitive and intolerable

for some patients, and/or the use of selected agents may be contraindicated in light
of the patient’s comorbid medical conditions. For example, the anticholinergic side
effects of TCAs can predispose medically compromised individuals toward
development of a delirium, limiting their utility. Interestingly, although the potential
for adverse effects of TCAs can render them poorly tolerable by palliative patients,
drop-out rates for patients treated with TCAs did not differ significantly from those
of other agents, i.e., SSRIs [84]. Furthermore, use of TCAs is contraindicated in
patients with closed-angle glaucoma, recent myocardial infarction, cardiac arrhyth-
mias, poorly controlled seizures, or severe benign prostatic hypertrophy.
It is noteworthy however, that it may take 2–4 weeks (and perhaps longer dura-
tions) at optimal doses before benefits of the antidepressants can be appreciated. As
such, the delayed response to achieve antidepressant efficacy may prove to be a
limiting factor for patients with short life expectancies. Use of psychostimulants,
e.g., methylphenidate or dextroamphetamine, has been advocated as alternatives for
rapid treatment of depression in the palliative care setting [86]. These agents may
offer an advantage of producing stimulating effects, e.g., potentially reducing
opioid-induced sedation [87, 88]. However, the utility of psychostimulants in pal-
liative care settings is uncertain; a recent review indicated that there was insufficient
empirical evidence to recommend the use of psychostimulants for the treatment of
depression [89].
Psychotherapeutic interventions, e.g., supportive therapy or cognitive-behavioral
therapy, may be helpful in mitigating symptoms of depression as long as there is
reasonable life expectancy to make such interventions worthwhile. Additionally, the
feasibility of psychotherapeutic interventions will be contingent upon the patient’s
cognitive capabilities and motivation. A recent meta-analysis, based on very few
randomized controlled trials, suggested that psychotherapy, and supportive psycho-
therapy in particular, is effective in mitigating depression among patients with
advanced cancer [39]; it is important to note that empirical investigations address-
ing the effectiveness and utility of such psychotherapeutic interventions are limited,
thereby making it impossible to make definitive statements about their utility in
palliative care settings [90].
Anxiety
Symptoms of anxiety are commonly encountered in the terminal phases of illness,

particularly as one confronts the stark reality of the limitations of treatment and a
limited life expectancy. Anxiety can manifest in a variety of forms, including symp-
toms of apprehension, restlessness, jitteriness, hypervigilance, distractibility,
tachycardia and palpitations, dyspnea, and numbness [91–93]. In addition, patients
may experience distressing rumination and worry [40]; a sense of foreboding can
predispose one to catastrophizing and a preoccupation with the inevitability of
harm/threat which can strain the patient–physician relationship and thereby undermine
treatment [94]. Although many of the aforementioned symptoms can mimic those
of an underlying medical conditions, consideration of, and formal assessment for,
the presence of a treatable anxiety disorder should be considered.
Estimates suggest that anxiety disorders are relatively common among terminally ill
patients [35], reportedly ranging between 7 and 13% [32]. Frequently, anxiety can
coexist with other psychiatric conditions, including depression [30, 95]. Commonly
encountered anxiety disorders include panic disorder, post-traumatic stress disorder,
and generalized anxiety disorder [30, 94]. Anxiety disorders can incur significant func-
tional deficits among afflicted patients [96]; greater impediments to functioning are
likely to be encountered when anxiety and depression coexist [95].
Screening for anxiety can be accomplished with instruments such as the State
Trait Anxiety Inventory (STAI) [97] and the HADS. The STAI was not developed
specifically for medically ill patients, and due to its length, may be cumbersome for
use in palliative care settings [26, 27]. The HADS is perhaps more commonly used,
owing to its brevity and because it simultaneously screens for depression, despite
some of the previously mentioned concerns about its sensitivity and specificity [78,
79]. As noted previously, it serves as an effective screening instrument, but should
not be employed for diagnostic purposes [78]; ultimately, diagnosis of an anxiety
disorder would depend upon a thoroughly conducted clinical interview based upon
DSM diagnostic criteria.
As with depression, in evaluating a terminal patient with symptoms of anxiety, it
is essential to consider whether other factors, apart from a functional anxiety disor-
der, may be precipitating or exacerbating the symptoms. Thus, medical conditions
(e.g., hypoxia arising from chronic obstructive pulmonary disease, pulmonary
edema, congestive heart failure, lung cancer; endocrine disturbances such as hyper-
thyroidism, hyperparathyroidism, carcinoid, pheochromocytoma; cardiac disease
such as myocardial infarction, congestive heart failure, arrhythmia; electrolyte dis-
turbances, e.g., hypocalcemia, hypomagnesemia) and adverse effects of medication
(e.g., bronchodilators, b-adrenergic receptor stimulants, corticosteroids, antiemet-
ics, i.e., metoclopramide and prochlorperazine, antipsychotic-induced akathisia,
and serotonin syndrome) ought to be given consideration, as these may have treat-
ment implications. Addressing these potential precipitating/exacerbating factors, if
possible, may well mitigate anxiety symptoms.
The treatment of comorbid anxiety can serve to reduce somatic preoccupation
and improve patient comfort, and therefore is a necessary component of compre-
hensive palliative care. Benzodiazepines are effective for the rapid amelioration of
anxiety symptoms, e.g., apprehension, agitation, and restlessness, which are com-
monly encountered in terminal phases of illness [28, 40, 98, 99]. Several factors
need to be considered when making medication selections. For example, agents
with long half-lives, e.g., diazepam or clonazepam, may offer the advantage of more
sustained anxiolytic effects over those which are short-acting, e.g., lorazepam or
alprazolam, and thereby necessitate less frequent dosing. Abrupt discontinuation of
long-acting agents will precipitate less severe withdrawal phenomena as compared
with that associated with short-acting agents. On the other hand, side effects, e.g.,
excess sedation, memory impairments, and confusion, can be more troublesome
and enduring with long acting as compared with short-acting agents [99]. Adverse
effects associated with toxic accumulation of benzodiazepines can become especially
problematic in patients with significant hepatic dysfunction, necessitating that
benzodiazepine selection be restricted to lorazepam, oxazepam, or temazepam
instead. The routes of administration may influence selection of specific agents. For
example, only lorazepam and midazolam are rapidly and reliably absorbed fol-
lowing intramuscular administration, while diazepam can be effectively absorbed
through rectal administration and alprazolam from sublingual administration.
Although there is a risk of abuse encountered with administration of benzodiaz-
epines, this is rarely a concern in palliative care settings.
The use of benzodiazepines may be precluded because of the potential for adverse
effects, e.g., for patients with significant respiratory compromise or obstructive
sleep apnea, or those persons for whom excess sedation can be particularly inca-
pacitating or undesirable. It may be possible to employ alternate agents under such
circumstances. For example, buspirone or antidepressants with anxiolytic proper-
ties, e.g., SSRIs or SNRIs, may be considered, however, as alluded to previously the
time course required to achieve sufficient therapeutic benefits may be a limiting fac-
tor. Antipsychotics may be considered as possible alternatives, e.g., olanzapine or
quetiapine [99]. Opioids, although intended for analgesic use, can offer relief from
perceived dyspnea and anxiety as well, particularly in the late stages as death
becomes imminent [100].
Interventions such as relaxation training and deep breathing exercises may be
expedient measures to employ to mitigate periods of marked apprehension and
distress. Effective use of such self-soothing strategies may also foster the patient’s
sense of self-empowerment in being able to control and modulate periods of
distress. Although other strategies, e.g., Cognitive-Behavioral Therapy and
supportive psychotherapy, have also been advocated in the treatment of anxiety, the
utility and efficacy of such formalized interventions in the palliative care setting has
not been extensively established in empirical work. One meta-analysis, based
upon few randomized controlled trials, demonstrated only a marginal benefit from
psychotherapy in mitigating anxiety among patients with incurable cancer [39].
Delirium
The presence of delirium can be a significant source of distress among patients in

the advanced phases of illness, interfering with functioning, adaptation, and
communication with others. Estimates suggest that the prevalence of delirium can
be astonishingly high, as much as 80%, among terminal patients in the weeks before
death [101].
The symptoms of delirium manifest with an inability or reduced ability to maintain
attention, fluctuation of consciousness, disorientation, and sudden and dramatic
memory impairments. Patients may experience distressing perceptual disturbances,
i.e., misperceptions of their surroundings and hallucinations (usually visual). The
patient is unlikely to perceive events in the environment accurately, e.g., may be

incapable of understanding what is said to, or done for, them and may have impairments
in communicating effectively with others. Because of these experiences, patients
may display fear, sadness, defensive and aggressive behaviors overtly. Family
members and caregivers may find the cognitive and behavioral aberrations alarming
and the impediments to providing care overtaxing.
Because of its pervasiveness, and the distress it produces for the patient and
caregivers alike, it is essential that clinicians be vigilant for delirium. The symp-
toms can be variable, often changing over time, contributing to misidentification,
e.g., it can sometimes be difficult to distinguish from dementia, mood disturbances,
anxiety, and psychosis e.g., [102]. Instruments available to assist in the identification
of delirium in palliative care settings include the Confusion Assessment Method
(CAM) [103] and the Memorial Delirium Assessment Scale (MDAS) [104], among
others. The use of screening instruments, when combined with appropriate physical
and cognitive examination along with laboratory investigations, can be useful for
diagnostic purposes and quantification of the severity of symptoms [26]. The CAM
is a simple, observer-based rating scale, useful for case finding, originally intended
for use by nonpsychiatric clinicians to assess patients in hospital settings. Its valid-
ity for use in palliative care settings has only recently been investigated but not yet
established [31, 105]. Although the CAM has been demonstrated to be reliable, its
sensitivity varies as a function of the skills of the individual completing the assess-
ment [106]. In one study conducted within a palliative care setting, the sensitivity of
the CAM when completed by nonphysicians was markedly enhanced when formal
instruction was provided to assist raters in detection of clinical signs of delirium
[105]. Because of these limitations, the CAM is primarily recommended for use as
a screening as opposed to a diagnostic instrument, formal neurocognitive assessment
is still necessary to enhance detection and to avoid missing subtle or atypical
presentations of delirium [107]. The MDAS, by contrast, has been developed for
use in palliative care populations, e.g., hospitalized patients with advanced cancer
and AIDS. One of the shortcomings of the MDAS is that it does not incorporate an
assessment of the time course over which symptoms manifest and the degree to
which the symptoms fluctuate over time, critics argue that without these features, it
is sometimes difficult to distinguish features of delirium from other conditions with
which some features may overlap, e.g., dementia. The MDAS is easy to complete,
has good sensitivity ratings, and when administered repeatedly, can provide an
indicator of the effectiveness of treatment interventions [104, 108].
Standard recommendations to the management of delirium include a tripartite
approach involving a search for the etiology, correction of the underlying cause(s),
and management of distressing symptoms associated with the altered mental state
[109]. Several points of interest are worth noting about this approach. It has long
been established that there are multiple causes for delirium including infection,
metabolic and electrolyte abnormalities, nutritional deficits, brain tumors/metasta-
sis, hypoxia, seizure, paraneoplastic syndrome, as well as medication use [101,
110]. Although identification and remediation of the pathology underlying delirium
is ideal, there are several limiting factors encountered in palliative care settings.
First, the extant literature suggests that it is often difficult to clearly establish a
Table 3.4 Medications with the potential for causing delirium

Anticholinergics, e.g., antihistamines, antispasmodics, atropine
Anti-inflammatory, e.g., corticosteroids
Antineoplastics, e.g., vincristine, vinblastine, asparaginase
Antimicrobials, e.g., acyclovir, aminoglycosides, vancomycin
Anticonvulsants, e.g., phenytoin, valproate
Antiemetics, e.g., metoclopramide
Analgesics, e.g., opioids (especially meperidine)
Cardiac medications, e.g., antiarrhythmics, beta-blockers, digitalis
Psychoactive medications, e.g., tricyclic antidepressants, lithium, antipsychotics
Sedative-hypnotics, e.g., barbiturates, benzodiazepines
Sympathomimetics, e.g., methylphenidate, ephedrine, phenylephrine, theophylline
[31, 109, 114]
specific cause for the delirium among patients with advanced diseases [41, 111]. For
example, there may be restrictions on pursuing extensive investigative studies and
diagnostic procedures for terminal patients because of concerns that these procedures
can be invasive, burdensome, or incur discomfort. Second, the causes are often
multifactorial [112, 113], however, determining which factors constitute essential
causes of the delirium as opposed to those which are facilitating factors, and not
necessarily directly related to the delirium, can be difficult. Third, even when causes
are unveiled, treatment may not be possible due to the irreversibility of the underlying
condition, e.g., brain metastasis.
However, the clinician should be aware that there are many causes of delirium
that can, nonetheless, be reversible and easily remediated. The most common revers-
ible medical causes of delirium include dehydration, electrolyte disturbances, e.g.,
hypercalcemia, and certain infections, e.g., urinary tract infections [101, 113].
Additionally, adverse effects of prescribed medication are capable of producing
alterations in cognitive status; several medication classes that are commonly
implicated in causing/exacerbating delirium are listed in Table 3.4. Consideration
must be given to the possibility of addressing delirium by modifying the patient’s
medication regimen, e.g., by means of dose reduction or substitution of an alterna-
tive agent [31]. Unfortunately, in the last days of life, delirium can remain refractory
to corrective measures, perhaps attributable to general organ failure [101].
Several medications can be used to address the symptoms associated with delir-
ium. Antipsychotic medications are frequently invoked for the management of the
psychomotoric restlessness, distress, and confusion encountered in delirium. Evidence
for the efficacy of antipsychotics in the treatment of delirium has largely been anec-
dotal (based upon case reports and case series). Although conventional agents, e.g.,
haloperidol, have been frequently employed because of ease of use (parenterally,
intramuscularly, subcutaneously, and orally), there are potential risks associated with
their use. For example, extrapyramidal side effects, e.g., parkinsonism and akathisia,
may, in turn, become particularly distressing to patients, precluding their use in
patients with certain comorbid conditions, e.g., Parkinson’s disease and Lewy-body
dementia. Because of concerns that delirium may be related to disruptions in central
nervous system cholinergic transmission, highly anticholinergic agents may be best

avoided as these can potentially exacerbate delirium. More recently, atypical antipsy-
chotics, e.g., risperidone or olanzapine, have been employed as alternatives [115,
116]. However, very few randomized controlled trials have thus far been conducted,
thereby limiting the ability to make definitive statements about the efficacy of the
atypical antipsychotics in the management of delirium in terminal disease [114, 116,
117]. In severe forms of delirium refractory to antipsychotic use, sedation with agents
such as midazolam or propofol may be useful to mitigate distress and induce marked
sedation [118–120]. However, these agents, by virtue of their central nervous system
effects, can significantly interfere with processing of sensory information, impede
memory formation and thereby, contribute to further cognitive decline [109].
Lastly, there are several environmental and psychosocial interventions that can
be helpful in mitigating patient and caregiver distress. It is imperative that the risks
of inadvertent harm be reduced by ensuring that the environment is safe. Patients
may be calmed by reducing unnecessary stimulation, e.g., noise and light, and by
having familiar objects, e.g., photographs and personal mementos, and familiar per-
sons around them. Afflicted patients may require frequent redirection, it is impera-
tive to invoke simple, clear directives, and to gently redirect the patient with soft
vocal tones and physical contact. Education of family members may help to miti-
gate caregiver distress. They may need to be advised not to overinterpret erratic
behaviors, gestures, and grimacing and to avoid personalizing hostile, resistive, or
aggressive behaviors; education can demystify such aberrant behaviors when care-
givers are informed that such behaviors are likely to instead reflect disturbances in
processing/integration of information and coordination of goal-directed behaviors
[109, 121]. Transition to a higher level care, e.g., acute settings or hospices, may be
required if appropriate safety measures cannot be implemented in the home or if the
burdens to caregivers exceed what they can reasonably provide to the patient.
Conclusions
The approach of palliative care medicine is embedded in the perspective that treat-
ment efforts, albeit noncurative, should be directed at reduction of suffering and
improving well-being. Palliative care guidelines recognize the indispensable psy-
chological, existential, and social domains to the comprehensive management of
patients in the terminal phases of illness. A multimodal approach, i.e., employing
psychotherapeutic and psychopharmacologic treatments, may therefore be neces-
sary to address psychological distress, e.g., grief, spiritual distress, and existential
concerns, along with psychiatric complications, e.g., adjustment disorder, depres-
sion, anxiety, and delirium that significantly impact quality of life. Care of the patient
can be greatly enriched when mental health specialists are enlisted in the assessment
and treatment of the terminal patient, working in a coordinated fashion with pallia-
tive care physicians, nurses, caregivers, and family members. Although advances
have been made in identifying the psychiatric comorbidities and subthreshold
psychological states that impact the terminal patient, further investigation is required
to inform evidence-based treatment guidelines as well as to determine which treat-
ment approaches are most practical and under what circumstances and for whom
such interventions prove to be most effective.
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Review Questions
1. Which of the following is the most common psychiatric disorder encountered in

palliative care settings?
(a) Adjustment disorder
(b) Depression
(c) Anxiety disorder
(d) Delirium
2. What is the primary treatment for adjustment disorders in the palliative care
setting?
(a) Anxiolytics
(b) Sedatives
(c) Psychotherapy
(d) Hypnotics
3. Psychostimulants may be a reasonable consideration for the treatment of a termi-
nal cancer patient who is experiencing which of the following?
(a) Generalized worry and apprehension, with episodic dyspnea and perceived
palpitations
(b) Depressive symptoms and incapacitating opioid-induced sedation
(c) Depressive symptoms including insomnia, anorexia, and irritability
(d) Alcohol withdrawal
4. Which of the following is the best assessment for diagnosis of an anxiety disor-
der in palliative care settings?
(a) Clinical interview based on DSM criteria
(b) Hospital Anxiety and Depression Scale
(c) State Trait Anxiety Scale
(d) Distress Thermometer
5. Each of the following factors is likely to bode favorably in terms of adapting to
the challenges faced at the end-of-life except:
(a) Having a spiritual framework
(b) The perception that one has an accessible social support network
(c) Believing that one’s illness and clinical course is uncontrollable and
unpredictable
(d) The perception that one has a repertoire of skills with which to manage
stressors
Answers
1. Answer: (d). As high as 80% of terminally ill patients can experience delirium,
especially in the weeks before death. Depression and adjustment disorders have
a prevalence range of 13–22%, and 10–22%, respectively. Anxiety disorder is the
fourth most common psychiatric comorbidity ranging from 7 to 13%.
2. Answer: (c). Psychotherapy is the primary treatment for adjustment disorders.
Anxiolytics, sedatives-hypnotics can be used as an adjunct for patients who
experience incapacitating symptoms that can impede their ability to participate
in psychotherapy.
3. Answer: (b). Although there is insufficient evidence to recommend the use of psy-
chostimulants in palliative care settings, these agents have been advocated for the
rapid improvement of depressive symptoms. In addition, psychostimulants offer the
potential benefit of reducing incapacitating opioid-induced sedation. The potential
adverse effects, e.g., insomnia, anorexia, and heightened anxiety, would preclude
their use in patients experiencing many of these symptoms. Psychostimulants would
not be indicated for the treatment of alcohol withdrawal.
4. Answer: (a). The Hospital Anxiety and Depression Scale, State Trait Anxiety
Scale, and Distress Thermometer are screening instruments. However, a clinical
interview based on DSM criteria is the gold standard in diagnosing anxiety
disorders in the palliative care setting.
5. Answer: (c). Terminal patients can successfully navigate the adaptational
challenges posed in the advanced phases of illness. Among the factors listed
here, inflexible and maladaptive beliefs, i.e., perceiving that one’s illness is
uncontrollable and unpredictable, may bode poorly with regard to managing
psychological distress.
Chapter 4
Hospice for the Terminally Ill
and End-of-Life Care
Jamie Capasso, Robert Byron Kim, and Danielle Perret
Introduction
Some healthcare professionals are privileged with the opportunity to care for
patients at or near the end of their lives. This is an important and vital service
that can make a significant and lasting difference in the lives of patients and their
families. Patients nearing death have unique needs that frequently are more complex
or urgent than patients with transient or chronic disease, and therefore require
specialized care.
Most patients cared for during the terminal portion of their life are a challenge
for clinicians, and those that are best prepared for this challenge have knowledge in
several areas. These include advanced pain and symptom management, knowing
how and when to enlist the assistance of programs such as hospice or home care,
how to customize treatment plans in accordance with the patient’s changing clinical
status, and being familiar with the natural progression of signs and symptoms in the
actively dying patient.
J. Capasso, D.O. (*)

Department of Medicine, University of California,
Irvine School of Medicine, Irvine, CA, USA
e-mail: jcapasso@uci.edu
R.B. Kim, M.D. • D. Perret, M.D.
Department of Anesthesiology & Perioperative Care,
University of California, Irvine School of Medicine,
Irvine, CA, USA

DOI 10.1007/978-1-4614-5164-8_4,
50 J. Capasso et al.
The Beginnings of Hospice: A Historic Perspective
St. Christopher’s Hospice, widely regarded as one of the most important founding
hospice institutions, was founded in 1967 by Dr. Cicely Saunders. Located in
London, it was founded to help address the changing climate of death and dying.
As medicine advanced, more treatments were available to end stage patients.
Consequently, more patients were dying in hospitals rather than in their own homes,
as had been the case for hundreds of years.
Patients were living longer with “terminal” diagnoses due to new medical inno-
vations but progress in pain and symptom control unfortunately lagged behind.
This lag left a critical need for new methods of caring for dying patients [1, 2].
In the early 1960s, Dr. Saunders spoke at Yale University about her vision for
comprehensive, comfortable, and dignified end-of-life care for patients and support
for their families. The dean of nursing, Florence Weld, who attended this event, later
said that the encounter changed the direction of her life. She decided to leave Yale
to learn more about Dr. Saunders’ vision and to train at St. Christopher’s in London.
Upon her return in 1974, she established Connecticut Hospice in Branford,
Connecticut [3].
Over the next several years, the hospice movement gained momentum, and by
1980 there were 138 hospice programs in the USA The hospice Medicare benefit
was established in 1982, and although initially opposed by many, it allowed for
widespread expansion of hospice with increased availability to patients. Today,
there are over 4,700 hospice organizations in the USA. This exponential growth has
led to hospice evolving from a relatively insignificant part of the US health care
system to the fastest growing component of Medicare spending. The National
Hospice and Palliative Care Organization estimates that the number of patients
served in 2007 was 1.4 million [4].
Hospice Defined
In the US, hospice is the predominant model of care for the diverse group of
patients with life-limiting illness or injury. It is centered on the philosophy that all
individuals should have the ability to die with comfort, dignity, and on their own
terms. It consists of a team-oriented approach to medical care, pain and symptom
management, and emotional and spiritual support for both patient and the family
unit. This care is provided by an interdisciplinary team consisting of experts in
their specific component of patient care (see Table 4.1). The team consists of a
physician, nurse, social worker, chaplain, home health aide, and volunteers, all
with specialized training in hospice. Additionally, a physical, speech, occupational,
massage, or music therapist may be available to address specific needs if necessary.
The team members meet frequently as a group with the goal of creating a cohesive,
inclusive care plan [5].
4 Hospice for the Terminally Ill and End-of-Life Care 51
Table 4.1 Interdisciplinary team members

Hospice medical director • Leads the interdisciplinary team in developing the
plan of care
• Provides consultation to other physicians
regarding hospice care
• Certifies patient for hospice eligibility
Hospice physician • May serve as primary care physician (PCP) or
consultant managing patient’s pain and symptoms
after enrollment in hospice
• Assesses patient needs, manages and prescribes
treatments
• Co-certifies patient for hospice eligibility
Registered nurse • Assesses patient and family needs
• Ensures patient has adequate pain and symptom
control
• Coordinates team visits
• Ensures plan of care is successfully implemented
Social worker • Assesses patient and family emotional, social,
financial, and spiritual needs
• Provides bereavement support
• Provides direct counseling or referral to appropri-
ate community agencies
Chaplain • Assesses patient and family spiritual needs
• Assists with memorial preparations
• Provides counseling and bereavement support
Therapist • Provides physical, occupational, speech, massage,
or music therapy, if necessary
Volunteers • Provides needed nonmedical services such as life
review, letter writing, and respite care
• Provides support and companionship to patient
and family
Home health aid • Provides direct personal care to the patient
• Provides comfort measures and reports issues to
be addressed to the registered nurse
Hospice Benefits and Coverage
Medicare regulations require hospice to cover medications and interventions that

provide comfort related to the terminal diagnosis. This coverage includes durable
medical equipment such as a hospital bed, commode, and oxygen, medications for
symptoms such as pain, dyspnea, depression, and anxiety, as well as the profes-
sional services of the interdisciplinary team. Medicare hospice benefit requires the
hospice to provide a minimum of 13 months of bereavement care to the family after
the patient’s death. Hospice also provides around the clock emergency services for
symptom management. The benefit does not cover custodial services—care that can
be provided by a family member or nonlicensed caregiver—such as cooking and
cleaning. Hospice also does not cover services related to nonhospice conditions,
whether they are preexisting such as diabetes or hypertension, or are acute new
conditions such as nonpathological fractures [5].
Levels of Care
Hospice has several levels of care available. The most commonly employed level of
care is routine home care. It is provided at the patient’s residence and is flexible to
ensure a level of support that is tailored to the individual patient and family. These
weekly visits from the various team members include 2–3 nursing visits, 1–2 bath
aide visits, and social work, chaplain, and volunteer visits commensurate with
patient need, up to several times a week. There is an initial physician visit near the
time of enrollment, as needed for issues that require physician attention thereafter,
and at least one face-to-face encounter before each recertification.
Hospice also offers an inpatient option in appropriate circumstances. General
inpatient care (GIP) is given either in a dedicated hospice facility or nursing facility
for those patients with problems or issues that cannot be adequately controlled in a
home setting. It is used only for short, defined periods of time, typically only a few
days, until the problem is controlled. The problems are usually pain or poorly
controlled symptoms that require more than once a day nursing intervention or
medication adjustment. This level of care would also be appropriate for patients
whose home support is disrupted to the point where they would otherwise require
hospital admission. Respite care is also available for up to 5-day intervals. The
patient is placed in a facility in order to provide a break for the caregiver(s) that may
be experiencing “burn out” [6].
Another option for some patients is continuous care. With this level of care a
patient receives nursing care in the home for 8–24 h a day. Continuous care is
furnished only during brief periods of crisis for problems or issues that cannot be
managed at home with routine care. Like GIP, it is intended only for short-term use
of a few days with the target goal of control of the particular problem.
Hospice Funding and Eligibility
The majority of hospice services in the USA are paid for through the Medicare
Hospice Benefit or its Medicaid counterpart. Most hospice organizations use the
Medicare criteria for qualification, which are based on the guidelines of the National
Hospice and Palliative Care Organization (NHPCO).
Medicare requires that two physicians certify that if the patient’s condition
follows the natural course of its disease, the patient has reasonable likelihood of
living 6 months or less. “Reasonable likelihood” means that the majority of patients
in the same condition will die within 6 months—in other words, 51% of patients in
Table 4.2 Summary of Medicare guidelines

General debility/ Progression: Condition must be “life limiting”
failure to thrive 1. Documented progression of a but need not be a single or
primary disease, documented specific disease state
serially Patient and family have elected
2. Multiple emergency room visits or that goals of treatment consist
hospitalizations over the last 6 of comfort rather than cure
months
3. Homebound patients with decline
in function:
• Recent decline in function, dis-
tinguished from those with
reduced baseline functioning.
Documented using either:
(a) Karnofsky Performance
status of £50% [10, 11]
(b) Dependence in at least 3/6
activities of daily living
(ADLs)
• Recent decreased nutritional
status:
(a) Unintentional, progressive
weight loss of 10% < over
6 months
(b) Serum albumin < 2.5 g/dl
Cardiac disease 1. Symptoms of heart failure at rest 1. Ejection fraction <20%
(New York Heart Association class 2. Symptomatic, treatment-resistant
IV) supraventricular or ventricular
2. Symptoms of heart failure despite tachycardia
“optimal treatment” with 3. History of cardiac arrest
vasodilators and diuretics. If not on 4. History of unexplained
these agents, there should be a syncope
medical reason for foregoing these 5. Cardiogenic brain embolism
drugs, such as hypotension [12] 6. Concomitant HIV disease
Pulmonary disease 1. Disabling dyspnea at rest, despite 1. FEV1 < 30% of predicted
optimal treatment, that results in (postbronchodilator)
markedly reduced functional 2. Decrease in FEV1 on serial
activity testing of greater than 40 ml/
2. Function is frequently exacerbated year
with chronic cough or fatigue 3. Hypoxemia on oxygen:
3. Evidence of progressive disease: pO2 < 55 mmHg
increasingly frequent medical 4. O2 saturation < 88% on oxygen
attention for pulmonary infections 5. Hypercapnia: pCO2 > 50 mmHg
or failure 6. Weight loss of >10% body
4. Presence of cor pulmonale or right weight/6 months
heart failure. This should be due to 7. Resting tachycardia > 100 bpm
pulmonary disease, not left heart
failure or valve disease. May be
documented with: Echocardiogram,
EKG, CXR, or physical signs of
right heart failure [13]
(continued)
Table 4.2 (continued)

Dementia 1. Patient should be at or beyond 1. Patients receiving tube
stage 7 on the Functional feedings should have
Assessment Staging Scale (FAST): documented weight loss of
(a) Unable to ambulate without greater than 10% of body
assistance weight over 6 months
(b) Unable to dress without 2. Serum albumin < 2.5 g/dl
assistance
(c) Unable to bathe properly
(d) Urinary and fecal inconti-
nence; occasional or increasing
in frequency
(e) Limited communication—6
words or less per day
2. Difficulty eating, or refusal to eat
causing inadequate fluid/calorie
intake [9]
HIV/AIDS 1. CD4+ count < 25 cells/ml, as The following HIV-related
measured during a period where diseases are associated with <6
the patient is relatively free of months prognosis:
acute disease (a) CNS lymphoma
2. Patients with a persistent HIV (b) Progressive multifocal
RNA (viral load) of >100,000 cop- leukoencephalopathy
ies/ml (c) Cryptosporidiosis
3. Patients with lower viral loads, if (d) Wasting (loss of 1/3 lean
they: body mass)
(a) Elect not to use antiretrovirals (e) Mycobacterium avium
(b) Have a declining functional complex (MAC) bacter-
status emia, untreated
(c) Are experiencing persistent (f) Treatment-refractory
diarrhea for at least a year, visceral Kaposi’s sarcoma
regardless of etiology or have a (g) Renal failure without
persistently low albumin hemodialysis
(<2.5 g/dl) (h) Advanced AIDS dementia
(d) Are aged >50 years or have complex
severe heart failure (i) Toxoplasmosis
Important to consult with HIV
specialist regarding complex HIV
cases, as mortality is highly
variable due to new and changing
therapies, as well as individual
tolerance to treatment
(continued)

Liver disease The following factors correlate with Prognosis worsens with the
shortened prognosis with additive addition of:
effects: 1. Progressive malnutrition
1. Both serum albumin <2.5 and 2. Muscle wasting, reduced
prolonged PTT more than 5 s over strength/endurance
control 3. Continued active alcoholism
2. Ascites; refractory to sodium 4. Hepatocellular carcinoma
restriction/diuretics or due to 5. HBsAg positivity
patient noncompliance
(a) Spontaneous bacterial
peritonitis
(b) Hepatorenal syndrome
3. Hepatic encephalopathy, as
evidenced by:
(a) somnolence, obtundation,
emotional lability
(b) flapping tremor/asterixis
4. Recurrent variceal bleeding despite
treatments such as transjugular
intrahepatic portosystemic shunt
(TIPS), sclerotherapy/band
ligation, or oral beta blockers [14]
Renal disease Critical renal failure defined: Clinical manifestations:
Creatinine clearance < 10 cc/min (<15 1. Confusion, obtundation
for diabetics) and 2. Intractable nausea/vomiting
Serum creatinine > 8 mg/dl (>6 for 3. Generalized pruritus
diabetics) 4. Restless legs
Clinical signs and syndromes In hospitalized patients, increased
associated with renal failure: mortality is seen with:
1. Uremia: confusion, obtundation, 1. Mechanical ventilation
nausea/vomiting, pruritus, 2. Chronic lung disease
restlessness 3. Advanced cardiac disease
2. Oliguria (<400 cc urine/day) 4. Advanced liver disease
3. Persistent serum K > 7.0, unrespon- 5. Sepsis
sive to medical management 6. Immunosuppression/AIDS
4. Uremic pericarditis 7. Albumin < 3.5 g/dl
5. Hepatorenal syndrome 8. Cachexia
6. Intractable fluid overload [15, 16] 9. Age > 75
10. Disseminated intravascular
coagulation (DIC)
11. Gastrointestinal bleeding
(continued)

Stroke and coma Patients who do not die in the acute Computed tomography (CT)
hospitalization tend to stabilize findings that indicate poor
with supportive care only. Those prognosis or minimal recovery:
with continuous decline have a For hemorrhagic stroke:
poorer prognosis (a) Large volume hemorrhage
During the acute phase (immediately (>20 ml infra- and >50 ml
following CVA) any of the supratentorial)
following predict early mortality: (b) Ventricular extension of
1. Coma/persistent vegetative hemorrhage
state > 3 days (c) >30% surface area
2. In anoxic CVA, coma, obtundation involvement
with myoclonus > 3 days (d) Midline shift >1.5 cm
3. Comatose patients with 4/5 of the (e) Obstructive hydrocephalus
following have a 97% 2 month without ventriculo-peritoneal
mortality: (VP) shunt
(a) Abnormal brain stem response For thrombotic/embolic stroke:
(b) Absent verbal response (a) Large anterior infarcts with
(c) Absent withdrawal to pain both cortical and subcortical
(d) Creatinine > 1.5 mg/dl involvement
(e) Age > 70 (b) Large bi-hemispheric
infarcts
(c) Basilar artery occlusion
(d) Bilateral vertebral artery
occlusion
ALS Best to be educated on the natural Important factors that imply
history of amyotrophic lateral decreased survival:
sclerosis (ALS): 1. Rapidly progressing muscle
1. It progresses linearly with a fairly weakness, bulbar function
constant rate of decline, but this (swallowing, chewing,
rate can vary greatly from patient speaking)
to patient. Thus, it is important to Patient should develop the
know the history of the rate of majority of their disability
progression to prognosticate within the last year
2. Neurology involvement within 3 2. Critically impaired ventilatory
months of hospice assessment is capacity:
recommended for assistance FVC < 30%, significant
dyspnea at rest, O2
requiring, declines
tracheostomy/intubation
3. Critical nutritional impairment,
declining artificial nutrition
Continued weight loss,
dehydration
the same condition will die within 6 months. This is a somewhat outdated notion, as
even experienced hospice physicians have traditionally been unable to prognosti-
cate accurately, resulting in late hospice referral and decreasing lengths of stay.
Although physicians are compelled to utilize the hospice criteria for patient eligi-
bility, the resulting delay in referral can deprive patients from receiving the full
spectrum of hospice services. In 2008, the average hospice length of stay was 83
days, less than half of the 6-month criterion [7].
The first hospice benefit period is 90 days, and if a patient continues to decline,
he or she may be recertified for an additional 90 days, and then for an indefinite
number of 60-day benefit periods. These may be renewed as long as the patient
continues to decline [8].
Medicare uses the NHPCO criteria for several noncancer designated diagnoses
and specific guidelines for prognosticating in each condition (see Table 4.2). The
NHPCO uses evidence-based data from clinical experience and research in an effort
to provide these prognosticating guidelines. Unfortunately, despite these efforts, the
tools available to physicians for determining the appropriate point for hospice
referral are often cumbersome and ineffective. Some of the most widely utilized
prognostication guides include the modified Functional Assessment Staging (FAST)
tool for dementia [9], the Karnofsky Performance Status Scale for general debility
[10, 11], The Seattle Heart Failure Model for heart disease [12], and the Model for
End Stage Liver Disease (MELD) for liver failure [13].
As in any end-stage disease, optimum life-prolonging therapy should have been
exhausted or refused by the patient prior to consideration for hospice.
In dementia, stroke/coma, and amyotrophic lateral sclerosis (ALS), common
comorbid medical conditions additively portend a worsened prognosis. These include:
aspiration pneumonia, upper urinary tract infection (UTI)/pyelonephritis, septicemia,
multiple decubitus ulcers (stage 3–4), and recurrent fever after antibiotics [9].
Hospice Alternatives
Depending on the needs of the individual patient, various alternatives to traditional

hospice are available. To address basic medical needs, traditional regular home
nursing services are available for patients that may not need palliation or have a life-
threatening illness. These services may include medication or blood pressure
monitoring and patient education, and are typically available weekly.
Home palliative care is more comprehensive and can provide all the services of
traditional regular home health care plus providing skilled nursing care for pain or
symptom management. It therefore can provide a longer duration of home care for
the patient than traditional regular home health care as long as the patient has pain
or symptoms to be managed. It is more appropriate for patients who are not yet
ready for hospice. Home palliative care is less comprehensive than hospice and
lacks the interdisciplinary care of the hospice team, but its advantage over hospice
is that this care can be provided simultaneously with curative treatments in seri-
ously ill patients.
The most comprehensive alternative option is open access hospice. This new
phenomenon acts as a “bridge” from curative to comfort care. A small number of
larger hospices (serving 400 or more patients) are able to offer potentially life-
extending interventions to their patients simultaneously with hospice care. These
interventions may include TPN, chemotherapy, and radiation. These hospices are
able to offset the costs of these treatments from the increased revenue that comes
from enrolling more patients earlier in the course of the disease [17].
The Terminal Phase
While caring for someone with a terminal illness, the terminal phase of the illness
can be one of the most challenging times. The terminal phase of an illness is defined
as the time when a person’s disease process is incurable and their health deteriorates
to the point where he or she is not expected to live more than a few days, weeks, or
months. The goal at this point is mainly supportive: to ensure the most comfort for
the patient and the people providing care. Other goals at this point include symptom
management, emotional and spiritual support, assistance with personal care, trans-
portation assistance, and improving communication with health care providers [18].
Although these goals are not unique to the terminal phase, there is now an urgency
to address these goals in a limited time.
Functional Decline
As with any of the challenges during the terminal phase, the functional decline can
be met with increased burden of illness and diminished functional capacity for
activities of daily living (ADL). The earliest way to assess this clinically is a sudden
decline in the functional status that often signals shortened survival and acts as a
sentinel event that can be readily seen [19]. This decline before death differs by age
and with the chronically ill; it is the medical condition that influences the pattern of
functional disability [20, 21]. For example, patients with cancer tend to show a
steady decline in ADLs in the 6 months prior to death, while patients with noncan-
cerous illnesses tend to show a more variable course of decline [19, 22]. Although
in the USA, only 23% die from cancer [20, 23], a significant number of patients die
from acute complications of an otherwise chronic condition. End-of-life care should
also serve those who become increasingly frail, even without immediately life-
threatening illness [20, 24].
It may be advantageous to have assessments done by occupational and physical
therapists to help determine the degree of assistance required and if there is any
durable medical equipment (DME) that may assist with remaining functional capacity.
Occupational and physical therapists can have a significant impact on the quality
of life of terminally ill patients. While rehabilitation is often overlooked in the
critical care setting, occupational and physical therapists work with critically ill
patients to create realistic and meaningful goals for improving comfort, mobility,
socialization skills, and ability to care for oneself regardless of disease state and
medical status [25].
Reduced Oral Intake
Although oral administration of medication is generally preferable, a parenteral

route is often advisable in many circumstances during the progression of a terminal
illness. Not only are there problems of medication administration with reduced oral
intake, but also there are implications for food/fluid intake. Disease processes like
cancer have a profound impact on patients’ metabolism. Proteolysis and lipolysis
are accelerated while muscle protein synthesis is depressed, resulting in a loss of
lean body mass and fat tissue. Despite hypermetabolism and weight loss (exacer-
bated by stress, pain, infection, and surgical procedures), patients’ food intake is
usually not increased leading to further wasting [26].
Starvation and dehydration are not caused by lack of intake but by the disease
process itself. Providing or even forcing food and fluids will not prolong or enhance
life and may be a burden or detrimental. A healthy individual has an anabolic
metabolism, which can use nutrients to build and repair tissue. However, during the
dying process, the body shifts from an anabolic to a catabolic state. It is this cata-
bolic condition that leads to starvation and dehydration. This shift is a natural part
of the dying process and occurs whether or not food and fluids are provided.
Furthermore, there is a possibility of additional problems due to complications of
central line infections and metabolic derangement associated with total parenteral
nutrition (TPN). Even tube feeding is not without risks, which include dislodge-
ment, infection, discomfort, and aspiration [27].
It is often not realized that starvation produces a euphoric state that increases
comfort. As the body uses fat as the main energy source and ketones build up, the
resulting ketonemia causes euphoria. Even small amounts of feeding can prevent
ketonemia and prolong the sensation of hunger. The most common complaint
patients have when withholding food or fluids is a dry mouth; therefore, good mouth
care can alleviate most discomfort and provide an outlet for the caregiver to still
nurture [27].
Alternative Routes of Medication Administration
Pharmacologic symptom management can improve the quality of life of patients

with a severe life-limiting illness. Although pharmacotherapy is only one compo-
nent of end-of-life care, ensuring timely access to needed medication is a funda-
mental component of effective palliative care with increasing importance as death
approaches [28]. The loss of an oral intake route is a possibility that can occur at any
time; therefore, the need for effective alternate route for administering medication
may become more urgent due to the inability to swallow, dyspnea due to pneumonia,
and/or agitation due to end-of-life delirium. Additionally, since parenteral medica-
tions may not be available emergently, medications delivered via alternate routes
should be made accessible for immediate administration [29].
Transdermal Route
Transdermal fentanyl is an effective and well-tolerated pharmacotherapy for cancer

pain patients. It should not be used in opioid-naïve patients and watching for drug
accumulation is required when doses are increased [30, 31]. However, clinicians
need to be cognizant that the US/UK manufacturer’s recommendations for equian-
algesic dosing of transdermal fentanyl may result in initial doses that produce
subtherapeutic levels and unrelieved pain in some patients [31, 32].
Transdermal buprenorphine is now being prescribed in the US, but was initially
used in Europe and Australia for chronic and cancer pain management.
Buprenorphine’s mixed agonist/antagonist activity, dosage ceiling, and high affinity
to the opiate receptor limit its use to those patients who do not already require large
daily doses of opioids. Thus, buprenorphine may not be an appropriate medication
for some patients with advanced unremitting cancer pain [31, 33].
Transdermal scopolamine is effective for severe drug-resistant nausea and vomiting
in advanced cancer. It is most appropriate for vestibular causes of nausea and
vomiting precipitated or exacerbated by head or body movement, with or without
dizziness [34].
Most topical nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac,
have shown improved safety and tolerability compared with oral NSAIDs. Topical
salicylates and capsaicin are available in the US without a prescription, but neither
has shown substantial efficacy in clinical trials, and both have potential to cause
serious adverse reactions. Accidental poisonings have been reported with salicy-
lates, and concerns exist that capsaicin-induced nerve desensitization may not be
fully reversible and that its autonomic nerve effects may increase the risk of skin
ulcers in diabetic patients [35].
Good adhesion of the patch to the skin is essential for maximum efficacy; there-
fore, patients must be instructed on the proper technique for patch application. Hair
on the skin should be clipped, not shaved, in order to avoid abrasions where the
patch is to be applied. This skin should be clean, dry, and undamaged. After removal
of the plastic backing, the patch should be held firmly in place for about 30 s.
A finger should be run around the edge of the patch to ensure that adhesion has
occurred around all edges. The top of the patch should be rubbed for approximately
3 min. Patients should also be instructed to rotate sites when changing patches in
order to minimize changes in serum levels due to build up of subcutaneous depots
and to minimize skin irritation [31, 36].
Subcutaneous Route
Fluids can be administered as subcutaneous rehydration using NaCl 0.9%,

combined solutions of glucose 5%/NaCl 0.9%, and NaCl 0.45%. Site of injection is
primarily in the thighs, back, or arms at a maximum of 2 l/day [37].
A wide variety of medications can be given subcutaneously; these include anal-
gesics (morphine, hydromorphone, sufentanil, methadone, fentanyl, and ketorolac),
corticosteroids (dexamethasone), diuretics (furosemide), barbituates (phenobarbital),
anticholinergic agents (glycopyrrolate and scopolamine), antiemetics (ondansetron
and metoclopramide), neuroleptics (haldoperidol, levomepromazine), and benzo-
diazepines (clonazepam and midazolam). Many of these medications are off-label
for subcutaneous use, but are recommended for use in palliative care [37].
Transmucosal Route
An intranasal, sublingual, or buccal route of fentanyl administration is a treatment

option for breakthrough cancer pain (BTCP). Transmucosal fentanyl is an attractive
and convenient treatment modality in opioid-tolerant patients due to its quick onset
and short duration of action, noninvasive administration route, high bioavailability,
and avoidance of a hepatic first-pass effect. Few clinical trials have been conducted
with intranasal fentanyl, but all have confirmed its usefulness and acceptability in
BTCP treatment. It may be used in opioid-tolerant patients without nasal patholo-
gies [38]. Oral transmucosal fentanyl citrate (Actiq and Cephalon) is specifically
developed and approved for the management of breakthrough pain in cancer patients
and it has the potential to be a useful tool for clinicians [39].
Other medications can be used transmucosally, such as Lorazepam, Ketorolac,
Insulin, or Ketamine. The general rule is to start with the recommended IV dose and
titrate to desired response. As a safety factor, the bioavailability of the transmucosal
route will not exceed the intravenous route as absorption is only 35–70% [40–43].
Rectal Route
In some circumstances, it is impractical or even impossible (during nausea/emesis,

convulsions, uncooperative patients, and before surgery) to give medications in the
methods listed above. In these cases, the rectal route may represent a practical alter-
native. Rectal administration is now well accepted for delivering, for example, anti-
convulsants, non-narcotic and narcotic analgesics, theophylline, antiemetics, and
antibacterial agents. The rate and extent of rectal drug absorption are often lower
than with oral absorption, possibly an inherent factor owing to the relatively small
surface area available for drug uptake [44].
Specific Symptom Management
The prediction of impending death remains an imprecise science, but studies have
shown several common terminal signs and symptoms. Clinicians and family
members need to be aware of and be prepared to address specific symptoms during
the final few days without delay. These include symptoms of breathlessness, accu-
mulation of respiratory tract secretions (death rattle), and terminal delirium.
Death Rattle
The accumulation of respiratory tract secretions (ARTS) prior to death, which leads
to gurgling respirations, is presumably caused by a decreased gag and clearing
reflex. This “death rattle” occurs in 25–50% of dying patients, more commonly in
men, and in patients with brain and lung cancers, and predicts most (76% in one
study) will die within 48 h [45, 46]. Nonpharmacologic interventions such as stop-
ping parenteral fluids, repositioning, and postural drainage are frequently suggested
but have not been studied specifically. Oropharyngeal suctioning is considered
generally ineffective for this condition and may cause discomfort for both the patient
and patient’s family [45, 46].
A majority (50–80%) of patients respond to treatment with antimuscarinics
[45, 47]. Subcutaneous scopolamine (hyoscine hydrobromide) is immediately more
effective, in studies, than subcutaneous glycopyrrolate, but glycopyrrolate has a
longer duration of action. Since glycopyrrolate is a quaternary amine, it has the
advantage of not crossing the blood–brain barrier. Therefore, unlike scopolamine, it
is less likely to cause sedation or delirium [45, 48].
Terminal Agitated Delirium
Delirium is characterized by fluctuating disturbances in consciousness, cognition,

and perception, which occur in up to 83% of patients near the end of life [45, 49].
Terminal delirium is often associated with signs of decreased perfusion, which is
commonly divided into three types: hyperactive (with restlessness, agitation, or
hallucinations), hypoactive (with somnolence), and mixed (with alternating features
of both) [45, 50]. Terminal delerium is thought to be multifactorial in etiology and
often is confused with sedation, dementia, or near-death awareness. Frequent symp-
toms, including both the psychomotor and cognitive symptoms of hyperactive delir-
ium, can be enormously upsetting for families because they remain a lasting image
after a patient’s death [45, 51].
The moaning, groaning, and grimacing that often accompany delirium may also
be misunderstood as physical pain [45, 47]. Many experts feel that terminal delirium
may be precipitated not by the pain medication itself, but rather by poor pain control
[45, 52], and that uncontrollable pain rarely develops near death if it has not previ-
ously been a problem [45, 53]. While reversible factors such as psychoactive medi-
cations, metabolic disarray, or infection may be identified in up to half of cases,
terminal delirium management typically focuses on symptom control with medica-
tions [45, 53]. Benzodiazepines like Midazolam or Lorazepam can be used with
good success, but may result in disinhibition and increased restlessness [45, 46].
Haloperidol was demonstrated to be superior when compared to Lorazepam in a
small randomized controlled trial in delirium patients with AIDS [45, 54]. Other
antipsychotics (e.g., levomepromazine) have shown benefit in treating delirium with
dementia, but it is unclear how these results translate to the treatment of actively
dying patients [45, 55].
Normal Physiology of Death and Dying, Progression,

and Time of Symptoms
Several clinical features have been identified as indicators of death within days,
but evidence for the reliability of these signs is limited. Evidence does show that
physicians consistently overestimate patient survival, and those most familiar
with the patient are often the least accurate [45, 56]. One observational study
looking at terminally ill patients with cancer noted that patients, on average,
developed respirations with mandibular movement at 8 h, acrocyanosis at 5 h, and
radial pulselessness at 3 h before death but there was wide individual variation,
with most patients developing these symptoms less than 2.5 h before they died.
Decreased consciousness was identified in 84% at 24 h and 92% at 6 h prior to
death [45, 57]. Development of a death rattle is predictive of death within 48 h but
typically occurs in less than half of patients [45, 58]. Except for symptoms of
drowsiness, fatigue, and confusion; symptoms in patients with cancer followed at
home tended to improve in the last days of life [45, 59]. According to some expert
opinions, other signs of impending death include becoming bedbound, irregular
breathing, tolerating sips of fluid only, and cool or mottled extremities [45, 60].
Distressing physical symptoms are common at the end of life. The SUPPORT
study showed that during the last 3 days of life, 80% of dying hospitalized patients
suffered severe fatigue, 50% severe dyspnea, and 40% severe pain [45, 61].
Common symptoms reported by families during final week of life were fatigue,
dyspnea, and dry mouth, while the most distressing were fatigue, dyspnea, and
pain [45, 62]. Anorexia, anxiety, constipation, nausea/vomiting, incontinence,
pressure sores, and insomnia have also been identified as particularly distressing
in certain patients [45, 63].
Conclusion
The discomfort of dying patients is substantial and hospice represents a unique

interdisciplinary team-based approach to the management of the many symptoms
that burden patients at the end of life. Guidelines for hospice vary by terminal ill-
ness and disease; despite guidelines physicians typically refer patients to hospice
care late. Earlier referrals, when patients with terminal illness reasonably have 6
months or less to live, will maximize the resources that hospice can offer. As terminal
illness progresses, the urgency of symptom management becomes more impressive.
Functional decline and reduced oral intake are common. The hospice provider
should be well versed in employing other routes of medication administration for
analgesia and for management of terminal symptoms. In the final stages of life,
symptoms of breathlessness, accumulation of respiratory tract secretions (death
rattle), and delirium may be present and typically signal impending death. Being
familiar with the natural progression of signs and symptoms in the actively dying
patient as well as with advanced pain and symptom management, with knowledge
of how and when to enlist the assistance of hospice or home care, and with how to
customize treatment plans will allow the hospice provider the skill set necessary
to provide effective patient-centered end-of-life care.
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Review Questions
1. An 83 year-old man with end stage COPD comes to your office to discuss goals
of care. His breathing has deteriorated over the last few months, and he has been
hospitalized four times this year. He states that he would like to avoid returning
to the hospital if he were to get sick again and would like to focus on comfort.
He heard that hospice can offer him the opportunity to have symptom manage-
ment to focus on comfort for his remaining days. Which of the following
describes the covered services and items he could receive?
(a) Daily in-home caregiver
(b) Room and board at a nursing facility
(c) Hospital bed, oxygen, and commode for home use
(d) Homemaking assistance with cooking and light housework
2. Which of the following statements regarding Hospice care is false?
(a) Hospice care includes coverage for durable medical equipment, medica-
tions, and home visits for pain and symptom management
(b) Once signed on to the Medicare Hospice benefit, patient visits to their Primary
Care Physician (PCP) for a hospice related diagnosis are not covered
(c) Hospice care is revoked if a patient elects to go to the Emergency depart-
ment for an acute health issue related to their hospice diagnosis
(d) In order to receive Hospice benefits, the patient must agree to “Do Not
Resuscitate” Status
3. A 73 year-old patient with end stage dementia and failure to thrive on Hospice
begins to stabilize. Her oral intake is fair with hand feeding, she has not had
pneumonia or a urinary infection in over 1 year, and she continues to have peri-
ods of lucidity where she can hold a limited conversation. Which of the follow-
ing actions is most appropriate?
(a) Discharge the patient from Hospice; she may re-enroll in the future as her
condition progresses
(b) Keep her on hospice but provide her with a reduced number of nurse visits,
as she is doing well enough with only a bath aid visiting weekly
(c) Keep her on hospice for a limited period of 1 month and monitor her for
disease progression
(d) Discuss her case with her former primary care physician before making a
decision
4. A patient with stage IV liver cancer is in under home hospice care, with her hus-
band as her primary caregiver. She has intense pain and nausea, and is significantly
encephalopathic and agitated. Her husband and nurse are having difficulty control-
ling her symptoms. Which of the following is false regarding treatment options?
(a) This patient could benefit from a home visit from the hospice physician for
evaluation
(b) The patient could be transferred via EMS to the emergency department for a few
hours of intensive symptom management while remaining on hospice care
(c) The patient would qualify for general inpatient care due to her refractory
symptoms
(d) The patient’s uncontrolled symptoms qualify her for continuous nursing
care in the home for continuous pain control and monitoring
5. What is the current average length of stay on hospice?
(a) 10–20 days
(b) 3–4 months
(c) Over 8 months
(d) 80–100 days
6. A 72-year-old terminally ill female is showing decreased awareness of his sur-
roundings, decreased oral intake of solids or liquids, and is no longer able to get
out of bed. The most likely explanation for this constellation of findings is:
(a) Loss of hope
(b) Impending death
(c) Depression
(d) Uremia
7. A 24-year-old palliative care patient with terminal breast cancer with metastasis
to bone takes oral narcotics regularly for bone pain. The patient is no longer able
to swallow. What is an alternative route of medication administration while under
hospice care at home?
(a) Topical salicylates
(b) Transdermal scopolamine
(c) Transdermal buprenorphine
(d) Topical capsaicin
8. A 61-year-old male is in his final stages of death and now under palliative “terminal”
sedation. The primary goal with this type of sedation is:
(a) Relief of intractable pain or suffering
(b) Hasten the onset of death
(c) Improved tissue oxygenation
(d) Reduction in opioid medication usage
9. An 87-year-old home hospice patient becomes increasingly less mobile and is
physically limited to lying in her bed. A common complication of immobility
while caring for a patient like this is:
(a) Joint laxity
(b) Hamstring hypertrophy
(c) Pressure ulcers
(d) Cerebral vascular accidents
10. A terminally ill patient has advanced disease due to pancreatic cancer. The
patient is cachectic and now lost the ability to swallow. The patient’s family is
concerned for the patient’s nutritional status. The following are reasons to with-
hold nutrition except:
(a) There are metabolic derangements associated with total parenteral nutrition
(b) Aspiration and infections are possible with tube feeds
(c) Starvation produces a euphoric state that increases comfort
(d) Forcing food and fluids will help to prolong or enhance life
Answers
1. (c)
2. (d)
3. (a)
4. (b)
5. (d)
6. (b). While caring for someone with a terminal illness, the terminal phase of the
illness can be one of the most challenging times. The terminal phase of an
illness is defined as the time when a person’s disease process is incurable and
their health deteriorates to the point where he or she is not expected to live
more than a few days, weeks, or months. The signs and symptoms of impending
death are often very similar, even in patients with very different terminal
illnesses. Those caring for patients during this stage should be familiar with the
common signs and symptoms of impending death so that he or she can educate
the patient and caregivers about the dying process and support patients and
caregivers through the patient’s death. With impending death, the patient has
decreasing interest and awareness of his/her surroundings and a reduced desire
or ability to move around. The patient will have a marked decrease in food or
fluid intake and often develops difficulty with swallowing.
7. (c). Pharmacologic symptom management can improve the quality of life of
patients with a severe life-limiting illness. Although pharmacotherapy is only
one component of end-of-life care, ensuring timely access to needed medica-
tion is a fundamental component of effective palliative care with increasing
importance as death approaches. The loss of an oral intake route is a possibility
that can occur at any time; therefore, the need for an effective alternate route for
administering medication may become more urgent due to the inability to
swallow. Additionally, since parenteral medications may not be available emer-
gently, medications delivered via alternate routes should be made accessible for
immediate administration. Transdermal buprenorphine is now being prescribed
in the USA, but was initially used in Europe and Australia for chronic and
cancer pain management. Buprenorphine’s mixed agonist/antagonist activity,
dosage ceiling, and high affinity to the opiate receptor limit its use to those
patients who do not already require large daily doses of opioids. Thus, buprenor-
phine may not be an appropriate medication for some patients with advanced
unremitting cancer pain. Transdermal scopolamine is effective for severe drug-
resistant nausea and vomiting in advanced cancer. It is most appropriate for
vestibular causes of nausea and vomiting precipitated or exacerbated by head
or body movement, with or without dizziness. Topical salicylates and capsaicin
are available in the US without a prescription, but neither has shown substantial
efficacy in clinical trials, and both have the potential to cause serious adverse
reactions. Accidental poisonings have been reported with salicylates, and
concerns exist that capsaicin-induced nerve desensitization may not be fully
reversible and that its autonomic nerve effects may increase the risk of skin
ulcers in diabetic patients.
8. (a). The main goals of palliative care involve the relief of pain and suffering in
the dying patient. Terminal/palliative sedation describes the use of sedative
agents to treat pain or suffering in the dying patient when other treatment
measures are ineffective. This type of sedation is used to relieve intractable
symptoms in the dying patient, not to expedite the dying process.
9. (c). As a patient becomes progressively less mobile with advanced stages of
his/her disease, there are numerous complications associated with immobility.
Complications include muscle atrophy, constipation, joint stiffness and pain,
urinary tract infection, increased clotting risk, and pressure ulcers. Pathologic
fractures are not increased with immobility. Prevention of pressure ulcers can
be maximized with the use of turning and positioning techniques.
10. (d). Starvation and dehydration are not caused by lack of intake but by the
disease process itself. Providing or even forcing food and fluids will not
prolong or enhance life and may be a burden or detrimental. A healthy indi-
vidual has an anabolic metabolism, which can use nutrients to build and repair
tissue. However, during the dying process, the body shifts from an anabolic to
a catabolic state. It is this catabolic condition that leads to starvation and dehy-
dration. This shift is a natural part of the dying process and occurs whether or
not food and fluids are provided. Furthermore, there is a possibility of addi-
tional problems due to complications of central line infections and metabolic
derangement associated with total parenteral nutrition (TPN). Even tube feeding
is not without risks, which include dislodgement, infection, discomfort, and
aspiration. It is often not realized that starvation produces a euphoric state that
increases comfort. As the body uses fat as the main energy source and ketones
build up, the resulting ketonemia causes euphoria.
Chapter 5
Communication in Palliative Care
Dominique Anwar, Sean Ransom, and Roy S. Weiner
Introduction
Good communication skills are obviously important for any health professional, but
they are especially essential when taking care of patients facing a life-threatening
disease. It is never easy to give news about a diagnosis and/or prognosis that will
give patients a perspective of death far closer than imagined. Not only are these
communication skills important when breaking news initially and through patient
follow-up, but such skills also allow effective collaboration with other involved
health professionals. In the palliative context, these skills do not only facilitate the
proper management of physical symptoms, but also assist in other dimensions, such
as social, spiritual, and psychological, which all must be addressed. The patient
remains, of course, at the center of care with involvement of family/loved ones, but
each member of the healthcare team has specific competencies that must be
acknowledged and shared.
D. Anwar, M.D. (*)

Section of General Internal Medicine and Geriatrics,
e-mail: danwar@tulane.edu
S. Ransom, Ph.D.
Department of Psychiatry and Behavioral Sciences,
R.S. Weiner, M.D.
Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA

DOI 10.1007/978-1-4614-5164-8_5,
74 D. Anwar et al.
In addition, distressed, exhausted family members may sometimes be difficult to

manage. Family caregivers may show dysfunction, aggressiveness, or denial, but
their needs also must be addressed as these behaviors may be signs of intense suf-
fering. Finally, it is important to ensure that the needs of a “difficult” family do not
bring team members to exhaustion. This, also, is the role of a coordinated,
communicative team approach.
In complex medical situations, the patient usually receives care not only by the
primary care provider, but also by several specialists, sometimes in various locations.
If healthcare providers involved in the patient’s care fail to coordinate their efforts,
patients and their family members may hear several “stories” regarding the patient’s
present and future condition, which may be distressing or confusing. Implementing
a smooth transition and a relation of trust between the patient, family, and healthcare
providers can be achieved only if there is real collaboration/communication between
these healthcare providers, with understanding of the roles of each professional
involved.
Breaking bad news is not an easy task and will never be, whatever our profes-
sional training, experience, or level of empathy. Some individuals may have natural
communication skills, but one can always improve. Students and professionals from
various disciplines (physicians, nurses, medical school and nursing school students,
psychologists, social workers, chaplains) may learn how to better communicate at
any stage of their career. Observing skilled communicators is a good way to learn,
but observation will never take the place of “hands-on” training. Working with
standardized patients or role playing may promote improvement without the fear of
“hurting” a patient; thus, training in a formal, resourced environment is optimal.
Several communication skills training programs have been described in the medical
literature and have proven to be highly effective, including training models for medical
students [1, 2]and for oncologists [3, 4]. One Cochrane review confirmed that
several training models, both those for physicians and for nurses, appear to be
effective [5].
We will mainly focus on a very important aspect of communication in palliative
care: Breaking bad news. We will also explore briefly issues that are of special inter-
est too in this area: dealing with “difficult” families and communicating with other
health professionals.
Breaking Bad News
Throughout time, there has been an evolution from Hippocrates’ recommendation

(late fifth century BC) [6]: “Conceal most things from the patient while you are
attending to him. Give necessary orders with cheerfulness and serenity…revealing
nothing of the patient’s future or present condition. For many patients … have taken
a turn for the worse … by forecast of what is to come” and those from the American
Medical Association in the nineteenth century [7]: “The life of a sick person can be
5 Communication in Palliative Care 75
shortened not only by the acts, but also by the words or the manner of a physician.
It is, therefore, a sacred duty to guard him carefully in this respect and to avoid all
things which have a tendency to discourage the patient and to depress his spirits.”
Closer to us, in the 1960s, when oncological options were still scarce, physicians
tended to consider it inhumane to break bad news to a patient while knowing that
there would be no treatment option to offer [8]. Today, however, finds a tremendous
emphasis on the patient’s autonomy and right to know everything about his or her
condition and to make his or her own decisions. Physicians also face the challenge
of tailoring the delivery of bad news, depending on the assessment of the specific
patient’s wishes, needs, culture, and resources.
“I left my house on October 2, 1996, as one person, and came home another” [9]:
this quote from Lance Armstrong after being informed of his advanced oncological
condition illustrates how stressful and life-changing receiving bad news is.
Four key points need to be considered while delivering bad news:
1. Address the patient first, even if the patient appears confused or unwilling to
participate. If comatose, never talk to the family as if the patient were not pres-
ent. The patient must remain the center of care in all circumstances [10]
2. Ask the patient, if able to communicate, if and how the family/loved ones should
be involved in the discussion, to emphasize the right to privacy if desired [10]
3. Demonstrate that you and all the healthcare providers involved are going to team
with the patient and the patient’s caregivers/loved ones in this difficult period.
Fine et al. demonstrated that even though the first thing that the patient requests
is good symptom management, “companionship,” which means an active “part-
nership” not only with his family members but with the healthcare providers too,
is very high in the list of needs [11]
4. Do you need to get more involved in the patient’s decision-making process? This
is a rather provocative concept as today’s Western societies emphasize patient-
centered decision making and the concept of autonomy. Nevertheless, patients
may prefer their doctors to be partners and may sometimes ask physicians to take
difficult decisions for them. A recent study conducted by Chungon more than
8,000 hospitalized patients showed that even though 97% of respondents wanted
doctors to offer them choices and to consider their opinion, two out of three pre-
ferred however to leave medical decisions to their physician [12]
Several guidelines on the sequence to follow when delivering bad news have
been published, some of which being available in a convenient format, which are
worth having in the lab coat pocket for a quick double-check before a meeting,
especially at the beginning of training. Some are based on simple mnemonic
(ABCDE) [6],on steps [13, 14]or acronyms (SPIKES) [15, 16].All account for the
important elements of a good discussion not only while breaking bad news, but also
while discussing other important issues, such as advanced care planning or treat-
ment goals. One of these guidelines, SPIKES, was also assessed as an education
tool for the ED residents to ease the discussions with the family members after a
patient’s death [17].
76 D. Anwar et al.
Table 5.1 Checklist of key elements for a successful meeting while breaking bad news
Getting ready for the meeting
• Determine who will be present (a)
• Obtain/review all necessary information regarding the patient’s condition and plan of care
before the meeting
• Discuss briefly with the professionals who will be present, what the main point(s) to discuss
are, who will lead, and who will answer questions of various topics
• Determine the amount of time necessary to dedicate to the meeting
• Prepare an appropriate environment
• Minimize distractions from cell phones, pagers, disruptions. Ensure that every medical team
member is physically and mentally prepared
Initiating the meeting
• Be on time
• Introduce everybody; be sure that everybody is sitting comfortably
• The meeting leader will set up the timing and explain the goal of the meeting, and suggest
some “rules” (e.g., only one person speaks at a time, with no interruptions)
During the meeting
• Start by addressing the patient: “Mr. X, how are you feeling now?”
• Briefly assess patient understanding: “What do you know about your situation?” (b)
• Assess patient readiness for receiving the bad news, and the level of detail necessary to
provide: “What do you want to know” (c)
• Break the news (d)
• Respond to emotion (e)
• Be attentive (especially to the patient and the family reactions, nonverbal language, and
interactions)
• Plan the follow up (f)
After the meeting
• Create a written summary of the meeting, including date, participants’ names, decisions,
problems, plan of care, and specific elements of meeting
• Determine if the team achieved its initial goals
• Assess what went well and what did not
• Determine who is going to perform necessary follow-up tasks
• Reflect on your own and the team members’ limits (e.g., bad personal period, fatigue,
feelings of medical team members toward patients and patient family members) (g)
• Assess availability and access to our resources (h)
Table 5.1 presents a series of the main elements to consider in order to facilitate
communication when bad news is to be presented. Additional information regarding
some of these key points are detailed afterwards.
(a) Determine who will be present
It is important to determine how many family members are expected or are key
persons, and which team members’ presence would be helpful. It is better to be
accompanied by another member of the healthcare team, especially if not expe-
rienced, not knowing the situation well, or feeling uncomfortable or unready.
The patient needs to know that his or her physician will not neglect treatable
aspects of health, diabetes, hypertension, nutritional deficiencies, etc. There is

no shame in asking for help! Do not hesitate to send reminders of the meeting
and to request a confirmation from the participants, especially if you will meet
several key family members.
(b) Briefly assess patient understanding
Some possible questions
– “Could you describe your medical situation for me in your own words?”
– “When you first had this symptom, what did you think it might be?”
– “Are you worried about your illness or symptoms?”
– “What did my colleague (oncologist, PCP, radiologist…) tell you about your
condition or the procedure you underwent?”
In a study conducted by Rowland Morin, it has been shown that some of the
factors of satisfaction of the patients during initial interviews with physicians was
their use of silence or the reaction time latency between speakers [18]. As it has been
demonstrated that most patients take two minutes to answer your questions, but that
an average medical doctor interrupts the patient within 18–23 s, so hold on!
This important step may allow you to understand:
– What the patient knows (“I have lung cancer, and I need surgery”)
– What he understands about his disease (“the doctor said something about a
spot on my chest x-ray”)
– His level of technical sophistication (“I’ve got a T2N0 adenocarcinoma”)
– His emotional state (“I’ve been so worried I might have cancer that I haven’t
slept for a week”)
– His relations with his family members (“Let me talk for a change, I’m the sick one”)
(c) Assess patient readiness for receiving the bad news, and the level of detail
necessary to give
Some possible questions:
– “If this condition turns out to be something serious, would you want to know?”
– “Do you want me to go over the test results now and to explain exactly what
they mean?”
– “Some patients want me to cover every medical detail, but other patients want
only the big picture. What would you prefer now?”
– “Some persons prefer not to be told what is wrong with them, but would
rather have their family told instead. Both solutions are perfectly OK. What
do you prefer?”
(d) Break the news
The topics you would like/need to cover during the meeting may be extensive
and address the diagnosis, potential additional investigations, treatment options,
prognosis, and/or advanced directives.
It is very important to:
78 D. Anwar et al.
– Use softening language as you begin to prepare for the delivery of bad news.
You may say: “I feel badly to have to tell you this,” “I’m afraid the news is
not good,” “The report is back, and it is not what we hoped for.”
– Talk in a sensitive but straightforward manner.
– Avoid the single, steady monologue. Give pieces of information in small
chunks and pause frequently (“I’m going to stop for one minute to see if you
have some question at this point.”).
– Avoid technical jargon (no pathophysiology course) or euphemisms (the
“mass,” the “problem”).
– Check for understanding. (“You just received news that is not what you
expected. There is a lot going on right now for you and your family. Please
tell me if you understood everything I told you or if you want me to go back
to some specific issues.”).
(e) Respond to emotion:
– Be ready to face a broad range of reactions (e.g., denial, blame, intellectual-
ization, disbelief, acceptance, anger).
– Wait and be there. Silence and the use of nonverbal language are great tools
that we underuse.
– Have tissue papers available.
– Acknowledge the emotions.
– “I’m sorry” and “I don’t know” are OK!
– Avoid defensiveness regarding the medical care. Do not criticize other health-
care professionals.
– If things turn bad and you face an aggressive reaction, do not take it person-
ally and do not respond in the same way.
(f) Plan the follow-up:
– Give additional information on potential treatments options, further neces-
sary investigations, and appropriate referrals. (“We’ll go step-by-step.”).
– Maintain realistic hope. “There is nothing we can do for you” is the worst thing
we can tell our patients from an emotional standpoint, in addition to being
completely wrong. Palliative/EOL care has much to offer regarding symptom
management and can address the various dimensions specific to the patient.
– Allow extra time for final questions (while respecting the time allocated). Help
break the news to the family if no member is present during the meeting.
– Never leave the patient without having organized a follow-up appointment or
a phone call contact. Reiterate that you will be there to help in difficult
moments.
– Always double check: Is the patient alone? Driving? Depressive? Suicidal?
Living alone? Does he have former or current addictions?
– Organize, if needed, prompt social, psychological, and/or spiritual support.
– If the patient has been admitted, try to avoid holding the discussion at the
time of discharge. The patient may need the supportive environment of the
hospital to make his or her initial accommodations.
(g) Reflect on your own and the team members’ limits:

Breaking bad news may be challenging and may bring us above our limits. We
can experience a sense of failure and frustration with the inability to help more or
by judging our performance while breaking the news. Some professionals may
even desire to avoid a specific patient and family to escape these feelings. These
feelings can be exacerbated if we have simultaneously developed a close relation
and start to identify with the patient (e.g., patient who looks like our own father,
young patient with children the same age than ours, etc.), undergo a difficult
personal period, or are overwhelmed by a huge work load. These emotions may
affect both the patient’s care and our well-being. Such unexamined emotions may
lead to disengagement, poor judgment, distress, and burnout [19]. It is said that
approximately one of every three physicians will experience burnout at any given
time, which could lead in the worst cases to substance abuse, intent to leave medi-
cal practice, and suicide [20]. Even though a recent review failed to demonstrate
that burnout levels were higher in palliative care health workers than in other
contexts [21], we may imagine that in this specific context with a constant immer-
sion in a field where patients of all ages present very advanced conditions, the risk
of being overwhelmed may be higher than in other medical areas. For this reason
teamwork is so important. A health professional should not be the only one to
carry the weight of this difficult moment. Discussing with colleagues after the
meeting about what was said, what happened in the meeting, the plans for patient
care, and making plans to share responsibilities can be tremendously helpful.
(h) Access to our availabilities and resources
Also, it is important to make sure that you have personal resources and to know
that you can access them. For some of us, it is just our family circle, for others,
such resources can include extreme sports, nature, arts, meditation, or any of a
number of other sources of coping. Whatever it is, we need to know what can help
us. Seeking professional help can also be an asset in difficult moments. There is
no shame to request help from our peers, from our mentors, or from profession-
als. Remember that if you arrive in the stage of burn-out, you will not only hurt
yourself, but you will not be of any help to your patients and your team!
Other Important Issues
“Doc, how much time do I still have?” Physicians are not good prognosticators.
A 2000 study conducted by Christakis et al. asked 343 doctors to provide survival
estimates for 468 terminally ill patients (<6 months to live if disease ran expected
course). For this population, which finally had a median survival of 24 days, 63% of
the physicians were overoptimistic, and 17% overly pessimistic, a long relationship
with the patient being associated with overestimation [22]. Over-optimism as well
as unnecessary pessimism may harm, it may be wise to remain vague at the beginning
and to reassess on a regular basis rather than to cite a bunch of statistics. If a specific
80 D. Anwar et al.
patient requests statistics, it is important while giving them to emphasize that each
patient is unique, and that it is almost impossible to predict where in these statistics
the particular patient will fall.
“To touch or not to touch?” We are often concerned about being disrespectful of
the patient’s private sphere if we touch his hand or his shoulder. Usually, patients
with oncological situations, especially ones presenting with mutilating lesions, may
feel rejected and find comfort in being touched. Holding a patient’s hand may also
give you important clues: Is the patient cold? Shaking? Myoclonic? If the patient
does not find comfort in being touched, the patient will tell you, either directly, or
through nonverbal signs.
What Does the Patient Remember?
Several studies have shown that the patient may not remember points physicians
addressed. In a recent study, Olson et al. interviewed patients on their discharge day.
Among the patients, only 57% knew their present diagnosis while 77% of the physi-
cians were sure that they were aware of it [23]. Even more relevant, when a new
medication had been prescribed, 20% of the patients said their physician never told
them about it, while all the physicians said they had told them about it. Regarding
the side effects, only 10% of the patients said they were told about them while 81%
of the physicians said they had described them. This discrepancy is probably even
more present when the patient has to assimilate bad news.
The Importance of the Body Language
Four components are important:

– The first impression: Shake hand, make eye contact, be seated
– The physician’s nonverbal language
– The patient’s nonverbal language
– The family members’ nonverbal language
The first two components will help you create a good relation with your patient
and family members. These elements should be addressed in any communication
training. The last ones will bring you invaluable elements which may help you to
obtain a global vision necessary to build up a strategy of care.
Cultural and Spiritual Issues
As society becomes more pluralistic, physicians will face increasing numbers of

patients from various cultures or religious backgrounds. The more we know about
the different needs of diverse patient groups, the more tools we will have to deal
appropriately with situations involving them. Studies have shown that people from
many different cultures are more likely to believe discussing death can bring death
closer, including Native Americans and immigrants from Africa, China, Korea, and
Mexico [24]. Even though patient autonomy is a strong cultural value in the USA
and other Western cultures, it is not the same in some non-Western cultures, such as
those found in Asia and Latin America, where primary decision makers are often
supposed to be the family members. The more we know about these different
visions, and the more we respect them as well as their spiritual beliefs, the more it
will help build a relation of trust between the patients and us. It is often rewarding
for the patients and their families when physicians ask questions about their culture
and their beliefs. It is also always possible to contact a spiritual leader or an
influential member of a specific community to obtain as much relevant information
as possible—all within the requisite of patient confidentiality and trust.
Communicating with “Difficult” Families
Integrating families and loved ones in patient care is a mandatory part of good pal-
liative medicine as defined by the most recent WHO definition [25]. The patient
needs to know that we take care of the needs of loved ones, too, and that these loved
ones can be part of the decision-making and care process if the patient so wishes.
Also, it is often extremely difficult for patients to know they are leaving behind
beloved ones after death, and the patient sometimes worries more about them than
about him or herself. For this reason special emphasis is placed on end-of-life fam-
ily conferences. Several guidelines have been developed to help organize these con-
ferences [26, 27].
It can likewise be extremely difficult for family members to see their beloved one
decline and sometimes suffer or be confused. Family members may feel guilty
because they cannot help the patient more. Often, these family members are them-
selves on the verge of exhaustion. Sometimes family members and loved ones are
left in terrible distress, and for this reason bereavement services are offered as part
of regular hospice care for up to 13 months following the patient’s death.
Relationships physicians develop with the patient’s family members and loved
ones are often excellent, rewarding, and helpful. The longer physicians interact with
these caregivers and the more the family trusts the physician, the better this relation
may become. Especially effective physicians consistently emphasize the important
role family members play in their beloved one’s care, gather family members’ opin-
ions on this care, and allow them to ask any question they may have [10].It is also
important to ask family members on a regular basis how they are feeling and coping
with this terrible situation. It may be useful for the physician to acknowledge that
this caring may be a physical and emotional drain on family caregivers. Proactively
suggesting “respite” may relieve guilt and promote better relationships between the
patient and the family caregivers as well as between the family and the physician.
82 D. Anwar et al.
In some occasions however, the communication with the family may be more
challenging than the patient’s care himself, whether the patient is still able or not to
communicate accurately. Some family members may express their suffering in various
ways that can be difficult for the healthcare providers to handle. This may be the
family members’ way trying to deal with a reality they find intolerable. Physicians
must understand that unpleasant reactions may only be the expression of an intense
suffering. Family members may be extremely demanding, come back again and
again with unrealistic expectations and hopes, interfere with best care practices (“no
morphine, I don’t want him to receive dangerous medications,” even while the
patient is in excruciating pain or severe dyspnea), or sometimes be very aggressive
and question the physician’s every suggestion. Healthcare professionals may also
face the occasional pathologic personality among family members, such as
narcissistic, antisocial, or other personality disorders. Some family members may
also present with active addictions that will also interfere with the patient’s care.
If the patient’s family members had very disappointing interactions previously
with other healthcare providers, sometimes believing that the patient has been not
diagnosed on time, or did not receive the care they would have desired, they may not
be quickly willing to trust any doctor again, and the medical team may need more
time and a united effort to gain their trust again.
Past or ongoing conflicts among family members are sometimes exacerbated in the
end-of-life period. Some family members, who may not have been present and involved
in the patient’s care previously, may feel a form of guilt and aggressively manifest these
feelings by trying to exert control in the situation, which may upset other family mem-
bers. There may also be financial concerns or interests. And family members may
inappropriately expect members of the healthcare team to determine who is right or
wrong, which may put physicians and others into difficult situations [27].
Some important points:
1. If a scheduled family meeting is expected to be difficult, it is important to prepare
the meeting carefully. Make sure that all the main family members will be pres-
ent and ask them confirm their presence. Prepare a team approach and have all
the relevant team members available before starting the meeting. If you expect
six family members, try not to be alone; show a coherent interdisciplinary
approach. On the other hand, with one or two family members only, having them
to face a whole healthcare team may be overwhelming.
2. Try to figure out as soon as possible who holds the patient’s power of attorney,
whether there is a living will if the patient is not able to communicate, and deter-
mine clearly who will be the main contact among the family members.
3. Be especially clear in your expectations during this meeting. Difficult family members
often lead to difficult meetings. Expectations regarding meeting time, how the meeting
is led, as well as ground rules on participation—that all members participate in turn and
that shouting, cursing, and violent behavior are not accepted. When situations are
expected to be particularly tense, be sure to have prompt access to security. If you see
that you do not have any more control of the situation, and the discussion arrives at a
dead end, it is better to call for a “time-out” and to reschedule another meeting.
4. No member of the healthcare team should be recruited to judge family conflicts.

Likewise, family conflicts should not be mirrored by healthcare team members.
Dysfunctional family members may be highly skilled at recruiting others into
their orbit and thus splitting the healthcare team. In some occasions, it is worth
asking an angry person to address you rather than another member of the family
to avoid a spiral of discord or violence.
5. Before the meeting, try to gather as much information regarding the specific
cultural and spiritual context of the present family as possible. Showing your
knowledge, your interest and, most importantly, your respect for other cultures
and religions may help improve communication and create trust relations with
the family members [28].
6. As usually, remember that it is always better to ask for help if needed: a more
experienced colleague, a palliative care physician, or an ethics committee con-
sultation may be of help.
7. After the meeting, take time to debrief the situation within the team. Document
all possible elements, the family and team members present, what was discussed
and the decisions taken. Do not forget that there is always a risk of lawsuit, par-
ticularly when family members are angry, excessively distressed, or otherwise
highly emotional.
Communication Among Health Professionals
Patients and their loved ones with advanced disease face numerous, well-docu-
mented problems—the poor prognosis, symptom burden, and suffering, as well as
the logistical difficulties of a heavy schedule of appointments, sometimes in various
locations, with conflicted schedules, heavy costs, and long waiting times—but such
difficulties are only exacerbated when the patient and his loved ones receive
conflicted opinions from various healthcare professionals. It is especially difficult if
one professional questions openly the attitude of another one.
Another difficult situation when the patient switches abruptly from a primary care
provider to a specialist like an oncologist, and the switch can be even more distress-
ing when going from the specialist from whom he expected potential cure to pallia-
tive or hospice care.
In these terrible moments when the patient faces death, the patient needs even
greater trust in the healthcare providers, and to know that they will work all together
to offer the best option appropriate to the specific situation, adjusting to changes in
the disease state and goals of care. If we go back to Fine’s survey conducted among
hospice patients and asking the simple question: “What would be the most useful
way I can be of help to you today?”, symptoms relief came first of course, but close
to this came the request of companionship [11].
It is also well represented in this African proverb quoted by Spruyt: “If you want
to travel quickly, go alone. But if you want to travel far, you must go together” [29].
84 D. Anwar et al.
In fact, there is a lot to do in the travel toward death in a palliative condition, and the
way is sometimes long. We need to join our efforts to help our patient and the patient’s
loved ones to go through this travel as smoothly as possible. We need to collaborate and
communicate better, whether among team members, or the various physicians involved.
Interdisciplinary Team Communication
A well-conducted hospice team meeting is a wonderful example of the effective-

ness of interdisciplinarity. Medical students or young residents who attend these
meetings for the first time are very often surprised to see that the physician is not
the “leader” of the team. Each team member, physician, nurse, psychologist,
social worker, chaplain, pharmacist, volunteer, is important, as each of them has
a specific expertise and unique skills and values that work in synergy with those
of the other team members. We know the importance of close communication,
respect, shared team philosophy, as well as good interpersonal relationships
among the team members if we want to offer the best care to our patient [30].
Communication Among Physicians
This is as important as the interdisciplinary communication. It is not rare at the hospital

to have a patient assessed by several specialists, sometimes giving contradictory opin-
ions regarding treatment options or global attitudes, without discussing with their col-
leagues, leaving the patient feeling powerless and confused. The first question at any
moment should always be: “Who will take the decisions and organize the care offered
to the patient.” This “captain” should obtain information from all the specialists and
organize the plan of care accordingly. Regular meetings among all involved specialists
are ideal of course, but due to the busy schedule of all the physicians such meetings are
difficult to coordinate sometimes. The communication between the primary care physi-
cian, the specialists, and then the palliative care or hospice physician must be main-
tained to avoid the patient distressing transitions. It is also a good way to gather new
information, to have a better idea of the “reality of the other,” and to demonstrate our
respect for our colleagues. Finally, the technology that surrounds us is wonderful, but
sometimes a simple phone call or a visit to a colleague will be more helpful and per-
sonalized that the most sophisticated electronic letter.
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Review Questions
1. In a global population discharged from the hospital, how many patients can tell
you their current diagnosis?
(a) 90%
(b) 75%
(c) 57%
(d) 35%
2. For how long does a “standard” physician let a patient talk before interrupting him?
(a) 18–23 s
(b) 30–60 s
(c) 2–3 min
(d) Usually does not interrupt him
3. When you have to break bad news to a patient, what is one of the most important
initial step?
(a) To be sure that you will have time to address all the important issues, such as
diagnosis, prognosis, treatment, advanced directives
(b) To find somebody willing to do this for you
(c) To discuss in the corridor, standing, to avoid to spend too much time with the
patient
(d) To try to have all the relevant information available
4. Is Palliative Care a medical specialty with higher risk of burn-out than others?
(a) Yes
(b) No, it is ICU
(c) No, it is surgery
(d) No, the risk is the same in all medical specialties
5. The best way to improve your communication skills is:
(a) There is no way to improve, either you are an innate good communicator, or
you are not
(b) To observe skilled colleagues or mentors
(c) To learn from our mistakes
(d) To follow a formal communication training
Answers
1. (c) 57%
2. (a) 18–23 s
3. (d) To try to have all the relevant information available
4. (d) No, the risk is the same in all medical specialties
5. (d) To follow a formal communication training
Chapter 6
Guidance with Complex Treatment Choices
Introduction
Rightly or wrongly, good or bad, we take decisions and make choices every day, in
almost all aspects of life. These choices are made in response to questions that range
from the apparently simple (“which dress to wear tonight for the evening party”) to
perhaps the more complex (“which one to marry from the three prospective suit-
ors”). In terms of treatment choices too, decisions need to be made, again ranging
from the relatively mundane (“does the patient need an antibiotic? If so, which one,
which route, what dose, for how long?”) to relatively complex (“does the patient,
with extensive metastasis and limited survival probability, one who himself does not
wish to undergo any further surgery and simply wants to die ‘in peace and dignity,’
but whose family and friends want him to ‘live as long as possible and at any cost’
and consider that the patient may not have decision-making capacity now because
of brain metastasis related cognitive impairment, and finally where there are several
intervention options but none with a clear advantage over another, need a specific
intervention? If so, which one, what type, with what intensity, for how long?”).
Decision making and treatment choices can be extremely complex and uncertain,
especially in the context of a serious and life-threatening illness or in the terminal
stages. This is where, in the setting of palliative care, decision making may need
guidance or sharing.
S. Mitra, M.D. (*)

Department of Anaesthesia and Intensive Care,
Government Medical College and Hospital,
Chandigarh, India
e-mail: Drsmitra12@yahoo.com
N. Vadivelu, M.D.
Department of Anesthesiology,
Yale University School of Medicine,
New Haven, CT, USA

DOI 10.1007/978-1-4614-5164-8_6,
There are three general stages in any decision making. The first and foremost
essential stage is that of information. This information is necessarily about the
patient’s diagnosis, current condition, complications, other relevant background
information (e.g., allergy to certain drugs, other medications, coexisting conditions,
etc.), and scientific information regarding the effectiveness and safety of particular
interventions available in the current situation as well as the doctor’s clinical
experience-based information under the particular circumstances. However, this
“medical” or “objective” information, though clearly necessary for the decision
making to proceed further, may not be sufficient for this purpose, and there can be
a vital role played by information of another nature, that based on the values, prin-
ciples, priorities, and feelings of the patient, at times his family, and even rarely the
doctor (e.g., whether conducting a medical abortion is “right”).
This latter, “value” or “preference” based information becomes very important
during the second stage of decision making, the stage of deliberation. It is at this
stage that the information from the different sources mentioned above are analyzed,
their pros and cons weighed, and attempts are made to negotiate conflicting issues
if any (e.g., between medical information and patient preference). Finally the actual
stage of decision making is arrived at, when the final decision to be implemented is
made based on the previous two stages [1].
Models of Decision Making
In the general healthcare setting, the differences between these three stages described
above become apparent when we consider the models of decision making. Three
broad models of decision making have been described, with shades of gray in
between [1–3] (Table 6.1).
The first, “paternalistic model,” is the traditional model that has held its sway
over centuries of medical care and is still the dominant model in many parts of the
world. This is the “Doctor knows the best and hence decides” model. The patient
may receive some information and seek clarification but remains the passive person
in “receiving” the decision regarding treatment or any other intervention. Thus,
there is no actual partnership between the doctor and the patient. The information is
medical is nature, the deliberation is between different options but without the
patient taking any active role in it, and decision making is done solely by the doctor
or the treating team. The guiding basic bioethical principles behind this model are
beneficence (“do what is good for the patient”) and nonmaleficence (“do not do any
harm to the patient”).
The other extreme of decision-making models is called the “informed choice
model.” This model arose in response to the growing waves of consumerism, patient-
centered medicine, and patient rights movement, especially fuelled by the bioethical
principle of patient autonomy. Here the doctor informs, the patient deliberates and
decides. During the deliberation stage, it is the patient who weighs the medical
information provided by the doctor against his own values and preferences, which
6 Guidance with Complex Treatment Choices 91
Table 6.1 Models of decision making

Shared decision-making
Characteristics Paternalistic model Informed choice model model
Underlying Beneficence; Patient autonomy Combination of
bioethical nonmaleficence autonomy and
principle beneficence
“Center” of Person centered Person centered Relationship centered
orientation (doctor) (patient)
Partnership or No No Yes
collaboration
Decision-making
stage
Information base Medical Medical (personal Medical and personal
information not (shared)
shared with doctor)
Deliberation No No Yes
between doctor
and patient
Decision making Unilateral (doctor) Unilateral (patient) Bilateral (mutually
agreed)
he is not obligated to share with the doctor. Based on this, the patient makes the final
decision. The doctor may or may not agree with this final decision, but nonetheless
is obligated to implement it provided the patient is understood to retain decision-
making “capacity,” i.e., he can receive the relevant medical information provided by
the doctor, can retain the information long enough to weigh the pros and cons of
different intervention (including the choice of no intervention at all), can arrive at
the final treatment choice, and can communicate this choice to the treating team.
Note that in this model the principle of patient autonomy (what the patient thinks is
best for him) may conflict with the principle of beneficence (what the doctor thinks
is best for the patient). In case of such a conflict, under this informed choice model
for a patient with decisional capacity, patient autonomy wins. In a sense then, again
there is no true partnership or collaboration between the doctor and the patient.
The third, intermediate form is best known as the “shared decision model”
(SDM). This model is placed in between the other two. As the term suggests, here
information is shared, deliberation is interactive, and the final decision is mutually
agreed upon. The information domains cover both medical (objective) and personal
(subjective), where the patient shares his part of the “information” with the doctor.
The deliberation is a two-way process unlike both the earlier models. The negotia-
tions can be iterative and dynamic, and can involve—other than the doctor and the
patient—other members of the patient’s family, other members of the treating team,
and other staff of a multidisciplinary team (MDT) such as nursing staff and social
worker. The final decision is mutually agreed upon. Here the principles of auton-
omy, beneficence, and nonmaleficence are all attempted to be accommodated, and
conflicts are resolved by discussion. In this sense, the SDM is a truly partnership-
based collaborative model [3].
It is to be noted that there is no inherent “superiority” of any of these models, and

that intermediate forms (“shades of gray”) exist in real-life applications. For example,
in a case where there is a clear-cut treatment option with proven efficacy (e.g.,
antibiotic choice of known efficacy as determined by culture and sensitivity) the
paternalistic model would work fine. In another case where there are multiple
treatment options of proven efficacy but differing tolerability issues, the informed
choice model may be suitable. On the other hand, when there are multiple options
in a complex situation, with no clear-cut efficacy of one over another but with varying
pros and cons, the patient’s preference may be negotiated with the medical information
and a mutually agreeable final choice is finalized. This is the SDM, and it is
especially suitable for palliative care and end-of-life scenarios.
Preference-Sensitive Treatment Decisions in Palliative Care
“The need for some form of doctor patient partnership is most compelling when the
patient presents with a serious or life threatening illness; different treatment options
exist, with different benefits and risks; and outcomes are uncertain. In this situation,
the stakes are high and there is no one ‘right’ treatment. Since the patient will bear
the consequences of whatever treatment is implemented, it is important that his or
her values and preferences are known and respected.
Patients in this situation are likely to feel vulnerable and may not initiate such a
discussion; it is the doctor’s responsibility to ensure that this occurs” [3].
Palliative care involves a mix of complex medical information, a personal
emotional dimension, and options of care whose outcomes can be uncertain. Under
these circumstances, the dilemma of choosing between life-prolonging treatments
with potential side effects or maximizing quality of life can become accentuated.
Patients are faced with difficult decisions about a wide range of issues, such as place
of care, various options to treat symptoms, the use of opioids, palliative treatments
such as chemotherapy, advance directives, etc. [4]. Many of these decisions are
known as “preference-sensitive” decisions, where, because there is no one “right
answer,” patient (or family’s) preference to follow one course of action over another
gains priority and becomes the final deciding factor.
Not only this, but more importantly and to complicate matters further, the
decisions to be taken during palliative care keep on changing along the trajectory of
the life-threatening disease: from its diagnosis, through multiple points of curative
or disease-modifying treatments, remissions and relapses, through life-prolonging
or life-sustaining treatments, through comfort care, till the issue of where, when,
and how to die in order to have a “good death.” Each of these “decision transition
points” brings with it new questions, new dilemmas, and new priorities. Particularly
towards the end of this trajectory, patient’s and his family’s values, preferences, and
priorities tend to become progressively more meaningful and important that shape
the treatment choice. Eventually, end-of-life decisions arise, such as “Do not resus-
citate” orders, withdrawal or withholding of life-prolonging measures and where to
receive end-of-life care.
The types of decisions that are needed to be made depending upon the decision
transition points could be [5]:
• Selecting a surrogate and other advance care planning decisions
• Making various decisions regarding aspects of disease-modifying therapies
• Treatment choices when cure is not possible
• Whether or not to be admitted to intensive care unit (ICU) and receive life-
prolonging treatments or to focus on comfort care
• Where to receive end-of-life (EOL) care and other EOL decisions
A partial list of the goals of palliative care where decisions need to be made
include:
• Cure
• Slowed progression
• Remission
• Prolonging life span
• Achievement of life goals
• Maximizing normal life experience
• Maximizing periods of lucidity
• Maximizing comfort
• Minimizing pain and other symptoms
• Maximizing family access
• Having care and/or death occur in their preferred location
As mentioned above, these goals shift depending upon the decision transition
points. The important point to note is that in many of these decisions to be made one
needs to move beyond the narrow medical model of a disease and its treatment. The
choices to be made depend not only upon the medical circumstances of the “case”
but also center around increasing or at least optimizing the quality of life of the
“person,” which is the ultimate overarching goal of palliative care as defined by the
World Health Organization [6].
Guidance with Complex Treatment Choices
It follows that the SDM as described earlier intuitively appeals as the suitable model
to be followed in making complex decisions, given the uncertainty and multidimen-
sional nature of the situations, nonsuperiority of any particular interventions at
times, adverse effects of many of the interventions, and the need to take into account
the values, personal goals, feelings, and priorities of the patient and the family.
However, these same factors outlined above, and especially the complex treatment
choices with their own pros and cons, can be quite overwhelming for the patient.
Information overload can occur; the patient may feel perplexed and daunted; and each
“arm” of the decision-making process may come into conflict with one another. This is
true even in case of the so-called preference-sensitive decisions, because at times the
patient may not be clear as to what is “preference” is, because of conflicting values,
wishes, and needs. This can give rise to a state of “decision conflict,” which is defined as
“a psychological state of uncertainty around which course of action to pursue. Decisional
conflict occurs when choices are uncertain, involving value trade-offs between patient
judged benefits and harms and individually valued health states, when there is no clear
‘right choice.’ Unresolved decision conflict may result in regret over the decision” [5].
In the worst-case scenario, this may even lead to “decisional paralysis,” rendering the
patient passive and choiceless, leading the patient to defer to the clinician because he or
she considers the decision “too complicated” for the lay person.
Starting with the patient’s goals and values early in the consultation and tailoring
the presented options to those goals and values, one can individualize and narrow
the wide array of options to those most consistent with the patient’s values. It is
important to avoid burdening patients and families under stress with options that are
not desired, are unrealistic, or are presented in an array may simply be overwhelm-
ing or cause decisional “paralysis” as mentioned above. Hence it is important first
to sit together, discuss the various options, narrow down the possibilities, and then
present the information to the patient and family in a distilled and tailored fashion.
For all these reasons, the MDT remains an invaluable asset in guidance of patients
with complex choices. The MDT, in its multidisciplinary meeting, can discuss vari-
ous findings, options, their pros and cons, and can reach a consensus or at least
narrow down the options, which can then be discussed with the patient to arrive at a
final decision [7].
Decision Support, Decision Aids, Decision Coaching
As mentioned above, decision making can be quite daunting for patients at times
and can lead to decision conflict. Health care providers can develop patients’ and
families’ skills in SDM resulting in a preference for more active involvement. In this
connection, decision science and its application in healthcare can be of great help.
Decision scientists have designed techniques to promote SDM and relieve deci-
sional conflict that are collectively called “decision support.” Decision support is
really an umbrella term that encompasses a broad range of skills, interventions,
strategies, and processes that help the patient in making a choice based on the
options available and his personal values and preferences.
It is to be noted that decision support strategies do not make the decisions for the
patient; they only help or guide the patient through a structured process to clarify
different aspects of the difficult question that the patient has to answer ultimately.
Thus, they are adjuncts to the decision-making process. These support strategies
include, on one hand, focused counseling by a health practitioner, and on the other
hand, computerized interactive program modules. This term recognizes that, irre-
spective of the nature of the delivery system, any method that attempts to support
individuals facing decisions, either in dialogue with an agent, such as a health care
professional, or independently of such dialogues, is a patient-orientated decision
support intervention [8].
Table 6.2 Definitions

Decision science Study of understanding and improving the
process and quality of decision making
Decisional conflict Psychological state of uncertainty around
which course of action to pursue.
Decisional conflict occurs when choices are
uncertain, involving value trade-offs
between patient judged benefits and harms
and individually valued health states, when
there is no clear “right choice”
Decision support An umbrella term referring to clinical skills,
strategies, interventions, and other
processes whereby patients are provided
with structured support during an explicit
process of decision making that includes
focused counseling, and in some cases
employs a patient “decision aid” to enable
them to make informed health care choices
Decision aids Tools that help people become involved in
decision making by providing information
about the options and outcomes and by
clarifying personal values. They are
designed to complement, rather than
replace, counseling from a health
practitioner
Decision coaching Individualized support provided through the
decision process by a clinician who guides a
patient to consider the information relevant
to a particular decision and the patient’s
values to reach an informed preference
Shared decision making A process by which a healthcare choice is made
(SDM) jointly by the practitioner and the patient
and is said to be the crux of patient-centered
care. Briefly, SDM rests upon knowing and
understanding the best available evidence of
the risks and benefits across all available
options while ensuring that the patient’s
values are taken into account
Sources: [5, 9, 10]
[See Table 6.2 for various definitions used in this and other sections of this
chapter.]
Various decision support interventions can include: direct focused counseling;
use of several adjuncts such as leaflets, pamphlets, flip charts, question prompt
sheets, “issues cards,” “decision boards,” hand-held information tools, information
displayed on computer screens, video, DVD, etc.; and interactive instrumental
media via computer software or Internet where the patient may be guided through
successive interactive steps so as to clarify the final decision or narrow down the
choices.
Elwyn et al. [8] have classified the multitude of decision support interventions
into three broad categories:
Category 1: Those That Are Used by

Clinicians in Face-to-Face Encounters
These interventions are specifically designed for use by healthcare professionals

when they wish to involve patients in decisions. They typically display informa-
tion using short statements or graphics so that they act as materials that can be
easily shared across a desktop in a clinical encounter. They act as catalysts to
SDM by acting as prompts and props, typically by making options visible and by
organizing information according to attributes that patients find relevant. They
help the clinician engage the patient in a discussion about preferences. Examples
include risk communication tools, display boards, issues cards, etc. It is to be
noted that these are not stand-alone tools, but rather help to focus the clinician–
patient dialogue.
Category 2: Those That Can Be Used Independently

from Clinical Encounters
These are also more commonly known as “patient decision aids” or simply “decision
aids.” (The term “decision aid” is also broadly used as a generic term for all the
decision support interventions, but here it is used in reference to Elwyn’s Category
2) [8]. Decision aids are by far the most common type of decision support interventions
used. They are used by the patients independent of the actual clinical encounter,
either before (when the patient wants to come “prepared” for the discussion in
SDM) or after (if, following an initial consultative meeting, the patient wishes to
make the final choice).
Decision aids are defined in a broad way as “interventions designed to help
people make specific and deliberative choices among options by providing informa-
tion about the options and outcomes that are relevant to a person’s health status” [8].
Because this definition is very broad and practically synonymous with “decision
support” as defined above, a narrow definition has been offered: “Tools that help
people become involved in decision making by providing information about the
options and outcomes and by clarifying personal values” [9]. Most trials to date
have been undertaken with this type of intervention. Standards have been developed
to assess the quality of these decision aids: The International Patient Decision Aids
Standards (IPDAS) [11]. There are a number of websites that feature various deci-
sion aids, and the decision aids website of Ottawa Hospital Research Initiative hosts
an “A–Z” inventory of such tools [9].
Table 6.3 A partial list of online resources for patient decision aids and other decision
support interventions
http://decisionaid.ohri.ca/AZinvent.php
http://decisionaid.ohri.ca/decaids.html#poc
http://decisionaid.ohri.ca/index.html
http://pennstatehershey.org/web/humanities/home/resources/advancedirectives
http://www.americanbar.org/groups/law_aging/resources/health_care_decision_mak-
ing.html
http://www.fraserhealth.ca/
http://www.healthdialog.com/Main/Personalhealthcoaching/Shared-Decision-
Making/
http://www.healthwise.net/cochranedecisionaid/Content/StdDocument.
aspx?DOCHWID=tu1430
http://www.acpdecisions.org
http://www.calgaryhealthregion.ca/programs/advancecareplanning/
http://www.fimdm.org
http://www.healthdialog.com
http://www.healthlinkbc.ca/kb/
http://www.healthwise.org
http://www.mayoclinic.org
Table 6.3 gives a partial list of this and other resources.

In general, decision aids guide the patient through the following steps [12]:
Step 1: Clarify the specific decision involved
Step 2: Explore the options, with their pros and cons (benefits and harms)
Step 3: Clarify the values, beliefs, and wishes of the patient
Step 4: Screen for decisional difficulties (decisional uncertainty, need for more
information, clarity for conflicting values, etc.)
Step 5: Arrive at patient’s choice (which may include no intervention)
Decision aids have already been developed for some of the common decisions
faced in hospice and palliative care such as completing advance directives, appoint-
ing a surrogate decision maker, receiving a feeding tube, cardiopulmonary resusci-
tation (CPR), artificial nutrition and hydration, and place of care.
Category 3: Those That Are Mediated by More Interactive

and Social Technologies
Decision coaching is a term often used in this context. This refers to individualized
support provided through the decision process by a clinician (usually a nurse or
other professionals trained in decision support techniques) who guides a patient to
consider the information relevant to a particular decision and the patient’s values to
reach an informed preference [5, 13]. Decision coaches are health professionals
who (a) assess patients’ decisional conflict and related needs; (b) tailor decision
support to address patients’ needs by offering patient decision aids and/or providing
evidence-based information, verifying understanding, clarifying values, and building
skills in accessing support; (c) guide patients through the decision-making process;
and (d) monitor for factors that can influence implementing the decision (e.g.,
motivation, self-efficacy, barriers). Often conducted over the telephone, the coach
provides and discusses information with the patient, guides him to find other
resources, helps explain the issues, and supports the deliberation process. Decision
coaching goes beyond decision aids in that the individualized one-to-one discussion
is often iterative and is followed up once a specific choice has been made.
Newer modes of decision coaching can utilize computer technologies in what is
called “interactive health communication systems” (IHCS). An IHCS offers one
platform for providing the information, communication, and coaching resources
that cancer patients and their families need to understand the disease, find support,
and develop decision-making and coping skills. A particular IHCS called
Comprehensive Health Enhancement Support System, Lung Cancer module
(CHESS-LC) has been developed for patients with advanced lung cancer and their
family caregivers. CHESS-LC provides information, communication, and coaching
resources. In particular, it provides web-based interactive decision aids and follows
the decisions through coaching. Unlike decision aids that stop at the decision itself,
CHESS-LC also extends decision support to implementing and evaluating the
decision [14].
A large amount of literature is available on the effectiveness of using decision
support interventions, or decision aids in a broad way, in several outcome parameters
of decision making. A number of reviews, both narrative and systematic, have
attested to the general effectiveness of decision aids. A series of Cochrane reviews
has been published on this subject, starting from 2001. The latest updated review,
published in October 2011, included 86 randomized controlled trials involving more
than 20,000 participants from eight countries (Australia, Canada, China, Finland,
Germany, Netherlands, the UK, and the USA) [10]. The primary outcomes were
defined according to IPDAS. Decision aids performed better than usual care
interventions by increasing knowledge, reducing decisional conflict, and increasing
participation in the decision-making process. Further, people exposed to decision
aids chose major elective invasive surgery less often than conservative options.
There was no evidence of increased anxiety or other adverse effects of exposing
people to decision aids. This is important because one often anticipates that increasing
patient involvement in difficult decision making and imparting “bad news” regard-
ing disease and its complications and outcome may adversely affect the patients.
The authors concluded that: “Consistent with findings from the previous review,
which had included studies up to 2006: decision aids increase people’s involvement,
and improve knowledge and realistic perception of outcomes; however, the size of
the effect varies across studies. Decision aids have a variable effect on choices. They
reduce the choice of discretionary surgery and have no apparent adverse effects on
health outcomes or satisfaction” [10]. Similar results are available specifically in the
cancer setting where a meta-analysis of 23 randomized controlled trials found that
patients exposed to decision aids are more likely to participate in decision making
and achieve higher quality decisions [15].
Guidance with End-of-Life Decisions
Many of the issues regarding the decision-making process come into sharper focus,
at times with a sense of urgency, as the disease trajectory moves toward end of life.
Such end-of-life (EOL) issues are of two overlapping categories: clinical and non-
clinical. Clinical decisions that occur near the end of life further fall into two broad
categories: decisions to use potentially life-prolonging treatments for emergency
conditions such as respiratory failure or cardiac asystole (e.g., mechanical ventilation,
CPR, ICU admission), and decisions for situations that are nonemergent and typi-
cally involve the use of treatment modalities that emphasize quality of life (e.g.,
opioid use for pain, palliative sedation, other “comfort care”) [16]. The general
goals of treatment focus on relative emphasis on life prolongation vis-à-vis preser-
vation of quality of life. The specific areas of decision making may include:
1. Advance directives (what the patient does or does not want in terms of nature or
location of treatment [“Living will”]; proxy or surrogate decision maker when
the patient loses decisional capacity [“Durable power of attorney”])
2. Do not (attempt) resuscitation (DN(A)R) orders
3. Other life-sustaining therapies, such as mechanical ventilation; feeding tube or,
in general, artificial nutrition and hydration; antibiotics; hemodialysis
4. Palliative care issues, such as management of pain and other symptoms; relief of
psychological, social, spiritual, and existential suffering
5. Creating opportunity to address unfinished business [17]
Although a detailed discussion of all these issues is beyond the scope of this
chapter, some general directions can be given regarding the guidance for complex
choices in the EOL care setting. The basic principles discussed in the earlier sec-
tions all apply. Based on these, the following sections are focused particularly on
guidance with EOL related decision making. The steps underlined below are not
exactly discrete “steps” but rather represent a “flow” of sequences in waves that
merge with one another.
The first step in providing such guidance is initiating the process. Clinical indica-
tions for discussing EOL care include (a) Urgent Indications, such as imminent
death; talk about wanting to die; inquiries about hospice or palliative care; recently
hospitalized for severe progressive illness; severe suffering and poor prognosis; and
(b) Routine Indications, such as discussing prognosis; discussing treatment with
low probability of success; discussing hopes and fears; physician would not be sur-
prised if the patient died in 6–12 months [17]. The person ideally suited to initiate
such discussions is the physician with a long-standing professional relationship
with the patient. In the absence of such a relationship, a single physician should be
designated to coordinate and communicate the medical aspects of each patient’s

overall care throughout his stay in a given facility, including disease-related and
palliative care issues. This physician should encourage full participation by the
entire team, including nurses, social workers, pharmacists, clergy, and family
members, as desired by the patient, to maximize the development of a trusting
context for subsequent decision making. The role of the MDT assumes paramount
importance in this context.
The second step is assessment of the patient’s needs and the values and goals.
Physicians can help patients to make critical end-of-life decisions by first assess-
ing the patient’s current physical symptoms and psychological and spiritual
needs, assessing family and social support system, estimating and communicating
prognosis, and asking the patient to define his or her end-of-life goals. In one
study, the five most important components of quality EOL care identified by
patients were:
1. Adequate pain and symptom management

2. Avoiding inappropriate prolongation of dying
3. Achieving a sense of control
4. Relieving burden
5. Strengthening relationships with loved ones [18]
The third step is providing critical information to the patient and family. The physi-
cian needs to be truthful and clear, at the same time not appearing blunt, intimidat-
ing, or noncaring. Physicians need to avoid giving false hope of cure or of greater
benefit than likely or expected. On the other hand, physicians should avoid painting
the situation worse than it is in order to get the patient to decide what the physician
feels to be in his/her best interests. Goal is to hope for the best course of illness or
for best quality of life for the longest possible time but we need to plan for the worst
or the unexpected.
The fourth step is advanced care planning. Advance care planning is a process
whereby the patient, with the help of his/her health care providers, family members, and
loved ones, makes decisions about his/her future medical care. Advance Care Planning
involves discussion of the diagnosis, prognosis, the expected course of the illness and the
possible treatment alternatives, their risks and benefits and should be placed in the con-
text of the patient’s goals, expectations, fears, values, and beliefs [19].
It must be remembered that care planning is a process and not a single event. The
issues of advance directive, assessment of decisional capacity, appointment of
surrogate decision maker in the later event of patient losing capacity, and such issues
take time, and the patient (and family) may need time and support from the MDT or
its members to resolve these issues.
The fifth step is decision making for specific situations likely to arise during
EOL care, such as the need for mechanical ventilation, CPR, artificial nutrition and
hydration, other life support measures, admission in ICU, and location of care in the
final days of life. Several decision aids or decision support interventions discussed
above specifically address these issues. The A–Z decision aids inventory of the
Ottawa Hospital Research Initiative (http://decisionaid.ohri.ca/AZlist.html), for

example, mentions the following under the section “Guidance with End-of-Life
Decisions” [9]:
• End-of-life care: Should I have artificial hydration and nutrition?
• End-of-life care: Should I receive CPR and life support?
• End-of-life care: Should I stop kidney dialysis?
• End-of-life care: Should I stop treatment that prolongs my life?
• Making choices: Long-term feeding tube placement in elderly patients
• Understanding the options: Planning care for critically ill patients in the inten-
sive care unit
• When you need extra care, should you receive it at home or in a facility?
Another palliative care approach to aid decision making is a “time-limited trial
(TLT).” “A TLT is an agreement between clinicians and a patient/family to use
certain medical therapies over a defined period to see if the patient improves or
deteriorates according to agreed-on clinical outcomes” [20]. Examples include:
offering a time-limited trial of dialysis for patients with renal failure considering
dialysis; mechanical ventilation for patients suffering from hypoxic ischemic
encephalopathy, initial treatment of severe stroke and end-stage congestive heart
failure; and dialysis/renal failure in presence of limited functional or cognitive
status. If the patient improves, the therapy continues. If the patient deteriorates, the
therapies involved in the trial are withdrawn, and goals frequently shift more purely
to palliation. If significant clinical uncertainty remains, another TLT might be
renegotiated. During such a trial, there are many opportunities for health care
professionals to provide effective decision support. TLTs help establish mutual
expectations, guidance, and a regular dialogue about how the patient is progressing,
lessening the chance of conflict among treatment teams and the patient or family.
Also, patients and families may see this as a “middle ground” to satisfy them that
“everything possible” has been tried before “giving up.”
Conclusion
Palliative care often involves making difficult choices for the patient, the family,
and the treating team. As the disease progresses and the evidence of scientifically
robust effective therapeutic options becomes less certain, decisions tend to
become more preference sensitive, where the values, goals, and priorities of the
patient (and the family) gain increasing importance. In such a situation, the
shared decision-making model is more appropriate. The physician or the multi-
disciplinary team can provide guidance with complex decisions with the help of
various decision support interventions, or decision aids, which help to clarify the
patient’s knowledge regarding the decisions to be taken vis-à-vis personal
preferences and values.
References
1. Charles C, Gafni A, Whelan T. Shared decision making in the medical encounter: what does it
mean? (Or, it takes at least two to tango). Soc Sci Med. 1997;44:681–92.
2. Charles C, Gafni A, Whelan T. Decision making in the physicianpatient encounter: revisiting
the shared treatment decision making model. Soc Sci Med. 1999;49:651–61.
3. Charles C, Whelan T, Gafni A. What do we mean by partnership in making decisions about
treatment? BMJ. 1999;319:780–2.
4. Bélanger E, Rodríguez C, Groleau D. Shared decision-making in palliative care: a systematic
mixed studies review using narrative synthesis. Palliat Med. 2011;25:242–61.
5. Bakitas M, Kryworuchko J, Matlock DD, Volandes AE. Palliative medicine and decision sci-
ence: the critical need for a shared agenda to foster informed patient choice in serious illness.
J Palliat Med. 2011;14(10):1–8.
6. World Health Organization. WHO definition of palliative care. Geneva: WHO. http://www.
who.int/cancer/palliative/definition/en/. Updated 24 Oct 2011; cited 25 Oct 2011
7. Devitt B, Philip J, McLachlan S-A. Team dynamics, decision making, and attitudes toward
multidisciplinary cancer meetings: health professionals’ perspectives. J Oncol Pract.
2010;6:e17–20.
8. Elwyn G, Frosch D, Volandes AE, Edwards A, Montori VM. Investing in deliberation: a
definition and classification of decision support interventions for people facing difficult health
decisions. Med Decis Making. 2010;30:701–11.
9. Ottawa Hospital Research Initiative. Patient decision aids. http://decisionaid.ohri.ca/. Updated
2011; cited 31 Oct 2011.
10. Stacey D, Bennett CL, Barry MJ, Col NF, Eden KB, Holmes-Rovner M, et al. Decision aids
for people facing health treatment or screening decisions. Cochrane Database Syst Rev.
2011;(10):CD001431. doi:10.1002/14651858. CD001431.pub3.
11. Elwyn G, O’Connor A, Stacey D, Volk R, Edwards A, Coulter A, et al. Developing a quality
criteria framework for patient decision aids: online international Delphi consensus process.
BMJ. 2006;333:417–23.
12. O’Connor AM, Légaré F, Stacey D. Risk communication practice: the contribution of decision
aids. BMJ. 2003;327:736–40.
13. O’Connor AM, Stacey D, Légaré F. Coaching to support patients in making decisions. BMJ.
2008;336:228–9.
14. DuBenske LL, Gustafson DH, Shaw BR, Cleary JF. Web-based cancer communication and
decision making systems: connecting patients, caregivers, and clinicians for improved health
outcomes. Med Decis Making. 2010;30:732–44.
15. Stacey D, Samant R, Bennett C. Decision making in oncology: a review of patient decision
aids to support patient participation. CA Cancer J Clin. 2008;58:293–304.
16. Weissman DE. Decision making at a time of crisis near the end of life. JAMA.
2004;292:1738–43.
17. Quill TE. Initiating end-of-life discussions with seriously ill patients: addressing the “elephant
in the room”. JAMA. 2000;284:2502–7.
18. Singer PA, Martin DK, Kelner M. Quality end-of-life care: patient’s perspectives. JAMA.
1999;281:163–8.
19. Hawryluck L, Wahl J. Ian Anderson Program in end-of-life care. Module 4: end-of-life deci-
sion-making. Toronto: University of Toronto; 2000.
20. Quill TE, Holloway R. Time-limited trials near the end of life. JAMA. 2011;306:1483–4.
Review Questions
1. The following statement is not true of the paternalistic model of decision

making:
(a) Patient autonomy is the dominating bioethical principle
(b) The shared information is primarily medical in nature
(c) The deliberation and decision making is one way (doctor)
(d) There is no true partnership between doctor and patient
2. The following statement is not true of the informed choice model of decision
making:
(d) There is no true partnership between doctor and patient
3. The following statement is true of the shared decision making (SDM) model:
(d) There is a true partnership between doctor and patient
4. In the “preference-sensitive” decisions, as opposed to “effectiveness-based”
decisions:
(a) There is no single “right” decision
(b) The paternalistic model works best
(c) The “preference” refers to the doctor, not the patient
(d) Is more important in the early stage of disease rather than at end-of-life care
5. A preference-sensitive decision becomes more important in the context of:
(a) Disease modifying treatment
(b) End-of-life care
(c) Evidence-based care
(d) Diagnosis of cancer
6. For guidance with complex treatment choices in palliative care, the best model is:
(a) Paternalistic model
(b) Informed choice model
(c) Shared decision-making model
(d) None of the above
7. The various decision support interventions have been categorized into

(a) 3 categories
(b) 4 categories
(c) 5 categories
(d) 6 categories
8. The International Patient Decision Aids Standards (IPDAS) is concerned with:
(a) Classifying the numerous decision aids into coherent categories
(b) Formulating guidelines for decision aids
(c) Establishing an internationally approved set of criteria to determine the
quality of patient decision aids
9. Decision coaches are:
(a) Computer programs
(b) Web-based applications
(c) Resource materials
(d) Human beings
10. Specific areas of decision making at the end of life may include any of these
except:
(a) Disease-modifying therapy
(b) Advance directives
(c) Do not (attempt) resuscitation (DN(A)R) orders
(d) Management of pain and other symptoms
Answers
1. (a)
2. (c)
3. (d)
4. (a)
5. (b)
6. (c)
7. (a)
8. (c)
9. (d)
10. (a)
Chapter 7
Symptom Management
Angèle Ryan
Introduction
The definition of palliative care is subject to different interpretations by various

groups and organizations. Services such as assistance with decision making, defining
goals of care, and facilitating communication and continuity of care across diverse
care settings are frequently promoted, but symptom management remains a promi-
nent element of this type of care [1]. Indeed, untreated symptoms are what generate
numerous hospital admissions, utilization of healthcare resources, and crisis refer-
rals to palliative care teams. With control of physical symptoms, patients are better
equipped to address other components of suffering.
Pain
The most dramatic and feared symptom in advanced disease is pain [2] and is a
common stimulus for palliative care consultation [3]. It is estimated that up to 90%
of patients with advanced cancer report pain [4–6], 40–50% with moderate to severe
pain, and 25–30% with very severe pain [7]. This symptom has attracted much
attention in the medical literature and public media. Much of this attention is a
result of historical under treatment of this distressing accompaniment to illness.
A. Ryan, M.D. (*)

Department of Anesthesiology, Keck School of Medicine,
University of Southern California,
e-mail: angel@ix.netcom.com

DOI 10.1007/978-1-4614-5164-8_7,
108 A. Ryan
Table 7.1 Drugs commonly used in pain management

Analgesics Adjuvants
Nonopioids Augment analgesia
• Acetaminophen • Antidepressants
• Aspirin and other NSAID’s • Anticonvulsants
Opioids • Muscle relaxants
Weak opioids • Corticosteroids
• Codeine Control side effects
• Hydrocodone • Laxatives
Strong opioids • Antiemetics
• Morphine • Psychostimulants
• Hydromorphone
• Fentanyl
• Methadone
Despite the consensus that most end of life pain can be managed by noninvasive
tools available to most physicians [8–11] pain remains undertreated [12]. This is
likely due to physicians’ inexperience in the use of appropriate analgesics, accom-
panied by a unique fear of opioids from practitioners, patients, and families. This
knowledge deficit causes a dilemma for physicians who wish to continue providing
care for terminally ill patients while lacking the necessary confidence to provide the
aggressive treatments required. A systematic approach to the use of pharmacologi-
cal tools for the treatment of pain will allow successful control even in severe cases.
Expertise from pain and palliative care physicians will supplement the management
of routine problems by primary care providers.
The pharmacologic tools used for pain management consist of two general cat-
egories, analgesics and adjuvants (see Table 7.1). Analgesics are a familiar category
for most practitioners, consisting of nonopioids and opioids. Adjuvants are medica-
tions often with labeled indications other than treatment of pain, but nonetheless
useful as part of a comprehensive pain regimen. This adjuvant category is further
classified into those agents that enhance analgesia by alternate mechanisms, and
those medications that proactively treat anticipated side effects of the analgesic
drugs, thus allowing for optimal dosing.
The World Health Organization (WHO) has provided guidelines for pain
management specifically for cancer pain (see Fig. 7.1), based on the simple premise
of choosing an analgesic based on patient self-report pain score, essentially matching
the level of pain with the potency of the analgesic. The guidelines continue to provide
directions for the use of these medications: by the mouth, around the clock, with
attention to detail. The oral route is preferred for convenience, efficacy, and ease of
administration across multiple care settings. Around the clock dosing provides
uninterrupted analgesia for a chronic pain disease, and attention to detail requires a
custom regimen for each patient.
7 Symptom Management 109
WHO analgesic ladder

Freed
om
cance from
Opio r pain
id
to se for mode
ve rate
± No re pain
n-
+ Ad opioid 3
juvan
t
Pain
pers
or in isting
Opio crea
id fo sing
mod r
erat mild to
± No e pa
n in
+ Ad -opioid
juva
nt 2
Pain
or in persist
crea ing
sing
Non
-o
± A ptiona 1
djuv l
ant
Pai
n
Fig. 7.1 WHO analgesic ladder
Nonopioids
The nonsteroidal anti-inflammatory drugs (NSAIDs) provide a useful tool as part of

comprehensive pain regimen in end-of-life care. Noncancer diagnoses may present with
mild or moderate pain which responds to these medications. In more severe pain associ-
ated with cancer diagnosis, these medications provide coanalgesia with opioids via anti-
inflammatory action [13], and are particularly potent for treating the pain of bone
metastasis in cancer [14, 15], thus providing synergistic opioid sparing benefits.
Therapeutic effects arise from blockade of Type II cyclo-oxygenase (COX-II)
enzymes that facilitate the formation of deleterious inflammatory products. The
adverse effects of NSAIDs arise from the blockade of type I cyclo-oxygenase
enzymes (COX-1) that are responsible for the formation of beneficial prostaglandins
that are gastrointestinal, platelet, and renal protective. This results in gastropathy,
disruption of platelet function, and renal impairment [16]. Congestive heart failure
[17] and bronchospasm can occur in susceptible individuals. These undesirable
effects may be minimized by use of prophylactic measures such as careful patient
selection, co-treatment with gastrointestinal protecting agents such as proton pump
inhibitors, and assuring adequate renal perfusion. Consideration may also be given
110 A. Ryan
to using a nonacetylated salicylate such as choline magnesium trisalicylate for GI

and platelet sparing benefit [18]. Newly available selective COX-II inhibitors claim
reduced toxicities and may be beneficial in high-risk patients. Individual tolerance
to NSAIDs is variable, likely as a result of the unique relative degree of COX-1 vs.
COX-II inhibition of each drug. Therefore, sequential trial of different agents is
warranted if a patient does not tolerate an initial choice of NSAID. Although the
majority of NSAIDs require oral route, new formulations are available via topical
gel or transdermal route for patients who are not able to swallow. Ketorolac, generally
recommended for short-term use only, has been successfully used via parenteral
route for longer periods if other options are not feasible [19].
Acetaminophen, despite minimal anti-inflammatory effects, is beneficial in treating
mild to moderate pain and should be considered for additional opioid sparing mech-
anism of action. It is felt to have centrally active effect [20]. Lacking the antiplatelet
effect and GI toxicity associated with NSAIDs, it is a reasonable alternative to other
nonopioids. Risk of hepatotoxicity in high doses limits use to 4 g daily. Dosing of
all nonopioids is limited by end organ toxicities, producing a ceiling effect. This is
not of concern when prescribing opioids.
Opioids
Cancer is the prototype end-of-life diagnosis that presents with the most significant
pain treatment challenges. Opioids are the mainstay of treatment for this type of
severe pain.
Much of the mystery for the average practitioner in providing pain therapies
involves the escalation of medication to the category of pure opioids, step three in
the WHO stepladder.
The class of medications categorized as weak opioids is often combined with a
nonopioid. The toxicities of the nonopioid component of the formulation limit titra-
tion of the opioid component. For example, hydrocodone, an opioid frequently
classified in conversion charts as equipotent to morphine, is only available in the US
in combination with nonopioids, limiting dose escalation to optimal levels. Despite
this limitation, practitioners’ familiarity and comfort with these medications fre-
quently result in continued use of step 2 medications when step 3 agents are indicated
based on WHO stepladder guidelines. The narrow dose ranges of these combination
drugs, with clearly defined upper limits, promote physician comfort and continued
use of these medications despite lack of efficacy in more severe pain. Mixed agonist/
antagonists such as nalbuphine or butorphanol, are also not recommended due to
their ceiling effect, risk of psychotomimetic side effects, and potential to provoke a
withdrawal reaction when given to opioid tolerant individuals [21].
If good pain control is to be achieved, the practitioner must quickly move past
the familiar comfort zone and use pure opioids. It is often at this stage of a patient’s
disease, when pain levels exceed the level that can be controlled with nonopioids
and weak opioids, that expert consultation is requested. In many communities,
Table 7.2 Conversion table for common opioid medica-

tions based on Morphine 10 mg intravenous as standard for
comparisonb
Oral route Intravenous
Original drug dose (mg) route dose (mg)
Morphine 30 10
Hydromorphone 7.5 1.5
Methadonea 20 10
Oxycodone 20 n/a
Hydrocodone 30 n/a
Oxymorphone 10 1
a
Based on single dose
b
Aloysi AS, Bryson EO (2012) Prescription drugs: implica-
tions for the chronic pain patient. New York: Springer
however, if this resource is not available, the practitioner can use a methodical
approach to the use of opioids. The unique trait of opioids in lacking toxic effects
on end organs allows the prescriber to customize the analgesic regimen to the
patient’s precise needs. Thus, the feature of opioids that cause initial discomfort
for the prescriber also allows unlimited range in dosing (see Table 7.2). The dose
is only limited by physiologic side effects, which are frequently transient and
manageable. The following is a systematic plan for initiating and managing the
use of opioids.
Let us take the example of the patient who has experienced only mild to moder-
ate pain, managed by combination drugs according to step one and step two of the
ladder, but are no longer effective despite maximum recommended dosing. The first
step to continue pain control for this patient is to uncouple the opioid and nonopioid
of this compound drug and initiate dose titration with a pure opioid. Conversion to
an opioid alone allows self-titration by the patient to a satisfactory level of relief
unencumbered by a dose limited nonopioid. The initial dose may remain conserva-
tive. A conversion to 5 mg. oral morphine is not a significant deviation from the
previously administered medication either in dose or duration of action, providing
reasonable assurance that the medication will be tolerated without side effects. The
use of an immediate short acting agent allows for rapid and frequent dose change
based on efficacy. Dose finding may be achieved by increases of 5 mg increments
until effective. This technique duplicates the more familiar intravenous patient con-
trolled analgesia (PCA) method, applying the same titration principles using oral
route instead [22]. Self-titration by the patient provides his own pain relief, and
defines for the prescriber the dose required to achieve 24-h analgesia. After several
days of patient self-titration, the provider now has accurate information for conversion
to sustained action formulations (see Table 7.3). During this time it is essential to
stress upon the patient that this cycle of frequent medicating is merely a trial period
of dose finding and titration that will ultimately be replaced by a more palatable
112 A. Ryan
Table 7.3 Systematic titration of opioid doses

1. Uncouple nonopioid and opioid compound drug
2. Start short acting pure opioid in frequent intervals to allow self-titration. Adjust dose as
needed and tolerated
3. Allow patient to self-titrate to comfort
• Provide assurance that frequent medicating schedule is temporary intended for dose
finding only
• Aggressive treatment and education about side effects
• Education regarding misconceptions and fear of opioids
4. Conversion of cumulative 24-h dose to sustained acting formulation
5. Provide short acting rescue medication equal to 5–15% of baseline opioid
6. Consider appropriate adjuvants for opioid sparing benefits
7. Monitor and maintenance for ongoing titration
dosing schedule. Education and aggressive treatment of anticipated transient side

effects are an essential element in assuring patient compliance and acceptance of
opioid therapy. Misconceptions regarding this class of medications are common and
may compromise therapy if not addressed.
Once a stable 24-h dose is established by the patient, the provider can convert the
total dose to the convenient long-acting formulations generally administered every
12 h. For example, if the patient self-administered a total of 210 mg oral morphine
in a 24-h period, this may translate to 100 mg every 12 h of long acting morphine to
provide continuous baseline analgesia. Titration continues in this manner until pain
control is achieved. Astute monitoring of patient self-dosing will allow timely
adjustments in the regimen. Judicious incremental increases in opioid dosing will
prevent uncontrolled pain exacerbations while allowing gradual tolerance to side
effects to develop [20].
Breakthrough Pain
Initiating a long acting opioid to provide 24-h analgesic coverage does not preclude
the continued use of a short-acting agent. This provides rescue treatment for inci-
dents of pain that breaks through the analgesia provided by the long acting agent
and allows for continued titration. In general, this is approximately 5–15% of the
24-h dose [23].
Once the pain is stable on a regimen of this sort, it is essential to continue to
monitor the use of rescue medications. An acceptable level is no more than 3–4
doses of short acting agents in a 24-h period [6]. The increased use of rescue medi-
cations signals increasing pain levels and warns of an imminent loss of pain control.
A pain crisis, and unnecessary hospital admission, can be avoided by a timely
increase in the baseline long acting opioid. The increase is estimated as originally
calculated in the original titration. That is, to add all the doses of opioid in a 24-h
period, convert to a new baseline dose, and provide the proportionally appropriate
dose of the short acting opioid for rescue. This process can be applied at any time
that pain is not controlled and analgesic use escalates. If pain is well controlled, or
adverse effects are present, and no rescue doses are used, a trial of reduced baseline
dosing is justified.
Pain Emergencies and the Emergency Department
In end-of-life care, visits to emergency departments for treatment of uncontrolled

pain frequently generate a hospital admission. With judicious application of titration
principles, this can be avoided, and what is considered a dire situation may be
resolved in as quickly as 90 min using intravenous route [24]. The successful
achievement of pain control using rapid titration under the guidance of the practitioner
allows the patient to experience first hand the efficacy of opioids while avoiding the
dreaded side effects. This promotes patient confidence for continued self-titration
and long-term control of pain.
Side Effects
The adverse effect endpoint of opioids is defined by physiologic limits rather than
by end organ toxicity. Generally all opioids in equianalgesic doses produce the same
side effects, exerting greatest pharmacologic action on the central nervous system
and gastrointestinal system. Addressing these side effects proactively and aggressively
will assist greatly in promoting patient adherence to the prescribed opioid regimen.
It is important to stress upon the patient that the typical opioid side effects that
frighten patients, the mental clouding and nausea and vomiting, are short lived and
treatable [25]. Tolerance develops within several days to these side effects [26]. The
side effect that frightens providers is respiratory depression. Although serious, it is
generally rare, occurring in less than 2% of appropriate opioid applications.
Additionally, tolerance to this side effect occurs rapidly [27]. Of significant note, the
one side effect to which tolerance develops extremely slowly if at all is constipation.
This distressing symptom is predictable and treatment must be initiated concurrent
with opioid therapy. Less common side effects include urinary retention, generally
more a problem with spinal route than with oral or parenteral routes, and myoclonus
which occurs as a result of accumulation of metabolic by-products when high doses
of morphine are used.
In the event that the therapeutic window between adequate analgesia and
unacceptable side effects is excessively narrow, rotation to an alternate agent is
indicated. The basis for this technique is the variable affinities of the individual opi-
oids for the different opioid receptors in the central nervous system. A new opioid
114 A. Ryan
provides analgesia by binding to different receptors while toxic metabolites of the

previous opioid dissipate. This provides increased effect without the burdens of dose
escalation [28]. In fact, in stable pain conditions, reduction of opioid equivalent dose is
typically indicated. A general rule is 25–50% reduction of the calculated equianal-
gesic dose of the new opioid [20, 29]. Another option is rotation of the short acting
rescue drug. Titration principles continue to apply to the new medications. Typical
alternatives to sustained release morphine include sustained release oxycodone
or hydromorphone, or fentanyl patch. There are numerous equianalgesic tables
available, and they provide a guideline for opioid dosing. The choice of conversion
mathematics is secondary to the judicious monitoring of patient response. A word
of caution, patients and families may confuse initial side effects with allergic reac-
tion. Timely education will prevent unnecessary labels of “allergies” that may com-
promise later treatments.
Meperidine is not indicated for long-term treatment of pain due to its short half
life, low bioavailability, and accumulation of neurotoxic metabolites [20].
Caution is advised if methadone is considered for opioid rotation. Despite
benefits of high potency, long duration of action, cost effectiveness, and absence of
metabolites, this drug possesses characteristics that make it problematic for routine
use [30], such as drug interactions, variability of half life, and prolongation of QT
interval on electrocardiogram. The most significant concern with methadone,
however, is the nonlinear conversion ratio with other opioids which produces greater
potency at higher levels of opioid tolerance. Although this feature allows an effective
rotation in highly tolerant individuals (e.g., greater than 1,000 mg oral morphine
daily), it may also result in overdose due to effect on NMDA receptors and significant
reduction of tolerance. If rotation to methadone is considered, expert consultation is
recommended.
Adjuvants
The complexity of severe pain provides a challenge to the practitioner seeking a

practical treatment plan. The various components of pain do not all respond to the
familiar analgesics in medical practice, including the strong opioids. Drugs gener-
ally labeled for other indications have been found to provide benefit in these
conditions.
The most common indication for the use of adjuvants is the presence of a neuro-
pathic component of pain. This pain is caused by damage and pathologic hyperex-
citability of nerve issue, either by physical injury or by disease process, and results
in anatomical, physiological, and functional distortion of normal pain pathways.
Pain is generally described as burning, shooting, and pins and needles. Classic
examples are diabetic neuropathy and postherpetic neuralgia. This pain is less
responsive to opioids than nociceptive pain which results from injury to peripheral
tissue. The two major classes of medication that treat this pain are antidepressants
and anticonvulsants.
Antidepressants
Some psychotropic medications have been shown to be effective in the treatment

of some pain chronic pain syndromes, not only for treatment of concurrent emo-
tional components of pain such as anxiety or depression, but also for their analge-
sic enhancing properties when a neuropathic component of pain is suspected. One
of the first adjuvants considered in such circumstances is an antidepressant medi-
cation. The most studied agent for this indication is amitriptyline, a tricyclic anti-
depressant (TCA). The role of TCAs in the management of neuropathic pain is
well established [31, 32]. The mechanism of analgesia is a nonspecific inhibition
on the reuptake of norepinephrine and serotonin, providing analgesia in doses
lower than the antidepressant doses. This drug, however, is associated with adverse
effects which include cardiotoxity, such as conduction disorders and arrhythmias,
orthostatic hypotension, somnolence, and altered mentation, particularly in
patients with previous dementia, brain metastasis, or concurrent use of other cen-
trally acting drugs. The anticholinergic side effects such as urinary retention, con-
stipation, dry mouth, and blurred vision also can add to the symptom burden.
Other agents of this category, such as nortriptyline or desipramine, although less
studied, may be better tolerated.
The selective serotonin reuptake inhibitors (SSRIs) have not been shown to be
sufficiently effective in the treatment of neuropathic pain to justify their use over
tricyclics.
Serotonin norepinephrine reuptake inhibitors (SNRIs) are a newer class of medi-
cations that offer promise. The commonly used agents in this category are venlafax-
ine and duloxetine.
Anticonvulsants
Traditionally, the use of anticonvulsant agents such as carbemazepine and phentoin

for treatment of lancinating pain of neuropathic origin has been based on these
agents’ presumed effect on neural hyperexcitability [33]. Despite the benefits, high
incidence of side effects with these drugs led to a preference for newer agents.
Gabapentin is a current popular choice with a pharmacological profile that offers a
relatively high degree of safety, including no hepatic metabolism, and no drug–
drug interaction. Mechanism of action is believed to be action on GABA receptors.
If an anticonvulsant is considered, gabapentin is a logical first-line choice due to its
efficacy in treating pain of neuropathic origin in cancer patients [34, 35]. The most
common adverse effect from gabapentin is sedation, which may be a benefit if the
patient also experiences insomnia. Daytime sedation may be minimized by slow
upward titration to effect. Doses up to 3,600 mg daily have been reported [36].
Although gabapentin is generally well tolerated, it may be necessary to consider an
alternate agent in some patients. Clonazepam [37 ] or pregabalin [38] offer
additional options.
116 A. Ryan
NMDA Antagonists
N-methyl-d-aspartate (NMDA) receptors are located on the second order neurons

in the dorsal horn of the spinal cord. They are generally dormant and only acti-
vated after repeated stimulation by nociceptive input from peripheral tissues. This
excitation is believed to be involved in the development of neuropathic pain and
tolerance to opioids. NMDA antagonists offer promise in treating neuropathic
pain as these medications directly target this specific trigger. A trial of currently
available agents in this category, despite limited practical application, may offer
benefit.
The anti-NMDA effect of dextromethorphan, the popular ingredient in numerous
cough medicines, has attracted attention for the additional indication of analgesia.
The higher doses required for pain indication, however, are associated with unac-
ceptable side effects consisting of nausea, vomiting, mental clouding, and dizziness
and therefore limit its usefulness [39].
Ketamine is a dissociative anesthetic with analgesic properties in subanes-
thetic doses. Although psychotomimetic effects are seen when used in anes-
thetic doses, this is less common in the low doses used for pain control. The low
risk of respiratory depression from ketamine coupled with the significant opioid
sparing effect results in an improved balance between analgesia and side effects.
Creative use of oral route using parenteral solution has been used and generally
well tolerated in doses of 10–25 mg up to qid with upward titration up to 500 mg
daily [40]. Sublingual route is also an option if compromised swallowing is
present. Continuous subcutaneous or intravenous infusions in combination
with other agents have been used in cases of refractory pain with good results
[41–43]. Doses may start at 1–2.5 mg/kg/24 h with upward titration as needed.
Infusions as high as 600 mg/day have been reported without untoward effects
[44] and effective for long-term use [45]. The addition of benzodiazepines
or haloperidol may attenuate psychotomimetic effects that may occur at high
doses [39].
Nonspecific Adjuvants
Corticosteroids
There is evidence that corticosteroids are beneficial in reducing pain [46–48].

Mechanism of action of corticosteroids is unknown, but may include reduction of
peritumor edema and decompression on pain sensitive structures, in steroid responsive
neoplasms, reduction of tumor mass themselves, reduction of inflammatory media-
tors, specifically prostaglandins and leukotrienes, tempering of aberrant electrical
activity in damaged nerves. Like NSAIDs they are beneficial for bone metastasis.
The side effects of corticosteroids, such as gastrointestinal disturbances, fluid reten-
tion, osteoporosis, hypertension, neuropsychological effects, and myopathy, are well
known and physicians are wary of using these medications, but in the palliative care
setting, long-term treatment with relatively low doses is generally well tolerated and
often provides symptom relief that outweighs the burdens. For short-term use, doses
as high as 100 mg daily may be necessary for control of acute episodes of pain such
as that arising from superior vena cava syndrome or spinal cord compression [49].
Intravenous infusion of lidocaine, a sodium channel blocker, has been shown to be
effective for several pain situations, but most notably for neuropathic pain [50, 51].
Oral agents originally intended for cardiac arrhythmias have played a role in pain
management but their use has been curbed by high incidence of side effects, most
notably nausea. A more practical application of this mode is likely the local anes-
thetic patch of lidocaine.
Biphosphonates are commonly used for disease-modifying treatments of bone
metastases. In addition, they have efficacy in modulation of pain [52] and prevention
of fractures.
Radiotherapy has particular benefit in providing relief of pain caused by bone
metastases [53, 54], compression of neural structures [55], obstruction, and cerebral
metastases [56]. Surgical interventions are justified for debulking, venting. The role
of chemotherapy is less defined but there are promising agents that offer symptom
relief as well as life-prolonging benefit. Examples include gefitinib [57] and
gemcitabine [58].
GI Symptoms
Xerostoma
Dry mouth is a common complaint in advanced disease and predisposes a patient to

more distressing symptoms such as ulceration, infections, and compromised ingestion
of food and drink, leading to worsening of anorexia, nutritional deficiencies, and
weight loss. The ability to take nourishment is a strong emotional need for many
patients and families and is associated with fundamental well-being. As with most
symptoms afflicting patients in end of life, the causes are multiple and all potentially
treatable causes should be addressed. Commonly, this distressing condition may be
the result of treatments such as radiotherapy, medications, or dehydration. Direct
insult to oral mucosa may arise from disease-modifying chemotherapy as well.
Management consists of stimulation of natural saliva by mechanical chewing or
sucking on gum or sugarless candy, by a cholinergic stimulant such as pilocarpine,
or several saliva substitutes available [59].
Nausea and Vomiting
Despite the prevalence of this symptom and the current knowledge regarding
receptor-specific therapies, it remains undertreated [60], and the prescribing of
118 A. Ryan
Table 7.4 Antiemetic choices

Clinical clue Site of action Drug class Example
Serum toxins (chemo- Dopaminic Antidopamine Prochlorperazine 10 mg po
therapy, opioids) Seratonergic Antiseratonin or 25 mg rectal
Tumor toxins Chemoreceptor suppository q. 6 h as
Hypercalcemia, uremia trigger zone needed
Haloperidol 0.5–2 mg po q
6 h prn
Ondansetron 8mg po bid-tid
Bowel distention Cholinergic Anticholinergic Scopolamine up to 3
Vomiting center patches q. 3 days
Dizziness Histaminic Antihistamine Promethazine 12.5–25 mg
Inner ear q. 4–6 h
Cyclizine
Increased intracranial Cerebral cortex Corticosteroid Dexamethasone 2–4 mg po
pressure daily
Emotional factors pain, Higher brain Benzodiazepine Lorazepam 0.5–1 mg po or
fear center iv q. 6 h as needed
Anticipatory nausea
antiemetics is often sporadic, possibly limited by formulary and third party payer
restrictions. With known knowledge about the mechanisms for nausea and vomiting,
successful control of this unpleasant symptom is readily attainable when the inciting
factor is known (e.g., chemotherapy, radiation therapy) [61, 62]. In advanced
disease, however, when treating a patient in the absence of clearly identifiable
etiologies, a logical approach based on clinical response is indicated, a technique
not unlike the titration of pain medications (see Table 7.4).
A clinical systematic approach is suggested [63]:
1. Make a best educated guess regarding etiology.
2. Choose most likely neurotransmitter and receptors responsible.
3. Provide antiemetic most likely to counteract the responsible cause by route that
will be absorbed.
4. Encourage pt. to self-titrate to relief.
5. Reassess for efficacy. If partially effective, provide ATC.
6. Add second agent with new mechanism for as needed use for “breakthrough”
nausea.
7. Continue in this manner with subsequent agents for optimal coverage of all
mechanisms.
Inoperable bowel obstruction.
This unique etiology of nausea and vomiting is often encountered in end-
of-life care. In general practice, the occurrence of this complication typically
initiates plans for gastric decompression, hydration, and immediate surgical
correction. This may not be a realistic solution if the patient has advanced
disease [ 64 ]. A patient is deemed to have a poor prognosis if intraabdominal
carcinomatosis, ascites is present, and the patient has poor performance status.
In such a case, the recommendation is for pharmacologic treatment of symptoms
instead. Insertion of a nasogastric tube is indicated only for temporary use for
emergency gastric decompression, with percutaneous gastrostomy tube as the
preferred method for venting. There is ample support in the literature for the
benefit of pharmacologic treatments for inoperable bowel obstruction [65–67 ] .
The goal of treatment is to alleviate the symptoms caused by the sequence of
increased gastric secretions, distention of bowel, and motor activity against
obstruction, speci fi cally pain and nausea and vomiting. A classic triad of treat-
ments is described:
1. Morphine for pain, doses titrated to patient needs
2. Haloperidol for nausea, 2–4 mg daily orally, sublingually, or parenterally
3. Somatostatin for reduction of secretions and motility, starting at 200–600 mcg
subcutaneously in divided doses
The addition of corticosteroid may alleviate periluminal edema. This pharmaco-
logic regimen can be effective in controlling symptoms but may also correct the
obstruction and permitting oral intake [68].
Constipation
Patients approaching end of life often require medications with constipating side
effects, most notably opioids, although other medications and other illness factors
may contribute to this common symptom. Stool softeners are often prescribed as
monotherapy for constipation when opioid therapy is initiated, but this is inadequate
as a softener alone does not adequately treat the compromised peristalsis, that occurs
in the severely ill patient [69] (see Table 7.5). An effective first-line therapy is the
combination of softener and stimulant. If necessary, an osmotic agent provides more
stimulation by increasing the fluid content of stool. The addition of lubricant laxa-
tives will provide easier evacuation. Bulking agents containing indigestible fiber
require substantial fluid intake which may be difficult in the seriously ill patient and
should be avoided in this patient population. In addition, immobility and gastrointes-
tinal effects of medications compound this problem and this class of laxative should
be avoided in this patient population. The traditional opioid receptor antagonists such
as naloxone have been used in oral form for treatment of refractory constipation with
some success, but the potential for analgesia reversal limits the usefulness of these
agents. The recent introduction of peripherally active opioid receptor antagonists that
do not cross the blood–brain barrier represents a promising new mechanism for treat-
ment of opioid-induced constipation without compromise of analgesic effect [70].
The currently available parenteral formulation of methylnaltrexone offers a unique
solution for patients unable to tolerate oral intake, filling a void in current palliative
medicine formulary where most bowel preparations require oral or rectal route.
120 A. Ryan
Table 7.5 Bowel regimen

General measures
Hydration
Diet
Exercise
Stool softener
Docusate sodium 100–300 mg po daily
Stimulants
Senna 2 tabs (17 mg) qd up to 4 tabs bid
Bisacotyl 5 mg po or 10 mg pr
Cascara 325 mg po
Magnesium citrate 240 ml po
Milk of magnesium 15–30 ml po
Serotonin agonists prokinetic agents
Metaclopramide 10 mg AC and HS
Osmotic agent
Lactulose 15–30 ml po qd-tid
Sorbitol 15–30 ml po qd-tid
Lubricants
Mineral oil
Opioid receptor blockers
Methylnaltrexone 8–12 mg qod based on
weight administered subcutaneously
Enemas, suppositories
Cachexia Syndrome and Fatigue
Cachexia is a significantly distressing and most commonly encountered symptom in

advanced disease. Weakness and fatigue are predominant features of this syndrome
and is reported as the most troublesome and most common symptom in palliative
care patients [71]. The insidious nature of this disturbance in a patient’s function
often makes it secondary to more dramatic symptoms such as pain. It is not the sort
of symptom that generates emergency visits or hospitalizations, and yet it compro-
mises a patient’s sense of self in a profound manner.
Cachexia is defined by the group of symptoms consisting of fatigue, asthenia,
anorexia, muscle wasting, and weight loss [72]. It is essential to remember and pro-
vide education for patients and family that anorexia is a component of the syn-
drome, and not the cause. It is important to stress that availability of nutrients is not
the culprit, but rather the reduced assimilation of those nutrients caused by the
underlying disease. Cachexia is a systemic inflammatory response that is caused by
host generated cytokines and tumor factors that detrimentally alter carbohydrate,
lipid, and protein metabolism. Tumor toxins and cytokines from immune system
cause deleterious effects, increase skeletal muscle catabolism, decrease skeletal
muscle synthesis, and decrease glycogen and lipid stores. A common misconcep-
tion is that lack of nutrients is the culprit in this condition which leads to the initiation
Table 7.6 Reversible causes for cachexia

Mouth pain, compromised swallowing
Oral hygiene
Address mouth lesions and xerostoma
Dyspepsia, gastroparesis
Coating agents—carafate 1 g suspension
Proton pump inhibitors, antacids
Prokinetic agents
Relief of nausea and vomiting, constipation
Pain and other physical symptoms affecting appetite and interest in food
Emotional distressing
Anger, stress, depression, anxiety
Treatment of comorbidities
Anemia
dehydration
Infections
Insomnia
Beneficial medications for cachexia and fatigue
Prokinetic agents
Metaclopramide 10 mg AC and HS
Appetite stimulants
Megasterol up to 800 mg daily
Corticosteroids
Dexamethasone 4 mg qd-qid
Psychostimulants [77]
Methylphenidate 2.5–5 mg qd-bid prior to noon
Dextroamphetamine 2.5–5 mg in AM
Modafinil 100–400 mg in AM
Armodafinil 150–250 mg in AM
Antidepressants
Mirtazepine 15–45 mg daily
Thalidamide
Tetrohydrocannabinol (THC) 2.5 mg tid
Melatonin dose variable
Eicosapentaenoic acid, NSAIDs
of artificial nutrition. Although optimal nutritional status leads to improved benefit

from disease-modifying therapies, it is not always indicated and may often lead to
side effects more burdensome than beneficial. In 1989, the American College of
Physicians issued a position paper refuting the wisdom of artificial feeding in severe
disease [73]. Therefore when contemplating artificial nutrition, it is of paramount
importance to weigh benefits and burdens of what is a medically invasive treatment.
As with all symptoms, management begins with aggressive treatment of underlying
factors that contribute to the compromised nutritional state (see Table 7.6). Starting
with the oral cavity, efforts to treat bacterial, viral, and fungal infections as well as
ulcerations will ease any discomfort of oral ingestion. Antacids, prokinetic drugs, and
coating preparations will provide relief of dyspepsia and early satiety. An aggressive
122 A. Ryan
antiemetic regimen may be necessary to control nausea and vomiting, as well as a

solid bowel regimen to address constipation. Control of any other physical or emo-
tional symptoms will improve sense of well-being and promote increased appetite.
Depending on the prognosis, more aggressive measures may prove beneficial.
Appetite stimulants are indicated if life expectancy is estimated to be 3 months or
more and should be initiated early in the course of the disease to allow for desired
effect. Weight gain may not be achieved, but improvement of appetite will contribute
to sense of well-being and quality of life. Megastrol acetate in doses 160–800 mg
daily may be helpful. In cases with shorter prognosis, a course of corticosteroid is
useful for a state of well-being as well as addressing other symptoms that may be pres-
ent, such as nausea, vomiting, pain, respiratory distress. Dexamethasone 10–20 mg
daily is preferred for reduced mineralocorticoid activity. Mirtazepine is a promising
agent for treatment of cachexia and improved quality of life [74]. Additional benefits
of this medication are improved sleep and appetite, reduced nausea, and antidepres-
sant effect. There are reports of the therapeutic benefits attained with medical mari-
juana for improvement in appetite and relief of nausea and vomiting [75, 76].
Psychostimulants such as methylphenidate [77] may be helpful in treating fatigue, as
well as associated depression, sedation, and concentration [78]. Modafinil, a nonam-
phetamine psychostimulant, combats fatigue and depression by an alternate mecha-
nism of action on the hypothalamus [79]. Armodafinil, a newer addition to the market,
is composed of the active isomer of the racemic mixture of modafinil.
There are additional medications that offer promise. Thalidomide, despite the histori-
cal baggage as a teratogenic agent associated with its use as an antiemetic, is an agent
currently receiving attention for its anti-inflammatory antitumor effects for treatment of
some cancers, most notably multiple myeloma [80] but has also made an impression in
the palliative medicine literature for treatment of multiple symptoms [81]. Administered
at bedtime, the sedating side effects contribute to improved sleep and relief of nausea in
cancer patients [82], there is evidence that this agent offers promise for weight gain and
sense of well-being in AIDS patients [83]. The most significant side effects include deep
vein thrombosis and neuropathy, but the short-term low dose regimen applied in end-of-
life care may provide a favorable benefit/burden result. Melatonin, a naturally occurring
hormone, is gaining attention, not only for its sleep-inducing properties, but also for
benefit in cachexia [84]. Promising agents that target the inflammatory nature of cachexins
include omega 3 fatty acids, particularly eicosapentaenoic acid and nonsteroidal anti-
inflammatory drugs [85–87]. The continued quest for agents to promote appetite stimu-
lation and well-being underscores the principles of aggressive treatment of symptoms
even in the face of limited disease-modifying options.
Dyspnea
One of the prevailing mantras of palliative medicine is the assertive use of

disease-modifying treatments as a means of treating symptoms, and there are few
symptoms that exemplify this concept as dramatically as dyspnea. Dyspnea is
defined as the subjective sensation of difficulty breathing, not necessarily with
Table 7.7 Treatment of reversible causes of dyspnea

Examples of reversible causes of dyspnea Treatment options
Cancer tumor invasion of lungs, bronchi, lymphangitis Radiation, surgical debulking corticoster-
carcinomatosis, pleural effusions oids, stenting, chemotherapy
Cardiopulmonary disease Bronchodilators, corticosteroids, cardiac
strengthening drugs, diuretics
Anemia, fatigue, electrolyte abnormalities Transfusions, optimal nutritional support
Infections Antimicrobial therapies
Pleural effusions, ascites Aspiration, pleurodesis
Pulmonary embolism Anticoagulants
Pain Analgesic regimen
correlation to observed signs such as respiratory rate or arterial oxygenation.

Diagnosis is made by patient self-report. It occurs in up to 90% of terminally ill
patients with cancer, pulmonary disease, or cardiac disease [88, 89]. Although the
mechanisms regulating respiration are known, this distressing symptom brings ther-
apeutic challenges, as the causes are multifactoral and the physical sensation is
frequently accompanied by patient perceptions and emotions, much like the experi-
ence of pain, and is often interpreted as the harbinger of decline by patients and
families [90].
The numerous causes for dyspnea provide an extensive source of treatment options
based on the underlying pathology (see Table 7.7). Even slight improvements of
physiological components may bring significant relief and all therapies should be
considered regardless of disease stage or prognosis at the time of presentation.
Despite the medical efforts to reverse underlying pathology, there will be a point
where disease has progressed to advanced stage with increasing resistance to cura-
tive measures. As dyspnea is a symptom with physical, emotional, and spiritual
components, an interdisciplinary treatment plan that addresses all these components
will likely produce the most successful result. Education and advice regarding activ-
ity adjustments, positioning, cool air, psychological support are simple initial meth-
ods. Counselors on palliative care teams can play a significant role in addressing
nonphysical components of the dyspneic experience, providing coping tools and
anxiety reduction training that will empower patients with control over the dyspnea.
Caregivers who observe what appears to be signs of distress require attention and
explanations to ease anxiety. It is important to provide reassurance that the patient’s
sensation of dyspnea does not necessarily correspond to distress as is perceived by
observers [91].
Although the pathophysiology of dyspnea is not fully understood, there are
empirical therapies that have been effective. The mainstay of pharmacologic treatment
is systemic opioid. Mechanism is not entirely known but theories suggest both
central and peripheral activity. There is a good body of evidence to support this
therapy which is beneficial and well tolerated in patients with cancer and pulmonary
disease [92–94] and is considered a first-line therapy. Optimal dosing is achieved by
titration to patient response. In opioid naive patients with mild symptoms, weak
opioids such as hydrocodone or codeine may provide relief. In more severe cases, a
strong opioid such as morphine is the rational choice. A low dose of 5 mg orally
124 A. Ryan
every 4 h is a reasonable initial dose with titration as needed to provide relief. In

patients who are opioid tolerant as a result of an analgesic regimen, an increase in
baseline dose of 25–50% may be indicated for antidyspneic effect.
As emotional factors may play a role in patient’s perception of respiratory dis-
comfort, anxiolytics have been shown to provide additional benefit in patients with
COPD [95]. Oral Lorazepam or diazepam may be provided as needed, in combina-
tion with haloperidol if fear is present. Midazolam is a parenteral option if respite
sedation is needed for severe breathlessness [96]. Corticosteroids are often used for
treatment of specific pathology such as COPD, but for empirical treatment of dysp-
nea, may provide a broad spectrum of effects through reduced edema and for sense
of well-being. Dexamethasone is a popular choice in palliative medicine due to the
lower mineralocorticoid activity. Concerns regarding the well-known side effects
are weighed against the comfort benefit in a terminally ill individual. While oxygen
is a valid treatment of reversible hypoxemia, the value in treating dyspnea empiri-
cally is less clear. Patients and families view the administration of oxygen as a
potent symbol of medical intervention and, as such, this treatment may exert a
strong influence on the psychological components of dyspnea. The flow or air may
be the factor that is providing the relief and should be considered. Simple apparatus
should be used to avoid the cumbersome and intrusive mask devices. Careful patient
selection will identify individual who will derive benefits from oxygen therapy, and
the advantages must be weighed against the unfavorable burdens of cost, fire haz-
ard, psychological dependence, and equipment constraints [97]. Nebulized medica-
tions such as morphine [98, 99] hydromorphone [100] have been reported to be
effective in certain cases, but there is insufficient evidence to justify this route.
In extreme cases of dyspnea, it may be necessary to provide sedation for relief of
the distress. At this point the principles of Double Effect would dictate continued
titration of medications to desired effect.
Cough
Cough is often a debilitating symptom that contributes to worsening of other symp-

toms such as increased pain episodes, provoking vomiting, anxiety, and insomnia.
As in all symptoms in end-of-life care identification of the underlying cause will
dictate initial therapy. The causes of cough parallel the pathology in dyspnea and
include primary pulmonary or cardiac disease, irritation from infections, obstruc-
tions, or tumor invasion. It may be productive or nonproductive. In addition to
definitive disease-modifying treatments of underlying causes, there are general
measures that may be helpful.
Cough suppressants are an initial treatment that may abate an irritating dry cough.
Opioids are the most potent cough suppressants and offer first-line therapy. A weak
agent such as codeine is a logical first choice in opioid naive patients. Hydrocodone
has been shown to have a positive effect in treating cough when used as a single agent,
or when added to an ineffective opioid regimen, suggesting a specific antitussive
action when compared to other opioids and offers additional benefit for dyspnea,
which may often be a coexisting symptom [101]. In general, however, if a patient is
currently treated with opioids for pain, it is prudent to simplify the regimen and remain
with the same agent using upward titration of 20–25% [102], similar to the process
described for dyspnea. Expectorants are frequently used with benefit if liquification of
sputum is desired and the patient has strength to expectorate. In debilitated patients,
however, preferential use of cough suppressants is indicated.
Dextromethorphan, a centrally acting opioid derivative, has long been used as an
antitussive agent and provides an alternative to opioids as it is not associated with the
adverse mental clouding and gastrointestinal effects of opioids. Benzonatate, also a
nonopioid has been shown to be of benefit [103]. Humidified air, nebulized saline,
and chest physiotherapy can be used to supplement pharmacologic treatments.
Delirium
Delirium is a common occurrence in end of life and represents a poor prognostic sign.
It is caused by a medical condition and characterized by a fluctuating course of:
1. Disturbance of consciousness manifested by detached awareness of environment
and difficulty maintaining or shifting attention.
2. Cognitive impairment, manifested by disorientation, memory deficit, perceptual
disturbances.
Subtypes of delirium are categorized as hyperactive, hypoactive, or mixed, a
combination of both hyperactive and hypoactive types. Despite the prevalence of
this symptom toward the end of life, this is a symptom that is often undertreated
[104, 105]. The reasons for underrecognition are several. Although an agitated
hyperactive patient presents the most familiar picture and draws rapid attention
from care providers, the hypoactive or mixed type may elude diagnosis, as these less
disruptive symptoms receive less notice and may be confused with depression,
withdrawal, anxiety, or pain behaviors and may be missed by casual observation up
to 50% of cases [106]. The fluctuating nature of delirium and periods of lucidity
further compound the diagnostic insight. All subtypes of delirium have the potential
of being distressing for the patient. Decision to delay treatment of delirium empiri-
cally may be made based on perceived degree or lack of distress, such as a pleasant
vision of a previously deceased relative or friend. Although this experience is not
uncommon during terminal stages of life, the variable course of this symptom dic-
tates judicious monitoring for rapid development of a more disturbing experience.
Therefore, any patient who presents with new onset of changes in behavior, percep-
tion, or function should be screened for delirium to assure prompt treatment.
In management of delirium, as with all symptoms, efforts should be made to
assess for reversible causes, with appropriate diagnostic tests as tolerated by patient’s
condition (see Table 7.8). With advanced disease, however, multiple factors may
play a role and treatable etiology may not be found. In less than 50% of cases it is
126 A. Ryan
Table 7.8 Common causes of delirium

Drug or poison intoxication
Opioids
Sedatives and hypnotics
Substance withdrawal
Chemotherapy agents
Corticosteroids
Metabolic disturbances
Encephalopathies
Hepatic
Renal
Hypoxemia
Electrolyte imbalance
Hypercalcemia
Dehydration/poor nutrition
Infective process/fever
Direct tumor invasion in central nervous system
Presence of unrelieved symptoms
Pain
Fecal impaction/urinary retention
Spiritual distress/fear
Table 7.9 Pharmacologic treatment of delirium

Haloperidol 1–2 mg q 2 h titrate until settled
Risperdone 0.5–1 mg po as alternative
Benzodiazepine if agitation is present
Diazepam 2–5 mg po or iv q 1–4 h
Midazolam 1–2 mg hourly iv or sq
Chlorpromazine 25–50 mg tid to qid
Olanzepine 2.5–5 mg q 12 h po
Phenobarbital 90–180 mg tid po or iv
Propofol 10–50 mg hourly iv
possible to identify a treatable source [107]. Several nonpharmacologic supportive

interventions may be initiated, including relaxation, reductions in environmental
distractions at night, familiar surroundings. If pharmacologic treatment is required
(see Table 7.9), a neuroleptic antipsychotic is the drug of choice in treating delirium.
Haloperidol is generally well tolerated, is available in oral or parenteral formula-
tion, and the wide therapeutic window allows for titration to effect. In the presence
of agitation, benzodiazepines are commonly used, but they are not beneficial when
used alone, and may paradoxically aggravate symptoms. If the sedating properties
of benzodiazepine are indicated, the combination of a benzodiazepine with a neuro-
leptic agent may provide a synergistic benefit as the benzodiazepine protects against
the potential extrapyramidal effects of the neuroleptic and the neuroleptic protects
against the possible paradoxical effect of the benzodiazepine [104]. Other agents
that may be used include resperidone, a nursing facility-friendly alternative to

haloperidol. Olanzepine offers the advantage of fewer extrapyramidal effects than
haloperidol. In cases where the delirium is not responsive to standard therapies, a
trial of respite sedation may be necessary. Short acting agents such as propofol or
midazolam offer opportunity for rapid titration as well as reversibility.
Insomnia
Insomnia is defined as a disorder of poor or inadequate sleep generally accompa-

nied by daytime fatigue and adverse effect on daytime function. It is a symptom that
exerts a major impression on any patient who suffers from it, as lack of sleep impairs
physical and mental well-being, with significant impact on function and quality of
life. Although insomnia is prevalent in the general population [108], sleep distur-
bance is even more problematic in patients with advanced disease who already have
compromised function from other multiple symptoms [109], but frequently remains
undertreated [110]. Patients with advanced disease have multiple contributory
pathologies that may contribute to insomnia. Features may include difficulty initiat-
ing sleep, failure to stay asleep, or premature waking. Tools are available for detailed
assessment of insomnia [111].
A typical assessment of causes for insomnia consists of determination of under-
lying factors, physical, emotional, environmental, with goal of treating underlying
problem. In patients with advanced disease these morbidities are multiple and
heightened [112, 113]. In keeping with the general principles of palliative medicine,
aggressive approach toward reversal of causative triggers is warranted. Medical
conditions that are responsible for primary insomnia such as sleep apnea or restless
leg syndrome should be excluded.
Therapy will vary depending on contributory causes. Initially it is essential to
assure that optimal physical comfort is provided, emotional and spiritual suffering
is addressed, and assistance offered with difficult care settings and caregiver con-
cerns, all the services typically associated with an interdisciplinary palliative care
team. Interventions include sleep hygiene training and behavioral-cognitive thera-
pies. A thorough questioning regarding patients’ bedtime habits, environment, and
patterns will provide an opportunity to focused education aimed toward the elimina-
tion of habits that perpetuate insomnia. Although such behavioral treatments have
been shown to be effective [114] and offer an integral component of treatment, the
patient with advanced disease with limited prognosis should also be considered for
the more rapid pharmacologic solution (see Table 7.10). The first line of therapy is
a hypnotic agent, either a benzodiazepine or benzodiazepine-like agents. The typi-
cal concerns of benzodiazepine use in other populations, such as dependence, cog-
nitive impairment, and increased risk of falls, are weighed against the immediate
anxiolytic and sedative benefits in the palliative care setting. The favorable side
effect profile of the benzodiazepine-like “Z” agents, zolpidem and zaleplon, and
eszopiclone may be preferred for shorter metabolic half life, reducing the risk of
128 A. Ryan
Table 7.10 Approach to insomnia

Treat contributory symptoms
Physical nausea, pain, dyspnea, psychological e.g., anxiety, depression
Sleep hygiene education
Cognitive behavioral therapy (e.g., guided imagery, meditation) if warranted by prognosis
Pharmacologic
Hypnotics
Benzodiazepine
Lorazepam 0.5–2 mg po
Clonazepam 0.25–1 mg po
Nonbenzodiazepine-“Z” drugs are preferred for their short metabolic half life
Zolpidem 5–10 mg po
Zaleplon 5–10 mg po
Eszopiclone 2 mg po
Sedating antidepressants
Mirtazepine (low dose) 15 mg po
Tricyclics, e.g., amitriptyline 10–25 mg po
Melatonin receptor agonist
Ramelteon 8 mg po
residual daytime sedation. They are generally well tolerated [115]. Both classes exert
effect via the gabaminergic system.
Sedating antidepressants such as tricyclics or mirtazepine or an antineuropathic medi-
cations such as gabapentin will provide dual benefit for a patient with neuropathic pain or
depression. Neuroleptics such as olanzepine may be added if there is a component of
delirium present. Older agents such as chloral hydrate or barbiturates are problematic due
to side effects and have limited use. Over-the-counter aids exert action via antihistamine
mechanism. The benefit for insomnia in these patients is short lived and use should be
limited to situations where an antihistamine may benefit other symptoms such as nausea.
Melatonin, a hormone secreted at night by the pineal gland, is a popular medica-
tion in the public media, and a preparation of ramelteon, a derivative of melatonin,
is now available for sleep onset disturbance. It is a selective melatonin receptor
agonist with rapid onset and short duration. It is felt that the specificity of action at
the melatonin receptors rather than the gabaminergic system is the feature that lim-
its side effects typical of the benzodiazepines [116].
Conclusion
When a clinician is faced with the suffering patient, exhibiting a multitude of symptoms,
it presents a difficult challenge to determine the most effective evidence-based therapies.
This field of medical study is in its infancy and the research that has been conducted in
this discipline frequently offers the conclusion that “more studies are needed”. With
growing interest and continued emphasis on end-of-life care, the knowledge base will
continue to expand as our profession embraces this area of medical practice.
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134 A. Ryan
Review Questions
1. Tolerance develops rapidly to all the following opioid side effects except:
(a) Respiratory depression
(b) Sedation
(c) Dysphoria
(d) Constipation
(e) Nausea
2. All the following drugs provide antineuropathic benefit in the treatment of pain,
with the exception of:
(a) Tricyclic antidepressants
(b) Nonsteroidal anti-inflammatory drugs (NSAIDs)
(c) Serotonin norepinephrine reuptake inhibitors (SNRIs)
(d) Anticonvulsants
(e) Ketamine
3. Which of the following statements about dyspnea is true:
(a) Nebulized opioids are an established treatment for this symptom
(b) Emotional factors contribute to the severity of dyspnea
(c) The extent of dyspnea is reliably measured by respiratory rate and arterial
oxygenation
(d) Anxiolytics may result in respiratory depression and should be avoided
(e) Disease-modifying therapies are rarely beneficial in treating dyspnea
4. For the management of delirium in advanced disease, which of the following
statements is false:
(a) Aggressive use of benzodiazepines is required to treat the agitation typically
associated with delirium
(b) Review of medications is essential to assess for reversible causes
(c) Periods of lucidity do not rule out the presence of delirium
(d) Depression and pain behaviors may mimic the signs of delirium
(e) The provision of supportive familiar surroundings is an effective treatment
5. Beneficial interventions for the treatment of symptoms associated with inoperable
bowel obstruction include all the following except:
(a) Somatostatin analog
(b) Percutaneous gastric venting
(c) Haloperidol
(d) Corticosteroids
(e) Parenteral nutrition
Answers
1. (d). This symptom remains throughout the treatment course, tolerance developing
very slowly, if at all, thus requiring vigilance and treatment. The other side effects
dissipate within several days.
2. (b). Although anti-inflammatory drugs provide significant co-analgesia in many
pain states, the most commonly used agents for neuropathic pain include the
antidepressants, N-methyl-d-aspartate (NMDA) antagonists such as ketamine,
and anticonvulsants.
3. (b). Similar to the pain symptom, dyspnea is accompanied by fear and apprehension
regarding physical discomfort as well as the prognostic implications. Anxiolytics
are an important tool for alleviating the distress. Although nebulized drugs are used
in limited circumstances, the mainstay of pharmacological treatment is systemic
opioids. Since this is a subjective symptom, external measures are of little value in
assessing dyspnea. Correction of any underlying pathology is beneficial in alleviat-
ing the symptom burden.
4. (a). Although agitation is a component of the hyperactive category of delirium, ben-
zodiazepines, when used alone, may aggravate delirium. Review of medications is
important as drugs are a reversible etiology of this symptom. The variable course of
delirium which includes periods of lucidity and signs that mimic other disease states
(e.g., depression, pain) should be considered when making the diagnosis of delir-
ium. Nonpharmacologic modalities are an important component of therapy.
5. (e). The goal of treatment in this condition is to reduce the symptoms caused by
increased secretions and motility in the gut. Artificial nutrition adds to the meta-
bolic and fluid load and worsens symptoms. The other choices are all valid for
treatment of the associated nausea.
Chapter 8
Nutrition in Palliative Care
M. Khurram Ghori and Susan Dabu-Bondoc
Introduction and Epidemiology
Malnutrition is an immense problem in palliative care. It occurs in about a third of

all patients newly diagnosed with cancer. It is an independent risk factor for increased
morbidity and mortality, and is a primary cause of death in about 20 % of patients
with cancer [1]. Worldwide statistics have revealed that malnutrition can develop in
as much as 30–90 % of the time over the course of a malignancy [2]. It has been a
second leading cause of death in developed countries [3]. Cachexia is a debilitating
and distressing condition. It can prolong hospital stay and can cause delayed,
missed, or decreased tumor treatments and decrease cost–benefit and risk–benefit
ratios of anticancer therapies [4].
Cachexia is most commonly associated with tumors of the head and neck, lung
and central nervous system, pancreas and gastrointestinal (GI) tract. Patients with
tumors of the head and neck and of the upper digestive tract such as the esophagus,
stomach, pancreas, etc., often present with moderate to severe malnutrition at time
of diagnosis. On the other hand, patients with hematological tumors, such as leuke-
mia, develop the lowest rates and severity of weight loss. This may be due in part to
the rapid development of such tumors in relatively young patients.
Nutritional interventions have been developed in an attempt to prevent or coun-
teract the deleterious effects of cancer cachexia during different stages of the dis-
ease and its therapy that often compromise nutritional status. With expanding
knowledge and understanding of the pathophysiology of cancer cachexia, research
and investigations have focused on the efficacy and efficient use of pharmaco-
immunological nutrients, and on the development of new strategies for nutritional
planning and counseling.
M.K. Ghori, M.D. • S. Dabu-Bondoc, M.D. (*)

Department of Anesthesiology, Yale University School of Medicine,
New Haven, CT, USA
e-mail: susan.dabu-bondoc@yale.edu

DOI 10.1007/978-1-4614-5164-8_8,
138 M.K. Ghori and S. Dabu-Bondoc
Nutritional Care in Cachexia
Definitions
Anorexia is loss of appetite. Cachexia is defined as a significant weight loss due to

disease. Although cachexia often occurs with anorexia, cachexia is not caused
merely by decreased nutritional intake. It is a catabolic state that results from an
imbalance between nutritional demand and nutrient availability. Such imbalance
can be a result of multiple factors, such as metabolic and pathophysiological
changes, induced inability to ingest or utilize nutrients, social or psychological fac-
tors, or to toxicity resulting from treatment. Cachexia is characterized by increased
resting energy expenditure, preferential loss of skeletal muscle and fat, and increased
proteolysis and lipolysis. Chronic systemic inflammation and circulating tumor-
derived factors have also been implicated as possible causes [5, 6].
Palliative care is medical treatment that aims to relieve suffering and improve the
quality of life of patients with advanced disease. It encompasses the relief of physi-
cal, emotional, and existential suffering, as well as the support for best quality of
life for both patient and family caregivers. Palliative care has grown since the start
of the hospice movement in the USA in 1970s and in the UK in the 1960s. The
Medicare Hospice Benefit was created, in 1983, by US federal legislation. This has
since provided palliative care services to more than seven million terminally ill
patients. Under current regulatory and compensatory Medicare rules, patients are
eligible for hospice if their physician states that death is likely within 6 months, and
the patient is willing to forego attempts at curative or life-prolonging therapies.
Pathophysiology and Mechanisms of Cachexia
Cancer cachexia is multifactorial. It can be due to (a) inadequate food intake, (b) metabolic
disturbances leading to a wasting medical condition, and/or (c) humoral/anti-inflammatory
factors or responses. Anorexia and metabolic alterations are considered most important in
the development of nutritional declension. In addition, the adverse effects of interventions
often compound the underlying organic causes of the condition. Malnutrition develops as
a result of the “parasitic” activity of the tumor at the expense of the host, the impact of the
tumor on the metabolism of the host, and the adverse effects of cancer interventions.
Anorexia and Decreased Food Intake
Loss of appetite is a general effect of cancer. It is considered the most common and
most crucial contributing factor in the development of nutritional decline and weight
loss in cancer patients. It occurs in approximately 70 % of patients with advanced
8 Nutrition in Palliative Care 139
cancer and is often worsened by the cytotoxic effects of cancer therapy causing
nausea, mucositis, and/or dysphagia [7].
Several complex interrelated pathophysiological mechanisms are implicated in the
development of anorexia [2]. Depression and other psychological factors are often pres-
ent. Alterations in taste and smell exist in approximately 50 % of patients. About a third
of patients experience alterations in recognizing sweet taste; while sourness, saltiness,
and bitterness (responsible for dislike of meat) are less commonly altered. Several inves-
tigations have indicated that such changes in taste and smell correlated with poor
response to treatment, reduced intake of nutrients, and tumor extension and spread.
A variety of factors affect the GI tract. These include delayed digestion which can
cause early satiety, and gastric or intestinal atrophy, which leads to appetite loss. GI
obstruction due to tumors of the digestive and hepato-biliary tracts, as well as external
compression from metastatic masses, can all lead to early satiety, nausea, vomiting, or
GI obstruction. “Blind loop syndromes,” typically presenting with relapsing episodes
of bowel obstruction, can critically impair nutrient absorption. In several wasting dis-
eases, small bowel mucosa often atrophies and results in malabsorption. Several other
factors have been implicated in the etiology of anorexia, including altered plasma
levels of amino acids, cytokines or free fatty acids, resistance to insulin, elevated
plasma lactate due to anaerobic metabolism of cancer cells, etc.
Anticancer interventions such as chemotherapy can cause abdominal cramping,
bloating, nausea, vomiting, mucositis, malabsorption, and/or paralytic ileus. Despite
the availability of a variety of pharmacologic antiemetic therapies, vomiting remains
a common cause of malnutrition in cancer patients. Chemotherapeutic agents, particu-
larly adriamycin, cysplatin, fluorouracil, and methotrexate are known inducers of seri-
ous GI toxicity. Lined by rapidly dividing cells, known as enterocytes, the GI tract is
particularly susceptible to the cytotoxic effects of chemo- or radiotherapeutic agents.
Erosive lesions including mucositis, tongue ulceration, and esophagitis can all severely
impair food intake. Enteropathies, combined with ulcerations, necrosis, and mucosal
atrophy could be harbingers of marked radiation enterocolitis that can be complicated
by peritonitis, obstruction, or fistulas. Advances in radiation technology, such as bowel
shielding, fractioning, dosing and timing, and use of high energy, have been applied in
an attempt to prevent radiation-induced small bowel complications.
It should be noted that anorexia is often a major primary contributing factor of
cachexia. Its severity can vary as the cancer progresses and the toxic effects of dis-
ease intervention complicate the former. Given that nutrient intake is not always
impaired during the course of cancer, the degree of food intake may not necessarily
correlate with the nutritional status. This highlights the fact that cancer-associated
malnutrition involves not only systemic but also metabolic changes.
Metabolic Perturbations and Cachexia
Perturbations that alter energy expenditure (EE), as well as, metabolism of carbohy-
drate, protein, fat, and vitamins have all been associated with cancer [2].
Regardless of the nutritional status of the host, the tumor grows and maintains a
high degree of metabolic activity at the expense of the host. Cancer cells sustain a
high level of glycolysis producing significant levels of lactate. The presence of a net
uptake of amino acids by the tumor tissue, as demonstrated by scientific investiga-
tions, has proved that cachexia is caused by increased tumor metabolic require-
ments. However, despite the increased tumor metabolic demands, the host responds
by decreasing nutrient intake, which is not a normal mechanism of metabolic regu-
lation. Furthermore, cachexia may not necessarily be readily reversible by provision
of adequate nutrient. Evidently, abnormal tumor metabolism and associated anorexia
as well as alterations in host metabolism are all major contributory factors in the
development of cachectic syndrome.
Despite the initial controversy over whether cancer patients had elevated EE
relative to cachectic noncancer patients, normalization of EE following tumor
removal has favored the hypothesis that EE elevation is cancer driven. Depending
upon the type of neoplasm, EE appears to be related to an increased adrenergic state
and/or the presence of an inflammatory process. For example, patients with lym-
phomas are not metabolically different from healthy patients, while patients with
myeloproliferative tumors, and some, but not all hematologic cancers, demonstrate
major metabolic abnormalities. EE elevations in cancer, although usually modest
(10–15 %), can give rise to critical weight loss over time.
Apart from neoglucogenesis, the trapping of glucose and its conversion to lactate
and subsequent recycling of lactate to glucose by tumor cells, the carbohydrate
metabolism of the cancer patient is also characterized by glucose intolerance, due to
resistance of peripheral tissues to the effects of insulin. In addition, the pancreas
secretes reduced amounts of insulin in response to food intake.
Loss of fat mass in tumor patients may not only result from anorexia, but also from a
primary imbalance between lipolysis and lipogenesis. In cachectic but not normal weight
cancer patients, stored lipids are rapidly depleted due to increased peripheral fat mobili-
zation, and excessive fatty acids oxidation. This is reflected by increased plasma levels
of glycerol and FFA by-products of triglyceride hydrolysis. Studies demonstrating the
possible role of decreased lipogenesis in malnutrition remain inconclusive.
Adaptive mechanisms that decrease protein catabolism to preserve functional
lean body mass in conditions of starvation are absent in cancer patients. This
explains the rapid protein depletion and/or marked muscle atrophy that develop in
cancer states. The most common protein metabolism abnormalities found in cancer
include (1) increase in protein turnover, e.g., increased protein synthesis plus
increased muscle protein breakdown, (2) decrease in muscle protein synthesis, (3)
elevation of inflammatory hepatic protein synthesis, (4) a constantly negative nitro-
gen balance due to a relative greater reduction of protein synthesis, and (5) various
alterations in plasma amino acid profile. Some of these amino acid level changes
have been studied as potential markers of extent of cancer and as a basis for nutri-
tional intervention. Alterations in protein metabolism are regionally distributed.
This is evident by the presence of marked hypoalbuminemia in cachectic cancer
patients. A shift from peripheral to visceral redistribution of protein synthesis occurs
in either or both the host and the neoplasm.
Inflammatory and Humoral Activities in the Host–Neoplasm

Interaction
Various humoral and inflammatory factors have been implicated in anorexia, meta-
bolic perturbations, or weight loss associated with cancer. The role of cytokines and
other mediators in appetite regulation and in metabolic abnormalities are poorly
understood. Elevated cytokine (e.g., IL-1, IL-6, gamma interferon, tumor necrosis
factor-alpha) activity, abnormal eicosanoid production, excessive monocyte and
macrophage activation and TNF production, altered lymphocyte functions, abnor-
mal IL-2, or peptidoglycan production have all been described. Various interrela-
tionships exist among these factors and perturbations in inducing and maintaining a
state of catabolism. Development of new therapeutic interventions against cancer
cachexia has targeted such inflammatory and humoral responses.
Effects of Nutritional Support on Tumor
An ideal nutritional support would be one that nourishes the patient but not the
tumor. There have been attempts to modulate tumor growth by nutritional manipula-
tion, both in animal and human models, but conclusive results are yet to be achieved.
Results of several trials performed in GI and head and neck malignancies placing
subjects on enteral or parenteral nutrition consisting of varying amounts of protein
and calories favored a lack of increase in cancer size with nutritional support.
Different approaches of nutritional component manipulation to limit metabolism by
cancer cells have been investigated. These include restriction of protein, use of halo-
genated carbohydrates, 2-deoxyglucose or pentoses, and use of medium-chain trig-
lycerides and omega-3 fatty acids. Regimens consisting of high nonprotein calories
(e.g., 90 % medium chain [MCT] and long chain [LCT] triglyceride lipid mixtures)
were found to maintain stable patient weight and tumor volume for several months.
Studies involving the use of inhibitors of neoglucogenesis, such as hydralazine sul-
fate have yet to demonstrate improved clinical outcome. Newer pharmaconutrients
such as arginine, glutamine, and omega-3 fatty acids have been target of research for
their impact on immune status.
Evaluation of Nutritional Status and Diagnosis
Nutritional assessment is an essential tool in palliative care. There are several reasons
why nutrition is a very important component in the management of patients with
advanced, incurable cancer. First, anticancer treatments often lead to deterioration of
energy intake [8, 9]; second, chemotherapeutic agents can directly affect skeletal
muscle [10], and third, tumor responses to cancer therapy are often associated with
cachexia-related symptoms [11, 12]. Therefore, continuous monitoring of patients’

nutritional intake, weight, and other symptoms such as fatigue or early satiety are
valuable.
Nutritional assessment is important in order to:
1. Identify patients who may benefit from dietary counseling
2. Determine the severity and cause(s) of malnutrition
3. Identify patients at risk of complications from surgery, chemo- or radiation therapy
4. Assess the efficacy of nutritional support
Nutritional assessment warrants periodic evaluation and reassessment as malnu-
trition evolves over the course of a malignant or advanced chronic disease and
its intervention. Nutritional parameters to assess nutritional status during the
course of the disease, from baseline at diagnosis to remission or cure, are avail-
able. Such parameters have sufficient sensitivity and specificity to reliably
assess nutritional status. Nutritional management should be tailored to the
patient’s needs by combining nutritional assessment and monitoring of perfor-
mance status and quality of life.
A standardized, easy to use, validated, and accepted tool to evaluate nutritional
status must be applied [13]. Nutritional indexes or scores have been developed to
evaluate and to triage patients according to need for counseling or immediate nutri-
tional support. Subjective global assessment (SGA) [14, 15] estimates the degree of
nutritional depletion and identifies patients at risk of malnutrition. It correlates
closely with objective parameters (e.g., serum protein levels, anthropometric mea-
surements) and predicts postsurgical clinical outcome accurately (82 % sensitivity,
72 % specificity) [16]. A training period of a few days is typically needed to mini-
mize an inter-observer variability and satisfy reproducibility.
Validated for adults and children, nutritional risk score (NRS) is a 5-item ques-
tionnaire that classifies severity of malnutrition. Assessing weight loss, body mass
index, appetite, ability to eat spontaneously, and intercurrent diseases, it compares
favorably with clinical judgment and other nutritional risk indices. It is fairly repro-
ducible among different nutrition professionals, including nurses, nutritionists, and
dieticians. Other indexes and screening tools for the community, hospital, and geri-
atric care homes (9-item questionnaire, Zeno Stanga’s MUST/NRS/MNA), all with
moderate to substantial inter-rater reliability, were created to identify patients who
are malnourished or at risk of malnutrition. These tools should be utilized as part of
the global initial assessment to guide nutritional management.
Weight change is a good indicator of nutritional deficit. A weight loss of 10 % or
more within the prior 6 months, or 5 % or more within the prior month, indicates
malnutrition and correlates well with clinical outcome. Use of other variables such
as subscapular/triceps skinfold, mid-arm muscle area/circumference to estimate
body fat, and fat-free mass have poor inter-rater reproducibility, and have not been
validated in cancer patients. Biological measurements such as use of anabolic pro-
tein, e.g., transferrin, transthyretin, and albumin plasma levels are more utilized
than nutritional/immunological (lymphocyte, IGF-1) proteins, which are generally
expensive and have impractical clinical utility. Changes in muscle function such as
hand grip strength and impedancemetry measurements require well-trained and

highly motivated operators.
In many institutions, appetite and rehabilitation clinic teams have been created
and are responsible for completing medical, nutritional, speech, swallowing and
physical therapy evaluations for cachectic or terminally ill patients. The goal is to
create an individualized program that will meet patients’ needs and improve overall
quality of life.
Management of Anorexia and Cachexia
The main goals of intervention in palliative patients include nutritional manage-

ment, pain control, home recuperation support, and relief of spiritual pain.
Development of a variety of nutritional interventions has evolved, along with the
expanding knowledge on the pathophysiology of anorexia and cachexia and the
results of clinical application investigations.
Nutritional Counseling
Nutritional management in cachexia or palliative care commences with dietetic

counseling. Depending upon the severity of malnutrition or its risk, different levels
of nutritional support can be designed. Individual patient’s needs, preferences, and
eating habits are important considerations for the nutritionist, both for the purposes
of assuring satisfaction and/or for controlling symptoms [17].
Nutritional counseling is an important aspect of care in cancer or advanced
chronic disease. Simple dietary recommendations can signi fi cantly increase
oral protein-energy intake by cancer patients even when the bene fi cial effect
on weight is not so apparent [18]. There is good evidence that individualized
nutritional counseling improves outcome. In patients with GI and head and
neck malignancies, for example, results of investigations favor the use of
intensive dietary counseling to prevent weight loss and treatment interruptions
[ 19]. In addition, Ravasco and his group, have demonstrated improvement of
diarrhea, flatulence, and abdominal distention during the late effects of radio-
therapy in the nutrition intervention group (group 1), compared with the less-
intensive counseling groups (group 2-nutritional supplements, group
3-control). Furthermore, 4-year survival rate was reported to be astoundingly
100 % in group 1, when compared with groups 2 and 3 (88 % and 75 % 4-year
survival rate, respectively). Malnutrition has been shown to be a risk factor for
decreased survival and postoperative complications in cancer patients [20–23 ] .
Despite this risk, however, few interventions, as that one in Ravasco’s trial,
exist to improve poor outcomes.
The impact of systematic nutritional assessment and counseling on cancer rele-

vant outcomes has also been documented by other investigations. One [24] random-
ized controlled trial of oncology outpatients, compared nutritional counseling plus
oral nutrition supplementation versus a less aggressive approach, and demonstrated
improved energy intake and quality of life with the former. Another study [25]
showed that the inclusion of enteral nutrition support in a comprehensive symptom
control and pain management can lead to improved nutritional status and increased
rates of completion of palliative anticancer therapy. Overall et al. [26], in a study
involving 21 palliative home care services as well as telephone interviews with 621
patients, a high frequency of utilization of both combined oral nutrition and oral
supplements (41 %), and artificial nutrition (14 %) was reported. Conducted quali-
tative interviews indicated that patients and family member gain physical, social,
and psychological benefits from home nutritional support. Some of the concerns
raised by majority of patients with advanced cancer include eating less and weight
loss [27]. Based on this, interventions have been developed utilizing , and authoriza-
tions of patient to “support eating well,” and “self-action.”
The dietician is responsible for calculating food consumption, evaluating nutri-
tional status, and anticipating the nutritional risk of both cancer and its therapy. The
main goals are to maintain adequate nutrition in the normo-nourished and to mini-
mize or prevent cachexia in the malnourished. Type of tumor, its extension and
planned treatments, as well as, patient’s socioeconomic background are typically all
accounted. Working in collaboration with the oncologist, surgeon, anesthesiologist,
nutritional team members, dieticians monitor the patient’s nutritional status and
intake, the efficacy of dietary advice or treatments, recommend possible needs for
enteral or parenteral support, and participate in training staff on nutritional
management.
The importance of early detection of nutritional risk and malnutrition must also be
recognized. Screening tools are available in daily clinical practice and have been discussed
in the previous section. Nutrition guidelines have been formulated by the American Society
of Parenteral and Enteral Nutrition, the American Cancer Society, and the European
Society of Parenteral and Enteral Nutrition (the ACS webpage can be found at http://www.
cancer.org/acs/groups/cid/documents/webcontent/002577-pdf.pdf).
Oral Nutritive Supplements
Several oral nutritive supplements (ONS) are used when oral calorie-protein intake
is insufficient. Preparations vary according to osmolarity, energy density, type of
protein content, lactose/gluten/fiber content, flavor, and formulation. Addition of
immunonutrients, such as arginine, nucleotides, and n-3 fatty acids to ONS to
increase their cost–benefit ratio have been studied but results are inconclusive.
Normo-nourished cancer patients undergoing treatment stress have a resting
energy expenditure (REE) of 20–25 kcal/kg of usual weight per day. Calorie (non-
protein) amounts of 100–200 % of their REE should typically maintain the nutri-
tional status of these patients. Normally, no restrictions are required while oral
feeding is intact other than in the presence of coexisting medical condition(s). The
optimum ratio of carbohydrates and lipids in oral nutritional support is still up to
debate.
Progestogens and Corticosteroids
Over the years, there has been a shift of cancer treatment response assessment from
traditional to symptomatic oncological outcomes, including functional status and
quality of life. Consequently, symptomatic treatments have been on the rise in recent
years.
Orexigens, such as progestogens (megestrol acetate [MA], medroxy-progester-
one acetate [MPA]) and corticosteroids, are the most studied treatments used to
improve appetite in the terminally ill with anorexia. Orexigens reduce the action of
cytokines at the level of both monocytes and the central nervous system. Systematic
reviews (11 RCTs, 1,767 subjects: RR 1.74) [7, 28] have found high-quality evi-
dence that progestins increase appetite and weight gain in cancer patients when
compared to placebo. However, they also increase the risk of adverse effects such as
lower limb edema, deep vein thrombosis, and vaginal bleeding in up to 30 % of
patients. On the contrary, a retrospective case–control study of 2,127 elderly nurs-
ing home residents with cachexia did not find a significant difference in median
weight at 6 months between subjects with and without MA [29]. Furthermore, same
study showed that the median survival of residents receiving MA was significantly
decreased (23.9 months vs. 31.2 months) compared with untreated subjects.
Corticosteroids have been shown to offer benefits in the terminally ill. Although
side effects have been found with their prolonged administration, six RCTs of 647
patients have demonstrated that prednisolone, methylprednisolone, or dexametha-
sone were shown to improve appetite in the short term (but benefit may decrease
after several weeks of use) compared with placebo [7]. In this study no results on
survival were reported. Adverse effects from prolonged intake of corticosteroids
included delirium, proximal muscle weakness, skeletal muscle atrophy, osteoporo-
sis, and immunosuppression.
To improve appetite in cancer patients, treatment of other symptoms such as
pain, depression, and side effects of cancer interventions may provide benefit.
Opiates can complicate food intolerance by causing or worsening constipation.
Antidepressants such as imipramines or fluoxetine can further reduce appetite and
nutrient intake.
Other Pharmacologic Approaches
Most of these agents still warrant further clinical research, and no firm recommen-
dations for use in clinical practice are made at this time.
1. Hydralazine sulfate—inhibition of gluconeogenesis: a systematic review found

no significant benefit with use of hydralzine sulfate.
2. Metoclopramide—attenuation of nausea and vomiting
3. 5HT3 receptor antagonists
4. Cyproheptadine—reduction of serotoninergic transmission
5. Other—melatonin, fatty acids, erythropoietin, androgenic steroids, NSAIDS, inter-
feron, cannabinoids, eicosapentaenoic acid, thalidomide, ghrelin, pentoxifylline
Artificial Nutrition
Enteral Nutrition
Artificial nutrition is recommended when oral intake is less than 60 % of nutritional

needs. The main goal of the use of artificial nutrition is to correct metabolic pertur-
bations of malnourished cancer patients over the course of the disease and disease
treatment. Functional lean body mass must be preserved through replenishment and
maintenance of active muscle and visceral cell mass. Artificial nutrition makes it
possible to limit the nutritional decline of cancer patients, the biological aggressive-
ness of the tumor, and or improve efficacy of cancer therapy [2]. Improved general
well-being and comfort and resumption of activity are the best evidences of efficacy
of artificial nutrition.
Enteral artificial nutrition (EN) is used if the digestive tract is intact and functional,
otherwise, parenteral nutrition (PN, also known as TPN) is utilized. EN and PN are
both safe and effective methods of administering nutrients. Neither route of nutri-
tion is indicated in well-nourished or mildly malnourished cancer patients.
Volitional nutritional support (VNS), i.e., orally consumed supplements, may
improve survival in the malnourished geriatric population, however, neither VNS
nor EN via a tube feeding can be routinely recommended in individuals with cancer
or other advanced chronic diseases, as some studies report no results in improved
appetite or weight gain [30]. Cancer patients undergoing major visceral surgery
who are severely malnourished may benefit from enteral nutritional support.
Parenteral Nutrition
Unless there are prolonged durations of GI toxicity (e.g., bone marrow transplant
patients), EN or PN is often not clinically efficacious for patients treated with che-
motherapy or radiotherapy. Current research has focused on the impact of nutrition
interventions and nutritional pharmacology on the clinical outcome of cancer
patients. Shang et al. [31], in a randomized controlled trial of 152 subjects with
advanced cancer, found that combining parenteral nutrition (PN) to enteral nutri-
tional (EN) support significantly increased mean BMI at 4 months (21.9 vs. 20.5)
and cumulative survival, when compared with EN alone. Similarly, Lundholm et al.
[32], also in a randomized controlled trial of 309 cancer patients with cachexia who
were followed for up to 24 months, demonstrated that combining oral and home PN
to the cyclooxygenase-1 (COX-1) selective inhibitor indomethacin plus erythropoi-
etin increased energy balance, however, no statistically significant differences
between groups in intention-to-treat analysis were found. Glutamine-supplemented
PN appears to be beneficial in bone marrow patients.
For both EN and PN, the recommended regimen includes a daily intake of
20–35 kcal/kg, consisting of a balanced proportion of glucose and lipids (50:50 or
60:50 glucose to fat ratio), and of a 0.2–0.35 g nitrogen/kg (~1.2–2 g protein/kg/day),
as well as, adequate provision of electrolytes, vitamins, and trace elements [2]. In
clinical practice, carbohydrate or glucose is commonly administered using 5 mg/kg/
min, and lipids at no more than 2.5 g/kg/day and no more 60 % of total calories from
fat is used. For patients who have no difficulty tolerating proteins, the common dose
given to “nonstressed” patients is 0.8 g/kg/day and 1.2–2.5 g/kg/day in critically ill
patients. The main goal of nitrogen supply is to limit muscle catabolism, while also
maintaining adequate supply, particularly the essential amino acids, to the liver to
maintain synthesis of proteins needed for immune defenses.
For obese patients, an adjusted body weight, about 120 % of ideal body weight
(IBW), is used to estimate calorie requirements. Lean body mass accounts for about
25 % of excess weight in obese people, using the formula:
⎡⎣(Actual weight − IBW )× 0.25⎤⎦ + IBW = adjusted weight
For patient whose weight is less than 90 % IBW, an average weight can be used
to estimate calorie needs as follows:
(Actual weight + IBW ) / 2 = average weight
Parenteral nutrition is known to carry a higher risk of line infection and associ-
ated sepsis. Therefore, nutritional support in palliative care should be based on the
potential risks and benefits of EN and PN, as well as the patient’s and the family’s
wishes.
In far advanced cancer, there is controversy on whether the use of enteral or paren-
teral nutritional support improves outcome. In terminally ill cancer patients, enteral
and parenteral nutrition appear to be overused, as reported by one recent review [33].
This review also indicated that education, implementation of guidelines, and shared
decision making could decrease the use of nutritional support. Another study reported
that gastrostomy tube feeding use is as high as 90 % in patients with advanced demen-
tia despite paucity of evidence that it improves clinical outcome [34]. There was also
a report of a preference against tube feeding by many patients and that about 15 % of
them had feeding tubes inserted regardless of documented refusal by the patient(s).
Physician education, in combination with palliative care consultation, has been

reported to decrease feeding tube insertion rates by half.
Other strategies of nutritional interventions:
1. Modification of taste and smell
2. Calorie and protein modifications
3. Use of lipid emulsions
4. Immunonutrition
Supplementation with zinc sulfate can improve metallic taste and other taste alterations
during head and neck irradiation. Antiemetics, setrons, and corticosteroids are regimens
that can have beneficial effects on taste disorders. Dietary adaptation to changes in taste
is considered the most effective measure, e.g., avoidance of unpleasant foods and rein-
forcement of salt and sweet depending upon level of sensitivity. It has been shown that
the outcome of taste disorders tends to follow that of the disease, i.e., reversal of abnor-
malities occur within a few days to weeks after the last cycle of chemotherapy. The data
on the benefit and/or risk of using lipid emulsions in cancer patients is conflicting.
Immunonutrition
It has been demonstrated that immunonutrition could improve the beneficial effects
of nutritional support during cancer, chemotherapy, or radiotherapy [1]. Immune
diets also appear to decrease the rate of infectious complications and the length of
hospital stay after GI surgery [2]. The immunonutrition substances, omega-3 fatty
acids, and amino acids such as glutamine, arginine, polyamines, antioxidant micro-
nutrients, are tested mainly for their effects. Megestrol acetate and corticosteroids
demonstrated their efficacy in short-term cures.
Clinical Indications of Nutritional Support
Nutritional support can be utilized during one or more of the following:

1. Perioperative period
2. Chemotherapy
3. Bone marrow transplantation
4. Radiotherapy
5. Palliative care
Complications of Nutritional Support
Nutritional interventions are often assumed to be safe; however, nutritional thera-

pies are not without potentially detrimental effects.
Refeeding syndrome is characterized by a series of clinical manifestations related to

electrolyte changes typically associated with the restarting of the nutritive contribution
of either enteral or parenteral regimens. It is not an uncommon entity in malnourished
patients placed on parenteral or enteral nutrition. In one study, it occurred in about half
of subjects, and it was associated with increased mortality rate and hospital stay [35].
Management of Dehydration
Decreased fluid intake is common in palliative care patients. Dehydration can be

due to a variety of factors such as anorexia/cachexia syndrome, loss of desire to
drink, nausea, generalized weakness, decreased level of consciousness, mechanical
bowel obstruction, or occasionally, no specific etiology could be identified. Routine
practice on management of dehydration varies widely geographically and between
care settings and, high quality evidence from the literature is scant [36]. Observational
evidence exists that terminally ill individuals may not experience suffering from
terminal dehydration, provided that good mouth hygiene is maintained [37, 38]. A
small prospective study of 32 comfort care patients [37] showed that thirst or dry
mouth could be alleviated usually by application of ice chips and lubrication to the
lips or with small amount of fluids. And in this trial, 62 % of patients experienced
either no thirst or thirst only initially during their terminal condition. Perception of
thirst has been associated with, as demonstrated in a small prospective trial of 88
terminally ill cancer patients [39], hyperosmolality (300 mosmol/kg or more), oral
breathing, stomatitis, use of opioids, and poor general condition.
Hydration can be performed either via gastrostomy, intravenously, or subcutane-
ously (hypodermoclysis). But among palliative care physicians, medically assisted
hydration remains an issue of much debate. A systematic review in 2008 identified
only five studies including two RCTs (93 patients) on the effects of short-term
hydration in terminal cancer. Such studies seemed insufficient to make recommen-
dations as trials were either underpowered or of insufficient quality [40]. Although
evidence was weak, there was indication that artificial hydration may improve seda-
tion and myoclonus. However, artificial hydration showed no beneficial effect on
other outcomes and there was increased fluid retention (e.g., pleural effusion,
peripheral edema, and ascites) compared with no artificial hydration.
Management of Nausea and Vomiting
Nausea occurs in up to 68 % of patients with incurable cancer and vomiting in about

13 % [41, 42]. Nausea and vomiting (NV) can adversely affect the patients’ quality
of life as it causes tremendous discomfort and lead to dehydration and electrolyte
disturbances. Chemotherapy induced nausea and vomiting and other chemotherapy-
associated toxic effects have been shown to delay chemotherapy in up to 50 % of
patients, and lead to longer hospitalizations and increased financial cost [43].
Effective treatments of nausea and vomiting have utilized treating the cause of
nausea and or vomiting. There are four main mechanism-based causes of nausea
and/or vomiting which have been coined by the so-called VOMIT acronym [44]: V
for vestibular etiology, O for obstructive (e.g., bowel obstruction), M for motile or
dysmotility of the gut, and I for infectious or inflammatory causes. Vestibular and
obstructive NV, as they involve histaminic, cholinergic receptors, they could be best
treated by anticholinergic/antihistaminic regimens such as promethazine, diphenhy-
dramine, scopolamine patch. Obstructive NV also involves 5HT3 receptors, so are
also best treated by senna products. Prokinetics such as metoclopramide are best
administered to motility-related NV. Treatment for infectious or inflammatory NV
should include anticholinergic scopolamine, antihistaminic (promethazine, diphen-
hydramine), 5HT3 inhibitor (ondansetron, granisetron), neurokinin 1 inhibitors
(aprepitant), and anti-inflammatory agents (corticosteroids).
There is weak evidence that supports the consensus-based guidelines for treatment of
nausea and vomiting in advanced cancer [45]. This emetic pathway neuropharmacolo-
gy-based approach to treatment of NV, however, may not necessarily be always appro-
priate in the setting of far advanced cancer. On the contrary, the empirical approach
(trying various antiemetics regardless of the cause of NV), though can be highly effec-
tive, has not been compared to its mechanistic counterpart in a scientific manner.
Nevertheless, it is recommended that the mechanistic approach should be utilized as a
basis in choosing first-line antiemetic agents. While uncontrolled studies demonstrated
a high (75–95 %) response rate to such standard regimens, randomized controlled stud-
ies reported much lower (18–52 %) response to these therapies. Although these
approaches are practical and simplistic, well-designed studies to find its impact on out-
come of such standard management on NV in the palliative setting need to be done.
There is strong evidence for the use of steroids in malignant bowel obstruction, and for
metoclopramide in cancer-related dyspepsia. Evidence is conflicting with regard to the
efficacy of serotonin antagonists compared with standard agents such as metoclopr-
amide, dexamethasone, and dopamine antagonists. Novel neurokinin antagonists are a
new class of antiemetic agents that hold potential promise for the future.
Management of Constipation
While the prevalence of constipation in patients using opioid for noncancer pain is
about 15–90 %, that of patients following WHO guidelines for cancer pain treat-
ment is about 23 % [46, 47]. Constipation prophylaxis is generally recommended in
all individuals placed on opioid agents. Commonly prescribed treatments for consti-
pation include oral laxatives, opioid antagonists, or rectally administered agents.
Laxatives
Lactulose is an osmotic laxative that is used to decrease hard stools in patients on

opioid treatment. Lactulose has been shown as equally effective as polyethylene
glycol 3350/electrolyte solution (PEG) in decreasing constipation [48].
Macrogels (e.g., PEG) are osmotic agents used to improve stool consistency and
their efficacy have been demonstrated in a placebo controlled trial.
Senna (a stimulant laxative) is another commonly prescribed oral anticonstipa-
tion agent. Unlike Docusate, Senna has been shown in controlled trials [49] to be as
efficacious as lactulose or herbal preparations for decreasing frequency of hard
stools in patients who are on opioids, or who have advanced cancer.
Docusate is a stool softener that is also prescribed in patients on opioid therapy.
However, literature does not show good evidence to back up its use [50].
Other oral laxatives that have been used for constipation include: Bisacodyl,
methylcellulose, magnesium salts, sodium picosulfate, ispaghula husk.
Opioid Antagonists
Opioid acts on peripheral opioid receptors in the GI tract. Opioid antagonists can be
used to block GI receptors to prevent constipation; however, they could also poten-
tially reverse the analgesic effects of opioids [51]. Commercially available opioid
antagonists include methylnaltrexone (MNTX) and alvimopan. The efficacy in
increasing the rate of bowel movements of subcutaneous MNTX in palliative care
or hospice patients with terminal cancer has been demonstrated in placebo-con-
trolled trials [52]. In these trials, constipation improved without interference of
analgesia. Alvimopan, in 0.5 mg and 1.0 mg doses, has significantly improved
bowel movements in patients treated with opioid for chronic back pain.
Rectally Administered Medications
Various rectally applied agents such as phosphate enemas, liquid paraffin, glycerol
suppositories, sodium citrate micro-enemas, and arachis oil enemas have been used
in patients on opioid treatment. However, no clinically important results about the
effects of these medications are found in the literature [53].
Care Facilities for the Palliative Patient
The palliative patient can be cared for in a hospice, hospital, nursing home, or in a home
health care setting. Financial, personal, personnel availability, or medical factors impact
which facility the palliative patient is cared in. Hospice utilization has been on the rise in
the USA, and at least 20 % of patients have received hospice care [54]. More than 80 %
of hospice care in the USA is provided through Medicare. Typically, patients are referred
to hospice care at later phases of their disease. As availability of palliative care services
is limited, patients who wish to pursue life-long treatments or those who have undeter-
mined prognosis are ineligible for hospice services.
Nonhospice palliative care has been increasingly available in US hospitals, but
access to nursing homes or community settings remains uneasy. Hospitals have pro-
gressively invested in palliative care services not only to reduce ICU and total bed
days but also to facilitate transitions from high-costs hospitals to more appropriate
settings such as the home [55, 56]. By the early part of this decade, at least a quarter
of US hospitals had a palliative care program.
Palliative patients on a stable general condition can be cared in a nursing home
or at their home provided that mobile palliative team or home health care support is
available. Such teams or family must be able to provide adequate or reasonable
amount of nutrition, hydration, and adequate control of symptoms and pain. Tube
feedings are utilized if it is the sole criterion that denies patient admission to nursing
home [57]. To avoid ethical or lawful dispute situations, comprehensive information
and advance directives on management and full power to the nursing personnel who
will provide care to the palliative patient must be in place. Goal directed therapy that
calls for improved quality of life of palliative patients may allow patient’s desire to
recuperate at home if possible.
Nutritional Care in Patients with Noncancer Chronic Illnesses
Nutritional support is important in critically ill patients. In acute lung injury (ALI)
and acute respiratory distress syndrome (ARDS), for example, characteristic pro-
inflammatory processes and excess catabolism can result in substantial nutritional
deficits. Nutritional support is essential to prevent significant caloric deficits, lean
body mass loss, muscle strength decline, and malnutrition [58]. In these patients
early administration of enteral nutrition was demonstrated to be associated with
modulation of stress and immune response, and attenuation of disease severity.
In patients with chronic diseases other than cancer, the role of palliative care is
often unrecognized [59]. In patients with heart failure, as prognostication is often
not easy, integrating patients’ preferences into goals of care becomes very impor-
tant. Despite disability and poor prognosis, patients with advanced heart failure and
chronic obstructive pulmonary disease (COPD) often do not receive palliative care
services. Similarly, because dementia is rarely viewed as a terminal illness, many

dementia patients suffer and die in pain due to little or no palliative care received.
Occurring in about five million Americans, dementia in advanced stages is a
leading cause of death in individuals older than 65 in the USA [60]. After the age of
85 years, about 50 % of individuals suffer from memory loss secondary to dementia.
During the most advanced stage of dementia, severe functional impairment, eating
problems, and malnutrition typically occur. Decisions to direct care towards either
to palliation or to invasive measures like placement of feeding tubes should be made
in these patients. Barriers to the provision of palliative care to these patients, phar-
macological or other treatment options for feeding problems are critical issues that
need discussion. Strategies to help clinicians provide effective support to patients
with advanced dementia and their family are crucial [61].
Enteral Tube Feeding in Advanced Dementia Patients
At least one-third of nursing home residents with advanced dementia have a feeding
tube inserted [61]. However, there is insufficient evidence to suggest that enteral
tube feeding is always beneficial in patients with advanced dementia. The use of
feeding tubes (FT) in patients with advanced dementia has been found, in two sys-
tematic reviews, not to improve survival, prevent aspiration pneumonia, heal or pre-
vent decubitus ulcers, or improve other clinical outcomes [62, 63].
Characteristics associated with higher rates of feeding tube (FT) insertion in nurs-
ing home residents with advanced cognitive impairment who were admitted to US
acute care hospitals have been evaluated (2,797 acute hospitals), 163,000 nursing
home residents with advanced cognitive impairment [64]. Approximately two-thirds
of nursing home residents in the USA who are tube fed had their feeding tube placed
during an acute care hospitalization, usually for an infection. In this study, the rate of
FT insertion was as high as 40 % per 100 hospitalizations; the mean rate of FT inser-
tions has been decreasing from year 2000 to 2007; higher insertion rates being associ-
ated with hospital features such as: (1) for profit ownership versus government owned,
(2) larger hospital size, and (3) greater ICU use in the last 6 months of life. Also in this
study, advance care planning such as having written advance directives, do not resus-
citate (DNR) orders, and orders to forego artificial nutrition and hydration were
reported to be associated with lower rates of FT placements.
Advance care planning is often lacking in nursing homes [65, 66]. Only about 6 % of
hospitalized nursing home residents with advanced cognitive impairment had an order to
forgo artificial hydration and nutrition. Advance care planning is apparently essential to
ensure that feeding tube placements are based on informed patient preferences [67, 68].
Ethical Aspects of Nutrition in Palliative Care
Nutritional support at the end of life is a critical decision. It is important that decision
making be transparent. If the decision is documented as part of an initial long-term
care planning, with involvement of patients and family members, then decision mak-
ing becomes transparent. The decision to stop or continue nutritional support becomes
an issue when there is no written or implied directive from the patient. At this point
consultation with palliative care physicians, hospital ethics committee, or legal system
of the state or country comes into play. Palliative care physicians are trained to improve
quality of end of life days. They use nutritional support as one of the most important
tools to improve quality of life. Nutritional support should be used to improve symp-
toms and to enhance patient satisfaction. In special circumstances like advanced stages
of dementia or cachexia, family members are faced with critical decision making on
whether aggressive tube feeding should be maintained or nutritional support be with-
drawn. Under such circumstances, previous examples of complex cases are used to
guide decision making. The most popular court cases of Terri Schiavo, Quinlan,
Nancy Cruzan, and others may be utilized as examples during the critical decision-
making process made by care providers and family members.
There is a lack of national or international guidelines for nutritional decision mak-
ing at the end of life. Differences of opinion exist among physicians and nursing staff
regarding withdrawal of nutritional support. Each group has different views regarding
the use of nutritional support to improve quality of care versus prolongation of life.
Medical literature has not kept pace with the need of merging palliative care with
curative care. Cancer-related cachexia is a primary cause of death in 20 % of all
patients. Though its cause is multifactorial, nutritional causes are most important,
where supply has to overcome increased demands of cancer-related malnutrition. It is
a consensus that provided that the risks, benefits, and alternatives are discussed with
both patient and relatives, the care provider’s personal judgment of conscience can be
used. The nephrology team can lead the patient and family through this process by
providing timely, realistic information to help them make the best decisions.
End-of-life decision making should be a part of an initial long-term care planning
that is shared with every patient and family. When conflicts persist and the need for
initiation of dialysis is urgent, it is necessary to initiate and continue treatment until
the resolution of these conflicts, making sure that a record of this decision is in place.
In certain circumstances, the use of advanced decision making by patients and family
members resolves many conflicts. If discrepancies arise in hospitals, care should be
continued until hospital ethics committee makes an informed ethical decision. Ethics
committee help decide whether to use or not to use ventilators, nutritional or hydra-
tional support. The availability of end-of-life care services was reviewed with respect
to strategies adopted by few administrators in Japan. It was concluded from the survey
that when patients become unstable in a long-term care (LTC) facility, referral to hos-
pitals becomes necessary. Palliative care consultants were necessary to manage these
patients in LTC facilities. In cancer patients, appropriate models are necessary for
good death. Once appropriate interventions are established from such models, future
LTC decision making may become easier to establish.
The psychiatrists of Oregon are divided into two groups for physician-assisted
suicide on compassionate grounds. Euthanasia and physician-assisted suicide are pun-
ishable acts under Canadian criminal law. It is a critical decision when the burden of
nutrition support outweighs the benefit to the patient. Open and effective communica-
tion, and respect of patient’s wishes, should be communicated effectively. According
to US DHHS survey, nursing home patients were more likely to be old, have dementia
and have other noncancer primary diagnosis, receive dietary/nutrition service, medi-
cation management and physician services, than home hospice patients. These chal-
lenges may be overcome by the creation of clear language that stresses the patient’s
goals of care. “Comfort feeding only,” an order that states what steps are to be taken
to ensure the patient’s comfort through an individualized feeding care plan, has been
proposed. Through careful hand feeding, “comfort feeding only,” when possible,
offers a clear goal-oriented alternative to tube feeding and, eliminates the “care-no
care” dichotomy imposed by orders to forgo artificial hydration and nutrition.
The increasing number of patients suffering from Alzheimer’s disease has
led to growing issues relating to the withholding and withdrawing of life-prolonging
treatments. In these patients, the most important factors in fl uencing the with-
holding or withdrawing of life-prolonging treatments include (1) advanced
directives, (2) the family intention, and (3) futility of treatment [69 ] .
Furthermore, the availability of advanced directives and family’s consent for
hospice care were found to facilitate critical decision making in the care of
end-stage Alzheimer’s disease.
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Review Questions
1. Cachexia is most commonly noted in patients suffering from all of the following
cancers except
(a) Head and neck
(b) Pancreas
(c) Leukemia
(d) Lungs
2. Cachexia in cancer patients is found to be related to imbalance of one of the fol-
lowing factors
(a) Carbohydrates
(b) Proteins
(c) Energy expenditure
(d) Fats
3. The following interventions have shown promising results to maintain weight in
cancer patients except
(a) High medium chain triglyceride and long chain triglyceride mixture nutrition
(b) Arginine and glutamine-rich diets
(c) Halogenated carbohydrate diets
(d) Omega 6 fatty acid rich diets
4. Nutritional assessment tools most commonly used are the followings except
(a) Subjective global assessment (SGA)
(b) Nutritional risk score (NRS)
(c) MUST/MNA/NRS
(d) Subscapular/triceps skin fold measurement
5. Nutritional interventions in cancer-related cachectic patients includes all except
(a) Modification of taste and smell
(b) Calorie and protein modification
(c) Use of lipid emulsion
(d) Use of high dose narcotic agonists
6. Enteral tube feeding in hospitalized patients with advanced cognitive impairment
is increased in all of the followings except
(a) For profit ownership vs. government owned hospitals
(b) Large hospital size vs. small hospital
(c) Greater ICU use in last 6 months of life
(d) Presence of advance directives for DNR orders
7. Complications of enteral and parenteral therapy include

(a) Dehydration
(b) Constipation
(c) Refeeding syndrome
8. The decision to withhold nutritional support in advanced Alzheimer patients
includes all of the following factors except
(a) Advanced directives
(b) Family intentions
(c) Futility of treatment
(d) Age of the patient
9. In the USA, the approximate prevalence of malnutrition as a primary cause of
death in cancer patients is about
(a) 2%
(b) 20 %
(c) 60 %
(d) 90 %
10. Ethical decision making for nutritional support of cancer patients is highly
influenced by
(a) Local State laws in the USA
(b) Physician training and belief
(c) Advance directive
(d) WHO ethical committee
Answers
1. (c) Leukemia
2. (c) Energy expenditure
3. (d) Omega 6 fatty acid rich diets (correct answer Omega 3)
4. (d) Subscapular/triceps skin fold measurement
5. (d) Use of high dose narcotic agonists
6. (d) Presence of advance directives for DNR orders
7. (d) All of the above
8. (d) Age of the patient
9. (b) 20 %
10. (c) Advance directive
Chapter 9
Nursing Perspective and Considerations
Ena M. Williams and Tong Ying Ge
Introduction
Palliative Care is defined by the World Health Organization (WHO) as an approach that
improves the quality of patients and their families facing the problem associated with life
threatening illnesses, through the prevention and relief of suffering by means of early
identification and impeccable assessment and treatment of pain and other problems, physi-
cal, psychosocial and spiritual. [1]
Palliative Care aims to:

• Affirm life and regard dying as a normal process
• Provide relief from pain and other distressing symptoms
• Integrate the psychological and spiritual aspects of patient care
• Offer a support system to help patients live as actively as possible until death
• Offer a support system to help the family cope during the patient’s illness and in
their own bereavement
Palliative Care is provided by those providing the day-to-day care to patients and
carers in their homes and hospitals as well as those who specialize in palliative care
(consultants, medicine, and clinical nurse specialists, for example).
E.M. Williams, R.N., M.S.M., M.B.A. (*)

Department of Perioperative Services, Yale-New Haven Hospital,
New Haven, CT, USA
e-mail: ena.williams@ynhh.org
T.Y. Ge, R.N., M.S.N. (Master Degree of Nursing)
Pain Advanced practice nurse, Sir Run Run Shaw Hospital,
Hangzhou, China

DOI 10.1007/978-1-4614-5164-8_9,
164 E.M. Williams and T.Y. Ge
This chapter will focus on the role of the nurse in palliative care and working
with the multidisciplinary team. The main practice areas for the nurse involved in
palliative care can be summarized into the following main focus areas:
1. Coordinating the program and treatment plan for patients and their families
2. Working with the multidisciplinary team
3. Symptom management
4. Education and research
The nurse spends the most time with the patient and therefore his or her role is to
ensure the following:
1. Relief of physical symptoms
2. Helping the patient to achieve the highest quality of life
3. Assist the patient in maintaining his or her independence
4. Provide relief for mental anguish and social isolation
5. Support patient and family members
6. Assist the patient to reduce isolation, fear, and anxiety
7. Support the process of dying well
The nurse should be available to enable convenience, respond to anger,
respond to colleagues, respond to family, and be present or available when death
occurs. The importance of palliative care has led to a new field of Palliative Care
Nursing. This type of nursing differs in essence from other areas of nursing care
and reflects a “whole person” philosophy of care across the lifespan and across
diverse health settings. It focuses on the patient and family as the unit of care.
In palliative nursing, the “individual” is recognized as a very important part
of the healing relationship. This relationship of the nurse with the patient and
family is crucial. Together with knowledge and skills, is the essence of palliative
care nursing and sets it apart from other areas of nursing practice. However, palliative
care as a therapeutic approach is appropriate for all nurses to practice. It is an
integral part of many nurses’ daily practice, as is clearly demonstrated in work
with the elderly, the neurologically impaired, and infants in neonatal units. The
palliative care nurse frequently cares for patients with major stressors, such as
physical, psychological, spiritual, or existential [2]
In caring for the suffering, the role of the nurse is one of coaching. “Coaching is an
interpersonal intervention that requires therapeutic use of self, involving one’s own mind,
past experiences, words, heart, and hand-to comfort those who suffer”. In coaching,
the nurse:
– Establishes a trusting partnership
– Assesses those who are at risk for suffering or who are vulnerable; reassures
patients that although their suffering may not disappear, they will not be
abandoned
– Identifies factors that may be eliminated or modified to alleviate suffering
– Intervenes to facilitate expression of feelings, find meaning in suffering,
help patients and families redefine the quality of life
9 Nursing Perspective and Considerations 165
Table 9.1 Six ways the nurse/health professional can relieve suffering
1. Being a companion to sufferers by identifying the pain of their losses and exploring the
circumstances and extent of their loss
2. By listening for statements of meaning from sufferers and allowing the person’s natural
instincts and energy to surface the issue of higher meaning
3. By valuing any self-disclosure on meaning that a sufferer offers, by analyzing the meaning of
the statements and learning what the statements reveal about the sufferer’s point of view of
him or herself
4. By encouraging the sufferer’s interpretation of their own experience
5. By validating the sufferer’s interpretation of their own experience while clarifying the
meaning and
6. The nurse can identify supportive resources and hope for the sufferer to extend his or her
identity and meaning in the future
The nurse must be self-accepting, secure in his or her own self-concept, and
feel confident in strengthening others.
Nurses and other health professionals can relieve suffering in six ways (see
Table 9.1).
Palliative Nurse and Interdisciplinary Care Team
The team design and composition varies depending on the needs of the patient and
available resources. What is most common is the presence of a nurse and a physi-
cian on the team. The nurse normally serves as the primary liaison between team
members, patient, and family and also brings the team’s plan to the bedside, whether
at home, in the clinic of inpatient setting. The nurse can also work with the physi-
cian to adjust and determine changes in treatment. This is due to the fact that the
nurse spends much time with the family and patient, and becomes intimate with the
patients condition. Other members of the team often include the chaplain and social
worker. No single discipline can meet the needs of most patients and their families;
an interdisciplinary team (IDT) is highly preferred.
Apart from assessment and management of pain, in which the nurse’s key
role has been clearly recognized, the other most important process in palliative
care is the family meeting to establish goals and objectives. This is a standard of
practice in institutions and especially in the Intensive Care Unit where sometimes
the outcome may be unknown for some time. It is in this meeting that families
received clarification, have their questions answered and are helped to understand
the patient’s condition and prognosis, can share their knowledge of the patients
values and preferences along with their concerns as well as receive emotional and
practical support. This meeting is the backbone of the informed, patient-focused,
decision-making about care goals and treatment. Nurses can contribute to these
meetings in many important ways:
– The nurse usually has the most current and up-to-date information about the
patient’s condition.
– This nurse is usually the clinician with the best knowledge of the strongest relationship
with the family.
– He/she has the most continuous presence, seeing and hearing interactions with
patients and families by clinicians from all disciplines, including the many spe-
cialties that are involved in the patient’s care.
– Following the family meeting, the nurse is the connectivity to all individuals who
may not have been present at the family meeting to ensure continuity of care and
treatment.
– Nurses are great at providing information that patients and families can
understand.
– Palliative Care Nurse Specialists are specially trained to address communication
and other needs of the patient and family in the context of complex and life-
threatening situations.
– The nurse is usually the one who needs to carry out the orders decided on at the
family meeting.
The essential role of the nurse cannot be understated in palliative care [3].
The Nurse and Hospice Care
Another area where nurses are essential and important is in hospice care of patient.
Chapter 3 provides more details on the hospice care. The role of the nurse in hospice
care which may occur at home or as inpatient involves three broad areas: (1) approaching
care from a patient and family-based, interdimensional care focus; (2) expertise in
end-stage disease symptom management; and (3) applying nursing process as a mem-
ber of the hospice IDT through a critical thinking approach that supports the Hospice
Experience Model. The hospice’s nurse initial role in end-of-life care is to work with
the patient and family to prevent or minimize the suffering that results from physical
and functional decline of advancing age or from end-stage disease progression [2].
Nursing Pain Management of the Palliative Care Patients
Nursing Assessment of Pain
Pain is one of the most common but also one of the most feared symptoms that palliative
care patients experience during the terminal phase of their lives. The cornerstone of
adequate pain management of the palliative care patient is a thorough patient assess-
ment and frequent reassessment. Nurses usually spend more time with a patient than
any other health care professional and therefore have the ability and responsibility
to perform a holistic pain evaluation. Pain is “whatever the experiencing person says
it is, existing whenever and wherever the person say it does”. According to the Agency
of Healthcare Research and Quality (AHRQ), the most reliable indicator of the
existence and intensity of pain is the patient’s self-report. Pain is affected most
importantly by physiological, psychological, and spiritual factors. The evaluation of
pain must consider the evaluation of these factors. When the clinician needs to
assess pain, there are some key areas or questions that are recommended
(Table 9.2) [4].
The information obtained will help determine the cause of pain and the design of
an appropriate pain management plan. It may help the clinician to determine if the
pain is caused by disease (e.g., direct invasion by cancer), treatment (e.g., constipa-
tion with opioids), debility (e.g., pressure sores), or other unrelated pathology (e.g.,
arthritis). Pain management should always encompass a holistic approach to treat
the cause of pain, including spiritual perspectives.
Care from Family Members and Education of Family and Patient
In some cultures, for instance in Chinese, Asian, as well as several other cultures,
interactions with family are extremely important and family members value being
able to help with each other. Family members play important roles in meeting both
the patient’s physical and psychosocial needs as well as accomplishing treatment
goals. They perform a wide range of tasks and invest huge amounts of time in taking
care of the patient. When the patient can no longer sit, walk, eat, or perform activi-
ties of daily living such as bathing, feeding, toileting, dressing, and turning they
require total support and physical strength from the family members. In addition,
family caregivers may be needed to assist with other necessary activities such as
preparing meals, managing medications, observing disease progression, and build-
ing links with health professionals. Family caregivers could be parents, spouse, chil-
dren, children-in-law, and relatives. Some of them may provide 24 h help when the
patient has terminal cancer.
People who are dying need care in four areas:
1. Physical comfort
2. Mental and emotional needs
3. Spiritual issues and
4. Practical tasks
Pain is one of main causes of physical discomfort. Pain can affect mood. Being
in pain can make someone seem angry or short-tempered. Irritability resulting from
pain might make the patient hard to talk, hard to share thoughts and feelings. Experts
believe that care for someone who is dying should focus on relieving pain without
worrying about possible long-term problems, such as opioids dependence or abuse
[5]. Family members should not be afraid of giving pain medicine as is prescribed
by the doctor. Pain is easier to prevent than to relieve, and overwhelming pain is hard
to manage. If the pain is not controlled well, the patient and his family members
should communicate with the doctor. It can be relieved safely and rapidly.
Table 9.2 Pain assessment terminology
168
Term Definition How to use clinically

Duration How long the pain has been experienced and • This information is critical for evaluating the effectiveness of the treatment
continues to be present (lasting minutes or plan
hours) • Duration of pain can be gathered as part of a comprehensive history of the
pain as well as each time pain is assessed
Frequency The number of occurrences in a specified period of • Knowing the frequency of pain is useful in developing treatment strategies
time; how often the pain is experienced in a and for individualized scheduling of care activities
given time period
Intensity The descriptive rating of the pain experience • Usually helpful to identify intensity for the older adult’s “worst pain” over
(or severity) a specified period of time as well as “the best the pain gets” in a particular
time period
• Assessing the present pain rating and an identified pain rating acceptable to
the patient is also important
• Use the most appropriate scale individualized to the patient’s cognitive and
sensory abilities (see Figs. Fig. 9.1 Example of a Numeric Pain Intensity
Instrument/Scale Fig. 9.2 Example of a Pain Assessment Tool/Scale.
Reprinted from Stuppy DJ. The faces pain scale: reliability and validity
with mature adults. Appl Nurs Res. 1998;11(2):84–9. Copyright 1998, with
permission from Elsevier 9.1 and 9.2)
Location Anatomic site(s) of pain • Older adults often have pain in more than one location
• Identify and document all sites with corresponding intensity and character
• Pain maps are very useful in documenting all pain locations, guiding
therapy, and as a tool in providing daily care (e.g., CNAs can use the pain
map to establish the least painful ways to turn and/or ambulate the person
they are working with)
Onset Description of the experience of the beginning of • The patient may describe a sudden or gradual development of the pain,
the pain associated with a known injury or illness
• Asking about onset can also help identify pain triggered by specific
movement or activity
E.M. Williams and T.Y. Ge
9
Pattern (or rhythm) The course of the pain over time including • Older adults can experience constant and/or episodic pain
variations, often influenced by times of day • Analgesic therapy should be tailored to these patterns
(e.g., certain hours of the day, night or day, • For example, short-acting analgesics are most appropriate for episodic pain,
monthly patterns), periods of rest, or specific whereas long-acting agents are best for constant pain. Routinely dosed,
or general activity/movement short-acting agents may work well as an alternative to long-acting opioids
in older adults
• Older adults with both constant pain and episodic increases in pain
(breakthrough pain) need both short-acting and long-acting medications
Quality Description of the characteristics of the pain, • Helpful in determining the type of pain to guide the most appropriate
(or character) preferably in the words used patient to describe analgesic
the pain • If the older adult has difficulty describing the pain, it may be helpful to
offer examples of descriptions
• These may include the following: aching, sore, cramping, pounding, sharp,
throbbing, dull, nagging, penetrating, shooting, numb, tingling, spasm,
Nursing Perspective and Considerations
burning, gnawing, pressure-like, radiating, stabbing, tingling, tender,

knife-like, etc.
169
0 1 2 3 4 5 6 7 8 9 10
None Mild Moderate Severe
Fig. 9.1 Example of a Numeric Pain Intensity Instrument/Scale
Fig. 9.2 Example of a Pain Assessment Tool/Scale. Reprinted from Stuppy DJ. The faces pain
scale: reliability and validity with mature adults. Appl Nurs Res. 1998;11(2):84–9. Copyright
1998, with permission from Elsevier
There are some myths about pain, which can hinder effective pain management.
Nurses should attach great importance to these myths when they educate patients
and their families (see Table 9.3).
Treatment Modalities for Pain
PCA and Other Treatment for Palliative Cancer Pain Patient
There are several treatment modalities that can be used to deliver effective pain
management. One of these methods is the use of a patient controlled analgesia (PCA).
This is the technique whereby patients can self-administer small doses of paren-
teral analgesics by means of a simple push button mechanism. PCA is an effective and
Table 9.3 Common myths about dying and pain management

1. Myth: Dying is always painful Not everyone who is dying experiences pain. Many
people die without experiencing pain
2. Myth: There are some types of Recent advances in medical area assure that all pain
pain that cannot be relieved can be relieved by using combined approaches,
such as medications and nerve block
3. Myth: If I get morphine, I will Morphine does slow down respirations in many people,
stop breathing however, proper doses of morphine usually do not
cause someone to stop breathing
4. Myth: To get good pain relief, you We used to think that opioids were not effective unless
have to take injections administered by injection. We now know that
morphine is effective when given orally or even by
suppository. There are some long-acting prepara-
tions of morphine which can be given every 12 h, or
some skin patches which can be applied every 72 h,
to simply the route of pain control
5. Myth: People should wait until Using it when it is needed in the early phases of the
their pain is bad to take morphine disease does not mean that opioids and morphine
so it will be effective when it is will be ineffective in the advanced phases of the
really needed disease
6. Myth: Once you start taking Morphine does not always cloud consciousness. It does
morphine, the end of your life is not initiate the final phase of life or lead directly to
always near death
7. Myth: Patients have to stay in a Patients can get safe and effective relief of severe pain
hospital to get effective pain relief at home. If treating the pain at home does not work,
the patient may need further treatment in a hospital
or outpatient setting or by a visiting nurse
safe treatment for cancer pain. PCA allows for more immediate relief of breakthrough
pain and can provide patients with a greater sense of person control over their pain.
A number of parameters on the PCA pump can be set, including:
– Drug concentration in the drug reservoir.
– Bolus dose can be delivered by a permitted request.
– Lockout time is the interval between two bolus doses is set to allow time for the
effect of the previous dose before the subsequent dose.
– Rate of background infusion is the amount of the continuous infusion. This
feature is optional.
– Hour limit is set as the maximum amount the patient can receive in 1 or 4 h.
Patient and family education is critical for safe, effective use of PCA. Education
must be provided to patients prior to initiation of PCA and must address their role
in pain management. The family also needs to be educated on the use, dosage, and
should be provided with answers and clarifications to questions they may ask.
Education needs to both written and verbal and must include the following
information:
• Definition of PCA and patient’s responsibility in PCA therapy
• Pump operation
• PCA by proxy
• Description of when to alert the nurse include the following symptoms:
– Inadequate pain relief
– Side effects of nausea
– Vomiting, constipation
– Urinary retention
– Itching
There are intravenous and subcutaneous routes of PCA. IV infusions require
the need for an intravenous access. As death nears, the burden of maintaining
IV access, especially in the home setting, can be enormous. The subcutaneous
PCA route is an acceptable alternative to intravenous PCA.
Pain Team
In many countries, if a terminal ill inpatient needs a complex pain management,

it is customary for the physician to refer the patient to a pain team. A pain team
consists of pain doctors and pain management advanced practice nurses (APN).
The pain doctor prescribes PCA orders based on the patient’s current total daily
opioid dose, and the pain management APN assesses the patient’s cognitive function
to determine if the patient is able to understand and participate in PCA therapy. In
palliative care, pain management therapies including PCA therapy are often con-
ducted in patient’s homes. Nurses are a vital part of pain therapy at home since
they are the liaison between patients and physicians in this setting.
After the initiation of PCA therapy, registered nurses assess the vital signs,
pain, sedation, and respiratory rate and quality frequently. Assessment results
are documented in the patient’s chart. If the patient has any side effects related to
pain treatment, registered nurses will contact the pain team [6].
The pain team will perform follow-up assessments every day and prescribe adjust-
ments of PCA orders based on the patient’s response to treatment. Meanwhile, a mul-
timodal approach is combined with PCA therapy. The pain team will communicate
strategies of pain treatment with the patient, family members, oncologists, and nurses.
Cultural and Spiritual Considerations
Losses and difficulties in life can challenge faith and philosophical systems. Those
experiencing loss and grief may differ regarding religious and spiritual perspectives
from which they seek answers, search for meaning, and to which they turn for ritual,
comfort, and support [7]. It is important that the nurse understand the ways that spirituality
or religion plays a role or not, facilitates or complicates the experience. The nurse
also needs to be aware of his or her own beliefs and experiences and be careful not to
allow those beliefs to negatively impact the patient and families in their care [8].
References
1. Jocham HR, Dassen T, Widddershoven G, Halfens R. Evaluating palliative care – a review of

literature. Palliat Care Res Treat. 2009;3:5–12.
2. Ferrell B, Coyle N. Textbook of palliative nursing, vol. 355. New York: Oxford University
Press; 2006.
3. Nelson J, Cortez TB, Curtis JR, Lustbader DR, Mosenthal AC, Mulkerin C, et al. Integrating
Palliative care in the ICU: the nurse in a leading role. J Hosp Palliat Nurs. 2011;13(2):89–94.
4. Cancer pain management in children. http://www.childcancerpain.org/frameset.
cfm?content=assess01. Accessed 22 Jan 2012.
5. Oliver DP, Wittenberg-Lyles E, Demiris G, Washington K, Porock D, Day M. Barriers to pain
management: caregiver perceptions and pain talk by hospice interdisciplinary teams. J Pain
Symptom Manage. 2008;36(4):374–82.
6. Nalini V, Urman R. Essentials of pain management. New York: Springer; 2011.
7. Matzo M, Sherman L, Witt D. Palliative care nursing: quality care to the end of life. New York:
Springer; 2005.
8. White KR, Coyne PJ. Nurses’s perceptions of educational gaps in delivering end-of-life care.
Oncol Nurs Soc. 2011;38(6):711–7.
Review Questions
1. Palliative Care is focused on only the care of the dying patient

(a) False
(b) True
2. Palliative care is defined by:
(a) JCAHO
(b) WHO
(c) The state
(d) Nurses
(e) Physicians
3. Palliative nursing is a new field of nursing that
(a) Differs in essence from other areas
(b) Reflects a whole person philosophy
(c) Focuses on the patient and family as a unit
(d) a, b, & c
(e) b only
4. The nurse can relieve suffering in the following ways
(a) By listening for statements of meaning from sufferers and allowing the per-
son’s exploring circumstances to surface the issue of higher meaning
(b) By encouraging the sufferer’s interpretation of their own experience
(c) By validating the sufferer’s interpretation of their own experience while
clarifying meaning
(d) a & c only
(e) All the above
5. What is the most common palliative team design
(a) A nurse and a physician
(b) A nurse only
(c) A nurse and social worker
(d) A physician and chaplain
(e) A physical therapist and a nurse
6. Pain is defined as whatever the patient says it is
(a) True
(b) False
7. The healthcare provider should be worried about patients becoming addict
because they need to take pain medicine over a period of time
(a) True
(b) False
Answers
1. (a)
2. (a)
3. (d)
4. (e)
5. (a)
6. (a)
7. (b)
Chapter 10
Physical and Occupational Therapy
in Palliative Care
Kais Alsharif and Justin Hata
Introduction
Rehabilitation in palliative care addresses physical limitations caused either by a

severely debilitating or life-threatening illness. Physical limitations may be caused
by tumor mass effects or by the treatments used for palliation of that illness.
Palliative rehabilitation can be divided into three categories: preventative, restor-
ative, and supportive. Preventative rehabilitation attempts to address and prevent
functional decline by addressing and correcting morbidity caused by cancer or its
treatment. When long-term impairment can be avoided, restorative rehabilitation
attempts to return patients to their premorbid functional status. Supportive rehabili-
tation attempts to maximize function after permanent impairments caused by cancer
and/or its treatment [1].
Rehabilitation in palliative care can be challenging due to the various types of
pathologies encountered in this field of medicine. The varied presentations, the gen-
erally poor prognosis, and the patient-specific response to disease and disease treat-
ments all represent challenges for the treating medical team. There is evidence to
suggest that therapy referrals are uncommon and underutilized in the palliative care
setting [2]. At the same time, palliative care patients express interest and are willing
to undergo therapy, especially walking and home-based programs [3]. Furthermore,
there is strong evidence that physical activity has a significant and positive impact
on the quality of life in palliative patients with advanced cancer [4], multiple scle-
rosis [5, 6], Alzheimer’s disease, spinal cord injury (SCI), brain injury (BI) [7–10],
cardiopulmonary disease [11, 12], and human immunodeficiency virus (HIV)
[13–18]. There is strong evidence that hospice patients participating in palliative
rehabilitation show decreased pain, decreased dyspnea, improved leg edema, better
K. Alsharif, M.D. (*) • J. Hata, M.D.

Department of Anesthesiology and Perioperative Care, University of California,
e-mail: fastkais@hotmail.com

DOI 10.1007/978-1-4614-5164-8_10,
178 K. Alsharif and J. Hata
mood, enhanced motor function, improved cognitive function from admission to

discharge, as well as increased mobility and better quality of life [19, 20]. In this
chapter, we will discuss the use of physical and occupational therapy in palliative
medicine, including the reported benefits and evidence behind their use.
Physiologic and Functional Changes in the Palliative Patient
Fatigue, cachexia, anorexia, and muscle wasting are very common in the pallia-
tive patient. Fatigue is the most common symptom, and has many causes in the
palliative patient, including primary and secondary etiologies [21]. Primary
fatigue is often due to the tumor itself and can occur through alterations in ATP
and muscle metabolism [21]. Tumor load and subsequent proinflammatory
cytokine production, including interleukin-1, interleukin-6, and tumor necrosis
factor-a, interact to contribute to cancer-related fatigue (CRF) in the end stages of
cancer [22]. Primary fatigue can also be due to central mechanisms including
dysregulated hypothalamic–pituitary–adrenal axis, serotonin metabolism, circa-
dian rhythm disruption, vagal afferent activation, or reduced recruitment of motor
units [21]. Comorbidities contribute to secondary fatigue and include anemia,
infections, depression, pain, dyspnea, sleep disorders, as well as prolonged physi-
cal inactivity. Medications—such as opiates and anxiolytics, often used to palliate
symptoms—can also contribute to fatigue [21, 22].
Cachexia is often accompanied by decreased muscle strength, often due to both
decreased muscle protein synthesis and increased proteolysis [23]. Skeletal muscle
protein turnover in cachectic patients is significantly reduced [23]. In addition, a
large percentage of palliative patients are elderly with lower lean muscle mass and
less maximal power output compared with younger populations. Other causes of
decreased muscle strength in the palliative setting include myopathies and neuropa-
thies. These can be induced by the cancer itself or more often due to toxic and meta-
bolic sequelae of antineoplastic treatments [24–26].
Progressive fatigue and anorexia–cachexia syndrome can contribute to loss of
physical function in the palliative cancer patient and to the detriment of overall
quality of life [22]. Up to one-third of all cancer deaths are related to poor exer-
cise and nutrition [27, 28]. The primary goal of palliative care is to maximize
overall quality of life for patients and their families [29], and physiotherapy does
so by maintaining optimum respiratory and circulatory function; preventing mus-
cle atrophy; preventing joint contractures; improving pain control; and optimizing
independence and function [30]. In addition, physiotherapy plays a role in the
education and participation of caregivers, as well as reducing the burden of care
for families and caregivers [2, 30]. It should be emphasized that in the palliative
patient, group exercise therapy, regular therapy, and energy conservation thera-
pies become more important in managing fatigue. Similarly, relaxation training
and guided imagery play important roles in decreasing nausea associated with
palliative treatments [31].
10 Physical and Occupational Therapy in Palliative Care 179
Rehab Team and Setting
The palliative rehabilitation team should consist of a physiatrist, physical therapist,

occupational therapist, a speech/respiratory therapist, recreational therapist,
nutritionist, a nurse, and a social worker. All team members should be trained and
be familiar with hospice and palliative care. The setting can be inpatient or outpa-
tient or home based, and will depend on the need for hospitalization for other pallia-
tive treatment. Inpatient rehabilitation is suited for patients able to tolerate at least
3 h of rigorous therapy, and who also have potential for significant functional
improvement [1]. Subacute inpatient rehabilitation, or “slow paced rehabilitation,”
often at a skilled nursing facility provides less intense rehabilitation for patients
who can tolerate at least 1 h each day. Subacute inpatient rehabilitation can serve as
a transitional program for palliative care patients before discharge from a medical
or surgical unit [1]. Most importantly, palliative patients tend to adhere to and
respond better to programs designed to address their own specific physical activity
interests and preferences [32].
The physiatrist should perform a complete initial historical and physical assess-
ment, paying special attention to the musculoskeletal and neurologic systems.
Further evaluation should include information on pathology location, staging, esti-
mated life expectancy, comorbidities, as well as pain symptoms. Several functional
scales can be used for prognosis of the palliative patient and are summarized in
Table 10.1 [1]: The team should be aware of previous and anticipated treatments and
therapies. Adequate pain control should be attempted to achieve appropriate levels
of analgesia without causing undue side effects such as nausea and sedation, which
can limit participation in therapy. Achieving this delicate balance requires close
cooperation between all team members, under the guidance and supervision of the
physiatrist or team leader.
Rehabilitation Strategies and Types of Therapy
Exercise is used to improve or maintain strength, to maintain flexibility, to improve

range of motion (ROM) of the joints and prevent contractures, and improve propriocep-
tion and balance. Exercises used include passive, active, active-assisted, resistive
exercises, flexibility (stretching) exercises, and aerobic conditioning [1]. Walking,
cycling, and aerobic devices utilized include treadmills, rowing machines, and
ergometers. Resistive exercises can include performing a set of 8–12 repetitions at
60–70 % of one maximal over a 12-week program in upper and lower extremities.
In prostate cancer patients receiving chemotherapy, such a resistive program was
shown to result in decreased fatigue and improvement in strength and quality of life,
without changes in body composition and with good patient tolerance [33].
Proprioceptive and balance training can include use of the biomechanical ankle
platform system (BAPS) board.
180
Table 10.1 Rehabilitation of the hospice and palliative care patient

Category Assessment tools Scoring system
Physical function Karnofsky Performance Scale (KPS) – 100-point scale (100 = normal function; 0 = death)
[39, 40] – KPS score of 50 or lower is associated with a limited survival
Palliative Performance Scale (PPS) – 100-point scale (100 = normal function and activity; 0 = death)
[41] – Lower scores are associated with limited survival
Eastern Cooperative Oncology Group – 5-point scale (0 = perfect health; 5 = death
(ECOG) Functional Index [42] – ECOG scores of 3 and 4 are associated with limited survival
Edmonton Functional Assessment Tool – 4-point rating scale (0 = functionally independent; 0 = total loss of function)
(EFAT) [43, 45]
Katz Activities of Daily Living – Measures six domains of function
(ADLs) [46, 47] – Each domain is rated as 0 (dependent) or 1 (independent)
– Total scores; 6 = full function; 4 = moderate impairment; and 2 = severe impairment
– Dependency in two or more ADLs contributes to clinical decline and limited prognosis
Lawton Instrumental Activities of – Measures eight domains of function
Daily Living (IADLs) [48, 49] – Each domain is scored either 0 (impairment) or 1 (normal function)
– Higher scores indicate higher functional status
Barthel Index (BI) [51] – Measures patients’ performance in 10 ADL tasks
– Each task is scored in increments of 5 points (5–10–15)
– Scores range from 100 (full independence) to 0 (bedridden state)
Functional Independence Measure – Yields a total score, motor score, and a cognitive score
(FIM) [52, 53] – The scores vary from 18 to 126; higher scores indicate higher independence levels
K. Alsharif and J. Hata
10
Balance/fall risk Berg Balance Scale [54] – 14-item performance based measure of balance
– Each task in measured on a 5-point scale ranging from 0 (lowest level of function) to 4
(higher levels of function) (total maximum score = 56)
– Scores correlate with fall risk; 41–56 = low fall risk; 21–40 = medium fall risk; and
0–20 = high fall risk
Tinetti Assessment of Balance and – Nine items for balance and seven items for gait
Gait [55] – Each task is scored on a 3-point scale from 0 (complete impairment) to 2 (independence)
– Maximum score for gait is 12 and balance is 16 (total of 28)

– Risk for falls if total score 19–24; high risk for falls if total score < 19
Timed Up and Go (TUG) [56-57] – High risk for falls if time to complete the task is ³20 s
Endurance 6 Minute Walk Test (6MWT) [58] – Primary measurement is total distance waked in 6 min
From: Javier NS, Montagnini ML. Rehabilitation of the hospice and palliative care patient. J Palliat Med. 2011;14(5):638–48. doi: 10.1089/jpm.2010.0125
Physical and Occupational Therapy in Palliative Care
181
Table 10.2 Activities of daily living (ADLs)

Bathing and showering
Bowel and bladder management
Personal hygiene and grooming
Toilet hygiene
Dressing
Eating
Feeding
Functional mobility
Personal device care
Sexual activity
Pulmonary rehabilitation includes programs to improve cardiopulmonary capacity

utilizing inspiratory muscle re-training, noninvasive mechanical ventilation,
breathing techniques, management of secretion, and postural drainage [1]. Aerobic
conditioning has been shown to reduce symptom burden [34]. In bone marrow
transplant patients, performance of cycling at 50 % heart rate reserve reduces:
declines in speed and walking distance, neutropenia, thrombocytopenia, and psychologic
distress [34].
Physical modalities for pain control can supplement medical treatments (discussed
in full elsewhere) and contribute to improved physical function. These modalities
include massage, heat, cold, ultrasound, transcutaneous electrical nerve stimulation
(TENS), manual lymphatic drainage, soft tissue mobilization, and diathermy [1].
Occupational therapy addresses and treats deficits in activities of daily living
(ADLs) (Table 10.2), work activities and employment, with the use of adaptive
equipment, as well as recreational activities. Therapists provide home assessment
evaluations and prescriptions for equipment, as well as provide education and
strategies for caregivers. Environmental modification may include the removal of
throw rugs from areas that cause falls, adding railings in staircases and bathrooms,
having a high stool in the kitchen to reach a cupboard, and adjusting the height and
arms of the chair to assist in transfers [1]. Adaptive equipment used to assist
with activities of daily living (ADLs) include reachers, rocker knives, cutting
boards, and holders for assistance with cooking and eating [1], as well as raised
toilet seats and shower chairs for assistance with toileting and bathing. Assistive
devices such as canes, crutches, walkers, wheelchairs, and scooters can be used to
assist with ambulation. Lifts, ramps, and transfer boards help with transfers. In
addition to helping balance and ambulation, these assistive devices also decrease
load on weight-bearing joints helping with joint instability, balance, and reliev-
ing weight bearing on affected extremities. Orthotics can also be used to improve
and optimize best joint mechanics and compensate for motor deficits. Examples
include ankle foot orthosis (AFO) used for treatment of foot drop, or thoracolumbosacral
orthosis (TLSO) in spinal compression fractures to limit spinal flexion.
Specific Strategies
Rehabilitation of Specific Cancers or Related Complications
Head and Neck Cancer
Treatments for head and neck cancers include conservative and radical surgical
resection, as well as postsurgical irradiation. Complications from surgical procedures
include damage to muscles and nerves within the zone of resection. Furthermore,
external beam radiation is associated with tissue necrosis and fibrosis. The combination
of surgical and radiation treatment can thus alter normal anatomy, often leading to
nerve palsies, weak cervical musculature with contracture and subsequent exagger-
ated thoracic kyphosis. Aggressive ROM should be initiated following surgical
healing (usually within 3–7 days depending on the type of surgery), and should be
continued during the radiation treatment and for at least 2 years following treat-
ment. Spinal accessory nerve palsy is another complication, and can lead to trape-
zius muscle weakness, with winging of the scapula and frozen shoulder. Active and
passive ROM exercises, strengthening of the remaining scapular stabilizers, and
postural modification are some of the rehabilitation techniques available.
Breast Cancer
Treatment of breast cancer often involves surgical treatments including modified

radical mastectomy (MRM), lumpectomy, axillary lymph node resection (ALND),
and transverse rectus abdominus flap breast reconstruction (TRAM-flap). These
procedures result in anatomic changes that require rehabilitation. Deficits in shoul-
der ROM following ALND are well documented, and the time course for rehabilita-
tion has been studied. Early exercises following ALND were initially discouraged
due to the possibility of lymphedema and seroma formation. However, a systemic
review [35] showed that early rather than delayed onset training did not affect the
incidence of postoperative lymphedema. Post-TRAM-flap rehabilitation to correct
abdominal muscle weakness and stabilize the trunk is essential, has been shown to
have long-lasting benefits and is well tolerated. Finally, axillary web syndrome is
the presence of a taut palpable cord originating in the axilla and the upper arm fol-
lowing ALND. Therapy to increase ROM, along with manual therapy to soften the
cords can be helpful.
Lymphedema
Lymphedema can develop following irradiation or resection of lymph nodes and

vessels as lymphatic congestion develops in the affected areas. Complete
decongestive therapy (CDT) is an intensive treatment tool available for managing
lymphedema. It combines manual lymphatic drainage followed by compressive

bandaging, therapeutic exercise, and elastic compressive garments. Manual lym-
phatic drainage is performed for 45–60 min, which is followed by the application
of a compressive bandage which can be left for up to 24 h. Following improvement
(usually after 3–7 days), the patient is then transitioned to a maintenance phase in
which compressive garments are used during the day, followed by compressive
bandaging at night, and manual lymphatic drainage as needed. CDT has been
shown to be effective in decreasing swelling, improving lymphatic flow and venous
return, maintaining skin integrity, and protecting the limb from trauma [36, 37].
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Review Questions
1. The most common complaint experienced by cancer patients resulting in

decreased physical function is?
(a) Pain
(b) Depression
(c) Fatigue
(d) Weakness
2. Which of the following are physiologic changes contributing to fatigue in the
palliative patient?
(a) Alteration in, or decrease in ATP
(b) Tumor load resulting in tumor proinflammatory cytokine production, includ-
ing interleukin-1, interleukin-6, and tumor necrosis factor-a
(c) Alterations in muscle metabolism
(d) All of the above are true
3. Physical modalities for pain control include all except?
(a) Massage
(b) Heat/cold
(c) Ultrasound
(d) Transcutaneous electrical nerve stimulation (TENS)
(e) Epidural injection
4. Regarding breast cancer rehabilitation following lumpectomy, axillary lymph
node dissection or modified radical mastectomy, which of the following is true?
(a) Early rehabilitation is associated with seroma formation and is discouraged
(b) Rehab usually begins 2–3 months following surgery
(c) Early rehabilitation results in better outcomes and is not associated with
postoperative seroma formation
(d) None of the above are true
5. Which of the following is true regarding axillary web syndrome?
(a) It is a congenital disorder
(b) It is a taut palpable cord in the axilla occurring following lymph node dissection
(c) It does not respond to manual therapy
(d) It is a vascular malformation of the axillary artery
6. A 78-year-old female with history of metastatic breast cancer on hospice care is
having difficulty reaching for objects in her kitchen, as well as more frequent
falls at home. Which of the following can an occupational therapist help with?
(a) Environmental modification such as removal of throw rugs to prevent falls,
addition of railing to staircase, etc.
(b) Evaluating for adaptive equipment such as a reacher

(c) Providing a high stool in the kitchen
(d) Providing a cane or walker to assist with ambulation
(e) All of the above
7. Which of the following are essential to a successful evaluation of a palliative
patients’ rehabilitation needs?
(a) Close attention to the neurologic and musculoskeletal systems
(b) Awareness of previous therapies and treatments received
(c) Information on pathology location, staging, estimated life expectancy, and
other comorbidities
(d) Adequate pain evaluation and treatment
8. What is subacute rehabilitation?
(a) An outpatient rehab program for palliative patients
(b) An inpatient program for patients who can tolerate at least 3 h of vigorous
physical and occupational therapy
(c) Slow paced rehab, often at a skilled nursing facility which provides less
intense rehabilitation for patients who can tolerate at least 1 h each day, but
less than 3 h
(d) Another name for a nursing home
9. All of the following are true, except:
(a) There is evidence to suggest that therapy referrals are uncommon and
underutilized in the palliative care setting
(b) Palliative care patients are not interested and feel unable or unwilling to
undergo therapy
(c) There is strong evidence that physical activity has a significant positive
impact on the quality of life in palliative patients with advanced cancer,
multiple sclerosis, Alzheimer’s disease, spinal cord injury, brain injury,
cardiopulmanry disease, and HIV
(d) There is strong evidence that hospice patients show decreased pain, dyspnea,
leg edema and better mood, motor function, cognitive function from admis-
sion to discharge as well as increased mobility and better quality of life
10. Rehabilitation in the palliative setting is associated with all of the following
except:
(a) Maintaining optimum respiratory and circulatory function
(b) Preventing muscle atrophy
(c) Preventing joint contractures
(d) Prolonging life expectancy
(e) Improving pain control
(f) Optimizing independence and function
Answers
1. (c) Fatigue
2. (d) All of the above are true
3. (e) Epidural injection
4. (c) Early rehabilitation results in better outcomes and is not associated with
postoperative seroma formation
5. (b) It is a taut palpable cord in the axilla occurring following lymph node
dissection
6. (e) All of the above
7. (e) All of the above
8. (c) Slow paced rehab, often at a skilled nursing facility which provides less
intense rehabilitation for patients who can tolerate at least 1 h each day, but less
than 3 h
9. (b) Palliative care patients are not interested and feel unable or unwilling to
undergo therapy
10. (d) Prolonging life expectancy
Chapter 11
Social Work in Palliative Care
Janet Lucas, Bill Mejia, and Anne Riffenburgh
You matter to the last moment of your life, and we will do all we can
to help you not only die peacefully, but also to live until you die.
– Dame Cicely Saunders
Introduction
Palliative care has a unique place in medicine. It calls us to acts of compassion,

touches our deepest fears, raises profound questions of life and death, and offers the
possibility of transcendence. Social work, with its rich tradition of understanding
and assisting individuals in extreme circumstances, is well positioned to address the
special challenges faced by patients, families, and medical team members.
As palliative care social workers, we combine “what we know” with “what we
do” to contribute our specialized skills and services in three major ways:
• Collaboration with fellow members of the medical team
• Interaction with patients and families
• Promotion of social work ideals through research and training.
J. Lucas, L.C.S.W., B.S., M.S.W. (*)

Family Practice Residency Program,
Glendale Adventist Medical Center, Glendale, CA, USA
e-mail: jclucas11@aol.com
B. Mejia, L.C.S.W., B.S., M.S.W.
Palliate Care Consult Service, Huntington Hospital, Pasadena, CA, USA
A. Riffenburgh, L.C.S.W., B.S., M.S.W.
Huntington Cancer Center, Huntington Hospital, Pasadena, CA, USA

DOI 10.1007/978-1-4614-5164-8_11,
190 J. Lucas et al.
What We Know
The palliative care social worker uses a variety of skills and tools to enhance collaboration
and therapeutic interventions. The National Association of Social Workers (NASW)
has established essential areas of knowledge for social workers in palliative care.
These include:
• Recognition of the complex roles and functions of the clinical social worker
• Familiarity with the biopsychosocial stages of the dying process
• Understanding of the physical, psychological, and spiritual aspects of pain
• Expertise in a wide range of psychosocial interventions to alleviate suffering
• Recognition of the biopsychosocial needs of patients and family members
• Awareness of the effect of ethnic, religious, and cultural differences
• Capacity to navigate the health care system, interact effectively with health care
providers, and facilitate health care decision making
• Coordination of care and facilitation of communication among patient, family,
and health care providers
• Ability to operate in a wide range of settings that provide palliative and end-of-life
care, including hospitals, home care, nursing homes, and hospice settings
• Knowledge of available community resources and discharge planning options
• Sensitivity to the financial impact of illness and end-of-life
• Recognition of cross-cultural and socioeconomic disparities in accessing palliative
care services
• Adherence to guidelines established by accreditation and regulatory standards in
all palliative care settings
• Competence in working with diverse populations, including those with special
physical, mental, emotional, and developmental needs (NASW 2011).
What We Do
Palliative care social workers intervene in a wide range of settings, such as hospitals,
clinics, freestanding hospices, nursing homes, and private homes. We work with a
variety of individuals and populations, including children, adults, the frail elderly,
caregivers, and families. We are adept at creating a therapeutic environment to
enhance trust, promote communication, and alleviate suffering. The palliative care
social worker will:
• Assume leadership in promoting compassionate end-of-life care
• Assist with end-of-life decision making and care planning
• Assist with the resolution of ethical dilemmas
• Act as a liaison between the patient/family and medical staff
• Promote cultural competency
• Participate in/facilitate family conferences
11 Social Work in Palliative Care 191
• Educate healthcare professionals, patients, and family members in the psychosocial

aspects of end-of-life care
• Conduct and document psychosocial assessments
• Provide psychosocial interventions (crisis intervention, supportive counseling,
and grief counseling)
• Advocate for patients’ and families’ wants and needs
• Provide community resource information
• Supervise social work interns
• Provide lectures, presentations, and training
• Conduct and publish research that promotes evidence-based practice in palliative
and end-of-life care (NASW 2011).
The Palliative Care Social Worker and the Team
Although palliative care social workers demonstrate a high degree of autonomy, our
care and practice skills are enhanced by our participation as members of an interdis-
ciplinary team. In the palliative care arena, multiple team configurations exist, rang-
ing from the simple, such as:
• Physician/nurse
• Physician/palliative care social worker
• Physician/nurse/palliative care social worker
…to the more comprehensive, such as:
• Physician/nurse/palliative care social worker/ward or unit social worker/chaplain/
music therapist/art therapist/volunteer
Evolution of the Team
Much has been written about the process by which a team evolves from disorganization
to cohesiveness. Tuckman’s model [2] describes a fledgling team as uncertain about
roles, responsibilities, and team mission, further complicated by a lack of trust and
a heightened level of anxiety. During this stage, the physician is often the de facto
team leader. As the team begins to mature, cliques may form and power struggles
may occur. In this formative stage, the palliative care social worker plays an active
role in facilitating communication, clarifying goals, and building consensus.
In the example below, a palliative care social worker describes the growing pains
of forming a cohesive team.
Our program began with a physician, nurse practitioner, and social worker. The
first few weeks were productive and exciting. Staff members were supportive of this
192 J. Lucas et al.
new venture and eager to help us succeed. As we began to establish our roles, chal-
lenges emerged. During consultations, the physician dominated the discussion, and
the nurse and I believed that our expertise wasn’t being utilized. We felt irritated
and frustrated. We also felt anxious about addressing the issue. I felt especially
unnerved because I’m supposed to be the “communication expert” on the team. At
our next team meeting, the nurse and I expressed our concerns to the physician
about his sense of control. He was surprised but receptive. He shared his own ner-
vousness about the success of the program and acknowledged his habit of “taking
over” in order to cope. He shared his intention to pay attention to his controlling
tendencies. There was such relief after this discussion that we decided to meet regu-
larly to air our concerns. We found that creating an atmosphere of honesty and trust
was paramount in developing a cohesive and effective team.
As the team matures, consensus is achieved more easily, roles and responsibili-
ties are clear and defined, and important decisions are reached as a group. Smaller
decisions may be delegated to individuals or subgroups. The team feels an increased
sense of commitment and unity. Leadership is shared and the group hierarchy
becomes more fluid. The fully mature team is characterized by a shared vision and
commitment to strategic goals. Each member enjoys a high degree of autonomy.
Disagreements occur but are resolved through open communication and consensus.
Trust, mutual support, and team pride are well developed [2].
The Palliative Care Social Worker and the Consult
The team is often called upon to assist with complex aspects of palliative and
end-of-life care. Common consult requests include managing pain and symptoms,
establishing goals of care and care planning, discussing code status, and addressing
ethical issues.
During the initial consult, the social worker focuses upon the psychosocial issues
affecting the patient and family. However, the social worker may meet with refer-
ring medical staff first to clarify patient and family issues or to address the emo-
tional needs of the staff members themselves. A comprehensive social work
assessment may include:
• Mental status, mood, affect, willingness to engage
• Presence of suicidal/homicidal ideation
• Problems, questions, and concerns of the patient and/or family/caregiver
• Patient and/or family/caregivers’ understanding of diagnosis and prognosis
• Current medical concerns
• Patient and family goals
• Patient and family dynamics
• Developmental/life stage issues
• Patient’s living situation
• Psychosocial strengths and coping strategies
• Psychosocial stressors and vulnerabilities
• Past experience with illness, death, and loss

• End-of-life wishes (advance directive)
• Support network
• Spiritual needs
• Cultural values and beliefs
• Ethical concerns
Care Planning and the Patient–Family Meeting
The social worker’s assessment provides valuable input which deepens the team’s
clinical understanding of the patient. The palliative care team communicates with
the referring medical team and other involved staff to review the patient’s current
status and goals of care. Considering each treatment, relative to care plan goals
allows practitioners to evaluate the burdens and benefits of a particular regimen [3].
In palliative care, with its focus on relieving symptoms and maximizing quality of
life, evaluating the burdens and benefits of treatment is paramount.
The palliative care team meets with the patient and family to present recommen-
dations. One end-of-life care planning model, the Seven “Cs”, was developed by
social workers at the Keck School of Medicine in Los Angeles. The checklist below
provides a framework for developing a care plan in which interventions are consis-
tent with goals of care.
The Seven “Cs”
1. Condition
• Current status
• Diagnosis
• Treatments
The first step is to establish the patient’s immediate medical status: “What’s
happening right now?” This is an opportunity to determine whether the patient is
stable, deteriorating, in crisis, improving, or imminently dying. The team notes
the various medical conditions that are affecting the patient and the treatments
that he or she is receiving.
2. Capacity
• With capacity: The patient will participate in care planning
• Without capacity: The team identifies a surrogate decision maker
194 J. Lucas et al.
If the physician determines that the patient lacks capacity, the social worker
assists with establishing the patient’s surrogate decision maker. The social worker
determines if an advance directive exists; if not, the social worker begins to
explore the question of decision making with family members.
3. Clinical course expectations—what is the patient’s prognosis for:
• Surviving the hospitalization?
• Weaning from the mechanical ventilator?
• Achieving an acceptable quality of life (as defined by the patient or decision
maker)?
Relying on general descriptions for prognosis such as, “fair,” “poor,” and
“grave” can be vague and unhelpful. Linking a patient’s prognosis to relevant areas
of care can help patients and family members develop realistic expectations.
4. Care goals
• CURE the disease
• SLOW the progression of the disease
• ALLOW DEATH to proceed, and palliate symptoms exclusively
Once the team has established clinical course expectations, goals of care can
be considered. Goal setting becomes particularly important when cure is no lon-
ger possible. One of the tasks for the palliative care team is to assess whether a
proposed treatment is consistent with the care goal. For example, if the goal is to
allow death to proceed naturally, then attempting CPR would not be consistent
with a peaceful death. Likewise, maintaining blood draws or initiating TPN feed-
ing might be inappropriate.
5. Care plan
• Assess each treatment in terms of the care goal
• Assess each treatment in terms of its burden and benefits to the patient
Recommend to:
• INITIATE a treatment
• FORGO a treatment
• MAINTAIN a treatment
• WITHDRAW a treatment
6. Conference
• Discuss care plan recommendations with interdisciplinary staff involved with
the patient’s care.
• Discuss care plan recommendations with the patient and/or decision maker
and other involved family members
7. Chart
• Document the agreed upon care plan [4]
The Care Planning Model and the Role of the Palliative

Care Social Worker
During the team meeting, the palliative care social worker facilitates the team’s
progression through each of the seven steps in the care planning model. The social
worker helps provide the patient and family with a cohesive, structured discussion.
The overarching focus is to develop a care plan that is clinically consistent with the
agreed upon goals of care. Scheduled times may be established to review the care
plan. The social worker helps to clarify and justify the care plan recommendations
to initiate, forgo, maintain, or withdraw treatments, highlighting the burdens and
benefits to patients.
Cultural Awareness
A natural tension exists between recognition of our common human bonds and our
individual differences. In palliative care, understanding and honoring individual dif-
ferences help create an atmosphere of trust and rapport that contribute to optimal
communication and care planning. Researchers have found significant differences
in how cultural groups view illness, grief, death, and dying, and end-of-life decision
making. In addition, even within specific cultural groups, individual differences
exist [5, 6].
The first step in developing cultural awareness lies in the Oracle’s admonition,
“Know thyself.” Palliative care social workers must make conscious their own
beliefs, attitudes, and assumptions. When working with patients and families whose
values and traditions differ from our own, unconscious biases can creep into interac-
tions via body language, facial expressions, and speech, unintentionally alienating
those we seek to help. Those who feel judged often retreat physically and emotion-
ally, inhibiting open communication and a willingness to solicit or accept support.
Self-knowledge is a vital tool for palliative care social workers as we strive to remain
professionally objective, compassionate, and helpful.
A second step in promoting cultural awareness is recognizing that great
diversity exists, even within the same cultural group. Asking, not merely assum-
ing, is paramount to gaining an understanding of patients’ and families’ values
and beliefs [6, 7].
Sample questions may include:
• What do you know about your condition?
• How did this happen?
• What do you know about your treatment options?
• Tell me about your life before you got sick.
• Would you like us to give medical information to you or a family member?
196 J. Lucas et al.
• Do you want to make medical decisions about your care or would you prefer
to have a family members do so?
• Do you have any spiritual beliefs or traditions that are important to you?
• Tell me what else I should know about you (and your family) in order to
understand and help you.
While such questions may yield useful information, the possibility exists that not
every question may be culturally appropriate for a particular patient or family member.
It may be considered rude or disrespectful for a younger social worker to query an
older person, for a woman to question a man, or a stranger to seek personal informa-
tion. Developing cultural awareness takes courage, curiosity, and a willingness to
make mistakes. If a patient of family member finds a question rude or inappropriate,
rapport can often be reestablished if the social worker demonstrates willingness to
apologize or atone for the breach. In addition, patients and families can be remark-
ably forgiving when they recognize that the social worker has a genuine desire to
help [7].
Communication and the Care Plan
Thoughtful and accurate use of language is vital when communicating with patients
and families to develop a care plan. The palliative care social worker strengthens
clarity by promoting terminology used by the team that is specific, descriptive, and
consistent. Examples include:
Avoid saying: “We recommend that the patient be DNR”.
Do say: “We do not recommend attempting cardiopulmonary resuscitation (CPR)
or putting the patient on a breathing machine/mechanical ventilator”.
Rationale: The word “attempting” introduces the idea that resuscitation is not
always successful. The recommended language deliberately links CPR to the use
of a ventilator and opens the door to clarifying what a DNR order entails.
Avoid saying: “Life support” or “life sustaining treatment”.
Do say: “Mechanical ventilation” or “breathing machine”
Rationale: Euphemistic or vague terms can provide a false impression that
artificial treatment is promoting or sustaining life as opposed to prolonging death
and suffering.
Avoid saying: “Futile”.
Do say: “Not helpful” or “harmful” when describing a proposed treatment or
intervention.
Rationale: The word “futile” implies that a treatment or intervention has neither
harm nor benefit, when in fact many potential end-of-life options can lead to
trauma and suffering, reducing quality of life and impeding a peaceful death.
Avoid saying: “There’s nothing more we can do”.
Do say: “We will provide ongoing supportive care/symptom management/com-

fort care….”
Rationale: Patients and families commonly fear abandonment by medical per-
sonnel and may choose invasive treatment to ensure ongoing contact and care.
The palliative care team seeks to emphasize that care never stops, although the
focus will shift from curative treatment to comfort and quality of life. The rec-
ommended terminology provides a starting point for discussion of what this
ongoing care will look like.
Avoid saying: “What do you want us to do?”
Do say: “We recommend…” or “The treatment is/is not medically indicated”
Rationale: The question “What do you want us to do?” is likely to elicit the following
response, “We want everything done!” It is incumbent upon the palliative care
team to provide appropriate recommendations based upon the team’s expertise
and recognized standards of care. Patients and families can be overwhelmed if
they are asked to make end-of-life decisions without appropriate education and
guidance.
Do say: “We are hopeful that we’ll be able to help you leave the hospital to spend
time tending your garden.” “We are hopeful that you will be able to spend
Christmas with your grandchildren.” “We are hopeful that you’ll be able to sit on
your horse, Zephyr, and maybe even take him for a couple of turns around the
corral”.
Rationale: Redefinition of hope can help ease the transition from curative to pal-
liative care [8]. When cure is no longer possible, linking the word “hopeful” to a
patient’s realistic and achievable goals helps shift the focus from emphasizing
medical intervention to fulfilling meaningful last wishes.
Tools for the Family Meeting: Integrating a New Reality
Ideally, a family meeting results in consensus. Often, however, conflicts arise. One
primary reason for conflict is the inability of one or more family members to accept
the reality of the patient’s functional decline or grave prognosis. The social worker
can use several strategies to help families gain understanding and acceptance of the
patient’s diagnosis and prognosis. Family members can be encouraged to:
• Share stories and memories about the patient before he or she became ill
• Participate in bedside care
• Meet regularly with the palliative care team for updates and discussion.
The use of narrative is recognized as an important tool in creating meaning and
guiding the care plan [9, 10]. Sharing stories about the patient allows family mem-
bers to compare and contrast the patient’s former status with his or her current
condition, shedding light on the new reality. In addition, family members, as well as
the team, may gain insights into patient’s wishes and preferences regarding care
198 J. Lucas et al.
plan goals. Participating in bedside care allows family members to witness the
patient’s physical and mental changes firsthand, enabling a better understanding of
the care plan recommendations. Meeting regularly with the palliative care team
enhances trust and communication, which can prevent or mitigate conflict.
The following vignette illustrates the effective use of care planning strategies.
Mary G
Mary G. was a 74-year-old female with end stage lung cancer. She was in the ICU
on a ventilator. The team determined that Mary would not likely survive the hospitalization.
The team’s recommended care plan goal was to allow death to proceed as peacefully
and comfortably as possible. The care plan included forgoing CPR and withdraw-
ing the vent, tube feedings, blood transfusions, and regular blood draws. The team
also recommended that IV pain medications and anti-anxiety drugs be maintained
and titrated as needed. The social worker arranged a meeting with Mary’s daugh-
ter, the designated decision maker, and other family members to discuss the team’s
recommendations. Although the family intellectually understood Mary’s grave
prognosis, recommendations to withdraw the ventilator and tube feedings met with
resistance. The social worker arranged the meeting in Mary’s room on the ICU.
While the physician provided education about the ventilator and tube feedings,
Mary’s bedside nurse performed suctioning. The family found this difficult to watch.
The social worker asked the daughter to share a favorite memory of her mother. She
tearfully described how the two of them enjoyed hiking on the trails behind Mary’s
home. There was silence for a moment, and then the daughter added, “She wouldn’t
want this, but I’m afraid.” The social worker asked, “What are you afraid of?” The
daughter responded, “I don’t want my mother to suffocate and starve to death.”
Once this fear was expressed, the physician was able to successfully educate the
family regarding the use of opiates and anti-anxiety medications to treat any sensa-
tion of shortness of breath. She was also able to explain the body’s limited need for
nutrition at the end-of-life. The following day the family reached consensus, agree-
ing that the doctor should implement a “comfort care measures only” care plan.
Ramona F
Ramona F. was a 38-year-old woman with vaginal cancer admitted to the hospital
for symptom control. She had several treatment options, including radiation and
chemotherapy with the possibility of an aggressive, potentially curative surgery.
During the initial meeting, Ramona presented as frail, fatigued, severely under-
weight and emotionally overwhelmed. Through tears, she told the palliative
care physician and social worker, “I want to live.” In the next breath, however,
she confided, “I don’t know how I’m going to get through the chemo and radiation.
My partner and my parents are pushing me to not only have the chemo and
radiation but the surgery too.” Despite her expressed ambivalence, Ramona
stated her wish to pursue the first two treatment options. Surgery, however, was
another matter. “Look at me! If I had surgery now I KNOW I would die on the
table. Even if I survived, the complications might kill me.” She felt anxious and
fearful about the reaction of her loved ones. Together, the physician and the
social worker affirmed that their role was to help her understand the treatment
options, including the potential risks and benefits, and provide a safe environ-
ment where she could express her wishes. The social worker offered to arrange
a family meeting in which these issues could be openly shared and discussed.
Ramona reiterated her fear about communicating her wishes in the presence of
her partner and family. The social worker then presented examples of some of
the language that might be used in the family meeting. Ramona shared her relief
and hopefulness that her wishes would be honored and heard.
Core Therapeutic Interventions
Palliative care social workers have the unique privilege of spending time with
patients and families at the bedside. Through our use of key therapeutic
interventions, we facilitate adjustment to illness and disability along the continuum
from new diagnosis to impending death. As rapport and trust develop, opportunities
emerge to enhance coping and heal psychosocial wounds. Interventions include:
• Providing supportive listening
• Normalizing/validating feelings
• Asking open-ended questions
• Enabling patients and family members to “tell their story”
• Assisting patients in “finding their voice”
• Presenting options and facilitating decision making
• Identifying areas of resilience and coping
• Providing cognitive behavioral reframing
• Integrating the reality of diagnosis and prognosis
• Providing individualized therapeutic techniques, such as:
– Working with dreams and visions
– Breathing and meditation
– Relaxation and guided imagery
– Journaling
• Providing bereavement follow-up
The use of core therapeutic interventions helps elicit valuable information and
facilitates psychosocial healing. A comprehensive understanding of the patient and
family is a vital component in the development of an individualized and targeted
200 J. Lucas et al.
care plan. One challenge for palliative care social workers is that we must intervene
in a fast-paced environment, sometimes with just one or two interactions. In the
example below, the palliative care social worker used therapeutic interventions to
help the patient explore concerns about her family and her own spiritual care needs.
This therapeutic process allowed the patient to more fully accept her prognosis and
her need for hospice care.
Marcia R
The palliative care team received a referral to see Marcia R., a 42-year-old wife
and mother, with advanced ovarian cancer. Hospital staff had expressed concern
that the patient was “in denial” because she refused to consider hospice, despite
her deteriorating status. The social worker met with Marcia at the bedside. His
assessment showed that she was well aware of the serious nature of her prognosis.
Marcia shared her fear that accepting hospice would signal to her family that
she was giving up. Her plan was to try to maintain as much normalcy as possible
for her husband and two school-age daughters, by avoiding, for as long as possi-
ble, the trappings of illness. She identified durable medical equipment and having
strangers in the house as her two most pressing concerns. She also revealed her
need to “make peace with Jesus” before she could fully acknowledge that death
was near. The social worker thought that the most immediate need was spiritual.
He asked her, “What does making peace with Jesus look like for you?” She imme-
diately responded, “He would let me know that I was forgiven.” She spent some
time discussing the importance of faith in her life. As trust grew between Marcia
and the social worker, he was able to introduce the concept of hospice and show
the ways in which the hospice team could support her medical and faith needs as
well as the needs of her family. After leaving the bedside, the social worker made
a referral to chaplain services. During their next encounter, Marcia told the social
worker of Jesus coming to her in a dream. She described a loving presence, full of
forgiveness. Later that day, Marcia said, “I’m ready,” and accepted hospice care.
The palliative care social worker’s involvement is not limited to the patient and
family. In many settings, social workers are a key source for emotional support for
staff members. Palliative care social workers are routinely called upon to help staff
members process difficult emotions and circumstances. In the example below, a
medical resident sought out the palliative care team to process an emotional reaction
to a difficult case.
Dr. L
Dr. L was a young resident caring for a 22-year-old patient with end-stage
anorexia, who had dwindled to 75 pounds. Her organ systems were failing.
She remained a full code. Although the patient’s mother had a realistic under-
standing of her daughter’s condition, Dr. L struggled to reconcile the patient’s
failing status with her youth. He asked the palliative care social worker and
physician for help. The fi rst step was to help Dr. L understand that the patient’s
death was inevitable and that resuscitative measures would be traumatic and
without benefit. While Dr. L knew this intellectually, the emotional impact of
the patient’s youth impeded his ability to establish a “comfort measures only”
care plan. The palliative care social worker helped the resident to label his
feelings, which he described as “despair” and “helplessness.” By reframing
that a peaceful death was both “medically sound and compassionate,”
the social worker and physician helped the resident gain a new perspective.
This interaction not only addressed Dr. L’s emotional reservations but also
provided the language with which he could effectively engage the mother.
Keeping the Fire Burning: How Not to Burnout
Palliative care social workers are routinely asked, “How do you do your job? Isn’t it
depressing?” and “How do you keep from burning out?” Sometimes it is difficult for
people on the outside to comprehend the many gifts and rewards that come from
working with the ill and the dying. Nonetheless, there is a toll. Those who work in
palliative care are susceptible to a form of pervasive exhaustion called compassion
fatigue. Figley [11] has described compassion fatigue as “a deep physical, emo-
tional, and spiritual exhaustion,” which affects “those who do their work well.”
Researchers have distinguished between burnout and compassion fatigue. Burnout
is characterized by a withdrawal from patients and a depletion of empathy. Those
suffering from compassion fatigue, however, continue to dedicate themselves to
their work, often finding it difficult to balance their empathy and compassion with
healthy boundaries and adequate self-care [12].
Warning signs of compassion fatigue may include:
• Abusing drugs, alcohol, or food
• Increased anger/irritability
• High self-expectations/low self-esteem
• Depression/hopelessness/exhaustion
• Chronic lateness
• Physical symptoms, i.e., headaches, gastrointestinal complaints, hypertension
• Inability to maintain a balance of empathy and objectivity [12]
Palliative care social workers can engage in self-care activities to prevent or miti-
gate compassion fatigue:
• Acknowledge that palliative care is stressful work that carries an emotional toll
• Recognize that self-care is a professional responsibility
• Find an understanding peer or colleague who can listen
202 J. Lucas et al.
• Practice healthy behaviors: rouvtine exercise, good nutrition, adequate sleep,

rewarding leisure activities, etc.
The cornerstone of professional enthusiasm rests upon the balance between car-
ing appropriately for others as well as oneself. Appropriate boundaries come with
recognizing the limitations of the social work role. One palliative care social worker
notes, “My patients are in an incredibly difficult situation, my job is to offer them
support, guidance, and resources to make their situation a bit better.” Another says,
“I understand that I’m stepping into someone else’s journey. It’s not my journey.”
Noted psychologist Jonathan Young, who counsels those in the helping professions,
uses DaVinci’s powerful image of God and Adam in the Sistine Chapel as a metaphor
for the mutuality of the helping relationship. In Dr. Young’s view, God reaches for
Adam with the same committed intensity with which Adam reaches for God. The
lesson for palliative care social workers is that patients have the choice as to whether
they want to accept support and intervention. In the words of one palliative care social
worker, “I know I’m overstepping my boundaries if I’m working harder than the patient
or family.”
In the same vein, Father Gregory Boyle, founder of Homeboy Industries and the
author of Tattoos on the Heart: The Power of Boundless Compassion, shares the
dream of a boy he worked with, which led him to a deeper understanding of bound-
aries and burnout [13]. In the boy’s dream, Father Boyle is holding a flashlight in a
darkened room. There is a light switch on the wall. The boy feels grateful for the
flashlight. He knows Father Boyle will shine the flashlight on the light switch, but
he also knows that he alone must walk over and turn on the light. Father Boyle’s
definition of burnout: “…to always be trying to turn on the light switch for others.”
His antidote: “OK, I own a flashlight, I can aim it. That has to be enough. The rest
is up to you. I can’t turn the light on for you.”
These two anecdotes remind us that maintaining clear professional boundaries is
a crucial aspect of self-care and an important prerequisite for remaining inspired
and passionate, allowing us to bring our best to the patients and families we serve.
Promotion of Palliative Care and Social Work Ideals
Palliative care social workers are well positioned to promote the core principles of
both social work and palliative care. Modeling social work ideals begins with how
we conduct ourselves professionally. As experts in the areas of communication,
conflict resolution, and consensus building, social workers can lead by example as
well as explore the nuances of interpersonal dynamics in a variety of settings: as
part of a team, at the bedside, on the ward, and in the community.
As palliative care social workers, we have a responsibility to be the voice on the
team that provides insights into the psychosocial and spiritual aspects of end-of-life
care. Our presence ensures that the patient and family’s psychosocial needs and
concerns are integrated into the team’s consciousness. Misconceptions still exist
about the social work role. Bedside introductions can be met with, “No thank you,
I already have insurance” or “I don’t need welfare.” These interactions provide a

direct opportunity to educate patients and families about social work’s role in pro-
viding emotional support, finding useful community resources, and navigating the
challenges of illness and end-of-life. Our presence on the ward enables us to interact
with members of other disciplines—doctors, nurses, physical therapists, dietitians,
discharge planners, and chaplains—sharing what we do, and learning from their
experience and expertise as well.
Seasoned social workers can share their knowledge and wisdom through
supervising, educating, and training social work students. Supervision enables
students to learn through a combination of observation, practice, and in-service
training. In addition, providing an opportunity for students to process their expe-
riences helps them to cope with the emotional intensity of participating in end-
of-life care.
Finally, the need to advance social work and palliative care ideals goes beyond
the clinical setting into the greater community. As leaders in this new and innovative
field, we are called upon to promote our professional ideals through public speak-
ing, conference presentations, and published research.
Participating in the Mystery
Palliative care creates a portal that invites patients, family members, and social
workers to share an intimate journey along the continuum from illness to end-of-
life. The work is demanding, rewarding, heartfelt, and occasionally heartbreaking.
As palliative care social workers, we ask the hard questions and listen to the hard
answers. We help find solutions in the most difficult of circumstances. We strive to
alleviate suffering and promote healing, be it physical, emotional, or spiritual.
Sharing the end-of-life journey provides encounters that few experience in a profes-
sional setting. We offer a safe place where patients and family members can express
deeply held hopes, fears, regrets, and achievements. We listen as patients recount
dreams of the hereafter, interactions with deceased loved ones, and visions of the
sacred. Through these intimate connections, we bear witness to the power of faith,
hope, courage, and transcendence. We are the recipients of gifts beyond measure.
References
1. National Association of Social Workers. Standards for social work practice in palliative and
end-of-life care. Washington, DC: National Association of Social Workers; 2011.
2. Tuckman BW. Developmental sequence in small groups. Psychol Bull. 1965;63(6):384–9.
3. Harrington SE, Smith TJ. The role of chemotherapy at the end-of-life: “When is enough,
enough?”. J Am Med Assoc. 2008;299(22):2667–78.
4. Crary J, Lucas J, Carter J. A journey through the seven “C’s”, a care plan model. Keck School
of Medicine; 2000. Unpublished.
204 J. Lucas et al.
5. Blackhall LJ, Murphy ST, Frank G, Michel V, Azen S. Ethnicity and attitudes toward patient
autonomy. J Am Med Assoc. 1995;274(10):820–5.
6. Fadiman A. The spirit catches you and you fall down: a Hmong child, her American doctors,
and the collision of two cultures. 1st ed. New York: Noonday; 1997.
7. Rosenblatt PC. The culturally competent practitioner. In: Doka KJ, Tucci AS, editors. Diversity
and end-of-life care. Washington, DC: Hospice Foundation of America; 2009. p. 21–32.
8. Evans WG, Tulsky JA, Back AL, Arnold RM. Communication at times of transitions: how to
help patients cope with loss and re-define hope. Cancer J. 2006;12(5):417–24.
9. Charon R. Narrative medicine: a model for empathy, reflection, profession, and trust. J Am
Med Assoc. 2001;286(15):1897–902.
10. Farber S. Difficult choices: making decisions when cure is not possible. In: Doka KJ, Tucci
AS, editors. Cancer and end-of-life care. Washington, DC: Hospice Foundation of America;
2010. p. 25–38.
11. Figley CR, editor. Compassion fatigue: coping with secondary traumatic stress disorder in
those who treat the traumatized. New York: Brunner/Mazel; 1995.
12. Pfifferling JH, Gilley K. Overcoming compassion fatigue. Fam Pract Manag.
2000;7(4):39–44.
13. Boyle G. Tattoos on the heart: the power of boundless compassion. New York: Free Press;
2010.
Review Questions
1. Palliative care social workers contribute their specialized skills and services in
the following way(s):
(a) Collaboration with fellow members of the medical team
(b) Interaction with patients and families
(c) Promotion of social work ideals through research and training
2. Which of the following is not an example of the skills and tools used by palliative
care social workers:
(a) Familiarity with the biopsychosocial stages of the dying process
(b) The pros and cons of various pain medications
(c) Awareness of the effect of ethnic, religious, and cultural differences
(d) Knowledge of available community resources and discharge planning
options
3. Duties of the palliative care social worker include:
(a) Witnessing durable power of attorney documents
(b) Facilitating family conferences
(c) Acting as a liaison between the patient/family and medical staff
(d) Both b and c
4. In the formative stage of team building, which of the following is not a respon-
sibility of the palliative care social worker?
(a) Clarifying goals
(b) Facilitating communication
(c) Supporting a power hierarchy
(d) Building consensus
5. A comprehensive social work assessment may include:
(a) Developmental/life stage issues
(b) Psychosocial strengths and coping strategies
(c) Patient and/or family/caregivers’ understanding of diagnosis and prognosis
6. In the seven “Cs” care planning model, which of the following is not considered
a care goal?
(a) CURE the disease
(b) SLOW the progression of the disease
(c) WITHDRAW all care
(d) ALLOW DEATH to proceed, and palliate symptoms exclusively
206 J. Lucas et al.
7. Researchers have found significant differences in how cultural groups view:

(a) Illness
(b) Grief, death, and dying
(c) End-of-life decision making
8. The palliative care social worker strengthens clarity by promoting terminology
used by the team that is specific, descriptive, and consistent. Examples of
recommended language include:
(a) “Mechanical ventilation” or “breathing machine”
(b) “Not helpful” or “harmful” (when describing a proposed treatment or
intervention)
(c) “Futile”
(d) “We are hopeful”
9. Which of the following is not a therapeutic intervention employed by palliative
care social workers?
(a) Enabling patients and family members to “tell their story”
(b) Providing a timeline for grief
(c) Presenting options and facilitating decision making
(d) Integrating the reality of diagnosis and prognosis
10. Which of the following would not be considered a self-care activity?
(a) Develop strategies to distract yourself from disturbing emotions
(b) Find an understanding peer or colleague who can listen
(c) Acknowledge that palliative care is stressful work that carries an emotional toll
(d) Practice healthy behaviors: routine exercise, good nutrition, adequate sleep
Answers
1. (d)
2. (b)
3. (d)
4. (c)
5. (d)
6. (c)
7. (d)
8. (c)
9. (b)
10. (a)
Chapter 12
The Healthcare System: More
Questions than Answers
Jackie D.D. Carter
As the USA continues to struggle with how healthcare will look in the next 10–15
years, it is the patients and their families who will look toward their practitioner to
guide them through the maze known as healthcare. The healthcare system can be
frustrating to a relatively healthy person, but for a patient and their family dealing
with end-of-life issues the healthcare system can be overwhelming. It is important
to listen to their questions, assess their needs, and ascertain what services are avail-
able to them.
The patients and their family will have questions and will want you, as their
provider, to answer them. Questions may arise in the areas of the disease process,
insurance, and available resources. It is important to understand that you will not
have all the answers. Be honest and keep the lines of communication open. Key
issues in the care plan will revolve around communication with the patient and their
ability to access care.
Communication
Questions Asked of the Provider
As the provider, the patient and family will look to you to answer all kinds of ques-
tions, from “are you sure to how come you can’t fix it?” This is not intended to be
J.D.D. Carter, R.N., M.S.N., C.N.S. (*)

2537 Millbrae Ave, Duarte, CA 91010, USA
Department of Nursing, LAC+USC Medical Center, 1200 N. State Street,
Los Angeles, CA 90033, USA
e-mail: jsacar11@yahoo.com; jdcater@dhs.lacounty.gov

DOI 10.1007/978-1-4614-5164-8_12,
210 J.D.D. Carter
personal attack. “How can it be when they know nothing about you?” You are the
provider and as the provider you are expected to know all the answers. This, of
course is a myth. What you can do, however, is be accessible, answer questions to
the best of your ability, explain, prepare, do not waive (be consistent), and provide
resources. At times it will be uncomfortable, frustrating, and depressing. It can also
be peaceful, rewarding, and affirming.
Questions that you may initially receive are “how and why? How did this hap-
pen?” Give them the history as you know it. It may be a history of genetics versus
environment. It may involve a history of high blood pressure, aging, smoking, drug
abuse, etc. It may be none of the above. It may be that you do not know. As much as
possible try to alleviate the patients’ and families’ fears. Know that these fears may
be real or imaginary. Some family members will want to believe that they can pre-
vent this from happening to them. If possible, answer the questions. Be as honest
and compassionate as possible. It is normal for the patient and family members to
be scared, frustrated, and angry.
Be clear and concise. Do not use euphemisms. Families can hear the phrase “every-
day he lives is a miracle” and the family will believe their family member will survive.
Why not? They believe in miracles. It is not for you to give them hope or take it away,
but provide them with the needed information to make educated decisions.
Questions You Should Ask Yourself
Prior to meeting with the patient and their family you need to ask yourself what is your
goal? What is the purpose of the goal? How do you plan to accomplish the goal? It has
been found that providers in the USA are aggressive in their care [1]. Any procedure
that you may want to do needs to reflect the patients’ comfort and goal of quality of life.
Will the therapy be painful? What are the expectations of the therapy? What are the
risks and benefits? Are there any cultural barriers that may prevent your plan from
going forward? Alert the patient of the option of stopping therapy at anytime.
There are aspects of the patient life you need to know prior to making these deci-
sions. Is the patient in the hospital? Will the patient realistically leave the hospital?
If so, where will the patient go? What are the resources? This is when you will need
the aid of social workers and financial workers. They will be able to give you a
picture of the options prior to initiating therapy. What are the post-therapy resources
that are needed? Again, will they be available? Can the family provide them? Do
they have the space for the needed equipment? Other resources that may be avail-
able to you in assisting in the care plan of the patient include the visiting nurse and
chaplain. They will help to provide a clearer picture of the patient and family.
The ultimate goal for any patient receiving hospice is the control of symptoms
and a peaceful death. Any therapy initiated should reflect that therapy. Culture
should always be examined. A large portion of the African-American community
has preconceived concepts of palliative care and hospice. There is the thought that
hospice hastens death. Therefore, not many in that community utilize the services
[2]. The cultural that needs to be examined the closest is “the family.” The family
12 The Healthcare System: More Questions than Answers 211
will have their own problems which might influence the plan of care. Some of the
problems may need addressing, others will not. Acknowledgment of the issues and
recognizing when you are out of your depth is essential in building a trusting and
rewarding relationship.
Questions the Provider Should Ask
Questions that should concern you as the provider include what the future plans are
for the patient? What treatment plan is the patient following? Palliative care can
incorporate many aspects of care including palliative chemotherapy and radiation
therapy. What is the family expectation of therapy? Never assume that the family is
on the same page as you. Their plan may include for the patient to continue the same
course of therapy whereas your plan was to transition the patient to supportive ther-
apy and send the patient home. Be clear in your expectations. Listen to theirs. When
possible, mesh the two conversations into plan all can agree with. Does the patient
have a support system? Is it available 24 hours a day? Are they dependable? Never
assume that the family understands the goal of therapy. When all aggressive thera-
pies toward cure are complete and the patient is receiving supportive therapy, reas-
sure the family that the goal is to be just as aggressive in the management of the
patients’ symptoms.
What resources do the patient and family have? What will be needed? Will they
need a hospital bed? Is there room for one? What about a bedside commode? Does
the family have access to a restroom when needed? Never assume. Does the patient
require oxygen? Does anyone in the house (euphemism for all dwellings) smoke? Is
the patient’s plan of discharge realistic? Does the family want to take the patient
home? Some families will feel guilty if they do not take the patient home. Let the
family know if it does not work out what procedure is needed to have the patient
re-hospitalized. Utilize the social worker or case manager to assist with care plan.
Some families will not want to have someone to die in their home. Discuss this with
the family. Let them know there is no wrong choice.
Another issue that may arise when transitioning a patient from curative therapy
to comfort care is a feeling of desertion. A smooth transition from their primary care
to hospice care reassures the family that all is not lost. The care will continue but the
focus of the care has shifted.
Access
Information
The information age and the internet have allowed for anyone with a computer access to
a variety of information. The patient and family will have access to physician’s history,
hospital ratings, and complaints that may have been made against the physician or
212 J.D.D. Carter
hospital. Computers are providing the layperson with a wealth of access to information
on diagnoses, medications, end-of-life decisions, and patients’ rights [3]. The
information may or may not be accurate. It will be your job to weed through the
information presented by the patient and family and inform them of what is and what is
not true. It is not your job to convince them but provide them with the information.
Patients and their family may present with a plan of care that may or may not be
realistic with their available resources. It is important to know what information
they have and do they really understand the patients’ situation. This may or may not
give the patient and family confidence in the care plan. The key to gaining and
maintaining trust is to provide accurate and consistent information at all times. It is
all right to say you want to consult with a colleague and get back to them. It is better
for the family to feel that you can be trusted than for you to give information and the
family find information to the contrary.
Resources
What level of healthcare does the patient have access to? What are the goals of the
therapies being provided? This cannot be stressed enough. There is a belief that as
long as the patient is still going to the doctor, a cure exists.
Access to healthcare is something we assume everyone has, yet it is the level of
access that will determine what is available to the patient. It is very important to be
aware of the patients’ type of insurance. What will it pay for? Patients with unlim-
ited resources are easier to ensure care for than those with no or minimal insurance.
This does not mean that patients with unlimited resources should not be given the
same courtesy and honesty when it is time to transition their care from cure to
comfort.
There are several different levels to insurance. The list includes those who have
money as well as access to anything that healthcare can provide, those with private
insurance who need referrals from their provider to access other specialists (this
includes PPO’s and HMO’s), those with state aid insurance (i.e., Medicare/Medical),
and those with no insurance to name a few. There are extreme’s at each end of the
financial spectrum and all will have questions and require guidance.
Resources could be as limited. Limitations could include patient and family liv-
ing outside an area serviced by hospice. If so, what are the viable options? Will
home health services support the patient? Will the patient need a skilled nursing
facility instead? What care is realistic considering the insurance or lack thereof?
Insurance will also affect the medications and what is payable versus what is not.
Certain medications may not be available and if available at what price? What is the
reasonable alternative? Has the patient trialed the medication for efficacy prior to
discharge? Some insurance programs have restrictions on the amount of medication
for which they will pay [4]. Contact the pharmacist to assist in the amount of medi-
cation available per billing cycle of the insurance. Is there an institutional policy that
limits the number of medications prescribed to the patient? Discharging a patient
with pain medications still has many taboos. Some physicians will not give a com-
plete month supply, leaving the patient vulnerable to running out of medication,
prior to the next billing cycle. Provide the appropriate amount of medication to the
patient so that the patient will have one less concern during this time.
A trip to the doctor’s office is not necessarily easy for all patients. Some do not
drive and will rely on friends or family to get them to appointments. What appoint-
ments, if any, are really needed? Again, know the available resources. Does a family
member have to miss a day of work to bring the patient to an appointment? Does the
family have a car? Are they using taxi? Are they taking the bus? How are they get-
ting to the appointment and are there resources available to assist with transporta-
tion. When more than one appointment, what works best for the patient and family?
Get the case manager and the social worker involved. You are not expected to know
all of the ins and outs of the system. You need to learn and develop a working rela-
tionship with your resources for the best interest of the patient.
As the number of people growing older continues to increase so does the number
of people requiring hospice [5]. Caring for a patient at the end of life can be just as
complex as that of a patient in an intensive care unit. The outcome will still be loss
of a loved one, but the care received during this difficult period can make all the
difference to the patient and their family. Knowing that you are a part of a momen-
tous event should make the experience more important. It is not necessarily about
providing all the answers as much as it is about knowing the questions. All that is
possible is to make the hospice experience the best possible and provide resources
when needed. Utilize your resources; you are not in this alone.
References
1. McBride D. End of life care for advanced lung cancer differs between U.S. and Canadian
patients. ONS Connect. 2011;26(8):21.
2. Pullis B. Perceptions of hospice care among African Americans. J Hosp Palliat Nurs.
2011;13(5):283–7.
3. Healthnet. Navigating the health care system: a resource guide for consumers. 2008; Apr
1–14.
4. Brant JM. Practical approaches to pharmacologic management of pain in older adults with
cancer. Oncol Nurs Forum. 2010;37(5):S17–26.
5. Martz K, Gerding A. Perceptions of coordination of care between hospice and skilled nursing
facility care providers. J Hosp Palliat Nurs. 2011;13(4):210–9.
214 J.D.D. Carter
Review Questions
1. In order to assist the patient and family is important to

(a) Listen to their questions
(b) Assess their needs
(c) Determine services available
(d) All of the Above
2. Patients and their families will ask questions that include all the following
except:
(a) Are you sure of the diagnosis?
(b) Why is the treatment not working?
(c) You know all the answers, don’t you?
(d) How did this happen?
3. Emotions that the provider might experience include:
(a) Comfortable
(b) Peaceful
(c) Happy
(d) Content
4. The provider should use euphemisms in order to make the patient and family
feel more comfortable?
(a) True
(b) False
5. Questions the providers should ask themselves prior to meeting with the patient
and family include all of the following
(a) What will the procedure accomplish?
(b) What is the patient and families goal?
(c) Will the therapy or procedure be painful?
6. What resource can best assist the provider with the care plan?
(a) Patient
(b) Chaplain
(c) Social workers
(d) Case managers
7. What questions should the providers ask the patient and their family
(a) What is your understanding of the patients’ condition?
(b) What is the expectation of therapy
(c) What treatment plan is the patient following
8. All families are more comfortable if their family member can die at home
amongst family?
(a) True
(b) False
9. The availability of information via the computer can provide patients and their
families with a wealth of accurate information?
(a) True
(b) False
10. The type of insurance the patient has does not limit the care that is available to
the patient?
(a) True
(b) False
216 J.D.D. Carter
Answers
1. (d)
2. (c)
3. (b)
4. (b)
5. (d)
6. (a)
7. (d)
8. (b)
9. (b)
10. (b)
Chapter 13
Vascular Access: Ostomies and Drains
Care in Palliative Medicine
Patricia L. Devaney
Palliative care began with the hospice movement, where hospices were originally
places of rest for travelers in the fourth century. Hospices were established in the
nineteenth century in Ireland and London for the dying by a religious order [1].
They have grown from a volunteer-led movement to an important component of the
health care system, providing improved care for people dying alone, isolated, or in
hospitals. Hospital-based palliative care programs in the USA began in the late
1980s at a handful of institutions, Cleveland Clinic and Medical College of
Wisconsin. There are now more than 1,400 hospital-based palliative care programs [1].
Hospital palliative care programs care for nonterminal patients as well as hospice
patients. Both represent two different aspects of care with similar philosophy, but
different payment systems and location of services.
Palliative care is most often provided in acute care hospitals structured around an
interdisciplinary framework and focused on optimizing the patient’s comfort.
Patient’s comfort includes life-limiting, advanced disease, and catastrophic injury;
relief of distressing symptoms; coordination of patient- and family-centered care in
diverse settings; use of specialized care systems including hospice; management of
the imminently dying patient; and legal and ethical decision making in end-of-life
care [2].
Nurses who practice in the palliative care areas are responsible for managing and
alleviating pain and other physical symptoms—along with satisfying the emotional,
social, cultural, and spiritual needs of patients who are facing life-threatening ill-
ness [3]. Of all the symptoms experienced, pain is the most common and also the
most feared. A thorough evaluation of the patient’s complaint of pain is necessary
P.L. Devaney, R.N., B.S., M.S. (*)

Department of Diagnostic Radiology, Yale-New Haven Hospital,
New Haven, CT, USA
e-mail: Patricia.Devaney@ynhh.org; nursepatdi@yahoo.com

DOI 10.1007/978-1-4614-5164-8_13,
218 P.L. Devaney
to manage and maintain adequate pain control. Gastrointestinal symptoms, nausea,

and vomiting, are frequently experienced with advanced disease which lead to
nutritional depletion and dehydration. Anorexia and cachexia syndrome generate a
negative energy balance in which the food intake is inappropriately less than the
energy output, resulting in the net effect of loss of body weight. Delirium is not
uncommon in dying patients and can have many causes both metabolic and struc-
tural; examples are dehydration, infections, opioid analgesia, hypoxia, and electro-
lyte imbalances. Psychological problems, especially depression, are not uncommon
when patients are initially diagnosed. For some, this acute stress response may
persist and interfere with medical management.
Certain general principles in the evaluation of a patient’s pain are important.
Believe the patient’s complaint and intensity of pain. Occasionally, family members
may be summoned to corroborate the patient’s description of pain. Obtain a careful
history of the pain, when it occurs, its intensity, duration, character, as well as
precipitating and alleviating factors. Assign a pain intensity scale to determine
objective changes as various therapies are initiated. Social and psychological fac-
tors need to be addressed when evaluating if the therapy is achieving adequate pain
control. It is critical to determine the cause of the pain. Always remember pain is a
symptom.
Pain Service and Palliative Care specialties should be consulted when available for
a therapy plan that is individualized for each patient [4]. Usually non-opioid analge-
sics are the first-line agents for mild to moderate pain and include acetaminophen and
non-steroidal anti-inflammatory drugs. They are used orally with no tolerance or
physical dependence with repeated dosing. After the maximum effect is attained,
drug-related toxicity or advancement of the disease is evident by the variation of pain
control; opioid analgesics are the next line of therapy (Table 13.1). They are used for
moderate to severe pain and are distinguished by their complex interaction with mul-
tiple opioid receptors in the nervous system. The opioid-agonist drugs, morphine,
bind to specific opioid receptors, producing analgesia. The opioid-antagonist drugs
block the effects of morphine at its receptor. There are the mixed agonist–antagonist
drugs, which demonstrate either agonist or antagonist properties [5].
There are guidelines when using opioid analgesics to individualize therapy.
Avoid dosing “as needed” which produces sporadic blood levels and ineffective
pain control [5]. Scheduled around-the-clock dosing will provide a constant blood
level of the analgesic. Start with a low dose and titrate until desired control is
reached, avoiding drugs that increase sedation without enhancing analgesia. Drug
combinations that enhance analgesia may reduce drug side effects and limit the
need to titrate the opioid component in combination. Adjuvant or supplementary
analgesic agents represent a third group of drugs used to treat chronic pain. Their
analgesic mechanism of action is not known and not directly related to the opioid
receptor system. These include anticonvulsants, phenothiazines, antidepressants,
antihistamines, steroids, and antibiotics. Concerns about opioid addiction have not
been scientifically proven.
Other specialties may be consulted to assist with palliative therapies. For a patient
with interstitial lung disease or end-stage COPD, a tracheotomy may be considered.
13 Vascular Access: Ostomies and Drains Care in Palliative Medicine 219
Table 13.1 Opioids commonly prescribed [5]

Generic name Trade name Applicant/sponsors
Fentanyl Duragesic Extended Release Ortho McNeil Janssen
Transdermal System
Hydromorphone Palladone Extended Release Purdue Pharma
Capsulesa
Methadone Dolophine Tablets Roxanne
Morphine Avinza Extended Release King Pharms
Capsules
Morphine Kadian Extended Release Actavis
Capsules
Morphine MS Contin Extended Release Purdue Pharma
Tablets
Morphine Oramorph Extended Release Xanodyne Pharms
Tablets
Oxycodone OxyContin Extended Release Purdue Pharma
Tablets
Oxymorphone Opana Extended Release Endo Pharma
Tablets
http://www.fda.gov/SiteIndex/ucm148521.htm. Page last updated: 05/04/2010
a
No longer being marketed, but is still approved
This is a minor surgical procedure that creates an opening in the trachea allowing
the patient to be weaned from the ventilator, decrease the work of breathing, and
clear secretions. Failure to be weaned from the ventilator requires lengthy intuba-
tion and care in an intensive care unit [6]. Extended length of intubation can cause
erosion of the trachea and damage to the vocal cords, which can be avoided if a
tracheotomy is performed. Tracheotomy patients could then transfer out of the
intensive care unit and eventually be discharged with home care or to an extended
care facility. Patients and caregivers are trained to care for the tracheotomy tube
prior to leaving the hospital [7]. Some tubes have inner cannulas that are disposable
and replaced every twenty-four hours. For those that are not disposable, the inner
cannula is removed and soaked in an aseptic manner, dried and re-inserted. This
needs to be done every eight hours and as needed. The area around the insertion site
needs to be cleaned using warm water daily and as needed. The tracheostomy tube
is secured with ties around the neck for safety, ensuring skin integrity and changed
weekly. The use of supplemental humidified air or oxygen facilitates secretions to
be thin enough to be cleared by coughing and suctioning. An appropriate sized suc-
tion catheter is used with the suction regulator set between 80 and 120 mmHg [8].
The catheter is placed into the tracheotomy tube gently advancing until meeting
the end of the airway. As you pull back, slowly apply suction by intermittently holding
the thumb over the open side of the catheter. Make note of the secretion’s
characteristics.
Esophageal, head, and neck cancer patients lack sufficient nutrition measured by
serum albumin levels. Surgical intervention does not allow the patient to take
anything by mouth postoperatively; radiation treatment may cause esophageal strictures
220 P.L. Devaney
and head and neck tissue changes. All of these issues, inclusive of depression, can
cause anorexia or failure to thrive syndrome. Other sources contributing to
malnutrition may be the development of an oral candida infection commonly called
thrush or mucositis; both may be due to antibiotic therapy, poor oral hygiene,
dehydration, and chemotherapy.
Each patient will require a nutritional evaluation to maximize his or her dietary
requirements. Many patients who are still able to eat are ordered an unrestricted diet
with high caloric and protein supplements despite other medical conditions such as
diabetic or cardiac restrictions. Patients not able to eat due to oral lesions or esopha-
geal strictures may require enteral feedings via a temporary gastric tube placed
nasopharyngeal or, in more severe cases, a gastrostomy tube.
There are several kinds of nasogastric tubes and are selected according to the
type of feeding to be delivered, gastric or jejuna [9]. The tube is lubricated and
gently passed into the nares asking the patient to swallow to assist tube insertion.
Positioning the head forward with chin on chest opens the esophageal tract and
closing off the airway so that the tube is not inserted into the bronchial tubes. Many
opinions as to the technique used to safely confirm tube placement have been
examined with chest X-ray seemingly always the most reliable. Securing the tube
also has been debatable, to preserve skin integrity, prevent dislodgement, and safely
instilling feedings and medications. Most frequently adhesive tape is used to secure
the tube on the nose and occasionally a tegaderm may further secure it on same-sided
check.
A gastrostomy tube is placed when the patient can no longer swallow food due
to aspiration, esophageal strictures, surgery, or the effects of radiation.
PEG is an acronym for percutaneous endoscopic gastrostomy [9]. The tube is
placed endoscopically assisted through the abdominal wall into the stomach. There
are high and low profile type tubes. High-profile tubes are not flush to the skin but
extend out while low-profile tubes are flush to the skin and are called buttons. High-
profile tubes are secured to the skin to prevent trauma at the insertion site or inad-
vertent dislodgement. The insertion sites of all gastrostomy tubes are inspected
daily for skin integrity and any sign of complications. When the base of the tube is
too snug against the skin, an irritation or breakdown of the skin may occur allowing
gastric contents to leak. There may be a small amount of greenish mucous type
drainage around the insertion site that is normal. Cleanse the site and thoroughly dry
to avoid irritation. Feedings and medications can be administered after checking for
residual stomach contents and follow the doctor’s orders for withholding feedings.
Insufficiently crushed and dissolved medications may obstruct the tube. A small
amount of warm water in a plunger type syringe may clear the clogged area. If still
obstructed, try a carbonated liquid such as club soda or coca cola.
Other patients with gastrointestinal or urinary tract obstructions or diseases:
Crohn’s, ulcerative colitis, small bowel obstructions, perforations, trauma, or cancer
may be faced with the decision to have a fecal or urinary diversion [10, 11]. Fecal
diversion may be required on either a temporary or permanent basis and is classified
according to the segment of bowel utilized. A colostomy or ileostomy [11] is where
a portion of the bowel is brought up through the abdominal wall to drain stool.
Urinary diversion, an ileal conduit or ileal loop [10], is performed for bladder cancer
where a piece of ileum is resected, one end sewn shut, ureters are attached, and the
open end brought up through the abdominal wall as a stoma. The ostomy serves to
allow urine and mucous to drain out. Most medical centers have ostomy nurses that
are consulted to support and teach the patient and family members the maintenance
and care of their ostomy. The bedside nurse’s role is to reinforce teachings and
clarify any uncertainties through collaboration with the ostomy nurses and the
patient’s physician.
Patients are instructed to monitor stoma color, care of the skin around the stoma,
fecal, or urinary output, proper application of the stoma pouch, to empty the pouch
when one-third to half full, and how to change the pouch every 3 days and as needed
[12–14]. Normal stoma color is pink to red. The mucocutaneous junction is observed
for signs of separation or infection and surrounding skin to be intact. There may be
several days before fecal material begins to pass from the stoma. Dietary consider-
ations need to be discussed especially if a patient has an ileostomy. The recommendation
for these patients is to take at least 1.5 l of fluid daily to prevent stoma blockages.
Many foods such as nuts, raw fruits, and grains may not be compatible with an
ostomy. Patients need to trial their food choices to determine which are the least
disturbing to their gastrointestinal tract.
Pleural effusion is excess fluid that accumulates in the pleura, the fluid-filled
space that surrounds the lungs. Excessive amounts of such fluid can impair breathing
by limiting the expansion of the lungs during respiration.
Pleural effusion is usually diagnosed on the basis of medical history, physical
exam, and confirmed by chest X-ray. Once accumulated fluid is more than 500 ml,
there are usually detectable clinical signs in the patient, such as decreased move-
ment of the chest on the affected side, stony dullness to percussion over the fluid,
diminished breath sounds on the affected side, decreased vocal resonance, and
pleural friction rub. Above the effusion, where the lung is compressed, there may
be bronchial breathing and egophony. In a large effusion, there may be tracheal
deviation away from the effusion. Recurrent pleural effusions can be malignant or
nonmalignant in nature and caused by left ventricular failure, cirrhosis, neph-
rotic syndrome, pneumonia, pulmonary embolism, and cancer. Pleural fluid
accumulation can be managed long term with a drainage system called the Pleurex
catheter [15]. It requires a procedure that can be performed by a physician or
licensed independent practitioner and is used for intermittent drainage of symp-
tomatic, recurrent pleural effusions that do not respond to medical management of
the underlying disease. The catheter is placed under the skin into the pleural space
and referenced as a tunneled catheter. Once the catheter is placed, the fluid is
drained as prescribed and then closed with a new sterile cap at the conclusion of
each drainage. Frequency of drainage must be ordered by a physician or licensed
independent practitioner and performed using sterile technique. Removal of pleu-
ral fluid should be no more than one liter per lung per day, using only the drainage
lines and bottles included in the Pleurx kit. Pleurx catheters should only be flushed
by a physician or licensed independent practitioner trained in the use of these
catheters [16].
222 P.L. Devaney
Symptoms that need to be reported to the physician include infection at the

catheter insertion site, changes in the appearance or integrity of the catheter, severe
pain, shortness of breath, coughing, fever, decreased oxygen saturation, leaking of
fluid around the catheter, or less than 50 ml obtained for three consecutive drainage
attempts. Dressing changes are performed with each drainage procedure. Patient
and family education is completed before discharge and provided with a Carefusion
folder and DVD, with additional resources found at http://www.carefusion.com.
Homecare is prescribed using a registered nurse to reinforce care of the catheter and
supervise the drainage as well as aseptic technique.
There is a growing population of heart failure patients that become increasingly
symptomatic not due to an acute event or another chronic disease. Biventricular
pacemakers [17] are a consideration and have been shown to improve quality of life.
Three leads are placed: right atrial, right ventricular, and an additional lead into the
coronary sinus. The lead in the coronary sinus will pace the left ventricle in
synchrony with the right ventricle. It has been shown that single chamber, right
ventricular pacing, weakens the cardiac muscle where synchronized pacing actually
remodels the cardiac muscle improving cardiac output. Patient’s symptoms improve
enhancing their quality of life and return to activities previously unable to achieve.
Patients with chronic heart failure who have a very poor long-term prognosis and
are not transplant candidates due to factors such as advanced age, end-stage renal
disease, malignancy, non-compliance, or chronic obstructive pulmonary disease
may be considered for a left ventricular assist device [18, 19] and these are referred
to as destination devices. The left ventricular assist device offers a better treatment
for advanced-stage heart failure patients who require hemodynamic support and
become refractory to medical management. It has demonstrated the ability to restore
hemodynamics, increase survival, and dramatically improve functional status and
quality of life. Such patients will most likely die from their heart failure unless a
mechanical assist device is offered.
The patient who suddenly presents with acute heart failure, unable to be weaned
from cardiopulmonary bypass, massive acute myocardial infarction, acute
myocarditis, or severe cardiac decompensation, may be implanted for a short term
until improvement in cardiac function or implanted as bridge to transplant. Left
ventricular assist devices are surgically implanted by a credentialed cardiothoracic
surgeon. After implantation, they are cared for by the heart failure and cardiac
surgery teams in most centers. Patients with devices remain in the hospital until
either a compatible heart can be transplanted or cardiac function improves. When a
compatible heart cannot be found and cardiac function stabilizes, patients can be
discharged home but only after thorough education. Education consists of detailed
information about the technical principles, system set-up, function, maintenance,
infection control, and risks. Post implant, the most important education is directed
towards infection control strategies including strict hand washing, sick visitor
restrictions, and using aseptic technique when performing daily driveline dressing
change. Discuss signs and symptoms of infection and immediate reporting.
Anticoagulation therapy is also an important consideration and requires a strict
regimen following the vendor’s recommendations.
The domain of autonomy reflects the patient’s degree of informed participation

in decision making and planning concerning their illness. Rigorous research has
demonstrated that open communication about advanced illness does not compro-
mise the patient’s psychological distress [2, 20, 21].
Direct assessment of autonomy can be measured by the following questions:
• Are we doing all but only the things you desire?
• Do you feel in control of your care?
• Do you feel heard and listened to?
• Have you been told of the nature of your illness and what to expect of it?
• Are we following your wishes to your satisfaction?
• What worries you the most?
It is important to select an environment for these discussions and to facilitate
communication eliciting the patient’s knowledge of their condition and desire to
know about their condition. Open-ended questions and actively listening to the
answers tend to minimize the patient’s worries and concerns. This approach can
aide in the resolution of conflicts, minimize anxiety, enhance the sense of dignity,
and depression in the patient and their family.
Patients are encouraged to communicate with their loved ones about completion
of life affairs, contribution to others, life review, and legacy [3, 20, 21].
While only about one-fourth of the patients with advanced cancer consider them-
selves to be suffering, a significant fraction attribute their suffering to closure-related
problems, such as a pervasive sense of struggle, dependency, loss of identity,
control, or their role in the family, or society in general. In contrast, advanced
cancer patients who have a higher degree of peaceful acceptance of their terminal
illness suffer from less depression, anxiety, and post-traumatic stress disorder.
Where appropriate, opening a dialogue about closure may involve tactfully asking
any of the following questions:
• How would you want to be remembered?
• Is there anyone whom you have not seen in a long time and need to talk to?
• Is there anyone to whom you wish to offer (and/or ask for) forgiveness?
• What do you feel most proud of (in your life)?
• Are there things or times you regret?
• Is there anyone who you can talk to about your fears and plans?
• Do you feel prepared for what is still ahead of you?
• Have you been able to share important things or thoughts with others?
• What do you still want to accomplish in your life?
• What would be left unfinished if you were to die today?
One successful palliative intervention, Dignity Therapy [2], invites patients to
address issues that matter most to them or speak about things that they would most
want remembered. An edited “Legacy” transcript of the dialogue is then returned to
the patients for their review and sharing with others. Patients with advanced illness
and their caregivers frequently experience profound financial and social strain.
Family and friends provide most of the end-of-life assistance, for a mean of 43
224 P.L. Devaney
hours per week. Almost one-third of the families report loss of all or most savings
due to the illness and care giving. Furthermore, economic burden may profoundly
impact health care decisions. In one study, economic hardship on the family was
associated with a preference for comfort care over life-extending care in another;
substantial care giving needs were associated with endorsement of euthanasia
among patients with terminal illness.
Palliative care, initiated in the face of a life-threatening illness, is an interdisci-
plinary collaboration that focuses on patient-defined goals of care and relief of the
patient’s and family’s distress. Given the scope of the palliative care needs that arise
in patients with advanced illness, optimal care requires a unique evaluative approach.
While palliative care used to be seen as care that was provided for people who were
not receiving any active treatment for cancer and were in fact dying of their disease,
the principles of palliative care are equally applicable to early stage, potentially
curable disease, and to the terminal stages of a life-threatening disease. It also
extends to the bereavement period [21] following the patient’s death. Palliative care
can and should be provided alongside disease modifying treatment.
References
1. World Health Organization (WHO) definition of palliative care. http://www.who.int/cancer/

palliative/definition/en. Accessed 7 Jan 2011.
2. Steinhauser KE, Alexander SC, Byock IR, et al. Do preparation and life completion discussions
improve functioning and quality of life in seriously ill patients? Pilot randomized control trial.
J Palliat Med. 2008;11:1234.
3. Barazzetti G, Borreani C, Miccinesi G, Toscani F. What “best practice” could be in Palliative
Care: an analysis of statements on practice and ethics expressed by the main Health
Organizations. BMC Palliat Care. 2010;9:1.
hospital setting: a consensus report from the center to advance palliative care. J Palliat Med.
2011;14(1):17.
5. http://www.fda.gov/SiteIndex/ucm148521.htm. Page last updated 05/04/2010.
6. MacIntyre NR, Cook DJ, Ely Jr EW, Epstein SK, Fink JB, Heffner JE, Hess D, Hubmayer RD,
Scheinhorn DJ, American College of Chest Physicians, American Association for Respiratory
Care, American College of Critical Care Medicine. Evidence-based guidelines for weaning
and discontinuing ventilatory support: a collective task force facilitated by the American
College of Chest Physicians; the American Association for Respiratory Care; and the American
College of Critical Care Medicine. Chest. 2001;120(6 Suppl):375S.
7. Yale New Haven Hospital. Clinical practice manual, care of the patient with a tracheostomy.
Revised 4/2010.
8. Yale New Haven Hospital. Clinical practice manual, endotracheal or tracheostomy suctioning
of the adult. Revised 12/2011.
9. Yale New Haven Hospital. Clinical practice manual, enteral feeding-care of the adult patient.
Revised 1/2012.
10. Vasilevsky C, Gordon P. Gastrointestinal cancers: surgical management. In: Colwell J, Goldberg
M, Carmel J, editors. Fecal and urinary diversions: management principles. St. Louis: Mosby;
2004. p. 126.
11. Güenaga KF, Lustosa SA, Saad SS, et al. Ileostomy or colostomy for temporary decompression
of colorectal anastomosis. Cochrane Database Syst Rev. 2007;(1):CD004647.
12. Erwin-Toth P, Doughty D. Principles and procedures of stomal management. In: Hampton B,
Bryant R, editors. Ostomies and continent diversions: nursing management. St. Louis: Mosby;
1992. p. 29.
13. Colwell J. Principles of stoma management. In: Colwell J, Goldberg M, Carmel J, editors.
Fecal and urinary diversions: management principles. St. Louis: Mosby; 2004. p. 240.
14. Yale New Haven Hospital. Clinical practice manual, colostomy/ileostomy: care of the patient
with a fecal diversion. Revised 5/2009.
15. Demmy TL, Gu L, Burkhalter EM, et al. Comparison of in-dwelling catheters and talc pleur-
odesis in the management of malignant pleural effusions (abstract 9031). J Clin Oncol.
2010;28:643s.
16. Yale New Haven Hospital. Clinical practice manual, care of the patient with a chest tube.
Revised 7/2010.
17. Leclercq C, Cazeau S, Le Breton H, Ritter P, Mabo P, Gras D, Pavin D, Lazarus A, Daubert JC.
Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart
failure. J Am Coll Cardiol. 1998;32(7):1825.
18. Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D, Sun B, Tatooles AJ,
Delgado 3rd RM, Long JW, Wozniak TC, Ghumman W, Farrar DJ, Frazier OH, HeartMate II
Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device.
N Engl J Med. 2009;361(23):2241.
19. Vatta M, Stetson SJ, Perez-Verdia A, Entman ML, Noon GP, Torre-Amione G, Bowles NE,
Towbin JA. Molecular remodelling of dystrophin in patients with end-stage cardiomyopathies
and reversal in patients on assistance-device therapy. Lancet. 2002;359(9310):936.
20. Heyland DK, Dodek P, Rocker G, et al. What matters most in end-of-life care: perceptions of
seriously ill patients and their family members. CMAJ. 2006;174:627.
21. Wright AA, Zhang B, Ray A, et al. Associations between end-of-life discussions, patient mental
health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008;300:1665.
226 P.L. Devaney
Review Questions
1. Palliative care is an interdisciplinary collaboration focusing on patient-defined

goals of care
(a) True
(b) False
2. Hospital palliative care programs are for nonterminal patients and hospice
patients
(a) True
(b) False
3. Of all the symptoms experienced, pain is the most common and most feared
(a) True
(b) False
4. When using opioid analgesia, dosing is prescribed as only when needed
(a) True
(b) False
5. Failure to be weaned from the ventilator leads to:
(a) Lengthy intubation
(b) Be in an intensive care unit
(c) Erosion of the trachea and/or vocal cord injury
6. Esophageal and head and neck patients suffer from:
(a) Anorexia and malnutrition
(b) Oral candida, mucositis
(c) Dehydration
(d) All the above
7. Fecal and urinary diversions are always reversible
(a) True
(b) False
8. Patients who experience acute and chronic heart failure and are refractory to
treatment are considered for left ventricular assist device implantation
(a) True
(b) False
9. Left ventricular assist device patient education must emphasize infection con-
trol and anticoagulation therapy
(a) True
(b) False
10. Recurrent pleural effusions are caused by malignancies
(a) True
(b) False
11. Psychological distress will worsen if the patient is informed about their
advanced disease
(a) True
(b) False
228 P.L. Devaney
Answers
1. (a)
2. (a)
3. (a)
4. (b)
5. (d)
6. (d)
7. (b)
8. (a)
9. (a)
10. (b)
11. (b)
Chapter 14
Drug Formulary
Angèle Ryan
Patients with advanced disease requiring symptom management are frequently

prescribed a complex regimen of therapies that includes pharmacologic agents.
Avoiding the pitfalls of polypharmacy is a universal goal in the practice of medicine.
In palliative medicine this is of vital importance as these patients are already
compromised by the burdens of the disease, without the added complications of
drug adverse effects. To this end, medications should be carefully chosen to achieve
the maximum benefit with minimum use of drugs. A unique application of the term
“portmanteau” has been used in palliative medicine to describe this philosophy of
using medications with multiple effects in order to minimize pharmacologic assault
[1]. This is a French word meaning “a large suitcase” which carries numerous
objects. When applied to pharmacotherapy, this concept suggests an aggressive use
of medications beyond the labeled uses, and exploration of effects typically considered
adverse but potentially beneficial in end of life care. An example is the preferential
use of sedating drugs if insomnia accompanies other symptoms. Rediscovery of
older medications adds to this pharmacological armamentarium. To this end,
practitioners have come to rely on published lists of commonly used medications
that fulfill these requirements. The International Association of Hospice and
Palliative Care (IAHPC) has published a list of essential palliative care drugs based
on the most common symptoms encountered in palliative care (see Table 14.1) as an
incentive for other countries to develop lists based on need and resources [2]. The
World Health Organization (WHO) also includes a section of palliative care drugs
in their model list of essential medicines (see Table 14.2) [3, 4]. An independent
A. Ryan, M.D. (*)

University of Southern California, Los Angeles, CA, USA
e-mail: angel@ix.netcom.com

DOI 10.1007/978-1-4614-5164-8_14,
230 A. Ryan
Table 14.1 Most common symptoms in palliative care according to IAHPC [2]
Pain Dyspnea
Terminal respiratory congestion Dry mouth
Hiccups Anorexia/cachexia
Constipation Diarrhea
Nausea Vomiting
Fatigue Anxiety
Depression Delirium
Insomnia Terminal restlessness
Sweating
Table 14.2 Essential drugs in palliative care [5]

Drug Symptom
Morphinea,b Pain, cough, dyspnea
Fentanyl (transdermal)b Pain
Methadonea,b Pain
Dexamethasonea,b Pain, nausea, cough, dyspnea,
anorexia
Amitriptylinea,b Pain, insomnia, depression
Carbamazepinea,b Pain
Gabapentina Pain, insomnia
Haloperidola,b Delirium, nausea, hiccups
Metoclopamidea,b Nausea, vomiting
Midazolama Anxiety, terminal restlessness
Lactulose Constipation, hepatic
encephalopathy
Acetaminophen Pain, fever
Hyoscaminea (glycopyrrolate in the USA) Nausea, bowel obstruction,
drooling
Sennaa,b Constipation
Diclofenaca Pain
Clonazepam Anxiety, depression, pain,
insomnia, myoclonus
Megestrol acetatea Anorexia, cachexia
Diazepama,b Anxiety, insomnia
Codeinea,b Diarrhea, pain mild to moderate
Nystatin Candida
Tramadola Pain
a
World Health Organization essential medicines [3]
b
International Association of Hospice and Palliative Care list of essential medicines for palliative
care [2]
global survey of international palliative medicine practitioners produced a list of 20

essential drugs [5]. The most common symptoms encountered in advanced disease
have defined these lists. Patients receiving care in the home may also be supplied
with a specific “kit” containing common medications for anticipated symptoms [6, 7].
As novel new agents become available, the pharmacological toolkit continues to
14 Drug Formulary 231
evolve, and lists of the most popular palliative care drugs will grow [1, 8]. A
significant number of the widely beneficial medications are categorized in the
classes of analgesics and adjuvants, antipsychotics, antiemetics, and laxatives paral-
leling the common symptoms treated in palliative medicine. Thus, a collection of
medications that is particularly suitable for the most common symptoms seen in
advanced disease will likely provide a creative medicine bag for treating these
patients.
Medications Used for Analgesia (Opioids and Non-Opioids)
Acetaminophen is a synthetic centrally active non-opioid analgesic, a step one drug

on the WHO stepladder guidelines, commonly available over the counter and indi-
cated for treatment of mild pain and fever. Although it is an antipyretic drug, the
mechanism of action is the inhibition of cyclooxogenase enzyme and formation of
prostaglandins in the central nervous system, therefore does not share the peripheral
anti inflammatory actions of NSAID’s. It has the advantage of lacking the cardiac,
renal, and gastrointestinal untoward effects of the anti-inflammatory drugs. The
onset of analgesia is approximately 11 min after oral administration of acetamino-
phen [9], reaching peak serum concentration in 45–60 min in tablet form, and
30 min after liquid form. Bioavailability after oral administration is 60–85%, but
more variable after rectal administration ranging from 24 to 98% [10] and its half-
life is 1–4 h. Metabolism occurs in the liver, producing mostly inactive compounds
that are excreted by kidneys. One minor but liver toxic intermediate metabolite is
N-acetyl-benzoquinone imine (NAPQI), and is formed by a mechanism mediated
by the cytochrome system. Under normal circumstances, this metabolite is rapidly
conjugated by glutathione to a non-toxic byproduct, and subsequently safely
excreted by the kidneys. Toxicity results when acute administration of acetamino-
phen beyond recommended doses brings about a rapid rate of production of this
metabolite that exceeds the rate of deactivation. This results in accumulation of
NAPQI. Despite common use and benefit of acetaminophen, this drug has gained
attention as a result of this hepatotoxicity.
With appropriate use, however, acetaminophen has an important role for mono-
therapy in treatment of mild pain. For treatment of moderate to severe pain, it pro-
vides synergistic opioid-sparing benefit when combined with the stronger drugs.
Single doses must be limited to less than 1,000 mg every 4–6 h, as it reaches a thera-
peutic ceiling effect at this level in adults. Maximum dose in 24 h is 4,000 mg.
Acetaminophen is a safe drug in appropriate doses and offers an effective alternative
for elderly patients and patients with renal, cardiac, or gastrointestinal disease.
Morphine is the prototype opioid, a hydrophilic alkaloid, originally derived from
the juice of the opium poppy and has been used in medical practice for 200 years
[11]. It exerts its analgesic effect by binding to opioid receptors, most notably m
receptors, in the nervous system and peripheral tissues. This inhibits neurotransmitters
in the pain pathways. Morphine provides effective analgesic in nociceptive pain
232 A. Ryan
Table 14.3 Opioid side effects

Opioid-naïve patient Opioid-tolerant patient
• Nausea and vomiting • Constipation
• Clouding of sensorium, delirium • Nausea and vomiting, with dose escalation
• Respiratory depression • Myoclonus (high doses)
• Pruritis • Urinary retention
• Urinary retention (with neuraxial route) • Xerostomia
• Constipation • Pruritis
conditions that result from injury in peripheral tissues. In recent decades it has been
widely utilized for medical indications to become the gold standard against which
all other opioids are compared. There are many reasons why morphine enjoys this
status. It is effective and well tolerated in most patients, is manufactured in various
sustained release and immediate acting formulations and may be administered via
several routes. This flexibility allows administration via the gastrointestinal tract,
parenterally, and neuroaxial routes. Despite recent developments of newer opioid
preparations, morphine remains the drug of choice when a strong opioid is indi-
cated. Onset of action with immediate acting oral preparations occurs in 30 min,
reaching peak serum concentrations in one. Duration of action is 3–4 h. It is metab-
olized in the liver by glucuronization, forming active metabolites, morphine-3-
glucuronide (M3G) and morphine-6-glucuronide (M6G), which are, in turn, excreted
by the kidneys. The half-life of the M6G metabolite is greater than the parent com-
pound [12, 13] and may result in accumulation in the presence of renal compromise.
Caution is advised when renal insufficiency is present.
In contrast, M3G is not analgesic and is felt to possess neuroexcitatory actions
resulting in adverse effects such as hyperalgesia, myoclonus, and delirium.
Accumulation of toxic metabolites should be suspected in patients receiving high
doses of morphine who exhibit these symptoms.
Morphine, like all opioids, has no organ toxicity. There are, however. physiologic
side effects (see Table 14.3) that include mental clouding, nausea, vomiting, respira-
tory depression, constipation, urinary retention, pruritis, and myoclonus. It is asso-
ciated with histamine release and should be used with caution in asthmatics.
Morphine is available in several formulations of immediate release tablets, liquid,
and rectal suppositories. Coated, sustained release preparations allow convenient
dosing schedules for patients with chronic pain. These tablets may not be crushed
as this breaks the coated seal releasing large boluses of medication into the circula-
tion in a short period of time. A unique dose form of encapsulated pellets allows for
use with percutaneous feeding tubes in patients who are unable to swallow the intact
sustained release pills.
Although analgesic effect is the main feature of morphine, it has a history of
benefit for treatment of dyspnea and is a potent cough suppressor. The constipating
effect of opioids has been exploited historically for treatment of diarrhea.
Unconventional routes are frequently used for control of symptoms. The use of
sublingual morphine is common when patients have limited oral swallowing ability,
but it is likely that absorption is achieved by a slow swallow [14]. Concentrated oral
solution is combined with saliva, and eventually swallowed. Nebulized morphine is
frequently offered for treatment of dyspnea, but evidence is lacking to justify use of
this route over the systemic route. The required apparatus of mask and tubing may
be intrusive and obstructive for the patient, adding little benefit. There is also the
risk of inducing bronchospasm.
With the discovery of peripheral opioid receptors in inflammatory tissue sites,
there has been an interest in the use of topical morphine in ulcers [15].
Fentanyl is a purely synthetic opioid, the result of efforts to develop newer opi-
oids with more favorable profiles, specifically for use in anesthesia and analgesia
during surgical procedures. It is a low molecular weight, high potency lipophilic
agent with short duration of action making it useful as an anesthetic agent. After
intravenous injection, it has an almost immediate onset of action, and duration of
action between 30 and 60 min. This short duration of action and lack of histamine
release provide hemodynamic advantage over morphine, and produces no active
metabolites.
The popularity of this agent in palliative medicine is a result of the development of
the transdermal formulation, a unique skin patch delivery system that allows high-
dose opioids to be administered noninvasively. The low molecular size and the lipo-
philic nature of this drug make this delivery system feasible. The drug is initially
deposited in the skin layer and slowly diffuses to the blood stream approximating a
continuous intravenous infusion. Side effects are similar to those associated with other
opioids. There is some indication that risk of constipation is reduced [16], allowing for
decreased use of laxatives [17]. The disadvantage is the cumbersome timeline that
does not allow for rapid titration during sudden changes in pain levels. Stable steady
state is reached at 48–72 h after initial application or dose change.
This formulation allows high-dose opioid therapy for patients with compromised
gastrointestinal function and allows a lifestyle unencumbered by invasive drug
delivery apparatus. Transdermal formulations are available in 12, 25, 50, 75, and
100 mcg doses.
In intensive care settings, fentanyl is favored for intravenous use over other opi-
oids due to its lack of histamine release and short action, which allows rapid dose
changes in hemodynamically unstable patients. Newer formulations administered
by transbuccal [18], intranasal [19], and nebulized [20] route offer promise as res-
cue medication for patients lacking swallow ability. The rapid absorption and quick
clinical response via these routes provides safe and effective treatment of break-
through pain. The development of the fentanyl iontophoretic transdermal system
(ITS) offers an additional option for patients lacking oral route. This self-contained
patient-activated system delivers a preprogrammed dose on demand similar to an
intravenous patient-controlled analgesia device, using electric current to drive ion-
ized drug molecules across the skin to the circulation [21]. This active transport
system provides a rapid delivery of drug in contrast to the traditional passive trans-
dermal system currently in use.
Methadone is a pure synthetic lipophilic opioid indicated for the treatment of
heroin abuse. It exerts its action in a manner similar to morphine at m-opioid
234 A. Ryan
receptors with the added action of antagonism at NMDA receptors. It is a racemic

mixture of L and D isomers, with l-methadone providing most of the analgesic
effect [22]. Methadone has potency several times that of morphine, no known
toxic metabolites and is readily absorbed via multiple routes with a high oral bio-
availability of approximately 80%. After oral administration, methadone is rap-
idly absorbed, reaching peak plasma concentrations at 2.5–4 h [23]. It is
metabolized by hepatic cytochrome system and elimination is by redistribution
from the blood stream. This creates a whole-body reservoir and accumulation over
time. Along with high degree of protein binding, this makes for an unpredictable
and variable long half-life ranging from 10 to 75 h [24]. Clinically, this translates
to delay in reaching steady state following initial treatment or dose change, and
increased risk of delayed toxicity. Drug interactions are numerous due to the
involvement of the hepatic cytochrome system in metabolism of the drug.
Examples include some selective serotonin reuptake inhibitors, antiviral, and anti-
fungal agents. There are recent concerns regarding the occurrence of cardiac
arrhythmias with use of methadone, as it may cause prolongation of the QT inter-
val, particularly in doses higher than 200 mg daily [23]. Cardiac monitoring is
recommended when prescribing methadone.
Despite the complexities of dosing and titration, methadone has emerged as a viable
option for treating patients who experience a neuropathic component of pain, making
it a cost-effective rising star in the treatment of cancer pain. It is an opioid that provides
long-acting analgesia approximately 6–8 h, without requiring special formulation such
as sustained release morphine or oxycodone. The blockade of the NMDA receptors in
the spinal cord gives this drug the distinguishing feature as a broad-spectrum opioid .
The NMDA receptors are responsible for development of opioid-resistant neuropathic
and is also believed to be involved in development of tolerance.
These features allow noninvasive dosing options in patients who require high-
dose opioids. The potent conversion ratio in highly tolerant patients makes for con-
venient administration of high-level analgesia with use of convenient lower dose
formulation. The longer duration of action is not dependent on specialized coated
formulation, therefore, tablets may be crushed in small amounts of liquid for ease of
swallowing. Rapid onset of action occurs within 30 min after oral route [22].
Sublingual and rectal routes offers additional flexibility as a result of the lipid solu-
bility of this drug [25]. Alternatively, liquid formulation provides the flexibility of
administration via G-tubes. The rapid onset of action also makes it suitable for use
as a rescue medication. The lack of active metabolites makes it an excellent choice
for patients with impaired hepatic and renal function.
The robust opioid agonist coupled with anti-NMDA action that makes this an
effective analgesic in highly opioid-tolerant patients also brings pitfalls. The
action on NMDA receptors and reversal of tolerance result in a significant and
nonlinear conversion ratio when rotating from a different m-receptor agonist.
Skilled prescribing is required when attempting an opioid rotation, particularly in
highly tolerant patients. Conventional conversion tables are based on single doses,
and not reliable when rotating to methadone in an opioid-tolerant individual.
Several methods of rotation have been described [26, 27] with all methods sharing
Table 14.4 Methadone conversion ratios [28]

Pre conversion morphine equivalent daily dose Conversion ratio
Less than 90 mg 5:1
90–300 mg 8:1
300 mg or greater 12:1
the common themes of incremental conversion, conservative ratios, and intervals

of several days between dose escalation. A guide to conversion ratios is suggested
(see Table 14.4) [28]. As with any conversion tables, this is merely a guide for
initial dosing. Ongoing individualized titration according to clinical response will
provide optimal results.
Diclofenac as a representative of the general class of non-steroidal anti-
inflammatory agents (NSAID) is a non-opioid and is indicated for the treatment of
pain, fever, and inflammation. It merits a place on all three steps of the WHO step-
ladder. Like other NSAID’s it exerts its action by nonselective inhibition of the
cyclooxygenase enzymes (COX) that converts arachidonic acid to prostaglandins.
This enzyme consists of two forms, COX-I and COX-II. Effect is on both isoforms
of COX I and COX II.
After oral ingestion it has fast onset of action within 30 min, with approxi-
mately 60% bioavailability, a half-life of 2 h, and long action of approximately
8 h. It is readily absorbed after rectal and intramuscular injection. Metabolism is
by hepatic glucuronidation with subsequent elimination in urine and bile. Daily
oral dose of 75–150 mg has been shown to be well tolerated and effective in acute
and chronic pain conditions, with no dose adjustments needed for the elderly or
patients with renal or hepatic impairment. COX-I is associated with physiologic
regulation of gastrointestinal mucosa, renal perfusion, and platelet function,
whereas COX-II is responsible for formation of inflammatory products. The ther-
apeutic effect is a result of the blockade of COX-II, and adverse effects occur
from disruption of the physiologic benefit conveyed by the COX I isoform on the
target organs. This results in compromise of renal perfusion, gastrointestinal
integrity, and increased bleeding risk. The NSAIDs differ widely in their relative
effect on each COX isoform, which accounts for the variable benefit to risk ratio
that exists within this drug category. Diclofenac appears to have a favorable
COX-II selectivity. It is well tolerated in a wide variety of patients. Patients should
be monitored for dose-dependent adverse effects common to all drugs in this cat-
egory, which include gastrointestinal irritation or bleeding, fluid retention and
cardiac failure, coagulation disorder, and renal toxicity. When an NSAID is
required, the efficacy and favorable side effect profile makes this agent a suitable
first-line therapy or a reasonable alternate option when patient in unable to toler-
ate other NSAIDs [29].
Topical preparations in gel, solution, and transdermal formulations are available
with reduced systemic effects, thus providing additional improvement in the benefits/
burdens ratio [30], targeting specific sites for analgesic action while minimizing the
236 A. Ryan
load on metabolic systems. Adverse effects of topical preparations are generally

limited to localized skin reactions.
Tramadol is a unique synthetic analgesic with the dual actions of opioid and
non-opioid mechanisms and is indicated for the treatment of mild to moderate pain.
It exhibits a weak to moderate affinity for opioid receptors and also acts on the
transmission of noradrenaline and serotonin [31]. It has an oral bioavailability of
75%, is rapidly absorbed, reaching peak serum levels within 2 h. It has a half-life of
6–8 h, producing an active metabolite O-desmethyltramadol (M1), which has a
greater affinity than the parent compound for m opioid receptors and a longer half-
life of about 8 h [32]. Half-life is prolonged in the elderly or in patients with hepatic
or renal impairment [33]. It is metabolized by the cytochrome enzyme system in the
liver and excreted by the kidneys. Dose given is 25–50 mg every 4–6 h with titration
up to a maximum of 400 mg/daily.
The benefit of tramadol is the low incidence of typical opioid side effects on
gastrointestinal function and respiration, and may be considered for patients with
low tolerance to stronger opioids. The action on noradrenaline adds anti-neuropathic
mechanism. The most common adverse effects attributed to tramadol are nausea,
vomiting, dizziness, and sedation.
Tapentadol, a newer agent, is a centrally acting oral analgesic similar to tramadol
sharing the dual action as a weak m agonist and a norepinephrine reuptake inhibitor,
thus exhibiting both opioid and non-opioid analgesia. The potency of tapentadol is
between tramadol and morphine [34] and has a lower risk of gastrointestinal adverse
effects [35]. It is indicated for acute pain of moderate to severe intensity.
Codeine is a weak opioid, used for treatment of pain, cough, and diarrhea.
Although it is a naturally occurring compound, originally isolated from the opium
poppy, it is most commonly a manufactured drug, and one of the most commonly
prescribed opioids worldwide. Most of the activity of codeine is believed to be due
to conversion to morphine, its most active metabolite, by the CYP2D6 enzyme [36].
CYP2D6 function is genetically determined and accounts for variable metabolism
of codeine among individuals, affecting analgesic response. Codeine can be admin-
istered orally, subcutaneously, intramuscularly, and rectally. It is rapidly absorbed
after oral administration reaching peak levels in 1–2 h, providing analgesic onset
after 30–60 min.
In palliative medicine it may be of benefit in patients with mild to moderate pain.
Despite the historical use as an antitussive, validation in controlled studies has been
inconsistent [37], efficacy possibly linked to typically low doses used in most cough
preparations. The constipating effect of codeine is used therapeutically to treat
patients experiencing diarrhea.
Amitriptyline is a tricyclic antidepressant (TCA) drug indicated for the treat-
ment of depression. After oral ingestion, time to peak concentration in serum is
approximately 4 h, with an average half-life of 15 h. The onset of antidepressant
action, however, requires 4–6 weeks. Amitriptyline is metabolized by the liver pro-
ducing the active metabolite of nortriptyline. Excretion is by the kidneys with 18%
of drug excreted unchanged.
It has particular application in palliative medicine in that it is the most studied

antidepressant for the treatment of a wide variety of pain syndromes, specifically
neuropathic conditions such as diabetic neuropathy and post-herpetic neuralgia.
The analgesic benefit is independent of the antidepressant effect [38]. Amitriptyline
exerts action via the inhibition of the reuptake of serotonin and norepinephrine in
the nervous system, with the norepinephrine being responsible for the majority of
the analgesic result, and serotonin playing a lesser role [39]. Side effects are a result
of anticholinergic action, and include dry mouth, sedation, urinary retention, and
cardiac conduction abnormalities. The sedative effect is desirable for patients who
may be sleep deprived as a result of previously unrelieved pain. Initial analgesic
dose of amitriptyline is 10–25 mg orally at bedtime with escalation every 3–5 days.
Antidepressive doses may reach 150 mg daily, but this is rarely necessary for treat-
ment of pain. Parenteral route for intramuscular injection is available but should be
avoided as the use of intramuscular injections is painful. Other TCAs may be con-
sidered if a patient does not tolerate amitriptyline.
Carbamazepine is a first-generation anticonvulsant. It is also used as a mood
stabilizer and has demonstrated proven efficacy for treatment of trigeminal neural-
gia [40, 41]. As with other traditional anticonvulsants, its use has been supplanted
by newer agents that have the advantage of fewer drug interactions, better tolerabil-
ity, and broader spectrum of activity.
Gabapentin is a gamma-aminobutyric acid (GABA) analog, with indications for
treatment of epilepsy and post-herpetic neuralgia. Bioavailability varies with dose,
approximately 80% at lower doses (300 mg daily) and decreasing as low as 27%
with higher doses (3,600 mg daily) [42]. Absorption is relatively slow, and the drug
reaches peak plasma concentrations after 3 h. Elimination half-life is 5–7 h.
Metabolism is negligible and the drug is excreted essentially unchanged in the urine,
thus elimination from circulation is dependent on renal function. The relatively
short half-life requires multiple daily doses. Gabapentin has several mechanisms of
action with resultant increased GABA activity in the central nervous system and
decreased excitation of neurons [43]. The unique mechanisms of action of gabapen-
tin result in multiple uses. Indeed, more than 80% of prescriptions for this agent
initially involved off-label indications such as nonspecific neuropathic pain,
migraine headaches, spasticity, and bipolar disorder [44]. Gabapentin is also rapidly
becoming the first-line therapy for neuropathic pain of numerous origins [45, 46].
Classic studies have demonstrated benefit in the treatment of post-herpetic neural-
gia [47] and diabetic neuropathy [48]. The favorable side effect profile offers an
alternative to the traditional tricyclics and older anticonvulsants. Since it lacks
hepatic metabolism, drug interactions is not a concern, as with the older agents in
this category. The most common side effects of gabapentin are somnolence, fatigue,
dizziness, and weight gain, which generally resolve within the first 2 weeks of ther-
apy. Slow, gradual titration allows identification of optimal dose to achieve analgesia
while minimizing side effects. Dose adjustment is required in patients with renal
compromise.
238 A. Ryan
Medications Used for the Treatment of Symptoms

Other Than Pain
Haloperidol is an dopamine antagonist classified as an antipsychotic and prescribed

for treatment of Schizophrenia/Psychosis, Tourette Syndrome. It has a half-life of
10–20 h, onset in 30–60 min, reaching peak plasma levels at 2–6 h orally, 10–20 min
parenterally. It is extensively metabolized in the liver producing active and inactive
metabolites most significantly a toxic pyridium metabolite. It is believed that this
compound is responsible for the extrapyramidal side effects (EPS) of haloperi-
dol. The intravenous route, however, is associated with fewer EPS even when high
doses are administered [49], presumably due to lack of first-pass metabolism.
There are several applications in palliative medicine. It is a first-line drug in the treat-
ment of delirium, as it is effective, lends itself well to rapid titration, has few anticholin-
ergic, sedative, Autonomic, or hypotensive effects [49]. Doses of 0.5–1 mg hourly can
be given orally, intravenously, intramuscularly, or subcutaneously until symptoms abate.
Generally, doses of 1–10 mg daily are adequate to control symptoms [50], but doses as
high as 240 mg in 24 h have been reported [51] without adverse effect.
The potent antidopamine action also makes this an excellent drug for treatment
of nausea/vomiting, generally in doses of 1–2 mg daily [52]. It plays a role as part
of a classic triad of drugs used for treatment of symptoms associated with inoperable
bowel obstruction [53, 54].
Labeled warnings of prolonged QT interval and risk of torsade de pointes with
the use of intravenous haloperidol suggest that patients require cardiac monitoring
in such a setting. Evidence indicates, however, that in the absence of underlying
cardiac disease, electrolyte abnormalities, or other proarrhythmic drugs, the risk of
this is low when cumulative haloperidol doses less than 2 mg are used [55].
Metaclopramide is a prokinetic antiemetic indicated for symptomatic treatment
of diabetic gastroparesis and gastroesophageal reflux. The mechanism of action is
by the blockade of dopamine receptors. After oral ingestion, absorption is rapid,
producing an onset of action within 30–60 min, therapeutic duration of action is
1–2 h. Half-life is 5–6 h. The usual dose is 10 mg orally or intravenously, typically
given before meals and at bedtime.
In palliative medicine, it holds particular appeal not only as an antiemetic but
also for the positive effect on GI motility, a desired benefit for patients who
frequently receive medications that adversely affect GI motility.
Side effects may include extrapyramidal reactions including akathisia and dystonia.
Caution is advised when using metaclopramide in patients receiving other dopamine
antagonists.
Glycopyrrolate is an quaternary amine with anticholinergic actions and is repre-
sentative of anti-secretory class of drugs. It has the advantage that it does not cross
the blood brain barrier as do the tertiary amines, atropine, and scopolamine.
This agent was initially used for treatment of gastrointestinal disorders, and later
became widely used in the anesthetic setting [56]. The anti-secretory action
provides adjuvant antiemetic benefit in patients requiring multiple agents to control
nausea and vomiting. This action is particularly suitable in management of inoperative

bowel obstruction. In the terminal phase of illness, the drying effect prevents drooling
and spares family members from the distress associated with “death rattle.”
Senna is classified as a contact cathartic, a plant-derived glycoside that passes
through the small intestine unabsorbed and subsequently activated by bacterial
action in the large intestine. Active metabolites are produced that exert mechanical
and secretory action directly on intestinal mucosa to promote bowel activity. The
relatively gentle action of this vegetable-based compound makes it attractive to
many patients. It is a safe first-line therapy, usually in conjunction with a stool soft-
ener or emollient, for regular use for management of constipation.
Lactulose is categorized as an osmotic laxative, a synthetic, non-digestible
disaccharide composed of galactose and fructose. It is indicated for the treatment of
constipation and hepatic encephalopathy. Metabolism occurs in the colon, producing
acidic byproducts. Laxation of bowels occurs as a result of osmotic absorption of
large amounts of water into the bowel, formation of intraluminal gas from fermentation,
and increased peristalsis produced by the acidic environment created. It is this
reduced pH that inhibits ammonia production. The laxative effect also clears ammonia
forming flora in the gut and makes lactulose a viable treatment in hepatic
encephalopathy. Doses of 30–45 ml up to four times daily are generally effective in
promoting gut motility, and may be titrated to effect. Adverse effects include bloating,
cramping, and diarrhea. This agent is generally well tolerated as it does not rely
solely on osmotic action for effect.
Megestrol acetate is a progestational agent, used in the treatment of breast can-
cer. It is well absorbed orally, metabolized in the liver to free steroids and glucuronide
conjugates. Half-life is 13–105 h, time to peak serum levels is 1–3 h. The undesirable
weight gain effect [57] produced by that indication has attracted attention to the
potential use of this drug for treatment of cachexia. This perceived adverse effect
may be used creatively in palliative medicine as a positive benefit. It is considered
one of the most effective appetite stimulants in patients suffering from cancer
anorexia/cachexia syndrome, and associated with weight gain and caloric intake in
patients with some cancers and autoimmune deficiency syndromes [58–61]. The
impact on survival in not clear but if the goal is symptom management, quality of
life, and patient well-being, the effect is satisfactory. An initial dose of 80 mg bid
has been shown to be effective, with increased efficacy with higher doses [62, 63].
Titration to desired effect is suggested in order to obtain maximal clinical result and
minimize side effects.
Dexamethasone is a potent synthetic corticosteroid with potent anti-inflammatory
effects used for multiple indications in curative medicine. This diverse therapeutic
value makes it suitable in palliative medicine as a broad-spectrum drug. It shares the
common side effects of all corticosteroids, but lacks the mineralocorticoid properties
of other adrenal hormones.
In patients with advanced disease, it provides relief from a myriad of symptoms
including inflammatory and neuropathic pain, nausea and vomiting, anorexia, and
fatigue, with improved sense of well-being. Although the adverse effects of
corticosteroids are troublesome, they are not a concern when urgent control of symptoms
240 A. Ryan
takes precedence and life expectancy is short. Beneficial effects are short lived, but
highly effective for the treatment of patients experiencing severe symptoms and
having limited prognosis of less than 1 month.
In patients with less advanced disease, constant vigilance for adverse effects
mandates low doses of corticosteroids and limits usefulness. Short courses of higher
doses up to 16 mg daily are prescribed as temporary measures for emergency treatment
of spinal cord compression, cerebral edema, or superior vena cava syndrome pending
definitive disease-modifying treatments. The comfort level for most practitioners,
however, is to remain with low doses in the range of 4–8 mg dexamethasone, or
equivalent dose of alternate corticosteroid daily [64]. The use of doses in the range
of 16–24 mg of dexamethasone up to four times daily with low incidence of adverse
effects have been reported for terminal patients [65].
Benzodiazepines are a class of drugs with the common pharmacological effects
of anxiolysis, muscle relaxation, sedation, and anticonvulsant. In palliative medi-
cine, they are often indicated for the treatment of anxiety. In general practice, phar-
macology alone is not the optimal treatment for this disorder, and psychotherapy is
the preferred first-line therapy, but when treating distressing symptoms in severely
ill patients, time urgency mandates the early use of pharmacologic intervention. The
time constraints associated with short prognosis may not allow the fine tuning of
medications versus psychotherapy. The standard concerns regarding dependence
with the use of benzodiazepines in curative medicine are less relevant in patients
with limited prognosis, particularly in light of the effectiveness of benzodiazepines
for short-term treatment of acute symptoms. Instead, the cautions are focused on the
immediate side effects of mental clouding and impaired function that may affect
safety and quality of life. Specific characteristics of the individual agents will
dictate their use for the other indications in end of life care. The international list of
essential drugs in palliative care lists two agents in this class.
Midazolam is a short-acting water-soluble benzodiazepine formulated in inject-
able form and used to provide sedation during medical procedures and induction of
anesthesia. It shares the actions of other benzodiazepines of anxiolysis, sedation,
muscle relaxant, and anticonvulsant properties. The cardiovascular stability that it
provides makes it suitable for the intensive care setting. Water solubility allows for
painfree injection and use of subcutaneous route for continuous or intermittent
administration.
The drug provides benefits during use of palliative sedation for treatment of
agitation and restlessness or for the palliation of intractable symptoms. As oral route
is compromised during this state, the intravenous or subcutaneous [66] route is
preferred and is well tolerated. Onset of action is rapid within minutes. Coupled
with the short half-life and absence of any significant metabolites, it is an ideal
agent extended use, but also applicable for titration and short term respite sedation.
It is a useful tool in the home setting empowering family to provide rapid
unconsciousness during urgent and catastrophic events, such as uncontrolled
hemorrhage. A subcutaneous small gauge butterfly needle may be quickly placed to
administer a premeasured dose of medication, stored at room temperature, for
immediate use.
Clonazepam, an anti-epileptic drug used for certain types of seizures, is a benzo-

diazepine. It has been used for a variety of disorders such as panic attacks [67],
anxiety [68], spasticity [69], mania [70], and depression [71]. Clonazepam is rap-
idly absorbed after oral administration with bioavailablity of 90% and peak serum
concentration achieved after 1–4 h. Half-life is approximately 19–60 h [72], estab-
lishing it as a long-acting agent. It is completely metabolized by liver and inactive
metabolites excreted in urine. Doses range from 0.25 to 1 mg twice a day.
As a multipurpose medication, clonazepam plays a role in treating a myriad of
symptoms encountered on a palliative care practice. The antidepressant action is
a bonus for patients who may be treated with this medication for treatment of
anxiety, a common occurrence in patients suffering with advanced disease. The
anxiolytic effect is rapid, a clear advantage in patients with tenuous prognosis,
allowing use as needed [68]. It also offers a long-acting alternative in patients who
require frequent dosing of short-acting agents. In patients receiving high doses of
opioids, accumulation of metabolites may result in myoclonus [73], a condition
that responds to treatment with clonazepam [74]. Since myoclonus is frequently
associated with a high-dose opioid regimen, and high probability of neuropathic
pain, clonazepam will target both symptoms [75–77]. The sedating effect coupled
with the relief of myoclonus provides a dual mechanism for treatment of insom-
nia. An available rapidly dissolving tablet is a benefit for patients with limited
swallowing ability.
Nystatin is a traditional representative of a group of antibiotics, polyenes, used
to prevent and treat a broad spectrum of fungal infections, particularly candidiasis.
Nystatin exerts its antifungal action by binding and compromising the integrity of
ergosterol, a component of cell membranes unique to fungi. Nystatin has the unique
trait of not being absorbed from mucosal tissue, therefore passes through the gastro-
intestinal system unchanged. The direct topical effect on organisms prevents the
spread and development of generalized infections. As parenteral administration is
toxic, treatment is limited to topical application. Coupled with low absorption, this
produces a safe and effective therapy with essentially no systemic adverse effects.
When high doses are ingested orally, gastrointestinal symptoms include anorexia,
nausea, and diarrhea, but these are mild and transient. Oral suspension or tablet is
administered in doses of 0.5–1 million units four times a day.
Candida albicans is a common opportunistic organism in the oral cavity, pres-
ent in 50–60% of humans [78]. Patients on a palliative care service have multiple
risk factors for developing candidiasis including compromised immune status,
malignancy, drug therapies, hyperalimentation, advanced age, and often require
antifungal therapy. Newer systemic antifungal agents in the azole category sug-
gest improvement over the traditional polyenes, but the azoles mechanism of
action on the cytochrome P450 enzymes introduces the additional risk of numer-
ous drug interactions. . In contrast to the azole agents, development of resistance
remains low with nystatin [79, 80]. In balancing risk/benefits, nystatin remains a
readily available option for pre-emptive treatment of candidiasis in severely ill
patients.
242 A. Ryan
New Directions
Depression
Depression is a frequent symptom in advanced disease [81] and antidepressant agents

are frequently prescribed in the practice of palliative medicine. Mirtazepine is a newer
antidepressant with dual noradrenergic and specific serotonergic mechanisms that
enhance norepinephrine and serotonin neurotransmission (NaSSA). This is the result
of presynaptic adrenergic receptors which in turn facilitates serotonergic transmission
by action on adrenoreceptors on serotonergic nerve terminals. Mirazepine has high
affinity for histamine receptors. It is administered orally, with peak levels occurring
after 2 h, with a half-life of approximately 24 h allowing for once daily use. Unlike
first-generation antidepressants such as tricyclics, therapeutic effects may be seen
within 1 week, an advantage in patients with limited prognosis. Metabolism is via
multiple pathways of demethylation, hydroxylation, oxidation, and flucuronidation,
with resultant few drug interactions [82]. Mirazepine lacks the adverse anticholinergic
and cardiac effects of the tricyclic antidepressants and the potential for extrapyramidal
reaction and insomnia associated with the selective serotonin reuptake inhibitors. It is
effective for treating multiple symptoms, including anorexia, nausea, insomnia, anxi-
ety and depression [1]. The listed side effects of mirtazepine of increased appetite,
weight gain, and sedation are embraced as positive effects as is common in the prac-
tice of palliative medicine. Effects vary with dosage. Low doses of 15 mg are sufficient
for desired sedation to treat insomnia. The histamine effect that accounts for this is
negated by increased adrenergic effects at higher doses of 30–45 mg. An orally disin-
tegrating tablet is available for ease of swallowing.
Olanzepine is an atypical antipsychotic indicated for the treatment of
Schizophrenia. It is formulated for oral administration, reaching peak blood levels
within 5–8 h. The long half-life of 27–38 h provides convenient once daily dosing.
It has selectively higher serotonin receptor activity compared to dopamine receptors
and reduced incidence of extrapyramidal symptoms associated with older agents.
The unique binding profile at dopamine, serotonin, achetylcholine, and histamine
receptors also makes it a promising antiemetic for treatment of intractable nausea
[83]. Metabolism by multiple pathways makes for few drug interactions, and no
dose adjustments are required in patients with renal or hepatic compromise. The
side effects of sedation and weight gain, generally considered undesirable, can be
welcome effect in the terminally ill patient with multiple symptoms. Caution should
be exercised when prescribing for patients at risk for seizures as olanzepine reduces
seizure threshold. Initial dose is 2.5–5–10 mg orally daily, and may be increased up
to 20 mg daily. A dissolvable disk formulation allows for ease of ingestion for
patients with difficulty in swallowing.
Despite the higher costs of this agent compared to older medications, the value of this
medication for use in caring for patients with advanced disease lies in the benefit for
multiple symptoms of delirium, nausea, and cachexia [84], with reduced adverse effects.
This drug has also gained attention as a potential tool in pain management [84].
Levorphenol is a synthetic agent with similar action but longer half-life than
morphine. The sustained action was an advantage prior to the introduction of the
coated sustained release opioids. The non-opioid mechanisms that it shares with
methadone make it a potential tool in treatment of cancer pain [85]. In addition to
its affinity for the opioid receptors, it is also an NMDA antagonist and inhibits the
uptake of serotonin and norepinephrine. After oral administration, levorphanol is
absorbed and produces peak plasma concentrations after 1 h, is metabolized by the
liver to produce a glucuronide metabolite with no involvement of cytochrome oxi-
dase enzymes, and excreted by kidneys. Duration of analgesia is 6–15 h. Like meth-
adone, the long half-life requires that several days be allowed to establish steady
state, approximately 72 h [86].
The non-opioid mechanisms of this drug make it a potential tool in the treatment
of neuropathic pain and a logical choice for opioid rotation when standard opioids
fail. Side effects are similar to those of other opioids.
Buprenorphine is a strong opioid with unique classification as a partial m opi-
oid receptor agonist. It also exhibits additional affinity for an opioid receptor-like
(ORL-I) receptor, and antagonism to the kappa and delta receptors. It is adminis-
tered in parenteral, sublingual, and transdermal routes. The oral bioavailability is
low, about 10%, due to first-pass hepatic metabolism, dictating alternative modes
of administration. Since it is a partial agonist, the effect will be reduced when com-
pared to full m receptor and this is believed to account for ceiling effect of analge-
sia. Binding to receptors is slow to dissociate resulting in sustained duration of
action and lower risk of withdrawal symptoms if the drug is discontinued. The drug
is highly protein bound. Sublingual route is currently used for treatment of sub-
stance abuse, and a newer transdermal preparation offers promise for treatment of
pain. The highly potent, highly lipophilic nature, and low molecular weight of this
drug makes it a suitable candidate for transdermal application offering specific
benefit for patients receiving palliative care. This formulation allows for continu-
ous absorption of the drug with effect starting in 12–24 h and reaching steady state
in 24–48 h [87].
The non-opioid mechanisms and unique receptor affinities may result in block-
ade of central sensitization, and suggest a potential as an opioid with additional
anti-neuropathic action [88]. Although this agent duplicates the non-oral and nonin-
vasive advantages of the more widely used fentanyl patch, it adds specific targeting
of the more difficult neuropathic components of pain.
Modafinil is a psychostimulant approved for use in the treatment of narcolepsy.
Non-labeled uses applicable to the palliative care patient include depression [89] and
opioid-induced sedation [90]. Since sedation and fatigue are common complaints
encountered in the practice of palliative medicine, psychostimulants have played a
role in the treatment of these symptoms in patients with advanced disease, not only for
promoting wakefulness and cognitive function, but also as adjuvants for pain manage-
ment [91]. Modafinil represents the new arrival in this category. Although the precise
mechanism of action is unknown, modafinil appears to exert a unique action in the
hypothalamus [92] unlike the other commonly used stimulants such as methylpheni-
date or amphetamine. This selective action on arousal systems is not associated with
244 A. Ryan
adverse effects such as hypertension, appetite suppression, anxiety, or abuse potential

that is typical of older stimulants [90]. Modafinil reaches peak plasma levels approxi-
mately 2–3 h after oral administration, half-life is approximately 10–12 h. It is metab-
olized in the liver and inactive metabolites are excreted in urine. Dose used is typically
200 mg daily given as a single morning dose or divided in two doses in the morning.
There is involvement of the cytochrome system, and thus some drug interactions.
Reported side effects are generally mild, and include headache, nausea, diarrhea,
xerostomia, and nervousness [93]. This agent offers promise as a beneficial tool in the
treatment of multiple symptoms such as fatigue, sedation, and depression with less
adverse effect than the traditional psychostimulants.
Octreotide is a somatostantin analog, a synthetic drug that exerts action by inhib-
iting various hormones in the body. The synthesized drug has a longer duration of
action with a half-life of approximately 1½ h, completely absorbed after subcutane-
ous injection, but also well tolerated via intravenous injections or infusion. It is
indicated for the treatment of excessive hormonal states such as hormone-secreting
tumors. Its use for treatment of acromegaly is due to inhibition of growth hormone.
In the gastrointestinal tract, it inhibits the release of peptides resulting in decrease
peristalsis, splanchnic blood flow, and secretions. This provides effective treatment
for conditions such as gastrointestinal hemorrhage, management of fistulas, and
diarrhea. In oncology practice, its antitumor effect presents a treatment option for
patients for various neuroendocrine hepatic tumors [94, 95]
In palliative care, its use in the symptomatic treatment of inoperable bowel
obstruction has been frequently reported . The actions on the gastrointestinal result
in reduced secretions and peristalsis which quiets colic, pain, and nausea/vomiting,
the usual symptoms of inoperable bowel obstruction [54, 96–99]. Octreotide is typi-
cally administered subcutaneously. About 600–800 mg daily in divided doses is gen-
erally effective [100], although the intravenous route may be used for rapid results.
An intramuscular depot formulation is available for monthly injections, and may be
feasible in the home setting.
More recently, an increased role of octreotide in end of life symptom manage-
ment has been suggested. Many patients with carcinomatosis often present with
severe ascites, causing numerous symptoms of pain, pressure, peripheral edema,
and respiratory compromise. The use of this agent in the treatment of ascites has
been suggested through several postulated mechanism, including enhancement of
diuretic efficacy, direct tumor antisecretory effect, and reduction of splanchnic
blood flow [101]. When consideration is given to the burden of frequent paracente-
sis that are required to alleviate discomfort in the presence of ascites, a trial with
octreotide with aggressive use of diuretics is justified.
Octreotide may be considered in patients who have gastrointestinal fistulas. The
inhibitory action on copious secretions may provide relief from fluid and electolyte
depletions. This mechanism offers benefit in patients suffering from loperamide-
resistant diarrhea, as well [102].
In low doses, the drug is generally well tolerated. Mild transient gastrointestinal
symptoms of abdominal pain, dry mouth, flatulence, and steatorrhea may be
minimized with timing of doses between meals.
Although this is an expensive drug, the effectiveness, low side effect profile, and
multiple uses of this agent make evidently justifies its place in the palliative medi-
cine toolchest.
PRN as Needed Dosing
The prescribing of medications often is accompanied by specific instructions, as

patients rely on the healthcare provider’s expertise to guide him. In the management
of symptoms, this control if often shifted to the patient and care giver, as in the case
of taking medications “as needed.” As the goal of symptom management is comfort,
this is an endpoint that can only be determined by the patient himself, thus the burden
of titration to the desired outcome requires vigilant assessment and judicious medi-
cating. Obstacles to this include fear of medication and ignorance regarding appro-
priate use for a given medication, as in the case of rescue drugs for breakthrough
pain. It is essential that patients and care givers are empowered to self-titrate and
receive education about the value of pharmacologic tools prescribed for comfort and
quality of life, and encouraged to optimize the use of symptom-relieving therapies.
This will allow maximal comfort while reducing the feared side effects.
Routes
In the general patient population, there are few obstacles in taking prescribed medi-
cations as ordered. In the patient receiving palliative care, the availability of oral
route is not routinely guaranteed, and the ongoing quest for alternate routes is fun-
damental in providing drugs for these patients. The astute prescriber continually
assesses for factors that may compromise the oral route, such as disease status, GI
obstruction, or presence of nausea.
Loss of oral route is common in advanced disease. Thus, alternative and creative
methods for administering medications must be considered. In the hospital setting,
parenteral routes are readily available and taken for granted, but in transitioning to
other settings, the least invasive route is most compatible with normal activity and
quality of life. In the desire to maintain noninvasive administration, sublingual route
is often an optimistic route used in patients unable to swallow. There is little evi-
dence to support this practice when using hydrophilic agents such as morphine,
oxycodone, or hydromorphone, but more promising results with use of lipophilic
drugs such as methadone, fentanyl, and possibly buprenorphine [103, 104]. In addi-
tion to offering simplicity of administration and avoiding the more cumbersome
invasive techniques, sublingual route offers the potential advantage over the oral
route of rapid onset and avoiding the first-pass metabolism. Currently transmucosal
formulations for fentanyl are available. Some patients find the exercise of transmu-
cosal administration, such as fentanyl lozenges, unpalatable, and cumbersome
compared to a simple swallow, and may not use these medications appropriately
246 A. Ryan
resulting in diminished results. There are medications that are formulated with
convenient oral dissolving properties such as olanzepine orally disintegrating disk,
ondansetron orally dissolving wafers, and clonazepam disintegrating tablets, but
these features offer ease of swallow and not intended for absorption other than via
oral ingestion. Therefore, it is important to bear in mind that, although noninvasive
routes are preferred, reliability of absorption takes precedence.
Transdermal route has become very accepted and desirable since the advent of
Fentanyl in this formulation. There are other medications that are introduced with
this convenient method. The topical lidocaine patch offers a local anesthetic that is
effective without systemic absorption. Since most anti-neuropathic medications are
limited to oral route, a lidocaine patch offers a unique advantage. NSAID’s as in the
diclofenac patch may also be given transdermally.
Rectal route is an age-old method of providing medication, and provides a
noninvasive advantage over injections. What is generally considered unappealing in
general use, may provide a creative means of treating symptoms when oral or
parenteral routes become difficult. Limited availability of rectal formulations require
inventive use of other formulations, particularly in emergency situations outside of
an acute care setting. Crushing tablets in small amounts of water or use of liquid
formulations provide impromptu medications. Benzodiazepines are a class of
medications that are readily absorbed rectally and provide prompt treatment of
common symptoms that arise in advanced disease such as agitation or seizures.
Absorption is influenced by drug properties, formulation and volume, and rectal
health [105].
Subcutaneous route is frequently used for continuous infusions in the home
setting. Painful intramuscular injections are to be avoided as alternative parenteral
options are available.
It is our goal to utilize the most effective and efficient pharmacologic tools to
treat our patients and provide optimal quality of life with minimal polypharmacy.
The quest for the ideal formulary is a continual process as we make use of time-
tested agents, accept the conventionally defined “side effects” as desired benefit,
and learn from established mechanisms to develop newer agents for the best
treatment of our patients.
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Review Questions
1. Advantages of methadone use in palliative medicine include all the following

except:
(a) High-potency opioid-tolerant patients
(b) Anti-neuropathic mechanism via N-methyl-d-aspartate (NMDA) receptor
antagonism
(c) Short half-life
(d) No active metabolites
(e) Ease of administration
2. Which of the following medications are effectively administered by transmucosal
route:
(a) Olanzepine
(b) Morphine
(c) Fentanyl
(d) Tramadol
(e) Amitriptyline
3. All of the following medications offer benefit for the treatment of neuropathic
pain with the exception of
(a) Gabapentin
(b) Buprenorphine
(c) Carbamazepine
(d) Codeine
(e) Amitriptyline
4. Drug interactions are most likely with which of the following drugs
(a) Acetaminophen
(b) Diclofenac
(c) Gabapentin
(d) Haloperidol
(e) Methadone
5. Which of the following benefits is not provided by octreotide in the care of
terminally ill patients
(a) Reduction of secretions and gut motility in inoperable bowel obstruction
(b) Cost effective
(c) Management of fistulas
(d) Enhancement of diuretic therapy in treatment of ascites
(e) Treatment of diarrhea
252 A. Ryan
Answers
1. (c). A disadvantage of methadone is the prolonged and variable half-life which

limits rapid titration. It remains a viable opioid option for patients who are highly
tolerant or exhibit a neuropathic component of pain. Liquid formulation allows
for creative administration in patients with compromised swallowing.
2. (c). Fentanyl has high lipid solubility making it an excellent choice for transdermal
absorption. Although morphine, in concentrated liquid formulation, is often
placed sublingually for patients with impaired swallowing, it is essentially
swallowed with saliva. Similarly, an orally dissolving olanzepine disk is
formulated for ease of swallowing. Tramadol is rapidly absorbed by oral route.
3. (d). The common classes of medication for treatment of neuropathic pain are
anticonvulsants and antidepressants. Codeine is a weak opioid without
antineuropathic effect. Buprenorphine has unique non-opioid mechanisms of
action suggesting a role in treating neuropathic pain.
4. (e). Methadone is involved in numerous drug interactions as a result of metabolism
via the cytochrome system.
5. (b). Despite the effectiveness of octreotide in symptom management, the cost
remains an impediment to its use.
Chapter 15
Interventional Radiology in Palliative Care
Oliver Hulson, Neal Larkman, and Sreekumar Kunnumpurath
Introduction
Interventional radiological procedures have expanded greatly over the past decade.
What was once a small aspect of clinical care is now available to provide a significant
input in a variety of patients. A number of retractable and troublesome symptoms in
end-of-life care may be improved or abated by procedures. Many of which are performed
under local anaesthetic or sedation. In addition, many of these procedures are performed
percutaneously, through a single, small skin incision, thereby improving recovery
time and reducing hospital stay, imperative at a time when aiming to return a patient
home to rest is paramount [1].
A description of a selection of these procedures follows, along with the indications,
contraindications and a brief description of what the procedure entails. Whilst this
is not an attempt to train the reader in becoming competent at these procedures, it is
hoped that this will aid the palliative care team and the patient in making a fully
informed decision when considering such treatment options.
O. Hulson, M.B.Ch.B. (Hons.) (*) • N. Larkman, M.B.B.S., M.P.H.

Leeds and Bradford Radiology Training Scheme, Leeds General Infirmary,
Leeds, UK
e-mail: ohulson@doctors.org.uk
S. Kunnumpurath, M.B.B.S., M.D., F.F.P.M.R.C.A., F.R.C.A., F.C.A.R.C.S.I.
Department of Anaesthetics, Epsom and St Helier University Hospitals NHS Trust,
Carshalton, Surrey, UK

DOI 10.1007/978-1-4614-5164-8_15,
254 O. Hulson et al.
Angiography
Indications
Even with the advent and advances in CT and MR imaging techniques, conventional
angiography remains an essential adjunct in the assessment and imaging of the
vascular system, and is the basis of many more complex and technically
difficult procedures. The benefits of this technique over others is that, whilst
invasive, it can be both diagnostic and therapeutic, improving blood flow at the
same time as identifying the cause of a critically ischaemic limb.
In the palliative care setting, angiography may be employed in order to treat
symptoms related to the patients’ terminal illness, for example embolisation in
haemoptysis secondary to lung carcinoma, or for a condition independent of
this, such as limb ischaemia. Specific indications such as embolisation and
cerebral angiography will be discussed later in this chapter.
Contraindications
The only truly “absolute” contraindication to angiography is the unstable

patient with multisystem failure [2]. Other relative contraindications are listed
below. Those perhaps most relevant to a palliative patient are highlighted in
bold:
Recent myocardial infarction
• Electrolyte abnormalities
• Impaired renal function (due to the administration of contrast)
• Confused or uncooperative patient (may require general anaesthesia)
• Coagulopathy
• Inability to lie flat on operative table (due to congestive cardiac failure or poor
respiratory reserve)
• Pregnancy
While it may be felt that “pregnancy” is as an absolute contraindication to
exposure to any ionising radiation, in reality if it is felt that harm will come to
the mother by circumventing a study such as a CT or angiography examination,
then the study should not be ruled out [3 ]. Unfortunately, it is a simple fact of
life that if harm should come to the mother, then the risk of harm to the unborn
foetus is likely to be greater than the risk from radiation exposure. In practice,
if and when this scenario arises, a fully informed discussion between the
patient, a consultant radiologist and consultant obstetrician is likely to occur,
and steps taken to reduce the radiation exposure to the foetus.
15 Interventional Radiology in Palliative Care 255
Procedural Method
There are a wide variety of techniques, sheaths and catheters employed by specialist
vascular interventional radiologists, but the basic principles remain largely the
same. This relates to the Seldinger technique employed elsewhere in chest drain or
central line insertion, and involves three steps:
1. Vessel puncture (Fig. 15.1a): Performed under direct vision using anatomical
landmarks or under ultrasound or fluoroscopic guidance. The liberal use of local
anaesthetic agents from skin down to artery will increase patient comfort and
subsequently improve outcome. A “give” will be felt once the cannula passes
through the arterial wall, and pulsatile blood flow will confirm that the needle tip
lies within the lumen of the artery.
2. Guide wire passage (Fig. 15.1b): Once intraluminal access is confirmed, a dila-
tor or small incision adjacent to the puncture site may be needed to ensure smooth
introduction of the guide wire and catheter. A wide variety of guide wires are
available depending on indication and operator preference. The wire is intro-
duced and positioned ready for the insertion of the catheter.
3. Catheter insertion (Fig. 15.1c): Great care is taken when introducing the cath-
eter over the guide wire, to ensure that the guide wire is not advanced into the
artery in its entirety. Again, a variety of catheters are available from a variety of
manufacturers, varying in size, shape and flexibility (see Fig. 15.2). The catheter
and wire are then manipulated along the arterial system to the region of interest
(for example the aortic arch or lower limb vessels). At this point, the wire may
be removed, contrast medium injected and angiography performed, for an instan-
taneous, detailed image of the area in question. If a stenosis or occlusion is found,
intervention may be attempted.
Angioplasty
Angioplasty is the process of mechanically widening the lumen of a vessel, usually

due to a stenosis from atheroma, or an occlusion due to acute thromboembolism.
The interventional options are numerous and outside the scope of this text, but a
brief overview of treatment options is likely to be beneficial when considering such
treatment or caring for the patient post-operatively. In order to succeed in interven-
tion, the blockage or occlusion must first be traversed by the guide wire, which can
be difficult and take time.
Once the occlusion or stenosis has been successfully traversed, a balloon catheter
can be introduced over the wire, to the site of the occlusion, and inflated to reopen
the vessel. The balloon exerts a high pressure upon the vessel wall, stretching the
vessel to an appropriate size. A contrast run is then likely to be performed, to both
assess the degree of remaining stenosis, and also check for distal run-off (a recognised
complication is distal embolisation due to plaque dislodgment).
a
cannula
skin
vessel
b
Guide-wire
catheter
Fig. 15.1 (a) The cannula is introduced percutaneously, into the artery or vein. (b) A guide-wire
is introduced through the cannula and sits within the vessel lumen. (c) The catheter is introduced
over the guide wire into the vessel lumen, through which interventions such as angiography can
take place
If the vessel does not maintain an adequate lumen size post-angioplasty, a stent
may be introduced, aiming to mechanically maintain luminal diameter. However,
introduction of a stent in an artery with relatively sluggish blood flow may precipi-
tate further thrombus formation, and although drug-eluting stents counteract this to
some degree, it may not always be in the patient’s best interest to have a stent
inserted.
Complications
As with any procedure, post-operative complications can occur, and it is useful for
healthcare staff to be aware of such complications, to ensure early detection and resolution.
The Society for Cardiac Angiography and Interventions (SCAI) cite an incidence of
Fig. 15.2 Diagram Shepherd Hook, Cobra, Multipurpose,

showing variety of catheters Renals J Curve Vertebral
available [4]
0.5 % for local vascular complications; these include thrombosis of the punctured vessel,
dissection, retroperitoneal haemorrhage, haematoma, distal embolisation and false
aneurysm formation [4].
Embolisation Procedures
Indications
Deliberate embolisation of a vein or artery may be indicated in a variety of settings,

for instance in the acute setting in uncontrolled bleeding in pelvic or abdominal
trauma, and also electively in the treatment of subfertility by the selective embolisa-
tion of a testicular varicocele [5]. Of relevance in the palliative care setting, selective
chemoembolisation of hepatic metastases or indeed other tumours is a relatively new
venture utilising this technology [6]. Whilst the techniques describing the procedure
have been around for some time, as technology and embolic agents advance and
become more refined, the procedures attempted by the interventional radiologist
become increasingly diverse and complex.
Contraindications
Again however, it is a procedure not without risks, and correct patient choice is fundamental
in achieving a successful outcome. The absolute and relative contraindications of such
a procedure are the same as for angiography discussed previously. In addition, there
are considerations to be made when embarking on such a procedure, to minimise the
chance of a futile intervention, and maximise the chance of success. Patients who are
severely shocked due to presumed intra-abdominal bleeding are unlikely to benefit
from such a procedure, and exploratory laparotomy is often the only option.
Splenic trauma in the relatively stable patient however may be managed in this
way, with selective embolisation of the culprit branch of the splenic artery aiming to
Fig. 15.3 Intravascular coils,

displaying the fibrous,
thrombogenic surface ([1];
reproduced with permission)
contain the bleeding sufficiently to avoid laparotomy and splenectomy [7]. Also, the
treatment of uterine fibroids (or leiomyomata), once the bread and butter of the
gynaecological surgeon’s operating list, has been transformed by selective embolisa-
tion of the vessels supplying these benign tumours [8].
Embolic agents can be mechanical, including “coils” (so-called as they coil in
the target vessel, occluding flow) which are often made of stainless steel or plati-
num, with a fibrous thrombogenic surface (see Fig. 15.3). Particulate or liquid
agents including polyvinyl alcohol (PVA), sclerosants and glues are also available,
and can be either temporary or permanent depending on the indication.
The initial procedure is the same as for angiography and angioplasty discussed
previously, as adequate pre-embolisation angiography is vital in isolating the target
vessel and selecting the appropriate embolic agent. A catheter with a single end-
hole is used to ensure optimum position of the deployed embolic agent, and care is
taken to ensure that the embolic agent is delivered only to the target vessel.
Once successful embolisation has been achieved, close post-procedure monitor-
ing is vital, both for signs of further bleeding, and also infarction or ischaemia of the
target area. Post-embolisation syndrome and tissue necrosis are recognised compli-
cations from such a procedure [7].
Chemoembolisation and Radioembolisation
Two specific embolisation procedures employed in the oncology setting include

chemoembolisation and radioembolisation. These two novel techniques can be utilised
in the treatment of hepatocellular carcinoma (HCC) as a bridging therapy prior to
transplantation [9], and also in the treatment of unresectable liver metastases in
colorectal carcinoma for example [10].
Chemoembolisation, as the name suggests, is a targeted embolisation procedure
as described previously, but in this instance, the target vessel is one supplying the
lesion of interest. Chemotherapeutic agents are first instilled locally, providing loca-
lised, targeted therapy to the lesion, before releasing a traditional embolic agent to
severe the blood supply. Radioembolisation differs in that radioactive beads are
used as the emboli, providing localised radiotherapy whilst again aiming to reduce
blood supply to the lesion.
Points to Consider
Not all embolisation coils are safe to use in magnetic resonance imaging (MRI) and
so if it is known that a patient has undergone an embolisation procedure for a berry
aneurysm following a subarachnoid haemorrhage for example, it is imperative that
the radiologist is informed of this before requesting the examination, and ideally,
the surgical notes for the procedure interrogated to ascertain what material was
used.
Cerebral Angiogram and Coiling for Brain Aneurysms
Indications
Cerebral angiography is most commonly implemented for the investigation of suspected

intracranial aneurysms (in the management of subarachnoid or intracerebral haem-
orrhage for example) or arteriovenous malformations (AVM). It may also be
employed in the investigation of cerebrovascular disease, and in the preoperative
work-up for space-occupying intracranial lesions, but has largely been superseded
in these areas by computed tomography (CT) and magnetic resonance (MR) angiog-
raphy. It is by no means a routine procedure, and usually only performed by a select
number of individual interventional neuroradiologists in a specialist or tertiary-
referral centre.
In the context of palliative care, it is difficult to envisage many scenarios where
such a procedure may be indicated, except perhaps if debulking surgery of a space
occupying lesion were to be considered, or a similar procedure attempted in the
endovascular treatment of impending carotid blowout in patients suffering from

head and neck cancers [11]. It is important to acknowledge that the procedure is not
without its risks, and if such an intervention is to take place, a full and frank discussion
should occur between the patient (and significant others) in order to ensure that they
are fully aware of the potential benefits and risks, and confirm that the treatment is
in harmony with the ethos of good palliative care.
Contraindications
In patients who have recently suffered a stroke or cerebral haemorrhage, time should
be taken to ensure that their neurology has stabilised. Other general contraindica-
tions are the same as that for angiography discussed previously. Discussion with a
specialist interventional neuroradiologist is advised before requesting such a proce-
dure. Local guidelines should also be adhered to regarding anticoagulation, and
appropriate anticoagulant cover initiated whilst drugs such as warfarin are stopped.
Procedural Method
Depending on the indication, the procedure may be performed under mild sedation
or general anaesthesia (with adequate anaesthetic cover). If general anaesthesia is to
be used, local policies regarding preoperative starvation should be adhered to.
A Seldinger percutaneous catheter introduction technique is used, often
puncturing the right common femoral artery. Selective catheterisation of the
internal carotid artery is achieved by advancing the catheter (over a guide-wire)
through the arterial system and into the cerebral circulation. A number of “runs”
are performed when the catheter is in place. Contrast medium is injected into
the catheter under fluoroscopy, while ensuring that the vascular area in question
is adequately interrogated. Digital subtraction angiography (DSA) may be
implemented to provide adequate spatial contrast.
Again depending on the indication, an intervention may be attempted during
the same procedure. For example, the introduction of coils for cerebral aneu-
rysms or a carotid stent deployed in the prevention of carotid blowout dis-
cussed previously. Strict monitoring of the patient post-operatively is mandatory,
to ensure that any complications or sequelae from the procedure (such as distal
embolisation causing cerebral infarct) are identified promptly and dealt with
appropriately.
In cases of coiling following a subarachnoid haemorrhage, “triple-H therapy”
(hypervolaemia, hypertension and haemodilution) may be implemented in an
attempt to reduce the likelihood of cerebral vasospasm (and it is associated
complications), aiming to maintain cerebral perfusion [12]
Tissue Plasminogen Activator in Acute Ischaemic Stroke
Though not strictly an interventional procedure, the use of tPA in the treatment of
ischaemic stroke has gained some ground in recent years, due to a number of high-
profile health promotion campaigns, and the utilisation of early CT imaging to dis-
tinguish between ischaemic and haemorrhagic stroke. A recent review article
concluded that tPA can be effective when administered up to 4.5 h after symptom
onset, but time is key, and early administration of this thrombolytic agent.
Indications
The use of tPA in stroke has been shown to improve clinical outcomes at 3 months
despite the increased incidence of intracerebral haemorrhage [13]. That said, as
touched upon above, time is of the essence; Cronin, for the Journal of Emergency
Medicine concluded that, “the benefits of thrombolysis with tPA outweigh the risks
up to 4.5 h from symptom onset”, but that careful patient selection and strict criteria
should be applied before treatment. Thus the most obvious indications are that the
patient has suffered an ischaemic stroke, and that he/she has presented within the
treatment window. Hospital policy may vary internationally, but the timeframe is
likely to be similar to that discussed above. For UK practice, the National Institute
of Clinical Excellence (NICE) state that tPA should be commenced within 3 h of
symptom onset [14].
Immediate brain imaging is essential, in order to distinguish from haemor-
rhagic and ischaemic stroke, and treatment commenced as soon as possible.
NICE also stipulate that treatment should only be initiated in those centres where
there are staff trained in delivering thrombolysis and in monitoring for any asso-
ciated complications; and immediate access to imaging and re-imaging is
essential.
Contraindications
The narrow timeframe for patient presentation is currently the major limiting fac-
tor in the initiation of thrombolysis in acute ischaemic stroke, and an area in which
health promotion is aiming to improve public awareness. Haemorrhagic stroke is
also another absolute contraindication, and necessitates the utilisation of immedi-
ate brain imaging.
Other contraindications stated by Boehringher Ingelheim (the manufacturers
of Actilyse, the fibrinolytic agent licensed for use in the UK for the treatment of
stroke) are listed below. Those that may have increased relevance to the palliative
patient are highlighted in bold:
• Major surgery within 14 days of the stroke

• Haemorrhagic diathesis
• The use of oral anticoagulants
• Documented ulcerative gastrointestinal disease during the last 3 months
• Oesophageal varices
• Neoplasm with increased bleeding risk
• Severe liver disease, including hepatic failure, cirrhosis, portal hypertension and
active hepatitis
• Major surgery or significant trauma in past 3 months
• Platelet count <100,000/mm3
• Systolic blood pressure greater than 185 or diastolic greater than 110 mmHg (or
aggressive management necessary to reduce BP to these limits)
• Blood glucose <50 or >400 mg/dl
Procedural Method
Once the diagnosis of an acute ischaemic stroke has been made, haemorrhage has
been ruled out and the patient is within the appropriate time window, the tPA dose
is calculated. For Actilyse (used within the UK), the dose is weight related and thus
is calculated individually. Part of the dose is often given as initial intravenous bolus,
with the remainder infused over a set time period. Monitoring by nursing staff
trained in the usage of thrombolysis is vital, as the commonest side-effect is an
increased risk of bleeding. Reimaging may be necessary if the patient’s neurology
progresses at any point during or after treatment, as this may suggest the
development of concurrent intracerebral haemorrhage.
Intra-arterial Thrombolysis
Indications
Intra-arterial thrombolysis (IAT) is indicated in acute or acute-on-chronic limb ischaemia,

or in thrombosis or embolisation following an interventional or surgical procedure (for
example an occluded bypass graft). The degree of critical limb ischaemia is important,
and often dictates both initial and subsequent management. Table 15.1 outlines the
categorisation of an acute ischaemic episode, along with clinical signs and brief
management.
A recent review article in the European Journal of Vascular and Endovascular
Surgery surveyed 22 of the 24 UK centres who contribute to the “Thrombolysis
Study Group” and generated some interesting trends [16 ] . A decline in the use
of IAT was seen in 19/22 centres, with no centres reporting in an increased
use. The main reasons cited for this decline were due to the concern regarding
possible complications (including major haemorrhage) and regarding the
efficacy of the treatment. Related to the above categorisation, the study found
that the most popular use of AIT in limb ischaemia was in category I—no
sensory loss.
In everyday practice, IAT is likely to be considered as a useful adjunct to
either surgical or angioplasty intervention, and management choice is likely to
be formed between radiologist, clinician and surgeon on an individual case
basis.
Contraindications
As suggested in the above review article, IAT is not without risk, and appears to
be the co-contributor to its demise. The contraindications are the same as that
for thrombolysis in stroke and PE discussed previously.
Procedural Method
Once diagnosis of acute, reversible, critical limb ischaemia has been made and
confirmed by appropriate imaging, the decision for IAT, surgery or endovascular
intervention needs to be addressed. As stated previously, this often a multidisci-
plinary discussion, taking into account the patient’s comorbidities, clinical
condition and site of the occlusion for example. If it is agreed that IAT is the
most appropriate treatment option, a single arterial puncture is ideal (as mul-
tiple puncture sites increase the risk of bleeding complications). Arterial puncture
close to the site of occlusion is best, and puncture directly into a graft itself
may even be indicated. The catheter used to deliver the thrombolytic agent is
introduced and embedded in the thrombus, in order to maximise efficacy.
Unfractionated heparin may be infused concomitantly to reduce the risk of
catheter-site thrombosis. The exact infusion regimen will depend on operator
and centre preference, but angiography is often carried out at regular intervals
and the catheter tip repositioned as necessary.
Peri-procedural monitoring must take place in a dedicated vascular or high
dependency unit, as the risk of bleeding complications has been quoted as high
as 10 %. Regular arterial site checks and observations including blood pressure
and urine output are required, and interval assessment of the threatened limb,
to ensure resolution of the thrombus.
264
Table 15.1 Assessment of limb viability and subsequent management

Category Description Capillary return Muscle paralysis Sensory loss Arterial Doppler signal Venous Doppler signal
I Viable Not immediately Intact None None + +
threatened
IIa Threatened Salvageable if Intact/slow None Partial – +
treatment
commenced
promptly
IIb Threatened Salvageable if Slow/absent Partial Partial – +
treatment
commenced
immediately
III Irreversible Amputation Absent Complete Complete – –
regardless of
treatment
(Adapted from the Consensus report on thrombolysis, J Intern Med, 1996 [15])
O. Hulson et al.
Thrombolysis in Venous Thromboembolism
Indications
Intravenous thrombolysis may be considered in the treatment of pulmonary emboli

(PE) and associated deep vein thrombosis (DVT), which are often referred to under
the umbrella term of “venous thromboembolism” (VTE). The most recent guidelines
from the British Thoracic Society (BTS) date back to 2003; NICE guidelines on the
treatment of VTE are awaited.
The BTS guidelines state that thrombolysis is indicated as first line treatment in
“massive PE” (defined as one severe enough to cause circulatory collapse) diag-
nosed on computed tomographic pulmonary angiography (CTPA) or transthoracic
echocardiography (TTE). However, the guidelines do state that alteplase can be
administered on clinical grounds alone if it is felt that cardiac arrest is imminent
[17].
In non-massive PE, the guidance becomes more limited, and there is a relative
paucity of convincing data in favour of thrombolysis. A study undertaken in the
USA in 2002 found that there was no survival advantage in those patients with “sub-massive
PE” given thrombolysis compared to a control group [18]. The risk of haemorrhage is
stated to be twice that with heparin; the consensus view is that thrombolysis should
be reserved for those patients described above [19].
As for thrombolysis in stroke, treatment protocols may vary between centres.
The BTS guidelines state that in the case of impending arrest, a 50 mg intravenous
bolus of alteplase can be given. This is likely to be followed by an intravenous infusion,
either of tPA or unfractionated heparin. The contraindications for thrombolysis in
VTE is as described previously, and again, staff trained to look after patients receiving
thrombolytic agents is vital, to monitor for complications associated with
bleeding.
Inferior Vena Cava filters
Inferior vena cava (IVC) filters are an alternative treatment option in venous
thromboembolic disease, in cases where anticoagulation therapy is contraindicated
or has failed, or as a temporary device whilst anticoagulant therapy is ceased to
allow a procedure to be undertaken. It is likely therefore that the palliative care
team may come across such a patient, as both contraindications to anticoagulant
or thrombolytic therapy are more common in this patient subgroup, and the
increased thrombogenicity seen in patients with malignancy may increase the risk
of recurrent venous thromboembolism. The filter may either be permanent or
temporary depending on the indication, but filter thrombosis is a serious and recognised
side-effect; figures vary but have been quoted as high as 10 % within 5 years, and
so this must be considered if survival is expected beyond this.
Procedural Method
An internal jugular vein puncture is commonly used for access to the IVC. Once the
catheter has traversed the venous into the IVC, angiography is performed to assess the
size, patency and confirm position of the renal veins. Once this has been imaged and
necessary measurements recorded, placement of the filter can be decided by the
radiologist. It is preferable to place the filter below the renal veins, aiming to spare
these should filter become thrombosed at a later date. Once placement is decided,
the filter can be deployed, and further angiography may be indicated to ensure sta-
bility and patency. Ideally the patient will receive concurrent anticoagulation to
minimise the risk of filter thrombosis.
Temporary filters can be retrieved within two weeks of placement, beyond this the
filter begins to embed in the vein wall. Specialist retrieval devices are often manufac-
tured by the company providing the filter, and the retrieval procedure often involves
a jugular or femoral puncture (depending on insertion) and manipulating the filter
into a sheath before removal.
Tunnelled Central Venous Access
Peripherally introduced central catheters (PICC or PIC lines) or tunnelled central venous
catheters (CVCs) are utilised when long-term intravenous access is desirable for the
patient, for example for chemotherapy or total parenteral nutrition (TPN). Hospitals
increasingly provide a nurse or anaesthetist led “PICC service” but this may also be the
remit of the radiology department. Advantages of placement under radiological guidance
are in the accurate positioning afforded to the patient, hopefully minimising complica-
tions due to incorrect siting. A variety of lines are available depending on the indication,
including Hickman and Groshong to name two, and it is important to know what line the
patient has, as it may have a bearing on which lumen is used for medication infusion (in
the case of multi-lumen catheters) and also in the removal of the line.
Asepsis is mandatory, as septicaemia secondary to an infected central line can have
devastating consequences for a patient who may already be immunocompromised due
to chemotherapeutic agents or associated comorbidity. An article published in Cancer
cited the incidence of catheter-related infection as 18 % in a cohort of 71 patients with
cancer and a tunnelled CVC in situ [20]. This perhaps gives greater credence to the inser-
tion of such lines in an arguable cleaner environment such as the operating theatre or the
radiology interventional suite, as opposed to insertion at the patient’s bedside on a ward.
Procedural Method
The major steps in the insertion of any tunnelled CVCs are venous puncture, subcutaneous tun-
nelling and finally line positioning and securing; the order of the first two steps may vary
depending on which device is being inserted. Venous access is nowadays likely to be
achieved under ultrasound guidance, into the right internal jugular vein (IJV), although
the left IJV and subclavian veins can also be used. Whilst it is possible to successfully
cannulate these vessels using anatomical reference points, the risk of inadvertent arterial
puncture is reduced with the implementation of ultrasound [21].
Once venous access has been confirmed, a small skin incision is often made to
aid in the insertion of initially one or two dilators, to create a sufficient hole in the
vessel wall through which to introduce the catheter. Subcutaneous tunnelling can
then be commenced, with a tunnelling device usually included in the procedural
pack. A subcutaneous passage should be made with relative ease, and a considered
chosen exit site for the device is important to ensure ease of use and comfort the
patient.
Finally, the line is introduced over a guide wire, with the tip advanced under
fluoroscopic guidance to lie adjacent to the right atrium within the superior vena cava
(SVC). The line is then sutured in place, and, depending on manufacturer, may have a
locking device in place to secure the line whilst fibrosis around the cuff takes place.
Possible post-procedural complications include inadvertent arterial puncture
(hopefully recognised at the time of the procedure), pneumothorax (necessitating
the requesting of a post-procedure chest radiograph both to exclude this, and to
confirm line position), infection as discussed previously, and line thrombosis. For
this reason, regular line flushes with saline or heparinised saline may be indicated.
Percutaneous Vertebroplasty and Kyphoplasty
Percutaneous vertebroplasty and kyphoplasty are both bone augmentation techniques

that involve inserting a small amount of cement into a collapsed vertebral body.
The first percutaneous vertebroplasty were conducted in France in the early 1980s.
The aim of this percutaneous treatment is to obtain an analgesic effect by vertebral stabi-
lisation in patients complaining of back pain related to lesions weakening the spine [22].
Percutaneous kyphoplasty was first used in America in the early 1990s. It differs from
vertebroplasty as it uses an inflatable balloon prior to cement insertion with the idea of restor-
ing vertebral body height and reducing kyphotic deformity as well as relieving pain.
The superiority of each technique has been debated and whilst both do restore
vertebral height, kyphoplasty has been shown to increase it more but does cost
significantly more [23].
Non-blinded studies into both techniques have demonstrated better pain control
compared to medication[24, 25]. However a blinded study showed no significant
difference in pain improvement when comparing bone augmentation to sham proce-
dure control groups [26].
The indications for vertebroplasty and kyphoplasty are for treatment of
painful vertebral compression fractures secondary to osteoporosis or osteolytic
tumour infiltration that are refractory to conservative management.
The absolute contraindications include active infection within the bone,
uncontrolled bleeding disorders and unstable fractures involving the posterior
cortex of the vertebral body.
Both procedures use an aseptic technique and a local anaesthetic for analge-
sia and pre-procedural antibiotic cover. A spinal surgeon is required on standby
in case of any complication requiring surgical intervention. Depending on the
vertebrae involved a transpedicular or anterolateral approach is used for inser-
tion of varying gauge biopsy needles. The position of the needle and introduc-
tion of cement is monitored under fluoroscopic or CT guidance to ensure
correct placement and to avoid excessive cement migration.
Kyphoplasty differs as a balloon catheter is introduced and inflated to improve
vertebral height. It is then deflated and the cement is introduced. The bone
cement used in both techniques is methylmethacrylate based.
Complications include infection, neurological problems such as loss of
sensation in the lower limbs, no improvement or worsening of pain and a
risk of venous thromboembolism secondary to cement entering the local
venous system.
Coeliac Plexus and Superior Hypogastric Plexus Blocks
The coeliac plexus consists mainly of two coeliac ganglia connected by a

large network of fi bres that include pre-ganglionic and post-ganglionic sym-
pathetic fi bres, pre-ganglionic parasympathetic fi bres and visceral afferent
fi bres. It is located around the origins of the coeliac artery. It innervates
much of the upper abdomen including the pancreas, stomach, liver, gallblad-
der and bowel proximal to the transverse colon.
The Superior hypogastric plexus is similarly a network of mainly sympa-
thetic nerve fibres but is located around the bifurcation of the aorta. It inner-
vates the lower abdominal and pelvic organs such as the descending colon,
rectum and male and female reproductive organs [27].
Indication
If pain from organs innervated by these plexuses is not being controlled

by conventional analgesia then these interventions have been shown to be
effective in stopping pain or reducing pain and the amount of opiate anal-
gesia required [ 27 ] . Its use is not limited to cancer related pain, for example
coeliac plexus blocks can be used for chronic pancreatitis. Its ef fi cacy
depends on the ability to adequately access the plexus which may be pre-
vented by scar tissue, fi brosis or tumour in fi ltration even with good
procedural technique.
Procedural Method
There are both anterior and posterior approaches used to block the coeliac plexus.
No one approach is superior to the other in effectiveness but they have different
merits. One or two needles (depending on technique) are inserted under radiological
guidance in the region of the coeliac plexus.
Several posterior approaches under fluoroscopic guidance exist. These require
the patient to lie prone. The needles in the retrocrural approach remain behind the
diaphragms whilst the needles in the transcrural approach goes through the dia-
phragm. In the trans-aortic approach one needle passes through the aorta and the
splanchnic approach is one vertebra higher at T12 and targets the splanchnic
nerves.
The anterior approaches use ultrasound or CT guidance. These approaches are
useful for patients who could not tolerate lying prone. In can be done relatively
rapidly and has less chance of neurologic complications [28].
As with a coeliac plexus block, several approaches exist for the superior
hypogastric plexus block, with the classical approach again being a bilateral
posterolateral approach (and anterior approaches using CT guidance also
possible).
When the needles are in position a diagnostic blockade using a local anaesthetic
block can be performed; however in up to 28 % of cases this will not correlate with
the effect of a neurolytic agent [29]. The neurolytic agent is an alcohol or phenol
based solution.
Contraindications
The relative contraindications include uncontrolled bleeding disorders, infections,

large aortic aneurysms, severe atherosclerotic disease and invasion of the tumour
into anterior body wall as nerve supply is different.
Complications
For coeliac plexus blocks, complications include back pain, orthostatic hypotension and
transient diarrhoea secondary to the loss of sympathetic innervation to the bowel and
vascular supply. The approach used relates to the side effects experienced [30]. Other
complications include retroperitoneal haemorrhage, abdominal aortic dissection due to
direct trauma to the aorta, paraplegia and transient motor paralysis.
The complications for a hypogastric block include back pain, bleeding, haema-
toma and renal or ureteric puncture.
Biliary Interventions
Percutaneous cholecystostomy is indicated as management of both acalculous and cal-

culous acute cholecystitis. It can be used as a definitive or temporary measure if a patient
is expected to improve sufficiently for elective surgery. The decision to use it as a
definitive or temporary measure will depend on a patient’s response and multi-disciplin-
ary clinical discussion. It can also be used as an access to the biliary tract; however, it is
not the preferred method.
With regard to palliative care, this treatment may be considered in empyema of
the gallbladder that has not responded to antibiotics and where biliary duct stenting
has not improved the clinical picture [31]. Coagulopathy is a relative contraindica-
tion and should be corrected or improved prior to the procedure.
Procedural Method
Prior to the procedure, antibiotic cover and duration should be considered. Under
fluoroscopic and ultrasound guidance the gallbladder is punctured and a catheter
inserted via a transhepatic or transperitoneal approach using a trocar-needle catheter
or Seldinger technique. If fluoroscopy is used, contrast can be injected to confirm
position. The cholecystostomy catheter has to be left in to allow tract maturation
and reduce the risk of bile leakage into the peritoneum. The time it is left in will
vary and the tract may be injected with contrast under fluoroscopy to check tract
maturation prior to catheter removal
The major complications of the procedure include peritonitis and abscess (2.9 %) ,
sepsis (2.5 %), bleeding (2.2 %), transgression of adjacent structures (1.6 %) and death
(2.5 %) [32]. A later complication can be the displacement of the catheter.
Biliary Catheter insertion
Under the auspices of biliary catheter insertion are several procedures. A percutaneous
transhepatic cholangiography (PTC) is performed first and is indicated as a way of
demonstrating the level of obstruction in a dilated biliary tract. The PTC is rarely
used just for diagnostic purposes and is usually followed by a therapeutic intervention
such as balloon dilatation of benign strictures, stent insertion for malignant strictures and
drains for infected systems or difficult to pass strictures.
Contraindications
Coagulopathy is a relative contraindication for biliary interventional procedures and

should be corrected or improved prior to the procedure. Local guidelines should be
consulted and adhered to. Biliary tract sepsis is a relative contraindication but in
some cases may be the indication for the procedure.
Procedural Method
Prior to the procedure, antibiotic cover and duration should be considered, again in
line with local guidelines. Using ultrasound and fluoroscopic guidance, local anaes-
thesia and an aseptic technique, a chiba needle is inserted into the left or right lobe
of the liver. Contrast medium is injected to assess whether the needle is correctly
sited, and images outlining the biliary tree are taken.
At this point the needle can be removed, or if an intervention is to be conducted
then a guide wire is introduced, followed by a sheath through which catheters and
stents can be introduced over the wire. Post-procedural care includes monitoring the
patient for 6 h, antibiotics and regularly flushing of the external drains.
The complications of PTC include a 2 % risk of sepsis, cholangitis, bile leak,
haemorrhage or pneumothorax. The major complications of a therapeutic interven-
tion include a 2.5 % risk of sepsis or haemorrhage, 1.2 % risk of infection or
inflammation (abscess, peritonitis, cholecystitis or pancreatitis) and a 1.7 % mortal-
ity rate [32].
Percutaneous Gastrostomy
Gastrostomy can be performed surgically, endoscopically or radiologically. The two

percutaneous procedures were introduced in the last 30 years and the endoscopic
technique is the commonest method used today. Radiological inserted gastrostomy
has comparable mortality and morbidity rates to endoscopic insertion [33, 34]. In
the palliative setting its main advantage is that it can be done with minimal sedation
compared to endoscopic or surgical gastrostomy, however a smaller calibre tube is
inserted.
It is indicated, as with the other direct enteral methods, in patients who will be requiring
enteral feeding for a prolonged period and particularly in patients unable to undergo an
endoscopic procedure. The decision should be made using a multi-disciplinary approach.
Contraindications
Uncontrolled coagulopathy is an absolute contraindication to the procedure. Difficult

approaches due to a high lying stomach or colon overlying the anterior stomach
wall are also contraindications if no safe approach is found. Other relative contrain-
dications include gastric varices and neoplasm.
Procedural Method
The patient should be fasted prior to the procedure for 6 h if possible. Prophylactic
antibiotic coverage is not usually necessary unless patients are immunocompro-
mised. There are several catheter types available including loop, balloon and mush-
room catheters. They have differing benefits and limitations and should be chosen
based on patient and physician requirements. The catheters are inserted by either a
push (Sacks–Vine) or pull (Ponsky–Gauderer) technique. In radiological gastros-
tomy the push technique is more commonly used but the pull technique can be
performed. Gastropexy, where the stomach is fastened to the anterior abdominal
wall, can be used particularly in patients with ascites [35].
Complications
The major complications of gastrostomy include peritonitis, haemorrhage and

external catheter leaks. Nursing staff caring for and using PEG tubes in patients
should be trained to be aware of the signs of any of these complications.
Transjugular Intrahepatic Portosystemic Shunt

for End Stage Liver Diseases
A Transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneously

inserted stent between the portal and systemic venous systems within the liver.
The aim of the stent is to reduce the complications associated with portal
hypertension. It allows the abnormally high pressure within the portal system
to decrease by shunting blood directly from the portal veins into the hepatic
veins.
Indications for TIPS include variceal haemorrhage refractory to other medical
treatment, refractory ascites, portal hypertensive gastropathy, Budd–Chiari syn-
drome and hepatic hydrothorax [36].
Contraindications
Contraindications include uncontrolled coagulopathy, elevated heart pressures,

heart failure, unrelieved biliary obstruction, extensive metastatic or primary hepatic
malignancy, rapidly progressive liver failure, sepsis, severe hepatic encephalopathy
and polycystic liver disease.
Procedural Method
Prophylactic antibiotic cover should be considered prior to the procedure. A catheter is

inserted via the jugular vein into the hepatic veins and a hepatic venogram is performed.
Under fluoroscopic guidance a long curved needle is passed from the hepatic vein
through the liver into an intrahepatic portal vein; measures of the portal and systemic
pressures are taken, the passage is balloon dilated and a stent is passed. The reduction of
the portal:systemic gradient is assessed and the stent is dilated as required.
Complications
Important complications to be aware of include encephalopathy (which is common and

usually transient and medically manageable through can be severe and contribute to death
in some cases). Other major complications include shunt occlusion, haemoperitoneum
(0.5 %), gallbladder puncture (1 %), haemobilia (2 %), hepatic infarction (1 %) and hepatic
artery injury (1 %), renal failure, accelerated liver failure and cardiac failure [36].
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http://www.ncbi.nlm.nih.gov/pubmed/9762985.
36. Haskal ZJ, Martin L, Cardella JF, Cole PE, Drooz A, Grassi CJ, Mccowan TC, et al. Quality
improvement guidelines for transjugular intrahepatic portosystemic shunts. J Vasc Interv
Radiol. 2003;14(9 Pt 2):S265–70. doi:10.1097/01.RVI.0000094596.83406.19.
Review Questions
1. Absolute contraindications to interventional procedures include:

(a) Pregnancy
(b) Renal impairment
(c) Coagulopathy
(d) Significant haemodynamic instability
2. Regarding percutaneous interventional procedures:
(a) The Seldinger technique is rarely utilised
(b) Complications include retroperitoneal haematoma, pseudoaneurysm forma-
tion and vessel thrombosis
(c) Angioplasty is the process of inserting a stent into a vessel to maintain
luminal diameter
(d) The usual order to gain vascular access is vessel puncture, catheter insertion,
guide wire insertion
3. Regarding specific interventional procedures:
(a) Chemoembolisation and radioembolisation are new procedures that can
only be utilised in the treatment of unresectable liver metastases
(b) Cerebral angiography is a relatively risk-free procedure that is available in
most district general hospitals
(c) Computed tomography (CT) and magnetic resonance (MR) angiography
are useful alternatives to conventional cerebral angiography
(d) Triple-A therapy is often implemented in the management of patients who
have suffered a subarachnoid haemorrhage (SAH)
4. Regarding specific procedures:
(a) In ischaemic stroke, the benefits of tissue plasminogen activator (tPA)
outweigh the risks for up to 4½ h following symptom onset
(b) If ischaemic stroke is suspected out-of-hours, tPA should be commenced as
soon as possible, and imaging undertaken the following working day
(c) In stage III ischaemia, intra-arterial thrombolysis, amputation of the affected limb
may be prevented if intra-arterial thrombolysis (IAT) is commenced promptly
(d) It is desirable that peripherally inserted central catheters (PICC) lines are inserted
on the ward by appropriately trained staff, to avoid any patient disruption
5. Regarding specific interventional procedures:
(a) Potential complications in vertebroplasty and kyphoplasty include infec-
tion, neurological sequelae and worsening of pain and/or symptoms
(b) Percutaneous cholecystostomy is indicated as the first-line treatment in the
management of the empyema of the gallbladder
(c) Radiological inserted gastrostomy is advantageous in comparison to surgical
and endoscopic methods as a larger tube can be inserted
(d) TIPS procedure in the treatment of portal hypertension involves diverting
the portal venous blood to the adjacent hepatic artery
Answers
1. (d) is true. Whilst pregnancy, renal impairment and coagulopathy may all discourage
the radiologist from undertaking the procedure, if it is felt that the potential
benefits outweigh the risks, it may be undertaken. In reality, the only truly “abso-
lute” contraindication is haemodynamic instability such that the procedure cannot
be undertaken without further patient compromise. A full and frank discussion
should take place between the clinical team, the consultant radiologist and the
patient and his or her family.
2. (b) is true. The usual order of vascular access is vessel puncture, guide wire
insertion, catheter insertion. Angioplasty is the process of “ballooning” a vessel
lumen open, which may then proceed to stent insertion to maintain luminal diam-
eter. The Seldinger technique is standard procedure.
3. (c) is true. Chemoembolisation and radioembolisation are a possible treatment
option in the management of hepatocellular carcinoma (HCC). Cerebral angiog-
raphy is a procedure with significant risk attached, including stroke and death,
and is provided only in specialist centres. Triple-H therapy (hypervolaemia,
hypertension, and haemodilution) is implemented in the management of patients
with SAH.
4. (a) is true. Out-of-hours imaging is now available in the vast majority of hospitals,
and if stroke is suspected, CT imaging should be organised as soon as possible.
Stage III ischaemia, is by definition, irreversible, and amputation is inevitable.
PICC lines or tunnelled central venous catheters (CVCs) can be inserted on the
ward by trained staff, but insertion in a dedicated theatre or imaging suite is advan-
tageous as sterility can be ensured, and image-guidance available.
5. (a) is true. Percutaneous cholecystostomy is indicated when antibiotic treatment
has failed in the management of empyema of the gallbladder. Radiological
inserted gastrostomy is advantageous as it may be done under light sedation, but
the disadvantage is that a smaller tube is employed. Transjugular intrahepatic
portosystemic shunt (TIPS) procedure involves diverting the portal venous blood
to the adjacent hepatic venous system, to treat associated portal hypertension.
Chapter 16
Stroke, Epilepsy, and Neurological Diseases
María Gudín
Palliative care addresses the physical and psychological aspects of end of life. The
World Health Organization defines palliative care as: “an approach that improves
quality of life of patients and their families facing the problem associated with life-
threatening illness, through the prevention and relief of sufferings by means of early
identification and impeccable assessment and treatment of pain and other problems,
physical, psychosocial, and spiritual. Palliative care: provides relief either for pain
and other distressing symptoms; affirms life and regards dying as a normal process;
intends neither to hasten nor to postpone death; integrates the psychosocial and
spiritual aspects of patient care; offers a support system to help patient live as active
as possible until death; offers a system to help the family cope during the patient
illness and in their own bereavement, counseling, if indicated; will enhance quality
of life, and may also positively influence the course of the illness; is applicable early
in the course of the illness, in conjunction with other therapies that are intended to
prolong life, such as chemotherapy and radiation therapy and includes those inves-
tigations needed to better understand and manage distressing clinical complica-
tions” [1].
Even though palliative care was developed around terminal cancer care, nowa-
days palliative care principles are applicable to neurology illnesses. Given the
chronic course of the neurological life-threatening diseases, some authors support
incorporing palliative care in neurology in early stages of the disease. Current opin-
ion in neurology is to integrate palliative aid before the final stage of neurological
disease (i.e., approximately the final 2 week of life) [2].
M. Gudín, Ph.D. (*)

Neurology Department, Ciudad Real General University Hospital,
Ciudad Real, Castilla–La Mancha, Spain
e-mail: mariagudinrm@gmail.com; mgudin@sescam.jccm.es

DOI 10.1007/978-1-4614-5164-8_16,
280 M. Gudín
Stroke
Neurologist care for many patients who die because cerebrovascular disease is the
third leading cause of death in the USA [3]. The incidence of stroke continues to
rise [4] despite prevention strategies such as blood pressure control, treatment on
atrial fibrillation, smoking dishabituation, weight control, instituting a modest exercise
regimen [5], and aggressive treatment with thrombolytic agents [6, 7]. Stroke results
in high levels of mortality and morbidity, yet very little is known about the nature
and extent of palliative care services that are available to this patient group, and the
ways in which such services could be delivered. A critical review of the interna-
tional literature found only seven papers that attempted to identify the palliative care
needs of patients diagnosed with stroke [8]. The results of the review showed that
the preferences of stroke patients and their families in relation to palliative care
services are largely unknown. The review also indicated the paucity of data in regard
to the distinction between provision of palliative care services for patients who die
in the acute phase of stroke and for those patients who die later. Establishing reliable
assessments of need are central to designing and implementing effective interven-
tions and further research is required in this area. Further data on how the input of
palliative care experts and expertise could be of benefit to patients, and the most
effective ways these inputs could be targeted and delivered are required.
After the acute initial period in which the patient may die [9], stroke patients tend
to be chronically ill patients that need multidisciplinary support. In this sense, for
most stroke patients, palliative care is not related to end-of-life support, but it refers
to the measures that reduce disability and impairment. Most treatment techniques
focus on disability reduction, patients must learn new strategies to solve common
problems of daily life.
The particular combination of impairments increases disability and reduces the
possibility to reach independence [10].
Initial Attention of Stroke: Medical Care
First weeks after acute stroke, altered cognition and sensorimotor function contrib-
utes to distorted communication, immobility, pain, and depression.
Nutritional Needs and Access
Initially care must focus on the vegetative needs of the stroke patient; particularly
on feeding and excretional function. The patient must receive adequate nutritional,
fluids, and airways projection. Following stroke, the swallowing reflex is altered.
Oral feeding must begin as soon as the patient has recovered this reflex. If oral
intake seems to be dangerous, or ineffective, the nutrition can be delivered by tube
16 Stroke, Epilepsy, and Neurological Diseases 281
feeding. Nasogastric tube feeding must be replaced by gastrostomy within 2 weeks.

In order to implant the gastrostomy tube, the severity of stroke and the potential
duration of tube feeding must be taken in consideration. Percutaneous endoscopic
gastrostomy is a minimally invasive gastrostomy method with low morbidity and
mortality rates, and is easy to follow-up and to replace when blockage occurs [11].
Although it is necessary to indicate other factors, such as the physical status to
establish better rehabilitation networks, clinical assessment of swallowing in acute
stroke is very important to determine whether the patients can go home directly or
not [12].
Urinary incontinence following acute stroke is common, affecting between 40
and 60 % of people in hospital after a stroke. Bladder dysfunction is provoked
because the lesion interferes with the detrusor reflex. Conservative interventions
(e.g., bladder training, pelvic floor muscle training, and prompted voiding) are very
important to prevent urine retentions, and infections [13]. An integrated qualitative
evaluation must be conducted to ameliorate stroke survival. It has been confirmed
that post-stroke urinary incontinence is a predictor of greater mortality at 1 week, 6
months, and 12 months after stroke. However, patients who regain normal bladder
control in the first week have a comparable prognosis as the patients who do not
have micturition disturbances following stroke [14].
Care of Common Complications of Stroke
Venous Thrombosis
Neurological disorders are often associated with immobilization, thus placing

patients at increased risk for venous thromboembolism (VTE) and pulmonary
thromboembolism. This risk is very high in patients with acute ischemic stroke.
Nearly 10 % of post-stroke deaths are due to pulmonary embolism [15]. The benefit
of prophylactic strategies remains in discussion. After a comprehensive and system-
atic review of the literature, a panel of experts formulated recommendations for the
prevention of VTE in stroke and other neurological diseases. Patients with acute
ischemic stroke should routinely receive pharmacological prophylaxis to be started
within 48 h and continued for approximately 14 days; patients with acute hemor-
rhagic stroke should routinely receive mechanical prophylaxis, pharmacological
prophylaxis should be considered once the patient is stable; patients with neuromus-
cular degenerative diseases and with other major risk factors for venous thrombosis
should be considered for the administration of pharmacological or mechanical pro-
phylaxis [16].
Pressure Sores
The motor deficit leads to immobility and a constantly stressed skin tends to breakdown.
The stroke patient frequently suffers urinary incontinence. Once skin breakdown occurs,
282 M. Gudín
pressure, friction, and maceration related to incontinence must be prevented

with appropriate measures. In some cases plastic surgery may be required. To
help prevent pressure ulcers in stroke patient is important that healthcare providers
assess activity, moisture, nutrition, friction, and shearing, as well as psychological
assessment for depression [17].
Shoulder-Hand Syndrome
The hemiparetic stroke patient is most susceptible to shoulder trauma. To avoid

shoulder damage, the caregiver must have notions of how to move the patients
in bed or how to change patient from the chair wheel to other position. The
shoulder-hand syndrome (SHS) occurs in 20–30 % of patients despite optimal
rehabilitation programs [18].
The onset and severity of SHS appears to be related with the etiology of the
stroke, the severity and recovery of motor deficit, spasticity and sensory distur-
bances [19]. Based on systematic analysis of the literature, the following con-
clusions seem justified (1) the shoulder is involved in only half of the cases
with painful swelling of wrist and hand, suggesting a “wrist-hand syndrome”
between simple hand edema and SHS; (2) hand edema is not lymph edema; (3)
SHS usually coincides with increased arterial blood flow; (4) trauma causes
aseptic joint inflammations in SHS; (5) no specific treatment has yet proven its
advantage over other physical methods for reducing hand edema; and (6) oral
corticosteroids are the most effective treatment for SHS [20].
Palliative Care of Stroke Patients: Reduce Disability

and Impairment
There is evidence to support rehabilitation in well coordinated multidisci-

plinary stroke units or through provision of early supported provision of dis-
charge teams. Potentially beneficial treatment options for motor recovery of
the arm include constraint-induced movement therapy and robotics. Promising
interventions that could be beneficial to improve aspects of gait include fitness
training, high-intensity therapy, and repetitive-task training. Repetitive-task
training might also improve transfer functions. Occupational therapy can
improve activities of daily living; however, information about the clinical effect
of various strategies of cognitive rehabilitation and strategies for aphasia and
dysarthria is scarce. Several large trials of rehabilitation practice and of novel
therapies (e.g., stem-cell therapy, repetitive transcranial magnetic stimulation,
virtual reality, robotic therapies, and drug augmentation) are underway to
inform future practice.
Language and Perceptual Impairment
In general, improvement in auditory comprehension is significantly better than

improvement in language [21]. There is no standard therapy for aphasia, but actually
the notion that more practice leads to more improvement is widely extended and provides
good results. Some reports suggest that specific speech therapy program is only mod-
estly better than sustained conversation or stimulation by trained nurses [22, 23].
The main conclusion of this review is that speech and language therapy treatment
for people with aphasia after a stroke has not been shown either to be clearly effec-
tive or clearly ineffective within a RCT. Decisions about the management of patients
must therefore be based on other forms of evidence. Further research is required to
find out if effectiveness of speech and language therapy for aphasic patients is effec-
tive. If researchers choose to do a trial, this must be large enough to have adequate
statistical power, and be clearly reported [24].
This study was repeated in 2010, the authors found out some evidence that aphasia
treatment may be beneficial for patients [25].
Disturbances in visual perception show a prompt recovery from left neglect, anosognosia,
prosopagnosia and unilateral neglect. When the neglect also includes hemianopia,
hemiparesis, motor impersistence, or extinction recovery is slowed. Patients with exec-
utive problems, such as constructional apraxia and dressing apraxia, have only moder-
ate recovery [26]. There is no consensus about what type of therapy may be developed
for recovery of these functions [27].
Sensorimotor Training
Cortical plasticity underlies post-stroke motor recovery of the impaired extremity.

Motor skill learning in neurologically intact individuals is thought to involve the
primary motor cortex, and the majority of studies in the animal literature have stud-
ied changes in the primary sensorimotor cortex with motor rehabilitation. Whether
changes in engagement in the sensorimotor cortex occur in humans after stroke cur-
rently is an area of much interest. Twenty-eight studies investigating upper extrem-
ity neural representations (e.g., TMS, fMRI, PET, or SPECT) were identified and 13
met inclusion criteria as upper extremity intervention training studies [28]. The
results of this meta-analysis indicate that neural changes in the sensorimotor cortex
of the damaged hemisphere accompany functional paretic upper extremity motor
gains achieved with targeted rehabilitation interventions.
Patients exposed to more training decreased impairment and in some studies also
reduced disability [29–31]. Some investigators have employed neuromuscular stimulation
[32], and transcranial magnetic stimulation to improve recovery [33]. Robotic devices
have been designed to enhance sensorimotor training. Robotic rehabilitation tech-
niques have emerged to provide a repetitive, activity-based therapy at potentially
lower cost than conventional methods. Many patients exhibit intrinsic resistance to
hand extension in the form of spasticity and/or hypertonia. A robotic device that is capable
of compensating for tone to assist patients in opening the paretic hand [34, 35].
284 M. Gudín
Spasticity
Over the weeks flaccidity in paralyzed limbs is replaced by enhanced reflex responses
and increased muscle tone to passive and active movements.
Spasticity treatment must be considered in relation to other impairments with
functional goals defined prior to intervention. The effects of muscle co-contraction
and involuntary limb movement associated with exaggerated cutaneous reflexes or
efforts as well as stretch reflex hyperexcitability need to be considered. Exacerbating
factors such as pain must be identified. Physical therapy and conventional orthoses
are the mainstays of spasticity management during acute rehabilitation. Botulinum
toxin shows promise but needs further evaluation in the context of acute rehabilitation.
Phenol chemodenervation can produce good results in spasticity refractory to stan-
dard treatments. Muscle strengthening exercises may be appropriate in chronic
hemiparesis without adversely affecting tone. Electrical stimulation may be a useful
adjunct to other spasticity treatments [36].
Depression
Depression is a common mental health problem in palliative medicine, but it is

poorly understood, sometimes it is underdiagnosed, and not properly treated [37].
Post-stroke depression is difficult to quantify due to methodologic differences in
studies, but the prevalence appears to range from 17 to 61 % [38]. Stroke severity,
physical disability, and cognitive impairment have been consistently associated
with depression after stroke [39].
The theory that depression is more commonly associated with left than with right
hemisphere strokes and with lesions of the left anterior brain than with other regions
[40] is not supported by the data. In a systematic review of 48 studies, the relative risk
of depression after a left versus right hemisphere stroke was 0.95 (95 % CI 0.83–1.10)
[41]. Similarly, the risk of depression after a left anterior lesion compared with all other
brain lesions was 1.17 (0.87–1.62). Restriction of the analyses to reports from high-
quality studies or major depressive disorder did not substantially change the results.
Depression at 3 months is correlated with a poor outcome at 1 year, although causation
cannot be inferred from this [38]. Nonetheless, when patients are matched for initial functional
outcome, remission of depression is associated with a better functional outcome at 3 and 6
months than continued depression [42, 70]. There appears to be a relationship between depres-
sion and 12 and 24 months mortality, but confounders likely exist [43].
At the end of the chapter, it will review the possibilities of treatment.
Epilepsy
Patients with epilepsy whose seizures do not successfully respond to antiepileptic

drug (AED) therapy are considered to have drug-resistant epilepsy (DRE). This
condition is also referred to as intractable, medically refractory, or pharmacoresis-
tant epilepsy. As many as 20–40 % of patients with epilepsy are likely to have
refractory epilepsy [44].
Individuals with DRE have an increased mortality rate: community-based studies
and reports from more selected epilepsy populations consistently reveal persons with
epilepsy to have a mortality rate two to three times that of the general population [45].
The higher mortality is partly related to the underlying disorder causing epilepsy
rather than a direct consequence of the seizures. For example, mortality in cerebrovas-
cular diseases is increased, deaths due to neoplasms, and in particular brain tumors are
also increased among patients with epilepsy. But, other causes directly related to epi-
lepsy are also important: accidents, status epilepticus, and sudden unexpected death
(SUD). The risk of SUD is closely related to seizure frequency, being 40 times higher
in patients who continue to have seizures than in those who are seizure-free. In this
sense, individuals who become seizure free have no increased mortality [46].
Palliative Treatment
When a patient does not respond to medical or conventional surgical treatment,

there are some options of palliative care; such as non-conventional surgical
treatments, ketogenic diet, and vagus nerve stimulation.
Other Surgical Palliative Treatment
Hemispherectomy, corpus callosotomy, multiple subpial transections are sometimes

employed for palliative treatment in children and sometimes adults with catastrophic
epilepsy syndromes.
Hemispherectomy
Hemispherectomy is performed in children whose seizures are associated with a

disease that diffusely affects one cerebral hemisphere. The largest reported series of
pediatric hemispherectomy evaluated the post-operative outcomes of 115 children
with different pathologic substrates for seizures, including 16 children with hemi-
megalencephaly, 39 with hemispheric cortical dysplasia, 21 with Rasmussen
encephalitis, 27 with infarct/ischemia, and 12 classified as other/miscellaneous [47]
. The median age at surgery was 3.5 years.
The results of this study support early surgical intervention in children who have
severe refractory seizures. A shorter seizure duration before surgery was associated
with a better outcome regardless of the underlying pathology [48]. The post-surgical
developmental gains reported in these and other hemispherectomy studies are gen-
erally modest, but development is often limited by severe preexisting brain damage
that may involve the non-operated hemisphere [49].
286 M. Gudín
Corpus Callosotomy
In a corpus callosotomy, the fibers of the corpus callosum are surgically divided.
Typically, an anterior two-thirds callosotomy is performed first, with completion
of the callosotomy done only if seizures persist after the first procedure. The only
seizure type that has clearly been shown to benefit from this surgery is atonic
seizures, which are most commonly seen in epileptic encephalopathies such as
Lennox-Gastaut syndrome [50]. However, many reports suggest that a substan-
tive reduction in generalized tonic–clonic seizures and other seizure types can
result after corpus callosotomy, and that improvements in behavior, IQ, and over-
all quality of life are also possible [51].
Multiple Subpial Transections
Multiple subpial transection (MST) is a surgical technique mainly used when epi-
leptiform activity arises from eloquent or functional brain cortex. Neuroanatomic
studies show that the basic functional cortical unit is arranged vertically, and epilep-
tic activity spreads horizontally. Minimal cortical unit is essential for maintenance
of cortical activity. Vertical incisions in the cortex interrupt transverse synaptic con-
nections, preventing seizure propagation while preserving the vertical column sub-
serving neuronal function. In the past, it has been difficult to assess the efficacy of
MSTs per se, as they have usually been performed together with cortical resection
or lesionectomy. After MSTs, studies show that 33–46 % of treated children are in
Engel class I or II [52]. The permanent complication rate is low with no permanent
language or motor disabilities.
Vagus Nerve Stimulation
Ketogenic Diet
The ketogenic diet (high-fat, low protein) diet has demonstrated efficacy in children
with IE, with more than one-third experiencing a 50 % or greater reduction in
seizures
In two small case series of adult patients, the traditional ketogenic diet and a
modified Atkins diet reduced seizure frequency by 50 % or more in half of the
patients with DRE [55, 56].
Palliative Care in Terminal Stage of Other Neurological Disease
More than 15 years ago, the American Academy of Neurology has declared that
neurologist have a duty to provide adequate palliative care of their terminal patients
instead of assisted suicide or active euthanasia and avoid the euthanasia practice
[57, 58]. In the Netherlands in 1996 the euthanasia rate for Amyotrophic Lateral
Sclerosis was 4.1 % [59], 6 years later in the same country Veldink and coworkers
published the proportion of euthanasia in a cohort of ALS patient was 17 %, 3 % of
the patients in that study died as a result of physician-assisted suicide. An additional
48 patients (24 %) received palliative treatment, which probably shortened their
lives [60].
Neurological disease at terminal stage shows a high rate both of euthanasia and
medical-assisted suicide. In palliative care management of a disease is management
of symptoms, independently of the diagnosis. Subsequently, this article will focus
on the symptoms of neurological disease that may be ameliorated by palliative care
in terminal sate.
General Aspects
Communication
The firs aspect to deal with is how to communicate an awful diagnosis to a

patient. Patient and health care system benefits when clinicians engage in end-
of-life conversations with patients diagnosed with life-limiting illnesses, yet
most clinicians focus on life-preserving treatments and avoid conversations
about end-of-life care. It is not ready to standardize the way to communicate
such news; each case should be individualized. The diagnosis must be revealed
to the patient and relatives gradually. All questions must be answered honestly
but always avoiding provoking a hopelessness state on the patient.
Advance Care Planning
The Patient Self Determination Act of 1990 mandates healthcare providers to

speak with patients about end-of-life preferences and advance directives.
Individuals from differing ethnic backgrounds are likely to turn to their traditional
norms of practice when ill or treatment choices must be made. Healthcare pro-
vider must be aware of cultural differences in the current era of increased global-
ization. Education on cultural differences and how to lead discussions promotes
advance care planning. Initiating conversations about advance care planning can
be facilitated by using open-ended questions that respect the values and beliefs of
various cultures [61].
Depending on diagnosis many future situations may be foreseeing and dis-
cussed. Aspects such as refusal of terminal intubation in ALS patients should be
spoken. The conversations with patients and family must be noted in medical
records. It is very important to designate proxy decision makers to guide medi-
cal care after a patient has become incompetent [62].
288 M. Gudín
Routes of Drug Administration
The most useful route in palliative care is the oral route [63]. Intravenous routes
reduce the mobility of patient and are a source of infections [64]. Since most
patients will develop difficulty in swallowing alternative routes may be rectal
or subcutaneous. Parenteral routes—in necessary—may be sublingual or intra-
venous but using a syringe driver to avoid multiple injections.
Management of Symptoms
Dyspnea
Dyspnea is a common symptom experienced by many patients with neurologi-

cal disease, above all the ones that affect muscle strength and contraction
(myopathies, motorneurone disease, and polyneuropathies). Its significance is
amplified due to its impact on family and caregivers.
The antidyspneic medication must ameliorate the respiratory awareness, but pre-
serving the ventilatory drive. A respiratory rate of 15–20/min must be attempted.
Opioids in modest doses have been demonstrated to give effective relief of dyspnea,
whether or not identifiable reversible causes exist [65]. A dose of 5 mg diazepam
has a positive effect on improving sleep duration without worsening nocturnal
hypoxemia [66]. Medical management of dyspnea can be directed at the underlying
cause when the potential benefits outweigh the burdens of such treatment. In rare
cases where symptomatic treatment is unable to control dyspnea to the patient’s
satisfaction, sedation is an effective, ethical option.
Death Rattle
Noisy breathing (death rattle) occurs in 23–92 % of people who are dying. The
cause of death rattle remains unproven but is presumed to be due to an accumu-
lation of secretions in the airways. It is therefore managed physically (reposi-
tioning and clearing the upper airways of fluid with a mechanical sucker) or
pharmacologically (with anticholinergic drugs) [67]. Anticholinergic stop the
production of new secretions, there are no significant differences in effective-
ness or survival time among atropine, hyoscine butylbromide, and scopolamine
in the treatment of death rattle [68].
But it is important to aspirate secretions in order to avoid the noise that
sometimes must be associated to patient perceived dyspnea.
Terminal Restlessness
Dying patients frequently experience that, which is known as terminal restlessness,

this phenomenon must be accurately diagnosed as myoclonus, delirium, or pure
motor restlessness. There are treatable causes of restlessness such as pain, a dis-
tended bladder or rectum, cerebral anoxia or dyspnea, a paradoxical reaction to
benzodiazepines, or a response to anticholinergic drugs [69].
Findings suggest the need for comprehensive treatment plans to meet the special
supportive and information needs of these families, specific supportive strategies for
the professional caregivers and further studies to develop ethical criteria and evi-
dence-based guidelines for the use of sedation in the management of terminal rest-
lessness [70].
Delirium
Delirium is a common neuropsychiatric complication experienced by patients

with advanced illness, occurring in up to 85 % of patients in the last weeks of
life. Although some studies have identified agitation as a central feature of
delirium in 13–46 % of patients, other studies have found up to 80 % of patients
near the end of life develop a hypoactive, non-agitated delirium. Both the agi-
tated (hyperactive) and non-agitated (hypoactive) forms of delirium are associ-
ated with increased morbidity in patients who are terminally ill, causing distress
for patients, family members, and staff. Delirium is a sign of significant physi-
ological disturbance, usually involving multiple causes, including infection,
organ failure, and medication adverse effects. Often these causes of delirium are
not reversible in the dying patient, and this influences the outcomes of its man-
agement. Delirium can also significantly interfere with the recognition and con-
trol of other physical and psychological symptoms, such as pain. Unfortunately,
delirium is often misdiagnosed or unrecognized and thus inappropriately treated
or untreated in terminally ill patients. To manage delirium in terminally ill
patients, clinicians must be able to diagnose it accurately, undertake appropriate
assessment of underlying causes, and understand the benefits and risks of the
available pharmacological and no pharmacological interventions [71].
Standard management of delirium requires an investigation of the etiologies,
correction of the contributing factors, and management of symptoms.
Symptomatic and supportive therapies, including numerous pharmacologic
approaches, are important, but several aspects of the use of neuroleptics and
other agents in the management of delirium in the dying patient remain contro-
versial [72].
Starting treatment with neuroleptics may lead to extrapyramidal movement disor-
der, seizures, and drop in blood pressure. Symptomatic treatment of these con-
ditions may be provided, using antiepileptic drugs, saline fluids, and
anticholinergic drugs.
Drowsiness
Depending on the underlying pathology some patient will lose consciousness long
before death while other remains lucid until the end. Fainsinger and coworkers in a huge
290 M. Gudín
cohort find out that the level of consciousness by the day of death was alert (2 %),
drowsy (41 %), unresponsive (57 %) [73].
There are many causes of drowsiness in terminal neurologic patients: raise in
intracranial pressure, seizures, hypoxia, infections, drug side effects, etc. The drug
regimen must be reorganized and treatable causes must be looked for.
Epileptic Seizures
Epilepsy in terminal stages of neurological diseases is a frequent condition, and

must be considered if a sudden change in the level of consciousness occurs. EEG
must be performed and often is the only way to diagnose a non-convulsive status
epilepticus. If the patient presents a generalized tonic–clonic seizure 10 mg of diaz-
epam, immediate therapy consists of diazepam 10 mg rectally or midazolam 10 mg
parenterally. Sometimes antiepileptic drug medication with phenytoin or valproic
acid intravenously must begin.
Refractory status epilepticus (RSE) is defined as status epilepticus that continues
despite treatment with benzodiazepines and one antiepileptic drug. Focal RSE with-
out impairment of consciousness might initially be approached conservatively; con-
versely, early induction of pharmacological coma is advisable in generalized
convulsive forms of the disorder. At this stage, midazolam, propofol, or barbiturates
are the most commonly used drugs. Several other treatments, such as additional
anaesthetics, other antiepileptic or immunomodulatory compounds, or non-pharma-
cological approaches (e.g., electroconvulsive treatment or hypothermia), have been
used in protracted RSE [74].
Myoclonus
In terminal stage it is very frequent myoclonic movements, the causes for terminal
myoclonus include hypoxia, hypoglycemia, and secondary effects of drugs; such as
opioids and anticholinergic agents or terminal multiorganic failure. Pirazetam, clon-
azepam, and valproic acid are election treatment in terminal myoclonus in which a
treatable cause has been excluded.
Pain
Pain occurs less frequently in end stage of neurological disease than in cancer.
Nevertheless, chronic pain is a frequent component of many neurological disorders,
affecting 20–40 % of patients for many primary neurological diseases. Neurological
pain results from a wide range of pathophysiologies including traumatic injury to
the central nervous system, neurodegeneration, and neuroinflammation. Whether
pain originates in the central or peripheral nervous system, it frequently becomes
centralized through maladaptive responses within the central nervous system that
can profoundly alter brain systems and thereby behavior (e.g., depression). The
treatment of pain in neurological patients is greatly complicated by the lack of
objective measures; often it is sometimes difficult to obtain even a subjective evalu-
ation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer’s
disease [75].
Opioids are commonly prescribed for chronic non-cancer pain and may be effec-
tive for short-term pain relief. However, long-term effectiveness of 6 months or
longer is variable with evidence ranging from moderate for transdermal fentanyl
and sustained-release morphine to limited for oxycodone and indeterminate for
hydrocodone and methadone [76].
In terminal stages of neurological diseases it is frequent to find altered states of
consciousness. Patients with stuporous or comatose pose a huge dilemma in diagno-
sis and treatment of pain, in this state pain is misdiagnosed in 43 % of cases, in this
terminal stage is very difficult to determinate whether a patient is experiencing pain
and suffering [77].
Different therapies applied to treat neurological chronic pain [78, 79] are also
used to treat pain associated to neurological diseases. The most notably successful
are the anti-epilepsy drugs, but antidepressants, membrane stabilizers, and opioids
have also been used to treat chronic pain, with varying levels of success.
Headache due to raised intracranial pressure is a frequent symptom in terminal
neurological patients. Corticoid therapy is well known to treat elevated pressure
due to brain trauma [80] or metastasis [81]; but, glucocorticoids are not consid-
ered to be useful in the management of cerebral infarction or intracranial
hemorrhage.
Nausea and Vomiting
Nausea, the unpleasant sensation of being about to vomit, can occur alone or can
accompany vomiting (the forceful expulsion of gastric contents), dyspepsia, or other
gastrointestinal symptoms [82].
Nausea and vomiting are mediated primarily by visceral stimulation through
dopamine and serotonin, by vestibular and central nervous system causes
through histamine and acetylcholine, and by chemoreceptor triggers zone stim-
ulation through dopamine and serotonin. Treatment is directed at these path-
ways. Antihistamines and anticholinergic agents are most effective in patients
with nausea resulting from vestibular and central nervous system causes [83].
Depression
Diagnosing and treating depression in terminally ill patients involve unique chal-
lenges. Evidence of hopelessness, helplessness, worthlessness, guilt, and suicidal
ideation are better indicators of depression in this context than neurovegetative
symptoms.
292 M. Gudín
Depression is highly correlated with a reduced quality of life, greater difficulty

in managing the course of the patient’s illness, decreased adherence to treatment,
and earlier admission to inpatient or hospice care [84]. Depression also impairs the
patient’s capacity for pleasure, meaning, connection, and doing the emotional work
of separating and saying goodbye; it amplifies pain and other symptoms, and causes
anguish and worry in family members and friends [85].
Although terminally ill patients often have suicidal thoughts, they are usually
fleeting [86]. Sustained suicidal ideation should prompt a comprehensive evalua-
tion. Clinicians should have a low threshold for treating depression in terminally ill
patients. Psychostimulants, because of their rapid onset of action, are useful agents
and are generally well tolerated. Selective serotonin reuptake inhibitors and tricy-
clic antidepressants may also be used. Psychological interventions—including elic-
iting concerns and conveying the potential for connection, meaning, reconciliation,
and closure in the dying process—can also facilitate coping.
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296 M. Gudín
Review Questions
1. Current opinion in neurology is to integrate palliative aid before the final stage of
neurological disease. Please, mark the correct answer:
(a) The last 6 months
(b) The last 2 weeks
(c) The last hours
(d) When a permanent deficit is established that will short the patient life
2. Initially care of stroke must focus on:
(a) Feeding
(b) Excretional function
(c) Airways projection
3. Patients with stroke should routinely receive pharmacological venous throm-
boembolism (VTE) prophylaxis. Mark wrong answer:
(a) The VTE prophylaxis must be started within 48 h in patients with acute
ischemic stroke
(b) The VTE prophylaxis must be continued for approximately 14 days in
patients with acute ischemic stroke
(c) Patients with acute hemorrhagic stroke should routinely receive mechanical
prophylaxis
(d) Pharmacological prophylaxis is never used in acute hemorrhagic stroke
(e) Patients with neuromuscular degenerative diseases and with other major
risk factors for venous thrombosis should be considered for the adminis-
tration of pharmacological or mechanical prophylaxis
4. Patients with epilepsy whose seizures do not successfully respond to antiepilep-
tic drug (AED) therapy are considered to have drug-resistant epilepsy (DRE).
Mark the wrong statement:
(a) This condition is also referred to as intractable, medically refractory, or
pharmacoresistant epilepsy
(b) As many as 20–40 % of patients with epilepsy are likely to have refractory
epilepsy
(c) Individuals with DRE do not have an increased mortality rate
(d) The risk of sudden unexpected death (SUD) is closely related to seizure
frequency
5. When a drug-resistant epilepsy patient does not respond to medical or conven-
tional surgical treatment, there are some options of palliative care, such as:
(a) Hemispherectomy
(b) Corpus callosotomy
(c) Multiple subpial transections

(d) Ketogenic diet
(e) Vagus nerve stimulation
(f) All of the above
6. About dyspnea, say which of the answers is wrong:
(a) The antidyspneic medication must ameliorate the respiratory awareness, but
preserving the ventilatory drive
(b) A respiratory rate of 15–20/min must be attempted
(c) Opioids in modest doses have been demonstrated to give effective relief of
dyspnea, whether or not identifiable reversible causes exist
(d) A dose of 50 mg diazepam has a positive effect on improving sleep duration
without worsening nocturnal hypoxemia
(e) In rare cases where symptomatic treatment is unable to control dyspnea to
the patient’s satisfaction, sedation is an effective, ethical option
7. There are treatable causes of terminal restlessness such as:
(a) Pain
(b) A distended bladder or rectum
(c) Cerebral anoxia
(d) Dyspnea
(e) A paradoxical reaction to benzodiazepines
(f) A response to anticholinergic drugs
(g) All of the previous answers are treatable causes of terminal restlessness
298 M. Gudín
Answers
1. (d) When a permanent deficit is established that will short the patient life
2. (d) All of the above
3. (d) Pharmacological prophylaxis is never used in acute hemorrhagic stroke
4. (c) Individuals with DRE do not have an increased mortality rate
5. (f) All of the above
6. (d) A dose of 50 mg diazepam has a positive effect on improving sleep duration
without worsening nocturnal hypoxemia
7. (g) All of the previous answers are treatable causes of terminal restlessness
Chapter 17
Interventional Techniques in Palliative Care
Rinoo V. Shah, Alan David Kaye, Christopher K. Merritt,

and Lien B. Tran
Introduction
Minimally invasive and percutaneous procedures play a role in multimodal palliative

care. The concept is that a painful structure may be targeted under image guidance.
Then, depending on the type of pathology, the structure can be ablated (nerve,
tumor) or stabilized (bone). Targeted therapy complements systemic palliative care
with analgesics.
Neurolysis
Neurolysis is the destruction of neural tissue that subserves a painful tumor. The
neural tissue may be embedded within the tumor or may be remote from the tumor
[1]. The direct targeting of soft tissue tumors is beyond the scope of this book. This
chapter will focus on neural structures remote from the tumor. The neurobiology
of pain is extremely complex, but the actual practice of neurolysis relies on knowing
neural topography. Roughly, the nervous system is anatomically divided into central
and peripheral components. The peripheral may be divided into somatic and sympathetic
components.
R.V. Shah, M.D., M.B.A. (*)

Department of Anesthesiology, Guthrie Clinic-Big Flats,
Horseheads, NY, USA
e-mail: rinooshah@yahoo.com
A.D. Kaye, M.D., Ph.D. • C.K. Merritt, M.D. • L.B. Tran, M.D.
Department of Anesthesiology, Louisiana State University School of Medicine,
email: alankaye44@hotmail.com; cmerr2@lsuhsc.edu; lngo@lsuhsc.edu

DOI 10.1007/978-1-4614-5164-8_17,
300 R.V. Shah et al.
Destruction of neural structures occurs through the direct action of a chemical or

thermal agent. Injury is followed by the release of vasoactive substances and
thereafter, intraneural edema. Rising intraneural pressure leads to ischemia and
permanent interruption of neural impulses [1].
Agent
Alcohol
Ethyl alcohol is a clear and hypobaric (relative to water) solution. Direct applica-
tion leads to tissue dehydration. Neural components are extracted and precipitated.
Axonal destruction is followed by Wallerian degeneration. The Schwann cell
sheath/conduit is preserved, which allows for nerve regrowth. Sympathetic gan-
glia, however, are permanently destroyed. Higher concentrations of alcohol pro-
duce more complete destruction. Commonly used concentrations vary between 50
and 97%. A burning pain is followed by a warmth-type sensation, along the distri-
bution of the nerve. Local anesthetic, hence, should be placed prior to injecting
alcohol [1].
Since alcohol readily solubilizes and disperses, a large volume is required. This
may collaterally injure other tissues. Neuropathic pain, following the injection, may
last several weeks or months. Alcohol is rapidly metabolized by the liver, princi-
pally alcohol dehydrogenase. There is a low risk in reaching the legal limit for
alcohol intoxication. Alcohol neurolysis is most commonly used for the celiac
plexus, sympathetic ganglia, and spinal cord.
Phenol
Phenol is a chemical composite that is poorly soluble and colorless. Exposure to

light may cause a red tinge. Phenol is hyperbaric. The maximum concentration in an
aqueous medium is 6.7%. Since phenol is soluble in organic solvents, e.g., glycerol,
alcohol, and nonionic contrast, admixture with these agents can raise the phenol
concentration to 15%. Higher concentrations of phenol permit more complete neu-
ral destruction, but the risk of vascular injury is increased. When phenol is mixed
with glycerol, diffusion is slowed and spread is limited. This enables more precise
targeting, as compared to aqueous phenol [1].
Phenol is a nonselective neurolytic, acting via protein denaturation. Full degen-
eration may take a few weeks. Nerve cell body destruction is less successful with
phenol, as compared to alcohol. Lower concentration phenol, e.g., 3%, acts as a
local anesthetic. For this reason, phenol is less painful than alcohol neurolysis.
On the other hand, the quality of neurolysis cannot be evaluated at 24–48 h due to
the persistency of this local anesthetic effect. A full evaluation should be conducted
17 Interventional Techniques in Palliative Care 301
at 3–7 days. If inadequate, repeat neurolysis may be performed. Due to disruption

of the neural sheath conduit, nerve regeneration is more difficult; neuromas may
form. Phenol is used for peripheral, sympathetic, and central neurolysis [1].
Side effects may include nervous system stimulation, including seizures, hemo-
dynamic variability, nausea, and vomiting. Doses in the neurolytic range, e.g., 100–
300 mg, should not cause serious side effects [1].
Glycerol
Glycerol is a milder neurolytic and is used for trigeminal ganglion blocks. The
milder quality preserves facial sensation and V3 branch motor function. Usually,
small aliquots of 1–2 ml of 100% are used. A perineural injection damages myeli-
nated nerves [1].
Radiofrequency Thermocoagulation
A generator produces a high frequency (>250 kHz), alternating electrical current.

The current passes through an attached electrode and exits out of the tip of an
insulated needle. The current then passes through the body toward a grounding pad.
In the process, local molecular oscillations occur. Heat is generated and protein
denaturation occurs at the tip. Radiofrequency thermocoagulation affords very
discrete neural ablation, while sparing collateral structures. Lesion shape is typically
cocoon-like. However, ablation is nonselective and neuromas may form with somatic
nerve targeting. Neural destruction occurs at temperatures of 45°C. So, radiofre-
quency generator temperatures are set at 60–80°C. Higher temperatures risk tissue
boiling and tissue fragmentation. Typically, lesioning is continued for 60–90 s [2].
Patient-safety strategies include sensory stimulation (50 Hz, 0–1 mA) and
motor stimulation (2 Hz, 3–5 mA), prior to neurolysis. During this testing, patients
must be alert enough to communicate what they feel and what they can move dur-
ing testing. Although the procedure may be performed under conscious sedation,
these safety monitoring steps are essential. This will reduce the risk of inadver-
tent neural injury. This should be communicated during the informed consent
process [2].
Cryoablation
Extreme cold is analgesic. One advantage of this, over other methods, is the relative
absence of neuritis or neuroma formation. Nerve regrowth occurs, which makes this
effect “reversible.” Systemic side effects are absent. Pain relief could last for weeks
or months. Disadvantages include lack of access to cryoablation equipment, large
probe sizes (14–18 gauge), and the risk of frostbite [1, 2].
Cryolesioning occurs by freezing a small, 2–4 mm, segment of nerve tissue.

Pressurized nitrous oxide rapidly expands at the probe tip and cools to temperatures
of −60°C. The probe is left in place for 60–90 s. This is followed by a thaw period of
60 s, prior to removal. An ice ball of 2–4 mm forms near the nerve. Intraneural pressure
rises over the next few hours and reduces after a day. This pressure oscillates and
then stabilizes after 1 week. This leads to Wallerian degeneration and neurolysis [1, 2].
Complications
Chemical neurolysis is associated with some complications. Tissue necrosis and

skin sloughing may occur, secondary to ischemia. Neuritis and neuromas may occur.
Pain, allodynia, and hypersensitivity may be present. Some authors argue that nerve
cell body destruction is imperative to reduce the risk of this complication. Anesthesia
dolorosa or “painful numbness” may occur. Motor paralysis, along with bladder and
bowel dysfunction, is worrisome complication. Systemic complications include
impairment of the cardiovascular and central nervous systems [1, 2].
Radiofrequency neurolysis and cryoablation are safer, but require more precise
targeting.
Techniques
General Considerations
Informed consent is essential.

Staff members may include a physician, nurse, radiological technologist, and surgi-
cal technologist.
Equipment
Procedure room for sterile procedures with C-Arm fluoroscopy

Needles: 25 g for skin infiltration, 22 g spinal needle 6–8 , angiocatheter intro-
ducer, 20 g curve blunt needle, 18–22 g insulated radiofrequency needle (sharp or
blunt)
Emergency resuscitation equipment and drugs
Lidocaine 1–2%
Nonionic contrast, e.g., iohexol or isovue
Bupivacaine 0.25% or Ropivacaine 0.25%
Phenol 6–10%
Radiofrequency generator and electrode
Cryoablation equipment
Intrathecal Neurolysis
This is performed for segmental pain syndromes [1]. The baricity of the agent must
be taken into account when performing this procedure. Alcohol is hypobaric and
rises. So, a patient with severe pelvic pain due to a primary tumor or metastasis
could undergo a subarachnoid injection of 50–99% alcohol, in the lower lumbar
spine. The patient would then have to be positioned so that injection site is lower
than the nerve roots selected for ablation. The alcohol would rise. An ongoing sen-
sory examination would inform the practitioner when the block is complete. Phenol
is hyperbaric and the opposite positional approach is needed. If a patient has a chest
wall tumor, the patient should be placed in a decubitus position with the dependent
side down. The phenol injection should be carried in the mid-thoracic levels. After
the injection is complete, the patient should be rotated slightly posterior toward the
practitioner. The phenol should settle down on the dependent side and with a dorsal
positioning, the phenol should target the dorsal columns, sensory nerve rootlets,
dorsal root ganglia, and spinothalamic tract. There should be sparing of the motor
rootlets. The opposite strategy would be used with alcohol.
Peripheral Nerve Neurolysis
Peripheral nerve neurolysis is more commonly indicated for spasticity and not for can-
cer-related pain. However, some practitioners may perform intra-operative neurolysis
as an adjunct to surgery, e.g., rib resection, thoracic surgery, and limb amputation. The
methods employed are similar in strategy to those for peripheral nerve block, with use
of electrical stimulation and ultrasound guidance. Phenol may then be injected; this
agent is preferable to alcohol, secondary to the local anesthetic effect [1].
Celiac Plexus Neurolysis (Fig. 17.1)
Abdominal pain is the primary indication for celiac plexus neurolysis. The origin
may be due to primary tumors, secondary extension, or metastases involving the
following structures: stomach, liver, gall bladder, kidney, spleen, pancreas, descend-
ing aorta, lymph nodes, omentum, and retro peritoneum [1].
Intravenous access and volume preloading is imperative, e.g., 500–1,000 ml of
lactated ringers. Patient is placed in a prone position. Special consideration must
be given to increased pain in this position. Specific views under fluoroscopy are
needed for optimal visualization. A posterior anterior view is followed by cephalo-
caudad angulation to “square off” the endplates. The C-arm is slowly rotated until
the tip of transverse process is flush with edge of L1 vertebral body. The skin
entry point will be the intersection of the inferior border of the T12 rib, paraspinal
Fig. 17.1 Celiac plexus neurolysis
musculature, and horizontal extension of L2 transverse process/L1–2 interverte-

bral disc. Skin entry will be approximately 6–8 cm lateral from midline. This will
be repeated on the contralateral side. With a 45° angulation, relative to the skin,
the needle should be aimed cephalad toward the L1 vertebral body. The needle
should pass just lateral to the vertebral body and advanced anterior to the L1 ver-
tebral body. The needle tip should be aimed 1–2 cm anterior to the L1 vertebral
body. After negative aspiration, nonionic contrast should be instilled. A relatively
fixed prevertebral pattern (anterior to the aorta), with a vacuolated appearance
will appear.
With serial aspiration, 20–25 ml of 1% lidocaine or 0.25% bupivacaine that is
admixed (1:1) with 50% ethyl alcohol is instilled. Alternatively, 5–10 ml of 6%
phenol may be instilled.
Sympathetic Neurolysis
Lumbar
Lumbar sympathetic neurolysis may be useful in patients with peripheral vascular

disorders and tumors involving the lower extremities and urogenital structures [1].
The patient is placed in a prone position. Specific views under fluoroscopy are
needed for optimal visualization. A posterior anterior view is followed by cephalo-
caudad angulation to “square off” the endplates. The C-arm is slowly rotated until
the tip of transverse process is flush with edge of lumbar vertebral body.
A local anesthetic skin wheal is made, about 6–8 in. off of midline. Under
fluoroscopy, the needle is advanced inferior to the tip of the transverse process and
just lateral to the edge of the vertebral body. The needle should be close to the
inferior endplate of the corresponding vertebral body (L2, L3, and L4); avoid the
midline of the vertebral body, due to vascular (arterial) feeder vessels.
On a lateral fluoroscopic view, the needle is advanced just anterior to the
vertebral body. A “loss of resistance” or tactile pop may be felt, once the anterior
psoas fascia is penetrated. Aspiration should be negative for blood.
Contrast instillation should demonstrate a prevertebral filling pattern. The contrast
should not demonstrate spread along the psoas or the vascular structures. An A-P
view will demonstrate a vacuolated contrast pattern that remains fixed in position
with respirations.
The procedure may be repeated at other lumbar levels.
Then slowly instill 5–7 ml of 3–6% phenol. Radiofrequency thermocoagulation
is an alternate approach. Typically, insulated needles with 10–15 mm exposed
tip may be placed. Discrete lesioning may be commenced at three levels (L2–4)
to enhance efficacy. The location of the sympathetic ganglia is variable from
patient to patient, but usually located near the endplates. Sensory stimulation is
mandatory with radiofrequency thermocoagulation to reduce the risk of gen-
itofemoral neuralgia. Arguably, chemical neurolytics should be instilled through
an insulated needle to carry out sensory stimulation, as well. Sympatholysis
may be demonstrated by lower limb venodilation and a skin temperature
increase.
The needles should be flushed with local anesthetic, prior to removal.
Routine postprocedural care is necessary to ensure stable neurological and hemo-
dynamic functioning.
Complications include genitofemoral neuralgia, intravascular injection,
bleeding, and hypotension.
Thoracic
Thoracic sympathetic neurolysis may be useful in patients with peripheral vascular

disorders, and tumors involving the chest wall and visceral structures and upper
extremities. This procedure may help patients with chronic angina, upper extremity
lymphedema, vascular diseases, and dyscrasias.
The patient is placed in a prone position, with a pillow under the chest to aug-
ment thoracic kyphosis. Specific views under fluoroscopy are needed for optimal
visualization. A posterior anterior view is followed by cephalo-caudad angulation to
maximize the space between ribs. The C-arm is slowly rotated so that separation of
costo-transverse joint and facet articulation are visualized [1].
A local anesthetic skin wheal is made, about 4–5 cm off of midline. Under
fluoroscopy, the needle is advanced inferior to the tip of the transverse process/
proximal rib head and just lateral to the edge of the vertebral body. The needle
should be close to the inferior endplate of the corresponding thoracic vertebral

body; avoid the midline of the vertebral body, due to vascular (arterial) feeder
vessels. A single needle may be used for chemical neurolysis. Two to three needles
may be used for radiofrequency neurolysis.
The needle should be advanced anterior to the thoracic foramina. The needle tip
should be approximately at the anterior 2/3 / posterior 1/3 margin. There is no psoas
muscle equivalent in the thoracic spine, i.e., a muscle that separates the sympathetic
ganglia and nerve roots. So, needle placement is critical. The needle tip should be
located near the endplates.
A blunt needle should be considered for this procedure, in order to reduce the
risk of a pneumothorax. Aspiration should be negative for blood. Contrast instilla-
tion should demonstrate a “clamshell” type spread, which hugs the lateral margin of
the vertebral body. This spread should not dissipate with respirations and vascular
uptake should be negative. The procedure may be repeated at other thoracic levels.
Ten to fifteen milliliters of local anesthetic may be instilled. Sympatholysis may
be demonstrated venodilation in the hands, reduction in palmo-plantar hidrosis, and
a skin temperature increase. Then slowly instill 5–7 ml of phenol. Radiofrequency
thermocoagulation is an alternate approach. Typically, insulated needles with
10–15 mm exposed tip may be placed. Discrete lesioning may be commenced at
three levels, for instance, T2–T4, in order to enhance efficacy. The choice of level
depends on the location of the pathology. The needles should be flushed with local
anesthetic, prior to removal.
Routine postprocedural care is necessary to ensure stable neurological and
hemodynamic functioning. Complications include thoracic radiculopathy, pneu-
mothorax, intravascular injection, bleeding, and hypotension.
Trigeminal Ganglion
The trigeminal ganglion is an important neural relay for pain originating in face,
brain (meninges), head, and upper neck. This structure is accessible through the
foramen ovale, which transmits the mandibular branch (V3). This is an advanced
procedure [1].
The patient is placed in a supine position, with the neck slightly extended and the
jaw recessed. Fluoroscopy is used to identify the foramen ovale, which is located
medial to the upper portion of the mandible. The C-arm is positioned, so the image
intensifier is almost touching the chest (submental view).
A local anesthetic skin wheal, typically 2 cm lateral to the labial commissure. An
angiocatheter introducer typically advanced to the upper portion of the mandible,
inferior to the skull base. Direct palpation in the oral mucosa will determine if the
buccal mucosa is violated. Thereafter, a curved blunt needle is advanced into the
foramen ovale. The patient may feel pain due to dysesthesia along the V3 distribution.
The needle is then advanced 3–5 mm further. Sensory stimulation should produce
paresthesias in the distribution of V2 and V3. It is more difficult to get paresthesias
in the V1 distribution. Actually, the yield of sensory stimulation is limited since

many of these patients are sedated. Motor stimulation will lead to unilateral jaw
contractions. Care must be taken to protect the lips, tongue, mucosa, and other oral
structures. Neurolysis may be initiated. With radiofrequency thermocoagulation,
temperatures of 60°C for about 60 s are ideal. The corneal reflex should be moni-
tored during the procedure. With chemical neurolysis, glycerol may be used past the
foramen ovale. Glycerol is less likely to spread and damage motor fibers (V3), as
compared to phenol and alcohol. A curved, blunt needle is advised to do this
procedure.
Intercostal Neurolysis
Tumors that invade the chest wall or surgery that transects ribs and associated neural
structures can lead to severe neuropathic pain. The intercostal nerves may be inter-
rupted with neurolysis, typically with cryoablation or phenol. The procedure is per-
formed similarly to an intercostal nerve block [1].
After local anesthetic infiltration, a spinal needle is advanced 4–6 cm lateral to
the thoracic midline toward the rib. Once bone contact occurs, the depth is noted.
The needle is pulled back and advanced off the inferior margin of the rib to a depth
of a few millimeters. Aspiration should be negative for air and blood. Contrast
should demonstrate spread along the intercostal muscles and no spread proximally
into the spinal canal. There should be no vascular washout of contrast. Contrast
should not disperse with respirations. Thereafter, phenol 3–4 ml is instilled slowly
with intermittent aspiration. In the case of cryoablation, a double-needle technique
is utilized. Since the probe is large and since the ice ball will form at the distal tip,
the technique should be modified. The angiocatheter should be advanced to the
superior margin of the rib. The cryoprobe should be advanced through the angio-
catheter toward the cephalad rib. The probe should be passed under this superior rib.
Cryoneurolysis should be carried out. Despite greater invasiveness, cryoablation
may reduce the risk of neuroma pain.
Complications include pneumothorax, paralysis, hematoma, and infection.
Skeletal Metastases
Skeletal metastases may cause significant morbidity. Direct palliation, with

radiofrequency ablation and surgical removal, has been tried. These attempts
may lead to protracted improvement and significant morbidity respectively.
Vertebral augmentation and osteoplasty are viable alternatives. Cement produces
an exothermic reaction that results in neurolysis. Cement stabilizes bone metas-
tases and fractures. Vertebroplasty and kyphoplasty (Fig. 17.2) are two such
procedures [1, 3, 4].
Fig. 17.2 Kyphoplasty
After preprocedural planning, the patient is placed in a prone position. Cannulas

are advanced through the pedicle of the vertebral body. A unilateral approach is
used for vertebroplasty and bilateral for kyphoplasty. A balloon or curette may be
placed through the cannula into the vertebral body. These tools permit the creation
of a cavity. The balloon and curette are removed. Other manufacturers have
advocated implantation of biocompatible wafers to permit height restoration.
Thereafter, a cement, typically poly methyl methacrylate is prepared. Once a very
viscous consistency is reached, the cement is delivered in 0.1–0.5 ml aliquots under
live fluoroscopy. Careful monitoring is imperative to ensure that the cement does
not extravasate. Cement volumes may range between 3 and 7 ml. Degree of fill on
fluoroscopy will determine when to stop. Cement should not extravasate outside the
margins of the vertebral body. Sacral metastases may be targeted, as well as flat
bones such as the sternum. The latter have demonstrated efficacy and safety.
Complications include cement extravasation, cement emboli, neural damage,
spinal cord injury, morbidities of the patients, anesthesia, and pressure-related
injuries (eyes, bony surfaces, and peripheral nerves).
Neurosurgical ablative approaches are not commonly performed, but they include
neurectomy, sympathectomy, cordotomy, commissurotomy, mesencephalotomy,
thalamotomy, and cingulotomy. In reality, these procedures are extremely rare and
reserved for the most debilitated patients. These patients have very limited life
expectancies and the safety of performing these procedures in this population is
questioned.
Alternative options include neuromodulation with implantable devices.
Intrathecal opioid pumps are more common in this population, as compared to
spinal cord stimulation.
Fig. 17.3 Spinal cord stimulation
An intrathecal pump involves placing a catheter into the spinal canal. This
catheter is tunneled subcutaneously toward the anterior abdomen. A programmable
reservoir is placed subcutaneously in the anterior abdominal lower quadrant and
connected to the catheter. The pump reservoir holds the drug and the pump delivers
small aliquots of drug into the spinal canal. Typically, a preimplantation trial via a
subarachnoid injection of morphine, 0.25–1 mg is used. The pump then delivers the
drug continuously for pain relief. In some countries, patients can self-administer the
drug as a periodic bolus.
Interventional Procedures in Noncancer Palliative Care
Spinal cord stimulation (Fig. 17.3) is a neuromodulatory device that has demonstrable
efficacy in chronic angina and peripheral vascular disease. A special type of electrode
is placed in the cervical or thoracic epidural space. A small electrical current passed
to the spinal cord through the dura can help with pain control. These patients have
a visceral and somatic component to their pain. Spinal cord stimulation may help
with both of these types. Spinal cord stimulation does not block the pain to such an
extent, wherein a life-threatening ischemic episode is not noticed [5].
Thoracic and lumbar epidural catheters may be used as a short-term strategy for
acute or subacute pain syndromes. A catheter that is silastic and is cuffed may be
useful for longer periods, e.g., weeks. This may play an important role in patients
that are immunocompromised and have a short life expectancy.
The practicality of these procedures in patients with vascular disease is limited
by anticoagulation and immune status [5–8].
Future areas of investigation include the role of spinal cord stimulation in patients
with co-morbidities that are adversely affected by opioids or sedatives, e.g., sleep
apnea, pulmonary disease.
Intrathecal pumps may be a better option for some patients on anticoagulants.

However, this procedure will primarily benefit patients with thoracic, chest wall,
abdominal, pelvic, and lower extremity pain syndromes [5–8]. Some neurosurgeons
have reported direct cisternal or upper cervical catheter implantations for
cranio-cervical disorders.
HIV patients have a host of associated neurological disorders that may be
amenable to neuromodulation. Infection is an important consideration and the risks
should be carefully weighed with the benefits.
Neurolytic procedures, e.g., lumbar sympathectomy, may be of use in patients
with lower extremity vascular disease. Thoracic sympathectomy may be of use in
patients with chronic upper extremity insufficiency or Raynaud’s disease.
Conclusion
Palliative care specialists should be aware that the pain and fear of inadequate pain
relief are of major concern to patients. Since many analgesics have untoward side
effects or adverse events, consideration should be given to the above procedures.
Close consultation with an interventional pain specialist is advised.
References
1. Gehdoo R. Neurolytic agents and neurodestructive techniques. In: Baheti D, editor. Interventional
pain management: a practical approach. New Delhi: Jaypee; 2008. p. 27–35.
2. Sharma A. Radiofrequency thermocoagulation. In: Baheti D, editor. Interventional pain
management: a practical approach. New Delhi: Jaypee; 2008. p. 308–26.
3. Shah RV. Sacral kyphoplasty for the treatment of painful sacral insufficiency fractures and
metastases. Spine J. 2012;12(2):113–20.
4. Shah RV. Sternal kyphoplasty for metastatic lung cancer: image-guided palliative care, utilizing
fluoroscopy and sonography. Pain Med. 2012;13(2):198–203.
5. Longnecker DE. Anesthesiology. 2nd ed. New York: McGraw-Hill; 2012.
6. Gayle JA, et al. Anticoagulants: newer ones, mechanisms, and perioperative updates. Anesthesiol
Clin. 2010;28(4):667–79.
7. Raj PP, et al. Bleeding risk in interventional pain practice: assessment, management, and review
of the literature. Pain Physician. 2004;7(1):3–51.
8. Shah RV, Kaye AD. Bleeding risk and interventional pain management. Curr Opin Anaesthesiol.
2008;21(4):433–8.
Review Questions
1. Which of the following agents can be used for neurolysis techniques:

(a) Alcohol.
(b) Phenol.
(c) Glycerol.
(d) All of the above.
(e) None of the above.
2. Which is false regarding RFTC:
(a) A generator produces a high frequency (<1 kHz), alternating electrical
current in RFTC.
(b) The current passes through an attached electrode and exits out of the tip of
an insulated needle.
(c) Heat is generated and protein denaturation occurs at the tip. Radiofrequency
thermocoagulation affords very discrete neural ablation, while sparing
collateral structures.
(d) Lesion shape is typically cocoon-like.
(e) However, ablation is nonselective and neuromas may form with somatic
nerve targeting. Neural destruction occurs at temperatures of 45°C. So,
radiofrequency generator temperatures are set at 60–80°C.
3. Which is false:
(a) Ethyl alcohol is a clear and hypobaric (relative to water) solution.
(b) Direct application leads to tissue dehydration.
(c) Neural components are extracted and precipitated. Axonal destruction is
followed by Wallerian degeneration.
(d) The Schwann cell sheath/conduit is preserved, which allows for nerve
regrowth. Sympathetic ganglia, however, are permanently destroyed.
(e) Lower concentrations of alcohol produce more complete destruction.
Commonly used concentrations vary between 50 and 97%. Alcohol neu-
rolysis is most commonly used for the celiac plexus, sympathetic ganglia,
and spinal cord.
4. Which is true regarding metastasis and pain techniques
(a) Cement produces an exothermic reaction that results in neurolysis. Cement
stabilizes bone metastases and fractures. Vertebroplasty and kyphoplasty
are two such procedures.
(b) A cement, typically poly methyl methacrylate is prepared. Once a very
viscous consistency is reached, the cement is delivered in 0.1–0.5 ml ali-
quots under live fluoroscopy. Careful monitoring is imperative to ensure
that the cement does not extravasate. Cement volumes may range between
3 and 7 ml.
(c) Degree of fill on fluoroscopy will determine when to stop. Cement should
not extravasate outside the margins of the vertebral body. Sacral metastases
may be targeted, as well as flat bones such as the sternum. The latter have
demonstrated efficacy and safety.
(d) Complications include cement extravasation, cement emboli, neural damage,
spinal cord injury, vascular uptake, hematoma, and infection. Other complica-
tions may be due to the medical co-morbidities of the patients, anesthesia, and
pressure-related injuries (eyes, bony surfaces, and peripheral nerves).
(e) All are true.
5. Which is false:
(a) Spinal cord stimulation is a neuromodulatory device that has demonstrable
efficacy in chronic angina and peripheral vascular disease. A special type of
electrode is placed in the cervical or thoracic epidural space.
(b) Spinal cord stimulation does not block the pain to such an extent, wherein
a life-threatening ischemic episode is not noticed.
(c) Thoracic and lumbar epidural catheters may be used as a short-term strat-
egy for acute or subacute pain syndromes.
(d) A catheter that is silastic and is cuffed may be useful for longer periods,
e.g., weeks. This may play an important role in patients that are immuno-
compromised and have a short life expectancy.
(e) All are true.
6. Which is a false statement
(a) There is no role for neurolytic procedures in Palliative Care.
(b) Strict sterile technique is required for all interventional pain procedures.
(c) Significant side effects can occur in interventional pain medicine
procedures.
(d) Cryoablative procedures are indicated in certain pain states.
(e) Monitoring patients for interventional pain procedures is important, as
patients may require procedural sedation, and complications such as local
anesthetic toxicity, pneumothorax, nerve injury, vascular puncture, and bleed-
ing can occur.
7. Examples of interventional pain blocks include:
(a) Intercostal block.
(b) Celiac block.
(c) Transforaminal nerve root block.
(d) Lumbar facet block.
(e) All of the above.
8. Regarding spinal cord modulation:
(a) Options include neuromodulation with implantable devices.
(b) Intrathecal opioid pumps are more common in this population, as com-
pared to spinal cord stimulation.
(c) An intrathecal pump involves placing a catheter into the spinal canal. This
catheter is tunneled subcutaneously toward the anterior abdomen.
(d) A programmable reservoir is placed subcutaneously in the anterior abdominal
lower quadrant and connected to the catheter. The pump reservoir holds the drug
and the pump delivers small aliquots of drug into the spinal canal. Typically, a
preimplantation trial via a subarachnoid injection of morphine, 0.25–1 mg is
used. The pump then delivers the drug continuously for pain relief. In some
countries, patients can self-administer the drug as a periodic bolus.
(e) All are true.
9. Regarding peripheral neurolysis:
(a) Peripheral nerve neurolysis is more commonly indicated for spasticity and
not for cancer-related pain.
(b) Some practitioners may perform intra-operative neurolysis as an adjunct to
surgery, e.g., rib resection, thoracic surgery, and limb amputation.
(c) The methods employed are similar in strategy to those for peripheral nerve
block, with use of electrical stimulation and ultrasound guidance. Phenol
may then be injected; this agent is preferable to alcohol, secondary to the
local anesthetic effect.
(d) All are true.
(e) All are false.
10. Regarding trigeminal ganglion procedures:
(a) The trigeminal ganglion is an important neural relay for pain originating in
face, brain (meninges), head, and upper neck. This structure is accessible
through the foramen ovale, which transmits the mandibular branch (V3).
(b) The patient is placed in a supine position, with the neck slightly extended
and the jaw recessed. Fluoroscopy is used to identify the foramen ovale,
which is located medial to the upper portion of the mandible.
(c) The yield of sensory stimulation is limited since many of these patients are
sedated. Motor stimulation will lead to unilateral jaw contractions. Care must be
taken to protect the lips, tongue, mucosa, and other oral structures. With radiof-
requency thermocoagulation, temperatures of 60°C for about 60 s are ideal.
(d) All are false.
(e) All are true.
Answers
1. (d)
2. (a). It is >250 kHz
3. (e). Higher concentrations of alcohol produce more complete destruction
4. (e)
5. (e)
6. (a)
7. (e)
8. (e)
9. (d)
10. (e)
Chapter 18
Headache in Palliative Care
Nicholas Connolly, Matthew Peña, and Tara M. Sheridan
Introduction
Headaches comprise a relatively common pain condition with etiologies ranging

from benign to life-threatening. The International Headache Society categorizes
headaches into primary, such as migraine, cluster or tension headaches, and second-
ary, such as due to an underlying infection, neoplasm or other disease process. Many
patients experience headaches of a chronic nature, which are refractory to standard
treatments, and which require more intensive and/or invasive care. These patients
include those who are suffering from secondary headaches associated with poten-
tially terminal conditions, such as HIV encephalitis or intracranial tumor burden,
but also include patients suffering from more common, yet severe forms of benign
primary headache disorders. It is crucial to recognize life-threatening causes of
headache, as well as to identify benign but incapacitating etiologies. Here, we focus
on the differential diagnosis to consider in patients presenting to pain clinic with
refractory headaches, including appropriate work up and treatment options. As
migraine and cluster headache are two of the most common and disabling headache
disorders in the chronic pain patient population, this chapter highlights
considerations for these patients in particular.
N. Connolly, M.D. • M. Peña, M.D.

Department of Anesthesiology, Naval Medical Center San Diego,
San Diego, CA, USA
T.M. Sheridan, M.D. (*)
Department of Anesthesiology, Naval Medical Center San Diego,
Bethesda, MD, USA
e-mail: tara.sheridan@med.navy.mil

DOI 10.1007/978-1-4614-5164-8_18,
316 N. Connolly et al.
Migraines
Migraine afflicts approximately 6% of men, 18% of women, and 4% of children in

Europe and the USA [1]. Cases are most frequent in women of child-bearing years, the
gender difference beginning at the age of menarche, and falling off after age 60. Peak
prevalence occurs during the second and third decades of life, traditionally periods of
high productivity, and over half of migraine patients report significant impact on their
daily lives, such as requiring bed rest and missing school or work. The risk of having
migraines is 50% higher in relatives of migraineurs than in relatives of controls. The
majority of people who suffer from migraines do not seek professional advice from
primary care physicians, but instead self-medicate with over-the-counter medications.
However, surveys suggest that 5% of Emergency Department patients present with
migraine headaches, and that greater than 90% of those patients who do see their pri-
mary care doctor with a chief complaint of headache are diagnosed with migraine [2].
The fiscal impact of medical cost and lost worker productivity is estimated to be in the
range of $15 billion annually in this country [3].
Definition and Classification
Migraine is a paroxysmal primary disease occurring in otherwise healthy individu-

als. It is characterized by distinct periods of severe head pain, lasting from several
hours to days, often accompanied by photophobia (light sensitivity), phonophobia
(sound sensitivity), nausea, and vomiting.
Migraine is divided into four specific phases: prodrome, aura, headache, and
postdrome. The prodrome is a premonitory phase which occurs in about 20–60% of
migraine patients and consists of symptoms such as mood changes, food cravings,
yawning, fatigue, and increased urination. Patient may recognize these symptoms as
being indicative of impending headache pain.
About 20% of migraine patients experience aura prior to onset of headache pain.
Aura is a temporary, reversible change that causes focal neurologic findings. Visual
auras are most common, but sensory, memory, or speech changes may occur.
Typically, visual auras manifest as colored spots, flashing lights, or bright shapes
moving slowly across the visual field. Auras usually last 5–60 min and resolve com-
pletely, with headache following within an hour of onset. To be diagnosed as
migraine with aura, the patient must experience at least two such headaches [1].
The third phase of the migraine is the headache itself, characterized by unilateral,
moderate to severe throbbing pains, lasting 4–72 h. Migraines extending past 72 h,
regardless of therapy, are considered “status migrainosus.” Acute treatments are
partially or completely ineffective for status migrainosus, as the pain is only tran-
siently relieved by abortive medications.
The second edition of the International Headache Classification (ICHD-2)
defines diagnostic criteria for both migraines with aura (“classic”) and migraines
without aura (“common”) [4]. The criteria stipulate the following rules:
18 Headache in Palliative Care 317
1. At least five headaches lasting 4–72 h in duration, with no or unsuccessful

treatment
2. At least two of the following characteristics
(a) Unilateral location
(b) Throbbing quality
(c) Moderate to severe intensity
(d) Worse with routine activity
3. In addition, at least one of the following features
(a) Nausea/vomiting
(b) Photophobia
(c) Phonophobia
4. Normal neurologic examination, without evidence of another attributable
disorder
The fourth and final migraine phase is the postdrome, which occurs in approxi-
mately 65% of migraineurs. Patients notice symptoms such as fatigue, weakness,
irritability, depression, and scalp tenderness for several hours to days after
resolution of the headache pain.
Etiology and Pathophysiology
From the 1940s to the 1990s migraine was defined as strictly a vascular anomaly,
whereas it is now considered a more complex neurovascular disorder, involving
multiple genetic, environmental, and neurohormonal factors [5].
According to a theory postulated by Dr. Harold Wolffe in the 1940s, cranial vascu-
lar constriction leads to decreased cerebral blood flow and subsequent vascular vaso-
dilation, causing migraine pain. However, in the 1990s Jes Olsen’s blood flow studies
demonstrated that cerebral blood flow does not correlate with the symptoms of
migraine [5]. More current research suggests that cortical spreading depression (CSD)
is the basis of migraine aura, and is a trigger for headache pain [6]. CSD is a regenera-
tive wave of neuronal and glial depolarization that propagates slowly across the neo-
cortex, causing extracellular efflux of potassium ions, at a rate of approximately
2–3 mm/min [7]. It was first described by Dr. Aristes Leao, as he studied animal mod-
els of epilepsy [5]. The relationship between CSD and migraine aura was made by
observing the similar rates of progression between the two phenomena, as described
by Dr. Milner et al. in the 1958 paper entitled, “Note on a possible correspondence
between the scotomas of migraine and spreading depression of Leao.” These transient
scintillations and flashes track across the visual field just prior to the onset of headache
pain, moving peripherally over the course of 10–15 min at a rate of 2–3 mm/min.
Ongoing human neuroimaging studies (i.e., functional MRI/PET scan) [8] lend fur-
ther support to the correlation between neocortical spreading depression and migraine
aura. CSD causes plasma protein extravasation from the dura mater, triggering trigem-
inal ganglion-mediated pain pathways and activating parasympathetic nervous sys-
tem-mediated nausea and fatigue. More specifically, activation of the trigeminovascular
system’s nerves and vessels stimulates meningeal secretion of such neurotransmit-
ters as substance P, serotonin and calcitonin gene-related peptide, resulting in cranial
vessel dilation and inflammation [9].
Neuronal hyperactivity in the hippocampus may stimulate nociceptive activation
of the trigeminal nucleus caudalis, and be the initiating factor in nonaural (common)
migraines [7].
Diagnosis
Headache evaluation should include a thorough history, with special attention paid
to the character and pattern of head pain, associated symptoms, triggering factors,
and medication history. A physical examination to rule out systemic causes of
headache as well as a neurologic examination should be performed. High-risk fea-
tures of headache that should prompt neuroimaging include age greater than 50,
sudden onset of symptoms, history of trauma, accelerating pattern of headache,
altered mental status, and systemic features, such as fever, rash, or occipitonuchal
rigidity [10]. Neurologic deficits in patients with cancer or human immunodeficiency
virus (HIV) infection may signify increased intracranial pressure due to edema or
growth of a space-occupying lesion [11]. Headaches may also be associated with
chronic opioid use. Opioids can trigger migraine, tension or rebound headaches,
particularly when a patient is overusing short-acting opioids [12]. Headache is
reported by 40–50% of patients with HIV, especially in the later stages of disease.
The differential diagnosis includes HIV encephalitis, atypical aseptic meningitis,
opportunistic infections of the central nervous system (CNS), acquired immune sys-
tem deficiency syndrome (AIDS)-related CNS neoplasms, sinusitis, tension,
migraine, and zidovudine-induced headache [11].
As for what studies to order, computerized tomography (CT) detects the majority
of significant conditions that may cause headaches, such as acute head trauma,
subarachnoid hemorrhage, or osseous defects. These images are quick to obtain but
do expose the patient to relatively high radiation levels and are not ideal for identify-
ing vascular, infectious, or neoplastic lesions, particularly in cervicomedullar region
or the posterior fossa. Magnetic resonance tomography (MRI) is more sensitive that
CT in detecting posterior fossa, cervicomedullary or pituitary pathology, white mat-
ter changes, central venous thrombosis, subdural and epidural hematomas, and
meningeal disease. MRI does not expose patients to radiation and is safe during
pregnancy, although a small percentage of patients may have an allergic reaction to
iodinated or gadolinium contrast agents, or may not be able to tolerate the claus-
trophobia associated with obtaining this longer scan.
EEG is not useful in the routine assessment of headache pain, for either adult or
pediatric populations. However, it is notable that migraine and epilepsy share many
commonalities. Both are chronic, paroxysmal neurologic conditions with distinct,

sporadic episodes, and no appreciable symptoms after attack resolution. Both have
complex heritable components and are triggered by abnormal neuronal hyperexcit-
ability. In fact, antiepileptic drugs such as topiramate, valproate, and gabapentin are
successfully utilized as migraine prophylactic agents [5]. They may belong within a
common disorder spectrum, and additional findings suggestive of seizure disorder,
such as atypical aura, lapses in consciousness, or tonic–clonic movements should
prompt EEG evaluation in migraine patients [13].
Lumbar puncture is reserved for cases in which there is a high suspicion for such
diseases as meningitis, encephalitis, meningeal carcinomatosis, or lymphomatosis,
subarachnoid hemorrhage, and pseudotumor cerebra. MRI or CT is routinely per-
formed prior to lumbar puncture, to evaluate for risk of herniation, and platelet
count should be verified as being at least 50,000 prior to needle placement. Recording
the opening pressure is helpful in working up headache etiology. In order to reduce
the risk of causing a postdural puncture headache, which is a common complication
and may certainly confound diagnosis of the original, presenting headache, the
practitioner should use a small gauge (25 g) Sprotte or Whitacre pencil needle for
the procedure.
Serum studies are not usually indicated in the evaluation of headache. However,
certain exceptions may be warranted, such as an erythrocyte sedimentation rate
(ESR) or C-reactive protein (CRP) level in potentially inflammatory etiologies, such
as temporal arteritis in an older patient presenting with new onset migraine. ESR,
CRP, rheumatoid factor, and antinuclear antibody titers may be obtained to rule out
other inflammatory, autoimmune diseases, or collagen vascular diseases associated
with headaches, such as rheumatoid arthritis or systemic lupus erythematosis. In
teenagers with headache, arthralgia, and cervical lymphadenopathy, a monospot
assay may rule out mononucleosis. For immunocompromised patients, complete
blood count, liver function, HIV test, or Lyme antibody may be indicated.
Hypothyroidism may be associated with headache presentation, so a thyroid-stimu-
lating hormone level can be ordered in patients additionally complaining of fatigue,
weight gain, cold intolerance, dry skin, and hair loss. Endocrine studies are war-
ranted in patients with concern for a pituitary tumor. Symptoms vary depending on
the pituitary tumor type, size, location, and hormones secreted, if any. The most
common pituitary tumor, prolactinoma, is associated with headaches and changes in
menstruation, vision, and libido. Other tumor types may be associated with changes
in weight and blood pressure, as well as headache.
Patients determined to have migraines should be interviewed about the onset,
severity, and quality of their headaches, including exacerbating and relieving fac-
tors, identifiable “triggers” and other risk factors, such as head trauma or family
medical history of migraines. There are no specific laboratory abnormalities associ-
ated with migraines, and neuroimaging is not recommended for patients with
migraine presentation and a normal physical examination [13].
Headache triggers consist of a wide array of influences which make the patient more
vulnerable to, or actually precipitate migraine onset. Common factors include altera-
tions in sleep or meal patterns, emotional stress, physical exertion, and illness [14].
Other triggers may include bright or fluorescent lighting, elevated altitude, barometric
pressure or weather changes, and such odors as household cleaning products, car
exhaust, or perfumes. Dietary triggers that affect some migraineurs include monoso-
dium glutamate, aspartame, chocolate, citrus fruits, and tyramine containing foods,
such as aged cheeses and red wine. Other types of alcohol most frequently implicated
as migraine triggers include whisky, beer, and champagne. Nitrate or nitrite food
preservatives are associated with causing cerebral vessel dilation and triggering
migraines also. Of note, caffeine may be used as a treatment for migraines, speeding
the onset and effectiveness of other pain relievers by up to 40%. However, caffeine
overuse makes migraineurs particularly vulnerable to rebound headaches, and its use
should be otherwise curtailed in this population. In 60% of women of reproductive age
who experience migraines, normal cyclical fluctuations precipitate migraines, the fall
in estrogen levels prior to menses onset thought to be the causative factor [15]. A subset
of migrainous women experience catamenial (menstrual) migraines, which are defined
as attacks of migraine without aura that occur regularly on day 1 of menstruation, ±2
days, and at no other time [15]. Comorbidities frequently associated with migraine
headaches include obesity, depression and/or anxiety disorders, epilepsy, diabetes mellitus,
obstructive sleep apnea, and tension-type headaches [16].
A headache diary is a critically useful tool in helping to identify patterns in the
patient’s migraines, and to determine what factors trigger, aggravate, or alleviate the
process. Medication use and other treatment strategies should also be documented,
to track compliance, efficacy and side effects [17].
Previous observational studies suggested a possible relationship between patent
foramen ovale (PFO) and migraine [18]. However, further investigation has shown
no association, and screening transthoracic echocardiograms (TTEs) are not
indicated in the evaluation of migraines [18].
Treatment Options
In addition to alternative and complementary nonpharmacologic strategies, there

are two broad categories of medication therapy for migraines: acute/abortive and
preventative/prophylactic. Exclusive acute care migraine treatment is not enough
for those patients who suffer from frequent migraine attacks or who experience
severe disability despite appropriate abortive therapy. In fact, excessive use of acute
medications can result in decreased efficacy, increased head frequency, medication-
induced “rebound” headaches, and the development of chronic daily headaches
[19].
Abortive therapy targets acute head pain and associated symptoms, such as
nausea and vomiting. Preventative therapy aims to reduce the frequency and/or
intensity of attacks, to improve daily functioning and quality of life. Prophylaxis is
suitable for patients with frequent or severe migraines, considerable disability or
resistance to acute therapy. Neither type of therapy can substitute for appropriate
lifestyle changes or the avoidance of identifiable migraine triggers.
Table 18.1 Indications for migraine prophylaxis

1. 3–7 headaches/month (8 or more may be indicative of overuse headache)
2. Lasting longer than 2 days
3. Causing severe disability, including hemiplegia
4. Refractory to abortive therapy
5. For which standard therapy is intolerable, overused or contraindicated
6. With a predictable pattern of occurrence (such as menstrual migraines)
Nonpharmocologic Treatments
Some patients prefer nonpharmacologic strategies in lieu of, or in addition to

medications. A multimodal approach that incorporates both may include behavioral
treatments (relaxation training, biofeedback, cognitive therapy for stress manage-
ment) as well as pharmacologic prevention. Evidence-based recommendations for
the use of hypnosis, acupuncture, transcutaneous electrical nerve stimulation
(TENS), chiropractic or osteopathic cervical manipulation in reducing migraine fre-
quency and severity are quite variable [20]. Acupuncture has some success with
chronic headache treatment, and its effects are thought to be due to the release of
endogenous opiates, as well as activation of descending inhibitory pain pathways.
However, there may also be a significant placebo effect [21].
Prophylaxis
Although migraine prophylaxis cannot substitute for adhering to lifestyle improvements

and avoidance of known triggers, it can certainly benefit a large number of chronic
migraineurs, perhaps as many as 25% by some estimates, and studies suggest that
preemptive therapies are currently underutilized. Prophylaxis should be considered
in patients who experience two or more headaches per week, whose headaches
cause significant impact on their lives despite appropriate use of medication or who
require abortive medication treatment on 2 or more days per week, potentially
putting them at risk for chronic daily headaches (see Table 18.1). Prophylaxis is
considered effective if it decreases migraine frequency by at least 50% within 3
months [22]. The goals of prophylaxis include a reduction in the frequency and
severity of migraine symptoms, improved functionality and quality of life, decreased
reliance on, and improved responsiveness to, abortive therapies, and prevention of
migraine progression. Patients need to be educated about the potential risks and
benefits of any preventative medications that are prescribed, and advised that most
medications take 2–3 months to show full effect. Patients should be further encour-
aged to keep a daily headache journal during the trial of their prophylaxis, in order
to help in evaluating adherence, efficacy, and any adverse effects. For most medica-
tions, the lowest possible dose should be selected initially, and titrated up over
several weeks or months, as needed. Prophylactic medications are chosen based on
the patient’s headache characteristics, patient preference, side effect tolerability,

and any coexisting diseases. Efficacy of medications may be limited by poor com-
pliance from intolerable side effects, inadequate results, or need for daily
administration.
There are several medications demonstrated to be effective in decreasing the
number of migraines experienced monthly by half. These include antidepressants,
beta-adrenergic blockers, calcium channel blockers, nonsteroidal anti-inflammatories,
anticonvulsants, and botulinum toxin type A [23]. Patients with underlying hyper-
tension are often trialed on beta blockers or calcium channel blockers. Patients with
mood disorders such as anxiety or depression may be prescribed tricyclic antide-
pressants, serotonin antagonists, or venlafaxine [24, 25]. Obese patients, for whom
weight gain may be a particularly intolerable side effect, may prefer topiramate,
which can actually facilitate weight loss. Patients with concurrent seizure disorders
may benefit from treatment with antiepileptics, such as topiramate, gabapentin, or
valproate. Nonprescription prophylactic medications may include magnesium,
riboflavin (B2), Coenzyme Q-10, and butterbur. Other options include botulinum
toxin type A, occipital nerve blocks, and acupuncture [26, 27]. Refer to Table 18.2
for a synopsis of prophylactic medications.
• Botulinum toxin type A (Botox)
• Botulinum toxin type A is a focally acting protein that blocks the release of ace-
tylcholine from presynaptic nerve endings and the release of pro-inflammatory
nociceptive mediators such as substance P, glutamate, bradykinin, cytokines,
prostaglandins, and calcitonin gene-related peptide. Reducing these peripheral
nociceptive mediators decreases central sensitization and its attendant effects of
inflammation, vasodilation, and edema. Botox has been shown to be effective in
decreasing headache frequency in patients with refractory migraines, and the
effect lasts for approximately 3 months. Total doses of 100 units of Botox can be
injected into five sites (glabella, temporal, frontal, suboccipital, and trapezius)
with high safety and tolerability. Treatment efficacy is associated with a high
incidence of unilateral headaches and scalp allodynia—apparent predictors of
responsiveness to Botox therapy. Adverse effects include injection site pain,
blepharoptosis, diplopia, and atrophy of injected muscles, particularly the tem-
poralis muscle (“hourglass” concavity) [28, 29].
• Fluoxetine (Prozac)
• Fluoxetine is a selective serotonin receptor inhibitor that downregulates sero-
tonin receptors, thereby increasing synaptic serotonin. It is a good option for
those with comorbid depression as it has been shown to both decrease headache
frequency and improve mood in this population.
• Amitriptyline (Elavil)
• Amitriptyline, a tricyclic antidepressant, downregulates serotonin receptors,
increases the levels of synaptic amines (norepinephrine and serotonin), enhances
endogenous opioid receptor action and facilitates descending modulation of
nociception in the trigeminal nucleus caudalis. It is another good option for mood
enhancement as well as migraine prevention.
Table 18.2 Migraine prophylaxis medications

Medication Adverse effects Notes
Beta blockers
Fatigue, postural symptoms, Caution with diabetes mellitus,
asthma exacerbation, chronic heart failure, asthma,
depression, impotence cardiac conduction defects,
depression or Rayaud’s
syndrome. Useful in patients
with comorbid cardiovascular
disease or anxiety disorder.
Avoid abrupt discontinuation.
Trial for 1 month
• Propranolol (Inderal) First-line agent
20 mg BID (40–
160 mg/day)
• Atenolol (Tenormin) Fewer side effects than
50–200 mg daily propanolol
• Metoprolol Use short acting formulation
(Lopressor/Toprol) BID or longer acting QD
100–200 mg daily
Calcium channel blockers
• Verapamil (Calan, Constipation, hypotension, Evidence is mixed as to efficacy
Covera) dizziness, dry mouth, in migraine prophylaxis
40 mg TID (40–80 mg peripheral edema, weight
TID) gain
ACE inhibitor/ARB
• Lisinopril (Prinivil, Cough, teratogenic Moderate benefit demonstrated
Zestril)
20 mg daily
• Candesartan Dizziness, teratogenic Angiotensin receptor blocker
(Atacand) with benefit shown in limited
16 mg daily studies
Anticonvulsants
• Topiramate Paresthesias, weight loss, May be helpful in patients
(Topamax) fatigue, memory impairment particularly concerned about
25 mg qhs (25– weight gain as an intolerable
200 mg/day) side effect of migraine
prevention
• Gabapentin Sedation, dizziness, paresthe- Limited data showing efficacy
(Neurontin) sias, fetal anomalies
300 mg BID (900–
3,600 mg/day)
• Valproic acid Drowsiness, tremor, nausea, First-line agent but must be used
(Depakote) dizziness, weight gain, cautiously with liver disease,
250 mg BID (500– hepatotoxicity. Neural tube thrombocytopenia or
1,500 mg/day) teratogenicity pregnancy. Indicated for
atypical migraine aura and
for comorbid epilepsy, mania,
trigeminal neuralgia, tension
type or cluster headache.
Unclear mechanism of action
for headache prevention
(continued)

Antidepressants
• Amitriptyline (Elavil) Drowsiness, dry mouth, weight Tricyclic antidepressant (TCA).
10 mg qhs (10–75 mg gain Successful in multiple
qhs) studies, especially in patients
with mixed migraine and
tension type headache. One
of the most commonly
prescribed preventive drugs
in the USA
• Nortriptyline Less sedating TCA
(Pamelor)
10 mg qhs (10–150 mg
qhs)
• Venlafaxine (Effexor) GI upset, sedation, constipation Selective serotonin–norepineph-
75–225 mg daily rine reuptake inhibitor.
Useful in comorbid anxiety
disorder or tension type
headache
• Fluoxetine (Prozac) GI upset, somnolence, tremor, Selective serotonin reuptake
10 mg daily (10– impotence inhibitor (SSRI) of unclear
80 mg/day) benefit in migraine
prevention
Miscellaneous
• Naproxen (Aleve) GI upset, peptic ulcers, Short course therapy may be
500–1,000 PO QD coagulopathy, renal helpful for menstrual
dysfunction migraines: daily × 1 week
• Butterbur GI upset Good response after 4 months of
75 mg BID treatment shown in studies
• Coenzyme Q Well tolerated Potential benefit demonstrated in
100 mg TID multiple studies. Three
months to full effect.
Improves mitochondrial
function
• Riboflavin (Vitamin Few side effects Improves mitochondrial energy
B2) metabolism. Studied in
400 mg daily pediatric populations also.
Low cost
• Feverfew Potential ill effects from long Exact mechanism unclear, but
6.25 mg TID term COX-2 inhibition: i.e., thought to work by through
(6.25–18.75 mg TID) GI, pulmonary, coagulation inhibition of cyclooxyge-
nase-2 (COX-2), interleu-
kin-1 and tumor necrosis
factor
(continued)

• Magnesium Diarrhea, GI upset with higher Shown to be effective in certain
300 mg daily doses patients. May help in
(300–600 mg/day) preventing aura
• Botulism Toxin Type Few reports of ptosis, blurry Long duration of action,
A (Botox) vision, hematoma at requiring injections every 3
100 units injection site months for continued effect.
Good option for refractory
migraine or in patients with
poor compliance with, or
tolerance for other preventa-
tive strategies
• Acupuncture Rare. Patients must be tolerant Difficulty in conducting
of needles double-blind, randomized
controlled trials to minimize
sham, placebo or practitioner-
specific effects confounds
results. Nonetheless,
considered by some to be
extremely beneficial in
migraine prevention when
employed regularly. Effects
may be due to release of
endogenous opiates and to
the serotonergic descending
pain inhibitory pathway
• Topiramate (Topamax)
• Topiramate is an antiepileptic that blocks voltage-sensitive sodium and voltage-
activated calcium channels, inhibits glutamate release, and increases gamma
amino butyric acid (GABA) levels. It has been shown in several studies to be
safe, effective, and well tolerated in migraine prevention. Side effects include
paresthesias, anorexia, dizziness, and difficulty with word finding.
Abortive Medications
Using the patient’s headache diary to determine migraine pattern, severity and fre-
quency, and considering any other health conditions, a step-wise, individualized
pharmacologic management plan should be formulated. For milder headaches,
over-the-counter medications may be adequate.
• Nonsteroidal anti-inflammatory drugs (NSAIDS) and nonopiate analgesics
• The majority of migraine sufferers does not seek advice from their primary
care physicians, but instead self-medicate with over-the-counter analgesics.
Interestingly, the addition of an antiemetic may significantly improve the efficacy

of these regimens.
• A 2010 Cochrane analysis of ten recent studies showed that compared to pla-
cebo, 1,000 mg PO acetaminophen was effective in relieving migraine pain,
nausea, photophobia, and phonophobia. When 10 mg PO metoclopramide was
added to this acetaminophen dose, results were comparable to 100 mg PO
sumitriptan [30]. Another 2010 Cochrane review of nine relevant studies
showed that 200–400 mg PO ibuprofen was effective in relieving pain and
associated migraine symptoms by 2 h in 26% of patients (versus 12% in the
control groups). A separate Cochrane review showed that 400 mg PO ibupro-
fen was as effective as 1,000 mg PO aspirin. There was no information about
adding anti-emetics. Adverse effects were rare, but caution should be employed
in patients with impaired renal function or history of gastrointestinal ulcers or
bleeding [31].
• Oral NSAIDS alone, or in combination with caffeine and/or an anti-emetic are a
reasonable first-line choice for mild to moderate migraines. Ketorlac IM may be
administered as a rescue agent in the hospital or emergency room, but the evi-
dence for its efficacy is mixed.
• Antiemetics
• Oral antiemetics are a useful adjunct for the nausea and vomiting associated with
migraine. Metoclopramide IM/IV is particularly effective, and has also been
used as migraine monotherapy. Prochloperazine IV, IM and PR and chlorpromazine
IV are similarly effective in many patients.
• Triptans
• Triptans are the first-line treatment for migraine, and are specifically approved
by the Federal Drug Administration (FDA) for the treatment of migraines (see
Table 18.3). They are high-affinity serotonin (5-HT)1B/1D receptor agonists with
several mechanisms of action, and with few pharmacodynamic differences
between the different triptans available. They cause vasoconstriction of dilated
meningeal, dural, extracerebral, and pial blood vessels via the 5HT 1B receptors,
inhibit release of nociceptive neuropeptides (e.g., substance P, neurokinin) from
trigeminal nerve terminals via presynaptic 5-HT 1D receptors , and inhibit
ascending thalamic transmission of painful sensory afferents via 5-HT 1D recep-
tors in the trigeminal nucleus caudalis region of the brainstem. This drug class is
very effective in targeting migraine pain relief, but is neither preventative nor
curative, requires a prescription, and is relatively expensive. Triptans are well
tolerated with few side effects and a well-established safety record. They are
available in oral, subcutaneous, parenteral, and intranasal preparations, although
more than 80% of all triptan prescriptions are for the oral formations. However,
because of their vasoconstrictive effect, they are contraindicated in patients with
hypertension, cardiovascular, or peripheral vascular disease, arrhythmias, severe
liver disease and in those patients concurrently prescribed monoamine oxidase
(MAO) inhibitors. There have been reported associations with stroke and
myocardial ischemia, but the overall risk appears to be minimal when prescribed
18
Table 18.3 Triptans

Medication Dosing Notes
• Sumatriptan (Imitrex) 25, 50, 100 mg PO Patients with nausea and vomiting, as well as pediatric populations,
seem to benefit from the intranasal and subcutaneous forms.
5, 10, 20 mg IN spray
4, 6 mg SC injection Half-life of 2.5 h
• Zolmitriptan (Zomig) 2.5, 5 mg PO 2.5, 5 mg PO disintegrating tablets also available. Half-life of 3 h
5 mg IN spray
• Naratriptan (Amerge) 1, 2.5 mg PO Half-life of 6 h
• Rizatriptan (Maxalt) 5, 10 mg PO Half-life of 2–3 h
• Eletriptan (Relpax) 20, 40, 80 mg PO Half-life of 4 h
• Almotriptan (Axert) 6.25, 12.5 mg PO 12.5 mg dosing tends to be most effective. Half-life of 3–4 h
• Frovatriptan (Frova) 2.5 mg PO Long half-life (26 h) makes this a good choice for longer
migraines, such as menstrual migraines
• Sumatriptan + Naproxen (Treximet) The recommended dose is one tablet Combination of a triptan with an NSAID. Contraindicated in third
(85 mg of sumatriptan and trimester of pregnancy and during lactation, and caution with
500 mg of naproxen sodium) asthma. Half life of 2 h (sumatriptan) and 12–17 h (naproxen).
Do not take a second dose within 2 h of the first. Do not take
more than two tablets in 24 h
327
to lower-risk patient populations. They are all FDA Pregnancy Category C.

Although extremely successful as abortive medications, triptans must be used
cautiously to guard against medication-overuse (“rebound” or “drug induced”)
migraines. Some practitioners recommend acute therapy no more than two head-
ache days per week on a regular basis. Requiring more than this amount likely
indicates that preventive therapy is required.
• Opioids and barbiturates
• Neither opioids nor barbiturates are FDA-approved migraine treatments.
Opioids include morphine, codeine, and the opioid-containing drugs OxyContin
(oxycodone), Percocet (acetaminophen and oxycodone), and Vicodin (acet-
aminophen and hydrocodone). Barbiturate-containing drugs include Fiorinal
(aspirin, butalbital, and caffeine) and Fioricet (acetaminophen, butalbital, and
caffeine). A 2007 survey by the National Headache Foundation found that nei-
ther opioids or barbiturates are regularly prescribed as first-line migraine treat-
ments, but that when another first treatment fails, 25% of general
practitioners—but only 7% of neurologists—prescribe these drugs as second-
line treatments. There may still be a limited role for these opioids, such as for
pregnant patients, or for patients with heart disease, hypertension, or stroke
history, for whom triptans are not an option. However, opioids are clearly
linked to causing rebound headaches [19].
Chronic (“Transformed”) Migraine
Chronic migraine, previously known as transformed migraine, is defined by hav-

ing 15 or more headache days per month for more than 3 months. Chronic
migraines may be less intense, but more disabling and less responsive to treat-
ment. There are multiple genetic and environmental risk factors for transformation
from episodic to chronic migraine, including female gender, Caucasian race, lower
socioeconomic status, obesity, depression, sleep disorders, frequent life stressors,
and the overuse of caffeine and acute-headache medications (analgesics, triptans,
opioids, and ergotamine) [32]. The exact mechanisms of chronic migraine trans-
formation are unclear, but physiologic alterations are demonstrable in chronic
migraine patients. Magnetic resonance imaging and positron emission tomogra-
phy reveal baseline hyperexcitability in the occipital cortex and neuronal changes
within the periaqueductal gray matter, thalamus, and trigeminovascular system.
Also, cerebrospinal fluid studies demonstrate increased levels of inflammatory
neuropeptides, suggestive of persistent activation of nociceptive pathways. This
“central sensitization,” whereby the threshold for peripheral nociceptive input and
central processing is reduced, seems to be the anatomic basis for chronic migraine
pathology.
In regard to treatment options for chronic migraine, one of the most promising
agents is topiramate (Topamax), a GABA agonist, because it reduces cortical
hyperexcitability. Cutaneous allodynia is poorly responsive to triptan therapy,
because triptans cannot block ongoing sensitization of trigeminovascular neurons,

making successful headache treatment more challenging in these patients.
Refractory Migraines
There is a small but significant subgroup of migraine patients who do not respond
to accepted therapies, and who are considered to have refractory migraines. Rarely,
they may require care in-patient therapy, such as parenteral analgesics, antiemetics,
steroid, fluid or possibly, hyperbaric oxygen therapy (HBOT). Refractory patients
may also be offered preventative drug treatments with higher risks of side effects or
toxicity.
• Transcranial magnetic stimulation
• Noninvasive transcranial magnetic stimulation for the acute treatment of migraine
with aura has been shown in clinical trials to be effective in aborting headache
pain and in providing sustained pain relief at 24 and 48 h after treatment, with
minimal side effects. It may be a tool for certain patients in whom aura signals
an impending migraine, to neutralize headache progression. Optimum dosing,
appropriate patient populations and overall cost-effectiveness are yet to be fully
elucidated for this therapy, however [33].
• Hyperbaric oxygen therapy (HBOT)
• A recent Cochrane review of nine trials showed that there is some weak evidence
that hyperbaric oxygen therapy, the therapeutic administration of 100% oxygen
at environmental pressures greater than one atmosphere, may be effective in the
treatment of acute migraine attacks. Pooled data from three trials found evidence
that 70% of study patients obtained noticeable relief within 40 min of initiating
hyperbaric oxygen compared to a sham therapy. There is no evidence that it can
reduce the incidence of nausea and vomiting or decrease requirements for rescue
medication. As well, neither normobaric nor hyperbaric oxygen therapy has been
shown to have any effect in preventing migraine episodes. No serious adverse
effects have been recorded in studies to date on HBOT for migraine treatment.
However, high-dose oxygen may increase oxidative stress through free radical
species. Precautions against chamber fire in the oxygen rick environment must
be followed. Also, HBOT may cause aural, sinus, or pulmonary barotrauma from
supra-atmospheric pressures. Other risks include temporary worsening of short-
sightedness and claustrophobia. HBOT is relatively expensive and requires com-
plex equipment not readily available in many locations. It has not been specifically
studied in refractory migraine populations and cannot be recommended as a
routine therapy [34].
• Steroids
• For acute relief of severe, refractory headaches, such as patients who are with-
drawing from overuse of acute care medications, IV corticosteroids may alleviate
the severity of migraine pain. A British Medical Journal reviewed seven relevant
randomized, control trials conducted in Emergency Departments from 1999 to 2008,
in which corticosteroids were compared to placebo for efficacy in acute migraine

relief and prevention of recurrence at 72 h. Each trial, consisting of 55–205
participants, included a standard abortive migraine treatment plus the addition of
10–25 mg IV dexamethasone or a saline placebo. Dexamethasone and placebo
were equally effective at acute pain reduction, but dexamethasone was more
successful at reducing headache recurrence at 72 h [35]. No significant side
effects were found. The reviewers did not have enough data to perform subgroup
analysis to determine which migraine patients had most favorable results or to
compare differences between abortive agents chosen.
• Migraine surgery
• Certain patients who experience severe migraines may be candidates for surgical
decompression of peripheral nerves that act as migraine triggers. Surgical
intervention is a novel alternative for those patients who do not respond
adequately to traditional therapies or who cannot tolerate medication side effects.
Dissection of the supraorbital, supratrochlear, greater occipital, and various
trigeminal nerve branches have been described to deactivate frontal, temporal,
and occipital trigger sites, with excellent outcomes [26]. Careful patient selection
is extremely important, including a trial of injections with local anesthetic or
botulinum toxin in the described trigger sites to determine potential effectiveness
of surgical decompression. If trial with botulinum yields significant improvement
(at least 50% reduction from baseline frequency and/or severity for at least 4
consecutive weeks), then surgical treatment of the peripheral nerve triggers can
be considered [20].
Special Populations/Comorbidities
Pregnancy and Lactation
Migraine frequency tends to decrease during pregnancy, although some women

have worse headaches early in pregnancy until their hormones levels stabilize. By
the third trimester almost 90% of migraineurs report significant improvement [36].
The use of triptans, barbiturates, and aspirin-containing medications remain contro-
versial. Of the seven triptans marketed in the USA, three have voluntary pregnancy
registries. Animal studies conducted on each of the triptans suggest that these drugs
are relatively safe, and may be used if benefits outweigh risks. One observational
study suggested an increased risk of preterm delivery and low birth weight term
newborns [37]. Acetaminophen, opioids, and appropriate antiemetics, such as
prochlorperazine (Compazine) are the treatment options of choice for migraines
during pregnancy. Ergot alkaloids are contraindicated [37]. For prophylaxis, beta
blockers have been well studied in pregnancy, with few negative findings. Occipital
nerve blocks may also be employed.
A rebound increase in migraine severity tends to occur after delivery unless the
patient is breast feeding, in which case, this relapse may occur after cessation of
lactation, and resumption of regular menstrual cycles. Triptans are detected in breast
milk, but at very low levels unlikely to affect the infant.
Pediatric Populations
Migraine is a prevalent disease in children and adolescents, estimated to be up to

20% in the older age groups. Presentation is generally similar to adult patients,
except that children may have migraines that are of shorter duration and with bilat-
eral head pain. Also, in pediatric migraine clinical trials, there is noted to be a higher
response to placebo interventions [38], making it more difficult to identify clinically
helpful treatment strategies. There are not many randomized controlled trials
published on pediatric migraine care.
With regard to the teenage population, inability to participate in sporting and
social activities due to migraine headaches can be very distressing. As well, one
study demonstrated a 4.6 times higher incidence of suicidal thoughts in teenagers
who suffer from classic migraines headaches, compared to teenagers without
migraines. Another independent factor noted in this study was headache frequency,
with more than 7 days/month being significant. It was not clear from this research
whether there was an associated increase in suicidal behaviors [39].
Medications found most consistently to be successful for pediatric patients
include acetaminophen, ibuprofen, triptans (particularly 10–20 mg nasal sumitrip-
tan), and intravenous prochlorperazine for emergency department rescue [40].
Prognosis
Migraine is a chronic disorder and its prognosis has not been well established in any
given population of patients who suffer from this condition. There is wide variabil-
ity in long-term outcomes, with some patients having complete remission, others
partial remission, and still others a persistent, progressive course. In fact, a review
from 2008 revealed that over a 1-year period, 84% of patient continued to have
migraines, 10% had complete remission, 3% had partial remission, and another 3%
developed chronic migraine. Risk factors associated with progression, such as obe-
sity, depression, medication, and caffeine overuse, were confirmed in this study.
Partial remission tends to increase with age, especially in postmenopausal females.
There are a number of studies suggesting an increased risk for ischemic stroke in
patients with migraine, particularly women who experience migraine with aura.
Fortunately, this association between migraine with aura and ischemic cerebrovas-
cular events in otherwise healthy women also demonstrates good functional
outcomes for these patients [16].
In summary, those patients who are effectively controlled with appropriate
preemptive and abortive medications and lifestyle modifications (i.e., avoidance of
known triggers) have a more optimistic chance of partial or complete remission

from migraine than those patients who are incompletely or inadequately managed
in the care of this serious condition.
Cluster Headache
Introduction
Cluster headache is a primary headache disorder characterized by attacks of

excruciating unilateral pain with associated cranial parasympathetic symptoms and
restlessness. These attacks are considered to be the most painful of any headache
disorder, with some women sufferers comparing the pain as being worse than
childbirth and others contemplating or attempting suicide during the attack as a way
to end the pain. A hallmark of cluster headache is the regular periodicity of attacks.
A cluster attack is a single instance of pain, whereas a cluster period, or cycle, is the
period of weeks to months during which the attacks occur regularly. People of any
age can be affected by cluster headache, with a mean onset of 29–35 years old. The
prevalence of cluster headache is 0.1–0.2% of the population, based on European
studies. Overall, the male:female ratio is 4.3:1. However, males are even more likely
to have chronic cluster headache with a ratio of 15:1 compared to a male:female
ratio of 3.8:1 for episodic cluster headaches [41, 42]. Epidemiological surveys
indicate a genetic basis for cluster headache, with first-degree relatives being 5–18
times more likely to have cluster headache than the general population [43]. Cluster
headache patients have a markedly decreased health-related quality of life and expe-
rience greater limitations in social function than patients with migraine. Greater
than 75% of patients with cluster headache had restrictions in activities of daily
living and 13% report activity inhibitions outside their cluster cycle [44].
Definition and Classification
Cluster headache belongs to the group of primary headache disorders referred to as

trigeminal-autonomic cephalgias (TAC). This group is named for the distribution of
pain in the first division of the trigeminal nerve and accompanying ipsilateral
cranial autonomic symptoms.
Cluster headache is diagnosed clinically using the criteria defined by the
International Classification of Headache Disorders, 2nd edition (Table 18.4) [45].
A cluster headache is strictly unilateral with pain usually occurring without warning
and often being described as piercing, boring, or stabbing. The pain is associated
with cranial parasympathetic symptoms on the same side as the pain, such as con-
junctival injection or lacrimation, nasal congestion or rhinorrhea, eyelid edema,
forehead or facial swelling, miosis or ptosis. Additionally, patients are usually
Table 18.4 Cluster Headache Criteria (The International Classification of Headache Disorders,
2nd edition)
(A) At least five attacks fulfilling B–D
(B) Severe unilateral orbital, supraorbital or temporal pain lasting 15–180 min if untreated.
During part (but less than half) of the time course of cluster headache, attacks may be less
severe or of shorter or longer duration
(C) Headache is associated with at least one of the following:
1. Ipsilateral conjunctival injection or lacrimation
2. Ipsilateral nasal congestion
3. Ipsilateral eyelid edema
4. Ipsilateral forehead and facial sweating
5. Ipsilateral miosis or ptosis
6. A sense of restlessness or agitation
(D) Attacks have a frequency from one every other day to eight per day. During part (but less
than half) of the time course of cluster headache, attacks may be less frequent
(E) Not attributable to another disorder
Episodic cluster headache
(A) Attacks fulfilling the criteria for cluster headache
(B) At least two cluster periods lasting 7–365 days and separated by pain-free remission
periods of greater than 1 month. Cluster periods generally last between 2 weeks and 3
months
Chronic cluster headache
(A) Attacks fulfilling the criteria for cluster headache
(B) Attacks recur for greater than 1 year without remission or remission periods less than 1
month
agitated, unable to lie down, and characteristically pace the floor during an attack.
Cluster headaches have a frequency from one every other day to eight per day.
However, the majority of subjects have one to two headaches daily for weeks to
months at a time. To fulfill the criteria for cluster headache, one must have a history
of at least five attacks that cannot be attributed to any other disorder. As many as
90% of cluster headaches are episodic, which is defined as having attacks for 7 days
to 1 year with a break of at least a month between cycles for at least two cycles. In
chronic cluster headache, attacks recur over 1 year without remission, or have
remission periods less than 1 month.
Etiology and Pathophysiology
The pathophysiology of cluster headache is not fully understood and the disorder has
been known by many names (Table 18.5). Major features of cluster headache are a
trigeminal distribution of pain, cranial autonomic symptoms, and an episodic pattern
of attacks [4]. Triggers of cluster headache include alcohol, nitroglycerine, exercise,
and elevated environmental temperatures. Classically, cluster headache was referred
to as a vascular headache based on an angiographic observation of localized narrow-
Table 18.5 Older terms for cluster headache

• Erythroprosalgia of Bing • Petrosal neuralgia (Gardner)
• Ciliary neuralgia • Vidian neuralgia
• Migrainous neuralgia • Sluder’s neuralgia
• Erythromelgia of the head • Hemicrania angioparalytica
• Horton’s headache
• Histaminic cephalgia
Modified from [46]
ing of the internal carotid artery in the region of the cavernous sinus made during an
acute cluster headache. More recent theories implicate a neuronal discharge trigger-
ing vascular change. Pain afferents from the trigeminovascular system transmit sig-
nals from the cranial vessels and dura mater to the trigeminocervical complex,
trigeminal nucleus caudalis, and dorsal horns of C1 and C2. This, ultimately leads to
activation of the frontal and cingulated cortices, causing unilateral head pain. Reflex
autonomic activation of the parasympathetic nervous system via the facial nerve
(CN VII) acts in a positive feedback manner, causing lacrimation, eye reddening,
nasal congestion, and a partial Horner’s Syndrome. Neuropeptide release from cen-
tral and peripheral synapses of trigeminal neurons, particular vasodilatory peptides
substance P, calcitonin gene-related peptide, and vasoactive intestinal polypep-
tide, is a potential cause for cluster headache [46, 47].
Observations of the seasonal variation and circadian timing of cluster headaches
suggest the hypothalamus, as a regulator of biological rhythms, plays a role in these
attacks. Abnormalities in the serum levels of testosterone, cortisol, and growth
hormone during cluster periods have been demonstrated, further implicating the
hypothalamus as having a role in cluster headaches [48]. Positron emission
tomography imaging of nitroglycerin induced and spontaneous cluster attacks have
identified an activated area in the posterior hypothalamic gray area that is particular
to cluster headache [49].
Diagnosis
Proper classification of the headache is important to identify potential secondary

causes of headaches that may require investigation. Many individuals with head-
aches that have a typical history, clinical picture, and response to treatment have
been found to have a secondary cause on neuroimaging [50]. Patients who present
with a presumed diagnosis of cluster headache likely warrant a brain magnetic reso-
nance imaging scan. Identifying the attacks as cluster headache gives clarity to the
patient and focuses the treatments offered by the physician. Even among the head-
aches in the TAC group with similar features, patients can experience very different
responses to treatments.
With cluster headache being a relatively rare primary headache disorder, a high
index of clinical suspicion is required to make the diagnosis. Assessment includes a
thorough history and physical, including a neurological examination. A detailed his-
tory of the patient’s headaches should be sought, especially detailing the site of pain,
associated symptoms, periodicity, duration of symptoms, and family history. Known
triggers of cluster headache include alcohol ingestion and vasodilators, such as nitro-
glycerine and histamine; these triggers are known to only precipitate a cluster attack
during a cluster period [51]. During a particular cluster cycle, headaches always
occur on the same side of the head and have a similar severe intensity, although the
attacks at the beginning and end of a cycle may be submaximal. Most headaches will
remain unilateral on the same side throughout an individual’s history. Less frequently,
the attack may switch sides from one cluster cycle to another. The attacks often dis-
play great regularity. Commonly, a patient will have one to two headaches a day, each
occurring at approximately the same time of day and may even display seasonal
variation in the early course of the disorder. Approximately 50% of the attacks occur
during the night, usually occurring 90 min after the onset of sleep.
Treatment Options
The pharmacologic treatments for cluster headache can be divided into three cate-
gories: abortive, transitional, and preventive. These treatments are discussed in
detail below (see Table 18.6).
Abortive Treatment
Due to the sudden onset and short duration to peak intensity of cluster attacks, desir-
able characteristics of abortive treatments include fast onset, high bioavailability,
reliable headache relief, and minimal side-effects, even with multiple doses daily.
Subcutaneous sumatriptan, a 5-hydroxytryptamine receptor agonist, is the most
effective self-administered abortive cluster headache treatment and the only phar-
maceutical treatment that is FDA-approved specifically for cluster headache. In a
placebo-controlled trial, subcutaneous sumatriptan 6 mg was significantly more
effective than placebo at 15 min, with 74% of patients reporting complete relief
compared to 26% of those taking the placebo [52, 53]. The maximum recommended
dose of sumatriptan by injection is 12 mg/day. Contraindications to sumatriptan, as
with other medications from this class, are uncontrolled hypertension or a history of
myocardial infarction or stroke.
Intranasal sumatriptan has also been shown to be significantly more effective
than placebo, although it is not as efficacious as the injectable route. In a random-
ized, placebo-controlled study comparing intranasal sumatriptan 20 mg to placebo,
the 57% of patients taking the study medication reported an improvement in pain
from severe or very severe to mild or moderate at 30 min and 42% were pain-free at
Table 18.6 Medications for cluster headache
336
Medication Adverse effects/contraindications Notes

Abortive treatment
Sumatriptan 6 mg SC (up to 12 mg daily) Injection site reaction, nausea/vomiting, First-line treatment
dizziness, fatigue, paresthesias.
Contraindicated in patients with coronary
artery disease, uncontrolled hypertension
Sumatriptan 20 mg IN Bitter taste
Zolmitriptan 5–10 mg PO Paresthesias, nausea, dizziness
Zolmitriptan 5 mg intranasal Unpleasant taste, nasal discomfort,
somnolence, dizziness, throat tightness
Oxygen 7–15 L/min by nonrebreather mask for 15–20 min Safety concerns with smoking First-line treatment
Lidocaine 4% IN 1 spray every 10–15 min Nasal congestion, unpleasant taste
Olanzapine 2.5–10 mg PO Sedation Indicated for patients that do not respond
to oxygen and have contraindications to
triptans
Chlorpromazine 25–50 mg PR
Indomethacin 50 mg PR every 30 min (max 150 mg daily)
Octreotide 100 mcg SC Nausea, abdominal bloating, injection site
reaction, dull background headache,
lethargy
Transitional treatment
Prednisone 60–80 mg PO, tapered over 12 days First-line transitional therapy
Dexamethasone 4 mg PO BID for 2 weeks followed by
4 mg PO daily for 1 week
Dihydroergotamine 1 mg IM/IV BID-TID for 1–7 days Contraindicated in patients with peripheral
Or ergotamine tartrate 2–4 mg PO daily vascular disease, uncontrolled hypertension,
coronary artery disease or pregnancy.
Contraindicated within 24 h of using a
triptan medication
N. Connolly et al.
Medication Adverse effects/contraindications Notes
18
Greater occipital nerve blockade with 0.5 cc of lidocaine Transient injection site pain
2% with a mixture of long and short acting betametha-
sone (2.5 mL)
Naratriptan 2.5 mg PO BID for 7 days or Frovatriptan Nausea/vomiting, dizziness, fatigue, paresthe-
2.5–5 mg daily sias. Contraindicated in patients with
coronary artery disease, uncontrolled
hypertension
Preventive treatment
Verapamil 240–960 mg PO daily, in divided doses (TID Constipation, hypotension, dizziness, dry First-line treatment
recommended) mouth, peripheral edema, weight gain, risk
of AV block increases with doses over

480 mg/day
Lithium carbonate 300–900 mg PO daily Tremor, diarrhea, polyuria
Valproic acid 500 mg PO qhs, up to 3,000 mg daily Nausea, weight gain, hair loss, tremor, lethargy.
Possible pancreatitis, thrombocytopenia, or
hepatic dysfunction
Topiramate 25–200 mg PO daily Paresthesias, fatigue, anorexia, nausea,
cognitive impairment
Gabapentin 100–300 mg PO TID Sedation, dizziness, paresthesias, teratogenic
Melatonin 9–10 mg qhs None
Civamide 25 mcg IN Nasal burning, lacrimation, pharyngitis,
rhinorrhea
Baclofen 15–30 mg PO 3–4 times daily Sedation
337
this time, compared to 26% and 18%, respectively for placebo [54]. Similarly,
intranasal zolmitriptan 5 and 10 mg have been shown to be effective in the treatment
of cluster headache; patients with more frequent or less severe attacks may benefit
more from the 5 mg dose compared to the 10 mg dose since this may be taken more
frequently and possibly tolerated better [55, 56]. Triptans can be used up to three
times daily when administered intranasally. Oral zolmitriptan has been shown to be
more effective than placebo at alleviating episodic cluster headaches. In a double-
blind, randomized, crossover study of 124 patients, headache response, defined as a
2-point reduction on a 5-point scale at 30 min, for patients taking placebo, 5 mg, and
10 mg PO zolmitriptan was 29%, 40%, and 47%, respectively; this was statistically
significant for 10 mg zolmitriptan compared to placebo [57]. In the same study,
there was no significant difference between the treatments in patients with chronic
cluster headaches. At one time, cluster headache patients were thought to be free
from the risk of medication overuse headaches. More recent studies, however,
suggest some patients may experience increased frequency of their cluster
headaches or a mild daily headache as a result of medication overuse [58, 59].
Many of the patients who have reported these symptoms had histories of migraine
headaches or other frequent headache types.
Inhalation of 100% oxygen is an excellent abortive treatment for cluster headache.
Doses of 7–15 L/min delivered by firm plastic nonrebreather mask for 15–20 min have
been very effective. In a recent double-blind, randomized, placebo-controlled, cross-
over trial of 109 patients, oxygen, 12 L/min for 15 min rendered 78% of patients pain-
free or with adequate pain relief compared to 20% of patients treated with high flow air
[60]. There were no adverse effects associated with the use of oxygen and there is no
limit to how many treatments can be used in a day. In a recent survey of 1,134 individu-
als with cluster headache in the USA, patients reported difficulties getting oxygen pre-
scribed by their doctors, prescribed rates that are too low to be efficacious, a lack of
proper training on use and safety and a significant expense in obtaining the medical
grade oxygen [61]. There have been reports of an increased response to oxygen when
used together with a triptan. While some patients may not experience significant head-
ache relief from oxygen, a patient should not be considered refractory to oxygen treat-
ment unless a trial of up to 15 L/min for 20 min has been completed.
Other possible abortive therapies for patients who have intractable cluster headache
may be used on their own, but often are more effective when used to augment other
abortive therapies. Intranasal 4% lidocaine, given as one spray to the ipsilateral
nostril can be repeated every 10–15 min for a total of four doses per day [51, 62].
This therapy achieves a moderate reduction of pain in only one-third of patients.
Olanzapine 2.5–10 mg administered orally is often very sedating, but may be useful
in patients who cannot use triptans or who have failed oxygen therapy [63, 64].
Chlorpromazine suppository 25–50 mg can also be used for abortive treatment [63].
While not classically responsive to nonsteroidal anti-inflammatory drugs, indo-
methacin suppository 50 mg can be repeated every 30 min up to 150 mg/day to abort
a headache [63]. Subcutaneous octreotide, 100 mcg, was significantly superior to
placebo in the treatment of cluster headache attacks in a randomized, placebo-con-
trolled, double-blind crossover study of 57 patients with cluster headache [65].
Transitional Treatment
Preventive therapies are indicated in cluster headache due to the frequency of the
attacks, with many people experiencing more than one attack per day, and the duration of
cluster periods, lasting from weeks to months to years. To use abortive treatments as
monotherapy would be exhausting and risk toxicity from multiple daily medication
doses. Many preventive treatments take days to weeks to reach therapeutic levels. Thus,
a transitional therapy is indicated to provide headache relief and bridge the gap between
cluster headache diagnosis and the time when prophylactic therapy is efficacious. Oral
prednisone, 60–80 mg PO tapered over 12 days, and dexamethasone have both been
effective at inducing remission of cluster headache, typically within 24–48 h. In an
open label study, 77% of 77 patients with episodic cluster headache had substantial
headache relief and another 12% had partial relief [51]. The treatment is less efficacious
in chronic cluster headache. Although headaches may recur after the completion of the
corticosteroid taper, the long-term use of these medications is not advocated.
Dihydroergotamine, either daily intramuscular injections (1 mg once or twice
daily) or intravenous infusion (1 mg BID or TID), is typically effective at stopping
cluster headaches within 1–2 days of treatment; this effect can last days to months
[51]. This treatment often requires that the patient be admitted for 3–7 days of treatment
or use an outpatient infusion center. Dihydroergotamine is contraindicated in
patients with peripheral vascular disease, coronary artery disease, uncontrolled
hypertension, and during pregnancy. The use of sumatriptan and other vasoconstric-
tive agents cannot be used concurrently with dihydroergotamine therapy.
Greater occipital nerve blockade with corticosteroids has been shown to be an
effective office treatment. In a placebo-controlled trial of 23 cluster headache
patients treated with a 2.5 mL mixture of short- and long-acting betamethasone
mixed with 0.5 mL of 2% lidocaine, 85% of the patients were attack free at 1 week
and 61% of steroid-injected patients were attack free from within 72 h of treatment
and 4 weeks after compared to no patients treated with saline and lidocaine alone
[66]. The use of 2.5 cc of 0.5% bupivicaine combined with 20 mg methylpredniso-
lone has also been described.
Preventive Treatment
Preventive agents are started in conjunction with the transitional therapy and are
continued throughout the anticipated duration of the cluster period before being
taped off. Continuing to take the preventive agent between cluster periods does not
seem to prevent a subsequent cluster cycle from starting. Medications are typically
titrated rapidly at the onset of preventive therapy to get the desired therapeutic
response. Treatments are generally the same for both episodic and chronic cluster
headache. Medications may be used in much higher doses than those used for other
disorders when treating cluster headache. Polypharmacy may be required to
adequately control cluster headaches. If a patient gets partial relief with one agent,
adding another preventive agent may be beneficial.
Verapamil is typically the first-line preventive agent and can be used along with
sumatriptan, ergotomine, or corticosteroids. The initial starting dose of 80 mg TID
can be titrated over 3–5 days. Doses are then increased by 80 mg every 3–7 days
until the desired therapeutic effect is met. Cluster headache patients may require up
to 1,200 mg daily for headache control [63]. Another strategy would be to start a
patient at 60 mg daily and increase by 80 mg daily every second week with electro-
cardiogram control [67]. Electrocardiograms are necessary prior to each dose
increase above 480 mg daily and every 3–6 months while on stable doses above this
threshold to evaluate for atrioventricular conduction abnormalities. In a study of
108 patients, 19% had abnormalities in the AV conduction while on verapamil with
one patient requiring a permanent pacemaker [68].
Lithium carbonate is considered to be a standard preventive therapy, but has a
narrow therapeutic window and a high side-effect profile. In multiple studies, 78%
of chronic cluster headache patients and 63% of episodic cluster headache patients
have improved while on lithium [63]. Standard doses range from 300 to 900 mg
daily. During the initial treatment phase, serum lithium concentrations should be
checked repeatedly to prevent toxicity. Prior to treatment, renal and thyroid
functions need to be checked. Adverse effects often relate to tremor, diarrhea, poly-
uria, thyroid and renal dysfunction and cognitive effects.
Several antiepileptic drugs have shown promise in the preventive treatment of
cluster headache. In several open label and retrospective studies, valproic acid
treatment demonstrated favorable cluster headache response rates from 54 to 73%
[69]. Although a double-blind, placebo-controlled study of valproic acid published
in 2002 failed to show a significant improvement in the number of patients show-
ing a 50% reduction in headaches compared to placebo, it is still considered an
effective treatment for cluster headache [70]. Suggested dosing is extended release
divalproex sodium starting at 500 mg at bedtime, increasing by 500 mg daily every
5–7 days to a maximum of 3,000 mg [63]. Reported side effects include nausea,
weight gain, hair loss, tremor, and lethargy. Pancreatitis, thrombocytopenia, and
hepatic dysfunction have also been reported. There is also clinical evidence from
open-label studies that topiramate is efficacious in cluster headache at doses rang-
ing from 25 to 200 mg daily [69]. Adverse effects, such as paresthesia, fatigue,
anorexia, nausea, and cognitive impairment have limited its use. Limited clinical
data show gabapentin to be a potentially effective preventive treatment for cluster
headache that has been refractory to other agents. In a pilot open-label study of 12
patients with otherwise medically refractory cluster headaches, gabapentin was
initiated at 100 mg TID and increased to 300 mg TID after 3 days and all patients
were rendered headache free within 8 days with only minor side-effects (drowsi-
ness) reported [69].
Melatonin, which is under the regulatory control of the hypothalamus, is a sensi-
tive marker of circadian rhythm in humans. Serum melatonin concentration is
reduced in patients with cluster headache during a cluster headache period.
Melatonin 10 mg was evaluated in a double-blind, placebo-controlled trial. Cluster
headache remission within 3–5 days occurred in five of ten patients treated with
melatonin, compared to none in the placebo group [63]. Studies using lower doses
of melatonin have not shown significant efficacy. Melatonin 9–10 mg has also been
shown to decrease the doses of more traditional preventive treatments necessary to

treat cluster headaches [63].
Civamide, a synthetic isomer of capsaicin, is a vanilloid receptor agonist and a neu-
ronal calcium channel blocker that inhibits the release of excitatory neurotransmitters,
such as substance P and calcitonin gene-related peptide, and depletes neurons of their
neurotransmitter content. In a randomized, double-blind vehicle-controlled pilot study
of 28 patients with cluster headache, 100 ml of 0.025% civamide (25 mcg) intranasally
was shown to significantly decrease the frequency of cluster headache during the first
post-treatment week [47]. The most common reported side effect was nasal burning
after the application of the nasal spray. Further study is needed to determine the efficacy
of civamide for longer-term preventive treatment of cluster headache.
Surgical Treatment
Surgical treatment for cluster headache may be considered for headaches that are
refractory to medication management or when a patient’s history precludes the use
of typical cluster headache abortive and preventive medications. It is estimated that
10–20% of cluster headaches will fail to respond to medical therapy. Bilateral
procedure may need to be considered in the minority of patients that experience
cluster attacks that alternate sides. Early procedures aimed at the cranial parasym-
pathetic system, or sectioning the greater superficial petrosal nerve, the nervus
intermedius, or the sphenopalatine ganglion have provided inconsistent pain relief
and are associated with a high rate of headache recurrence [63]. Procedures directed
toward the sensory trigeminal nerve have been the most successful treatments, but
are associated with the possibility of severe adverse effects. These procedures
include alcohol injection into supraorbittal and infraorbital nerves, alcohol injected
into the Gasserian ganglion, avulsion of the infraorbital, supraorbital, or supratro-
clear nerves, retrogasserian glycerol injection, radiofrequency trigeminal gangliorhizol-
ysis, and trigeminal root section. Radiofrequency thermocoagulation is the most
commonly used surgical technique and provides one of the best options for pain
relief. In a retrospective analysis of 66 patients with refractory cluster headache
treated with radiofrequency treatment of the sphenopalatine gangion, this therapy
was found to be more effective in episodic cluster headache than in chronic cluster
headache. In this analysis, 60.7% of 56 patients with episodic cluster headache
experienced complete pain relief from 12 to 70 months compared to only three of
ten patients in the chronic cluster headache group [71]. In a more recent review of
15 patients with intractable chronic cluster headache, a significant improvement in
mean attack frequency and intensity for up to 18 months following radiofrequency
treatment of the sphenopalatine ganglion [72]. Epistaxis, cheek hematoma, and
reflex bradycardia have been reported following radiofrequency treatment of the
sphenopalatine ganglion [73]. Additionally, complications of radiofrequency treatments
include moderate to severe facial dysesthesia, corneal sensory loss, and anesthesia
dolorosa [63]. Pulsed radiofrequency of the spenopalatine ganglion may have an
improved side-effect profile compared to ablative treatments, but so far descriptions
of this technique are limited to few case reports [73].
Hypothalamic stimulation is a treatment that has come about after positron

emission tomography (PET) studies of patient’s during cluster headaches. These
studies indicated a unique activation of the ipsilateral inferior posterior hypothalamic
gray matter with cluster headaches [49, 74]. While it is unclear whether this
hypothalamic activation is a cluster headache generator or modulator, stimulation of
the ipsilateral posterior hypothalamus has been shown to be efficacious in the
improvement of medically intractable cluster headache. A recent review of multiple
case series of deep brain stimulation found that approximately 60% of patients had
a greater than 50% reduction in frequency or intensity of the cluster attacks [75].
While effective for medically refractory cluster headaches, deep brain stimulation
does have a small risk of fatal hemorrhage [75]. The postoperative and stimulation-
related side effect of visual disturbance has limited the amplitude and voltage of the
stimulation [49, 75].
Occipital nerve stimulation is a promising treatment for refractory cluster headaches
that involves placement of electrodes implanted in suboccipital region. In several
small studies, approximately 60% of patients with an occipital nerve stimulator
have experienced a greater than 50% reduction in headache severity or frequency
[76, 77]. There has been a significant latency period of 2 months or more between
the time of lead implantation and clinical effect [78]. Relatively few side effects,
mostly related to lead migration or battery depletion, have been reported with this
procedure [63]. The leads and impulse generator may be placed with the patient
under general anesthesia and ultrasound guidance may be used effectively [79].
Occipital nerve stimulation does not seem to have same potential risks as deep brain
stimulation and trigeminal nerve destruction and should be considered prior to these
more invasive or ablative therapies.
Prognosis
For patients diagnosed with episodic cluster headache at onset, 80.7% will remain
episodic, 12.9% will develop chronic cluster headache and 6.4% will develop a com-
bined form within a 10-year period. For those patients diagnosed with the chronic
form at onset, 52.4% will remain chronic, 32.6% will revert to episodic and 14.3%
will develop a combined form of cluster headache. Poor prognosis may be related to
an older age at onset, male gender, or disease duration greater than 20 years [42].
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Review Questions
1. What percentage of migraineurs experience aura?

(a) Less than 10%
(b) 15–20%
(c) 40–50%
(d) More than 80%
2. Common migraine triggers include all of the following except
(a) Abrupt changes in sleep patterns
(b) Hormonal fluctuations associated with the menstrual cycle
(c) Sinus congestion associated with seasonal allergies
(d) Tyramine containing foods, such as aged cheese and red wine
3. Which of the following is not a phase of the common migraine?
(a) Prodrome
(b) Aura
(c) Headache
(d) Postdrome
4. Which of the following treatments would be the least effective abortive agent for
a cluster headache attack?
(a) Sumatriptan 6 mg subcutaneous
(b) Oxygen 12 L/min via nonrebreather mask
(c) Lidocaine 4% intranasal spray
(d) Verapamil 300 mg PO
5. A 33-year-old male patient with a past medical history significant only for epi-
sodic cluster headaches has been taking sumatriptan 6 mg subcutaneously twice
daily over the past 2 weeks with partial relief of cluster headaches that occur 4–6
times daily. Which of the following would be the most appropriate next step in
his treatment?
(a) Deep brain stimulation of the posterior hypothalamus
(b) Start dihydroergonovine 1 mg IM BID in addition to continuing his current
therapy
(c) Increase frequency of subcutaneous sumatriptan to three or four times daily
(d) PO prednisone taper in addition to his current therapy
Answers
1. (b)
2. (c)
3. (b)
4. (d)
5. (d)
Chapter 19
Endoscopic Therapies for Palliation
of Gastrointestinal Malignancies
Henry C. Ho and Uzma D. Siddiqui
Introduction
Malignant diseases of the gastrointestinal tract are often diagnosed at advanced

stages when surgical options are limited. Due to involvement of luminal structures,
obstructive symptoms are frequent. From a gastrointestinal standpoint, there are
numerous endoscopic therapies available for palliative purposes to improve quality
of life and short-term survival. Our experience with these techniques has improved
with time and has provided alternatives to surgical or interventional radiology pro-
cedures. Furthermore, advances in imaging have allowed for better localization and
planning of procedures.
Esophagus
Esophageal cancer is often diagnosed at an inoperable stage. Palliation of dysphagia

and swallowing can be achieved via nonoperative techniques, thereby restoring
nutritional status. In general, endoscopic techniques include those that ablate or
displace neoplastic tissue. The principal techniques utilized for tissue ablation
include argon plasma coagulation (APC), photodynamic therapy (PDT), and laser
photoablation. Dilation and stent placement are used for displacement of malignant
disease.
H.C. Ho, M.D. (*)

Section of Digestive Diseases, Department of Internal Medicine,
Yale University School of Medicine, 333 Cedar Street, 1080 LMP,
New Haven, CT 06520-8019, USA
e-mail: henry.ho@yale.edu
U.D. Siddiqui, M.D.
Department of Medicine, University of Chicago Pritzker School of Medicine,
Chicago, IL, USA

DOI 10.1007/978-1-4614-5164-8_19,
350 H.C. Ho and U.D. Siddiqui
First, APC is monopolar, noncontact, high-frequency electrocautery that uses

ionized argon gas to cause tissue coagulation. Unfortunately, success with APC for
malignant dysphagia has been limited. In one randomized study, 93 patients were
treated with APC every 2–4 days until dysphagia improved. Patients were then randomized
to APC alone or treatment with brachytherapy or PDT. Patients who underwent combination
therapy had improved dysphagia-free period and limited side effects [1]. Unfortunately,
as the depth of tissue ablation with APC is shallow, this technique is typically ineffective
in ablating large, bulky tumors causing luminal obstruction [2]. There may be a role,
however, in controlling surface hemorrhage from friable tumor masses or treating
tumor in-growth in esophageal metal stents [3].
PDT uses a photosensitizing agent in combination with endoscopic, low-power
laser exposure. The photosensitizing agent accumulates in malignant tissue after
intravenous injection and the area is then endoscopically exposed to a laser that
initiates a photochemical reaction to produce tumor necrosis [4]. Although the pho-
tosensitizing agent is typically cleared from tissue within a few days, several organs
including skin can retain it for longer periods. Therefore, skin photosensitivity can
be debilitating and may persist for 4–6 weeks. In a prospective, multicenter trial
including 110 patients treated with PDT, 19% of patients experienced sunburn [5].
Laser photoablation using neodymium:yttrium-aluminum-garnet (Nd:YAG),
potassium titanyl phosphate (KTP), and argon lasers have been used extensively in
the palliation of malignant dysphagia. The majority of experience has been with the
Nd:YAG laser; though this technique is generally reserved for large centers with
expertise. The goal, as with the aforementioned ablative therapies, is to obliterate
neoplastic tissue in order to restore luminal patency. Exophytic masses in the mid or
distal esophagus are more easily accessed; however those near the esophagogastric
junction or near the cricopharyngeus are difficult [6]. Treatments are performed at
48–72-h intervals over three to four sessions. In a consecutive study of 30 patients,
luminal patency was achieved at 97%; however, only 70% of patients were able to
achieve improved nutritional status to leave the hospital. Relief of symptoms lasted
from 4 to 14 weeks [7]. Chest pain, odynophagia, low-grade fevers may occur post-
procedure. Disadvantages to this technique include high cost, frequency of treat-
ment sessions, and difficulty in managing long segments of tumor.
The endoscopic techniques that provide displacement of neoplastic tissue in the
esophagus include esophageal dilation and stent placement. Esophageal dilation,
however, provides only temporary palliation of malignant dysphagia and is often
used as an adjunct to other therapies. Most patients experience symptom improve-
ment from dilation to a luminal diameter of 12 mm (liquid to soft diet). Unfortunately,
dilation can be complicated by perforation in up to 10% of cases [8]. Blind passage
of Maloney dilators is not recommended in a complex malignant stricture due to
higher risk of perforation [9]. Esophageal dilation with through-the-scope balloon
(Fig. 19.1) or wire-guided polyvinyl bougie dilation catheter is most commonly
used. Again, the effects of dilation are typically transient, which has led to the
increasing use of esophageal stenting.
Esophageal stent use has increased rapidly due to ease of use and comparable
outcomes to other palliative therapies for malignant dysphagia. Rigid plastic stents
19 Endoscopic Therapies for Palliation of Gastrointestinal Malignancies 351
Fig. 19.1 Endoscopic view

of esophageal balloon
dilation
Fig. 19.2 Endoscopic

view of esophageal stent
have been replaced by self-expanding metal stents (SEMS). Most SEMS are
composed of nitinol, an alloy of titanium and nickel. SEMS are deployed over a guidewire
under fluoroscopic guidance in cases where an endoscope cannot be passed beyond
the obstructing tumor (Fig. 19.2). Oral contrast can be utilized with fluoroscopy to
elucidate the lumen if the stricture is too narrow to accurately pass a guidewire.
Accurate marking of the tumor margins (with recent contrast esophagram and initial
endoscopic examination) in relation to the end of the SEMS is important. In addition,
Fig. 19.3 Fluoroscopic

view of esophageal stent
smaller caliber ultrathin endoscopes can often be passed beyond a tumor for passage
of a guidewire and then placed alongside the guidewire allowing for stent deploy-
ment under both fluoroscopic and endoscopic guidance (Fig. 19.3).
Several variations in SEMS are available and include differences in coating
(covered, partially covered, and uncovered/bare SEMS). The goal of fully covered
stents is to prevent tumor in-growth and provide removability. However, they are
associated with increased migration rates. Furthermore, fully covered metal stents
are not approved by the Food and Drug Administration for removal (only self-
expandable plastic stents are). Covered SEMS can be an effective treatment for
management of esophagorespiratory fistula. SEMS vary in length from 7 to 19.5 cm.
Due to high migration rates, more often completely uncovered or partially covered
(ends are uncovered and body of stent is coated) SEMS are utilized for managing
esophageal tumors. Uncovered metal stents cause tumor and tissue necrosis to occur
and allow it to embed into the esophageal wall. There is little comparative informa-
tion on different types of SEMS. Common complications of SEMS include migra-
tion, procedure-related perforation, food bolus impaction, reflux esophagitis, and
aspiration (particularly when the stent is placed across the esophagogastric junction
and patients are advised to not lie flat for 3–4 h after eating). In one study of 100
patients, 76 patients had covered SEMS and 14 patients had uncovered metal SEMS.
Thirty percent of the patients had balloon dilation prior to SEMS insertion. Migration
was noted in 5% of patients with an average time of 140 days; tumor in-growth
through the stent and overgrowth at the stent ends was observed in less than 10% of
cases [10]. Also of note, large proximal or mid-esophageal tumors should be evaluated

view of enteral (duodenal)
stent
for tracheal compression. Those patients may need airway stent placement prior to
esophageal SEMS. Following stent placement, most patients should avoid dense
and fibrous foods. SEMS placed across the esophagogastric junction allow constant
flow of acid from the stomach and therefore patients are routinely placed on daily
proton pump inhibitors. Though less effective, esophageal SEMS may also be
placed for compression of the esophagus from extraesophageal malignancies.
Small and Large Intestines
Gastroduodenal obstruction most commonly occurs from pancreatic head cancer,

gastric and duodenal cancers, and metastatic disease. Obstruction can lead to nau-
sea, vomiting, malnutrition, and electrolyte imbalance. Traditionally, duodenal
obstruction has been treated surgically with gastrojejunostomy. More recently,
uncovered enteral stents have been developed. It should be noted, if there is known
or impending malignant biliary obstruction, biliary stenting should be considered
first since biliary access can be difficult after an enteral stent is placed into the
duodenum.
There are dedicated duodenal or enteral stents that can be deployed through a
therapeutic endoscope or colonoscope (Fig. 19.4). Often the diameter of the therapeutic
endoscope (approximately 13 mm) is too large to pass through the point of obstruction.

view of enteral stent (with
percutaneous biliary drain)
The length of the stricture can be assessed with injection of a radio-opaque contrast
agent and passage of a guidewire under endoscopic and fluoroscopic guidance
(Fig. 19.5). Complications related to the procedure include stent malposition, perforation
and bleeding; later migration, fistula formation, perforation and bleeding can occur.
While enteral stenting seems to have a similar success rate compared to surgical pal-
liation, many patients require re-intervention. With the arrival of newer enteral stents,
the levels of technical and clinical success are quite high. In a systematic review,
stent insertion in 606 patients had 97% technical success in placement and 87% of
patients achieved clinical success and were able to take a soft solids or a full diet
within 4 days. Bleeding or perforation was noted in only 1.2%; and migration in 5%,
which were mostly managed with additional stent placement. Stent obstruction did
occur in 18%, mainly due to tumor infiltration or tumor overgrowth [11]. In another
review of 44 publications on gastrojejunostomy and stent placement for palliation of
gastric outlet obstruction, there were no major differences in technical success (96%
versus 100%), early or late complications (7% versus 6% and 18% versus 17%), or
persisting symptoms (8% versus 9%). Recurrent obstructive symptoms were more
common after stent placement, however (18% versus 1%) [12].
Uncovered colonic SEMS have been proven to be effective in relieving
malignant colonic obstruction before definitive resection or to palliate obstructive
symptoms in advanced disease. In the first case, placement of a SEMS can allow
optimization of a patient’s medical status in order to avoid emergent surgery,
which may be necessary if there is complete obstruction with signs of systemic
toxicity. SEMS have also been used in proximal colon cancers, though most are
treated with primary resection and anastomosis [13]. It can be helpful to obtain a
rectal contrast CT or barium enema prior to colonic stent placement to assess
anatomy. Some consider prophylaxtic antibiotics prior to stent placement, partic-
ularly if there is a significantly dilated colon due to the risk of microperforation
and bacteremia. Since these SEMS can be deployed through the scope, it can be
done under direct visualization (Fig. 19.6); fluoroscopic assistance can be helpful

view of colonic stent

view of colonic stent
if the endoscope is unable to traverse the lesion (Fig. 19.7). Following stent
deployment, patients should be advised to maintain soft stool consistency to avoid
fecal impaction at the stent.
Complications include perforation, bleeding, abdominal pain, and migration.
Perforation rates may be higher with antecedent radiation therapy or attempts at
dilation at the time of stent placement. Failure to achieve decompression can be
related to ineffective stent deployment across the lesion, extrinsic compression,
early migration or fecal impaction. Stent failure could be managed with repeat stenting
and APC or laser treatment of tumor ingrowth [14]. Post-procedure bleeding is typi-
cally minor and related to tumor friability. A randomized trial comparing stents
versus surgery for palliation of malignant obstruction in the left colon was stopped
prematurely due to a high rate of complications (including perforation rate of 13.7%)
in the stent group on initial interim analysis [15]. Another study compared patency
and complication rates between patients treated with stenting versus surgery over an
8-year follow-up. If patients were able to receive a second stent, similar late patency
was achieved between surgical and stent groups. Regarding complications, how-
ever, in the stent group, two patients required emergent surgery for bowel perfora-
tion. Stent obstruction occurred in 7% requiring reintervention in all but one patient.
In the surgical group, 4.1% patients died in the immediate postoperative period.
Late complications appeared similar in frequency in both groups, requiring reinter-
vention [16].
Pancreas and Biliary Tract
Multiple studies of patients with pancreatic cancer demonstrate that only 15–20%
are resectable at the time of diagnosis [17]. Therefore, those with advanced dis-
ease commonly require palliation to relieve jaundice, duodenal obstruction, or
pain. For malignant pancreaticobiliary obstruction, stents may be used as pallia-
tive measures for nonsurgical candidates in the setting of primary pancreaticobil-
iary malignancy, metastatic disease, or external biliary compression. Biliary
decompression with endoscopically placed endoprosthesis via endoscopic retro-
grade cholangiopancreatography (ERCP) can prevent cholangitis and relieve
jaundice and pruritis.
Endoscopic relief of malignant biliary obstruction can be achieved by placement
of large-bore plastic or self-expanding metal stents (SEMS) across the malignant
stricture. A key determination is the location of the stricture, whether distal to the
bifurcation of the common hepatic duct or involving the bifurcation itself (hilar
obstruction). Cross-sectional imaging is important prior to procedure to avoid
attempts at drainage of an atrophic hepatic lobe or a lobe in which adequate drain-
age is not feasible due to significant metastatic disease. Injection of contrast during
cholangiogram without subsequent drainage has increased risk of bacterial
cholangitis.
The main limitation of plastic stents is the high rate of stent occlusion, but the
advantage is easy removability. The median time for stent occlusion for standard
large-bore plastic stents is approximately 3 months and patients need repeat ERCPs
for stent change depending on their survival. Stent occlusion leads to cholestasis,
recurrent jaundice, and usually cholangitis, which can be life-threatening (Figs. 19.8
and 19.9). SEMS, which can be uncovered or covered, have demonstrated superior
patency due to the ability to resist bacterial biofilm coating on the stent. Uncovered
SEMS are permanent and not typically removable endoscopically, whereas

view of plastic biliary
stent

view of plastic biliary stent
covered SEMS (CSEMS) can be removed endoscopically (Figs. 19.10 and 19.11).
In a study comparing plastic to metal stents in advanced pancreatic cancer, stent
occlusion was seen in 33% of patients with plastic stents after a median of 57 days;
stent occlusion was only seen in 19% of metal stents after a median of 126 days [18].
Newer CSEMS have also been demonstrated to improve patency rates by resisting
tumor overgrowth or tissue hyperplasia through the stent meshwork. In one study
of unresectable distal biliary malignancies, stent occlusion was only 14% in the
CSEMS group after a mean of 304 days compared to 38% after a mean of 166 days
in the uncovered group [19]. Though in a meta-analysis comparing stent patency

view of uncovered biliary
SEMS

view of uncovered biliary
SEMS
and survival of uncovered SEMS versus CSEMS, migration rates were higher in
the CSEMS group in three different studies [20]. Because the cost of SEMS is
much greater than plastic stents, placement of a SEMS is cost-effective generally
if the patient survives longer than 3–6 months. Therefore, life expectancy
is important when considering stent type. Furthermore, treatment of SEMS
occlusion with further SEMS insertion can provide longer patency and survival
and has been shown to be cost effective [21].
Pancreatic head cancer is the most common cause of malignant distal biliary
obstruction. If resection is planned shortly after diagnosis, routine ERCP for biliary
decompression may not be performed as complications may delay or prevent surgical
resection. Indeed, a large, multicenter randomized study published in the New
England Journal of Medicine (NEJM) 2010 demonstrated that preoperative biliary
drainage compared to surgery alone for patients with cancer of the head of the pan-
creas was associated with a higher rate of complications [22]. Patients were ran-
domized to either preoperative biliary drainage for 4–6 weeks then surgery or
surgery alone within 1 week of diagnosis. The rate of serious complication within
120 days was 39% in the early surgery group and 74% in the biliary drainage group.
There has been criticism of this study, however, based on several issues including
initial ERCP procedural failure rate of 25 and 46% of patients developing post-
ERCP-related complications, both of which are quite high. Furthermore, stent
occlusion accounted for the majority of cholangitis, which occurred in 26% of the
stented group. If ERCP is performed, many endoscopists will favor placement of an
SEMS for prolonged patency and then it can be resected along with tumor at the
time of surgery or can be left in place for prolonged palliation if unresectable
disease is found.
The indications for preoperative ERCP may therefore include acute cholangitis
and severe pruritis. Stent placement is also indicated when neoadjuvant chemora-
diation is administered because the time to surgical resection is usually prolonged.
Studies have demonstrated improved outcomes for SEMS compared to plastic stents
or surgical bypass in this clinical situation [23, 24]. However, the prior enthusiasm
for preoperative stenting has been tempered by the aforementioned NEJM publication
citing a high degree of complications.
Hilar strictures can be caused by cholangiocarcinoma or metastatic disease. The
clinical success rate for achieving adequate palliation for hilar tumors is less than
for distal lesions. Technical success rates for bilateral endoscopic stent placement
are lower. Most patients with hilar obstruction can be palliated with only unilateral
drainage. Patient whom have had both left and right biliary systems accessed during
ERCP with contrast require stenting to prevent progressive cholangitis. It is not as
clear that metal stents offer superior palliation compared to plastic stents for hilar
tumors, as in the case of distal strictures. At this point, SEMS appear to offer
improved palliation [25, 26]. From an endoscopic perspective, achieving successful
drainage is more difficult technically for hilar tumors than for nonhilar tumors and
a percutaneous approach may be necessary [27].
Photodynamic therapy (PDT) has been shown to be a feasible palliative treat-
ment to reduce cholestasis. PDT involves systemic application of photosensitizing
agent followed by localized illumination of the tumor at a specific wavelength [28].
PDT is not widely available, even in large tertiary care centers, and is only limited
to endoscopists experienced in this technique. In addition, endobiliary bipolar
radiofrequency ablation (RFA) has also been reported as a palliative treatment

within the bile duct; though, published data are limited [29].
Pain Management
For patients with significant pain due to pancreatic adenocarcinoma, celiac plexus
neurolysis can be offered and is discussed further in Chap. “Interventional Pain” of
this book. Non-narcotic medical therapies are often inadequate for intense and
refractory pain. Opioids commonly contribute to nausea and constipation, which
can themselves be debilitating.
Celiac plexus neurolysis involves injection of absolute alcohol via CT-scan or
endoscopic ultrasound (EUS)-guided techniques into the region of the celiac artery
take-off from the aorta which is where the celiac ganglia are located. EUS guidance
is usually safer and more long-lasting [30]. Potential complications, though rare,
include severe postprocedural pain, and retroperitoneal abscess. Not uncommonly,
there can also be transient diarrhea and hypotension due to sympathetic nerve block-
ade and unopposed visceral, parasympathetic activity. Occasionally, altered anat-
omy from bulky lymphadenopathy or tumors may limit area of injection. While
there are no large comparative studies to a percutaneous approach, the EUS-guided
method has been proven to be safe and effective while also allowing for further
tumor staging and tissue sampling if necessary. In a meta-analysis of eight studies,
the pooled proportion of patients with pancreatic cancer who experienced pain relief
was about 80%. Only a few patients developed self-limited diarrhea in the studies
reviewed, and there were no neurological complications seen [31]. More recently,
endosonographers have been able to identify the celiac ganglia and inject directly
into them rather than the general area. A small study of 17 patients by Levy et al.
demonstrated a high rate of pain relief (94%) in patients with directed celiac gan-
glion injection [32].
Nutrition
Most patients with malignant dysphagia need nutritional management for improve-
ment of functional status potentially before and after surgery, during chemora-
dioation, or as an adjunct to palliative measures. Studies performed regarding
percutaneous endoscopic gastrostomy (PEG) tube placement safety have demon-
strated that the procedure is associated with low mortality and minimal significant
complications (Fig. 19.12). In a prospective study of 128 patients followed after
PEG placement for at least 31 days, there was 90% survival rate at 1 month. Major
complications in 3% were seen including one aspiration pneumonia and two buried
bumper syndromes [33]. Minor complications include peristomal leakage, wound
infection, and tube dysfunction, which can generally be managed conservatively.

view of internal bumper of
PEG after placement
A surgical feeding jejunonstomy should be performed for patients undergoing

esophagectomy. Percutaneous endoscopic gastrostomy (PEG) is contraindicated if
gastric pull-up will be considered. In patients who have undergone esophagectomy,
or those with a SEMS across the GE junction, feeding via a PEG may lead to recur-
rent aspiration and a PEG with jejunal feeding tube extension (PEG-J) or direct
percutaneous endoscopic jejunostomy may be preferred. In a study of 38 patients
randomized to either PEG or PEG-J, 2 patients in the PEG group developed noso-
comial pneumonia compared to none in the jejunal feeding group [34]. PEG place-
ment can also be considered for those with bowel obstruction and refractory
symptoms for venting purposes [35]. Some of the barriers to PEG placement in a
palliative population include difficulty in avoiding interposing bowel in a patient
with prior abdominal surgery, or avoiding placement in a patient with ascites given
the fear of fluid leakage and peritonitis.
Conclusion
Clearly there are numerous, endoscopic therapies available for palliation of patients
with gastrointestinal malignancies. There is good evidence that many of the men-
tioned techniques are safe and effective. One must weigh the potential endoscopic
complications and technical failures with the decision for surgical bypass or decom-
pression. In general, patients with locally advanced disease and good performance
status are candidates for surgical options; while those patients who are frail with
more widespread, metastatic disease may be best palliated via endoscopic alterna-
tives to minimize short-term complications, prolonged hospitalization and recovery.
The options for endoscopic palliation are vast with increasing experience across
centers and convincing published data to support their use. With technological
improvements in endoscopic equipment and devices, there continues to be growing
opportunities for more advanced therapies that can be provided for palliative
treatments.
Conflicts of Interest
The authors have no conflicts of interest to disclose.
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dilation of esophageal strictures. Gastrointest Endosc. 2000;51:460.
10. Dobrucali A, Caglar E. Palliation of malignant esophageal obstruction and fistulas with self
expandable metallic stents. World J Gastroenterol. 2010;16(45):5739–45.
11. Dormann A, Meisner S, Verin N, Wenk Lang A. Self-expanding metal stents for gastroduodenal
malignancies: systematic review of their clinical effectiveness. Endoscopy.
2004;36(6):543–50.
12. van Jeurnink SM, Eijck CH, Steyerberg EW, Kuipers EJ, Siersema PD. Stent versus gastroje-
junostomy for the palliation of gastric outlet obstruction: a systematic review. BMC
Gastroenterol. 2007;8(7):18.
13. Repici A, et al. Stenting of the proximal colon in patients with malignant large bowel obstruc-
tion: techniques and outcomes. Gastrointest Endosc. 2007;66(5):940.
14. Lo SK. Metallic stenting for colorectal obstruction. Gastrointest Endosc Clin N Am.
1999;9(3):459.
15. van Hooft JE, Fockens P, Marinelli AW, Timmer R, van Berkel AM, Bossuyt PM, Bemelman
WA, Dutch Colorectal Stent Group. Early closure of a multicenter randomized clinical trial of
endoscopic stenting versus surgery for stage IV left-sided colorectal cancer. Endoscopy.
2008;40(3):184.
16. Lee HJ, Hong SP, Cheon JH, Kim TI, Min BS, Kim NK, Kim WH. Long-term outcome of
palliative therapy for malignant colorectal obstruction in patients with unresectable metastatic
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2011;73(3):535–42.
17. Shaib YH, Davila JA, El-Serag HB. The epidemiology of pancreatic cancer in the United
States: changes below the surface. Aliment Pharmacol Ther. 2006;24(1):87.
18. Weber A, Mittermeyer T, Wagenpfeil S, Schmid RM, Prinz C. Self-expanding metal stents
versus polyethylene stents for palliative treatment in patients with advanced pancreatic cancer.
Pancreas. 2009;38(1):e7–12.
19. Isayama H, Komatsu Y, Tsujino T, Sasahira N, Hirano K, Toda N, Nakai Y, Yamamoto N, Tada
M, Yoshida H, Shiratori Y, Kawabe T, Omata M. A prospective randomised study of “covered”
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Review Questions
1. Photodynamic therapy (PDT) is sometimes used for tissue ablation to palliate

obstructing esophageal cancers. Two potentially debilitating side effects which
have limited the widespread use of PDT include:
(a) Nephrotoxicity and tinnitus
(b) Diarrhea and vomiting
(c) Photosensitivity and stricture
(d) Headache and diarrhea
2. All of the statements below are true regarding endoscopic dilation of obstruction
due to esophageal cancer except:
(a) Can be complicated by perforation
(b) Usually done through the scope balloon
(c) Typically provides long-lasting relief of dysphagia
(d) Often does not provide palliation and patients require endoscopic stent
placement
3. Self-expandable metal stents (SEMS) are used in the biliary tract for palliation of
malignant obstruction. They can be covered, partially covered, or uncovered
(bare). Covered SEMS are associated with:
(a) Increased obstruction rates
(b) Unacceptable rates of deployment failure
(c) Increased perforation rates
(d) Increased migration rates
4. Gastroduodenal obstruction (e.g., due to pancreatic head cancer) can be treated
with enteral stent placement. The following should be considered prior to enteral
stent placement:
(a) Status of the biliary tract to assess need for biliary stenting
(b) Helicobacter pylori status
(c) PEG placement for tube feeds
(d) Stent placement only if the endoscope can be passed beyond the duodenal
obstruction
5. Several considerations should be made prior to plastic versus metal biliary stent-
ing for malignant obstruction. All of the following would be included in the
decision making process except:
(a) Survival
(b) Resectability
(c) Location of stricture
(d) Cost
(e) Age of patient
6. In malignant colonic obstruction, one should always dilate the stricture prior to
colonic metal stent placement
(a) True
(b) False
Answers
1. (c)
2. (c)
3. (d)
4. (a)
5. (e)
6. (b)
Chapter 20
The Role of Palliative Care in Cardiothoracic
Surgery
Amit Banerjee
Cardiothoracic Surgery covers a very broad and at times ambiguous anatomical

domain. Conflicting interpretations and controversial semantics often render the
patient a victim of gaps and overlaps. Traditionally, surgical conditions involving
anything within the thoracic cage viz., ribs, pleura, pericardium, heart, lungs, esoph-
agus, great vessels, and other mediastinal contents, and additionally the entire vas-
cular system, come within the jurisdiction of a cardiothoracic surgeon. However, in
the process of diagnosis, treatment planning and crucial decision making, crucial
roles may be played by cardiologists, pulmonologists, oncologists, etc. In many
parts of the world, cardiothoracic surgery has branched out with the creation of
cardiac surgeons, general thoracic surgeons, and vascular surgeons. An important
anatomical component of the thorax, viz., the esophagus, has been taken over by
gastrointestinal surgeons and several malignant conditions are treated by surgical
oncologists.
As we discuss about palliative care in cardiothoracic surgery as a unified disci-
pline, it needs to be pointed out that the connotation of the term palliation in cardiac
surgery is a shade different from that applicable to advanced malignant thoracic
conditions [1]. Palliative cardiac surgery comprises a subset of innovative, physio-
logically viable (without restoration of normal physiology) procedures usually per-
formed in very early childhood. They allow the patient to stay alive in a reasonably
satisfactory condition, as a stepping stone to more extensive and complex proce-
dures at a later stage. This is in contradistinction to quality-improving or life-pro-
longing procedures in patients suffering from end-stage malignancies, dealt with in
detail elsewhere.
A. Banerjee, M.S., M.Ch. (*)

Department of Cardiothoracic Surgery,
Maulana Azad Medical College, New Delhi, India
Govind Ballabh Pant Hospital, University of Delhi,
New Delhi, India
e-mail: dramitbanerjee@gmail.com

DOI 10.1007/978-1-4614-5164-8_20,
370 A. Banerjee
Palliation in Cardiac Surgery
Among ‘palliative’ cardiac surgical procedures, systemic-to-pulmonary arterial

shunts are by far the commonest. Conceived by Helen Taussig, a pediatric cardiolo-
gist at Johns Hopkins, and experimentally consummated by Vivien Thomas, a
surgical technician, this path-breaking procedure was first performed on a
15-month-old cyanotic baby by Alfred Blalock, the Chief of surgery at the same
university. Thus came into existent the Blalock–Taussig shunt, a procedure des-
tined to bring succor to thousands of patients suffering from tetralogy of Fallot
and other complex congenital cyanotic heart conditions [2]. The classic direct
anastomosis between subclavian and pulmonary arteries was subsequently
modified by Werner Klinner of Munich using an interposing vascular graft.
Alternate techniques were subsequently devised and deployed by different sur-
geons. Notable among these were the Potts shunt (anastomosis of the left pulmo-
nary artery to the descending aorta) and Waterston shunt between the ascending
aorta and right pulmonary artery, later modified by Denton Cooley who recom-
mended an intrapericardial anastomosis [3]. Currently a central shunt, wherein an
expanded PTFE graft is interposed between the ascending aorta and the main
pulmonary artery, is gaining in popularity [4].
William Glenn of Yale University designed a cavopulmonary shunt between
the superior vena cava and the right pulmonary artery principally for right-sided
cardiac anomalies like tricuspid atresia, Ebstein’s anomaly, etc. Subsequently,
the classic Glenn shunt underwent modifications like bidirectional Glenn proce-
dure, and atriopulmonary connections such as fenestrated Fontan and complete
Fontan circulation: all of them palliative options for the single ventricle. The
Sano shunt revisits an option abandoned by Norwood. It connects the right ven-
tricle to the pulmonary artery through an ePTFE conduit is found useful in
specific situations.
Palliative surgery for hypoplastic left heart syndrome [5] comprises a series of
essential components viz., atrial septectomy, anastomosis of the proximal pulmo-
nary artery to the aorta with homograft augmentation of the aortic arch, and a
suitable systemic–pulmonary connection. Application of this protocol is credited to
Norwood and has undergone considerable fine-tuning over the years.
Pulmonary artery banding is another palliative option in cardiac surgery [6]. It is
used as a stepping stone to definitive surgical corrections. Not too long ago, this
served as an initial intervention for infants born with intracardiac defects causing
severe left-to-right shunting and overloaded pulmonary circulation. Its primary goal
is to restrict excessive pulmonary blood flow and protect the pulmonary vasculature
from detrimental changes. Pulmonary artery banding has also been found to play a
role in the preparation and “training” of the left ventricle in certain situations such
as arterial switch procedure in older infants. Of late, good results following early
definitive intracardiac repair has reduced the popularity of PA banding as a mode of
palliation. Yet, it continues to find favor in certain subsets of very sick patients with
congenital heart disease [7]. In fact, the development of a percutaneously adjustable
20 The Role of Palliative Care in Cardiothoracic Surgery 371
pulmonary artery band which can be thoracoscopically implanted is underway.

The dependence on shunts in many cyanotic cardiac conditions, especially tetralogy
of Fallot, is also giving way to early intracardiac repair. However, it is too early to
imagine that operative palliation in cardiac surgery is on its way out.
An extended form of palliation in cardiac surgery is the use of ventricular assist
devices or artificial hearts in patients who are awaiting availability of suitable donors
for cardiac transplantation. These ‘bridges to transplant’ are genuine life-sustainers
before the patient gets a new lease of life following cardiac transplantation.
Palliation in Non-cardiac Thoracic Surgery
Surgical palliation in non-cardiac thoracic surgery has very limited but significant
role to play. Large, inoperable, life-threatening mediastinal or pulmonary masses
not amenable to surgical extirpation may need debulking to reduce compression on
vital structures. Thoracoscopic pleurodesis with talc in patients with mesothelioma
or pleural metastases may be adjunctive to biopsy.
One major avenue of palliation in thoracic surgery is pulmonary metastasectomy.
The use of intraoperative laser technology minimizes parenchymal loss as lobec-
tomy can be avoided in many instances. Nonsurgical interventional options includ-
ing placement of expandable stents in the airways and use of laser to restore block
airways are in the endoscopists’ domain, but within the treating surgeon’s circle of
responsibility [8].
Chest wall tumors can be painful and may produce fungating ulcers. Their
removal combined with reconstructive surgery of the chest wall defect might
improve quality of life even in advanced stages.
Malignant masses in the thoracic esophagus may produce severe dysphagia and
infiltrate the trachea creating a tracheoesophageal fistula. Various palliative intuba-
tion techniques have been available since long to re-create a passage for food to pass
through or block a fistula. These include Souttar’s tube, Celestin tube, Mousseau-
Barbin tube, Atkinson’s tube, etc. [9]. Currently, endoscopically implantable tubes
such as self-expanding metallic stents, Wallstent, anti-reflux stents, etc., are avail-
able. The advancement in endoscopic armamentarium has now made palliation
more satisfying through the dual approach of lumen restoration and wherever
needed, placement of stent [10].
Although at times palliation for intrathoracic conditions may extend beyond the
scope of a cardiothoracic surgeon, she/he is expected to take the lead, and not merely
define boundaries of responsibility, in restoring a comfortable and dignified life to
the patient.
372 A. Banerjee
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20 The Role of Palliative Care in Cardiothoracic Surgery 373
Review Questions
1. Systemic-to-pulmonary artery shunts as palliative cardiac procedures are

performed in:
(a) Children with coronary artery disease
(b) Adults with valvular heart disease
(c) Patients with acyanotic congenital heart disease
(d) Children with cyanotic heart disease
2. Helen Taussig was a:
(a) Cardiac anesthetist
(b) Pediatric cardiac surgeon
(c) Vascular Surgeon
(d) Pediatric cardiologist
3. Glenn’s original shunt was between:
(a) Superior vena cava and the main pulmonary artery
(b) Inferior vena cava and the right pulmonary artery
(c) Superior vena cava and the right pulmonary artery
(d) Superior vena cava and the left pulmonary artery
4. Indwelling stents are used for the palliation of:
(a) Chest wall tumors
(b) Pulmonary metastases
(c) Advanced esophageal cancer
5. All of the following are palliative surgical options except:
(a) Metastasectomy
(b) Pleurodesis
(c) Debulking
(d) Pneumonectomy
6. Palliation in cases of congenital heart disease is usually performed:
(a) At school-going age
(b) In early childhood
(c) In the third decade of life
374 A. Banerjee
Answers
1. (d)
2. (d)
3. (c)
4. (c)
5. (d)
6. (b)
Chapter 21
Management of Advanced Heart Failure
Patients
Dominique Anwar and Asif Anwar
Introduction
The incidence of heart failure (HF) patients in the USA is estimated to be around
six million, with half a million new cases adding each year [1, 2]. It is associated
with high symptom burden, frequent hospital admissions, diminished quality of
life, high costs, and remains the leading cause of death in the USA [3, 4]. It is
expected that 70–80% of patients younger than age 65 will die within 8 years of their
HF diagnosis, despite the availability of new medical and surgical options [2]. The
evolution of HF in patients is typically characterized by acute crises or exacerba-
tions followed by periods of stability lasting for months or even years. However,
these patients are 6–9 times more likely to die of sudden cardiac death than the
general population [2]. Several tools are available to help assess the prognosis in
advanced HF patients: some are single-item predictors (such as the B-type natriuretic
D. Anwar, M.D. (*)

Section of General Internal Medicine and Geriatrics,
Tulane University School of Medicine,
e-mail: danwar@tulane.edu
A. Anwar, M.D.
Heart and Vascular Institute, Department of Medicine,
Tulane University School of Medicine,

DOI 10.1007/978-1-4614-5164-8_21,
376 D. Anwar and A. Anwar
peptide [ 5 ] , maximal oxygen consumption [ 6 ] , creatinine level [ 7 ] , other

multivariable models (such as the Seattle Heart Failure Score [7] and the Acute
Decompensated Heart Failure National Registry (ADHERE)) [8]. Similarly multiple
prognostic factors are associated with increased likelihood of death in advanced HF,
especially when coexistent: frequent emergency department visits or hospitalizations,
symptoms at rest, dependency in activities of daily living, weight loss ³ 10%, albumin
2.5 g/dL, ejection fraction < 20%, symptomatic arrhythmia, prior cardiopulmonary
resuscitation, prior syncope, and embolic stroke. However, even while using these
algorithms and other tools, life expectancy remains difficult to predict in advanced
HF [3], and this is probably one of the reasons why less than 12% of these
patients benefit from hospice care [4].
The Role of Palliative Care and Hospice in the

Management of Advanced HF Patients
An integrative model, with palliation occurring while life-prolonging therapies

are administered, is currently considered as “the best available” option [9]. In
their 2005 guidelines, the American College of Cardiology and American Heart
Association recommended palliative/hospice care referrals for end-stage heart
failure (stage D, level of Evidence 1A) [10]. The role of a palliative care consulta-
tion teaming with the cardiologists is, as for any other patient with advanced dis-
ease, to assure comfort, quality of life, and dignity. A palliative care team
collaborating closely with the primary team may help not only for symptom man-
agement, but also support the medical decision-making process, allowing more
regular reassessment of the goals of care. The addition of palliative care to cardi-
ology expertise has been proved effective in regard not only to the patient’s qual-
ity of life, but amazingly may also have an impact on survival, even at the late
stages of the disease process when patients are referred to hospice. Indeed, a non-
randomized study conducted by Connor et al. on hospice patients with advanced
HF demonstrated a significant survival improvement of 81 days compared with
those who did not receive hospice care [11]. The authors of the study postulate
that this may be due to the avoidance of unnecessary procedures, less hospital
stays, better focus on symptom relief, support for exhausted caregivers, as well as
enhanced prevention of complications. Patient referral to hospice may also play a
role in the overall medical cost reduction. Appropriate hospice referrals, whatever
the diagnosis, can save up to 40% of healthcare costs during the last month of life
and up to 17% during the last 6 months of life, with an average savings of $2,309
per hospice user [12]. Focusing on the advanced HF population only, Pyenson
et al. demonstrated that hospice referral allowed a reduction in mean Medicare
cost per patient from $53,528 to $46,792 [13].
21 Management of Advanced Heart Failure Patients 377
Pharmacological/Nonpharmacological Treatments
for Symptom Management
Pharmacological Treatment of HF
Patients with advanced HF usually receive a combination of several oral agents,

usually ACE inhibitors or/and ARBs, diuretics (loop diuretics and spironolac-
tone), and beta-blockers [14]. In the end-of-life period, it is important to plan
which medications may be removed safely and in what time frame, in anticipation
of the moment when patient’s swallowing function may become compromised.
There is a need to identify medications that should be ideally tapered (to avoid
adverse discontinuation effects such as the risk of rebound tachycardia or hyper-
tension with abrupt stop of beta-blockers). Thus beta-blockers and diuretic are
probably the medications that should be maintained up to end to avoid worsening
symptoms.
In regard to inotropic agents, even though they have not shown survival benefit,
they may provide symptomatic relief for prolonged periods of time (Class IIB
indication for end-stage heart failure) [15, 16].
Specific Pharmacological Approach of Dyspnea
Opioids
Even though only a few and small randomized controlled studies addressed
specifically the HF population [17–19], there is evidence to support the use of short
acting oral or parenteral opioids to palliate breathlessness, whichever its origin,
while the use of nebulized opioids is not supported [20].
Benzodiazepines
The role of benzodiazepines has been studied mainly in the cancer and COPD population.
Even though some studies, such as those from Navigante et al., have demonstrated
an efficacy on the subjective sensation of dyspnea in patients with advanced cancer,
especially coupled with an opioid [21, 22], a recent meta-analysis did not show
evidence for a beneficial effect of benzodiazepines in the relief of breathlessness in
patients with advanced cancer and COPD [23]. As discussed in this Cochrane
review, studies focusing on HF-related dyspnea are urgently needed.
Nonpharmacological Approach of Dyspnea
No randomized controlled trials were identified addressing the specific issue of the
efficacy of oxygen in reducing breathlessness in patients with advanced HF, whether
hypoxemic or not [24]. Pursed-lip breathing, noninvasive positive pressure ventila-
tion for sleep-disordered breathing, relaxation, and hypnosis may all be of interest,
but there is little evidence-based data to support these approaches.
Management of Other Symptoms
Pain, related or not to the cardiac condition, should be addressed similarly as in

other oncological/nononcological conditions. As advanced HF patients have very
often compromised kidney function, they must often be monitored closely when
receiving opioids with active metabolites, such as morphine or hydromorphone, to
avoid side effects, especially opioid-related neurotoxicity. Fatigue and anorexia are
distressing symptoms, which are frequent in advanced HF. Unfortunately resources
to alleviate them are actually limited. Psychostimulants such as methylphenidate
have not been studied in this population, and their potential cardiac side effects
make them difficult to recommend in this population. Techniques, such as training
in energy conservation and aerobic exercise, have been recommended. Sleep apnea
may lead to fatigue and can be treated with noninvasive ventilation. Depression is
very frequent in advanced HF, but the efficacy of antidepressant agents has once
again never been assessed in the cardiac population.
Pacemakers
Many patients and families (as well sometimes team members) believe that the
pacemaker (PM) will keep them alive or alternatively will prolong the period of
agony. However, these are not resuscitative devices and will not keep a dying patient
alive. They do not prolong survival as acidosis that develops at the end of life will
not allow the myocardium to be depolarized by the PM stimulations [25]. In conse-
quence, there is no medical indication to deactivate it. In addition, bradycardia
symptoms will be alleviated by maintaining the PM function. Finally one must keep
in mind that a pacemaker must be removed if the patient is cremated.
Implantable Cardioverter Defibrillator
There is an increasing use of implantable cardioverter defibrillator (ICD) for pri-

mary and secondary cardiac death prevention. This growing patient population
requires a special attention in the terminal days. Indeed as heart failure worsens,
patients are likely to receive more frequent shocks from ICDs, which not only cause
significant pain and anxiety to the patient, but also tremendous distress to the family
and medical team [26]. Of note repetitive ICD shocks also induce myocardial dam-
age and are detrimental for the cardiac function. In light of these problems there is
a general consensus to deactivate the ICD in the final days. This has been exten-
sively addressed and reviewed by the American College of Cardiology, American
Heart Association, and Heart Rhythm Society [27]. Therefore, the concept of future
deactivation when approaching end of life should always be included in ICD pre-
implantation discussions with the patient and family. Unfortunately, even nowa-
days, clinicians infrequently discuss ICD deactivation issues with patients and these
devices may remain active until death [28]. Hospices usually require deactivation.
In the unusual case where deactivation was not performed, hospices may use a mag-
net to avoid painful and distressing shocks at the end of life [29].
Left Ventricular Assist Devices as Destination Therapy
Left ventricular assist device (LVAD) function is to unload the failing heart and to
provide an adequate forward cardiac output to maintain organ perfusion. Although
they were originally used as a temporary bridge to recovery, then as a bridge to trans-
plantation, they are increasingly used as a destination therapy. In the latter situation
LVADs are used without any plan for transplantation. LVADs have been shown to
improve quality of life and survival compared with inotropic agents, as well as exer-
cise tolerance, end-organ function, and emotional well-being [30]. However, they are
also associated with significant rates of long-term complications such as bleeding,
infection, and neurologic events [31]. Some baseline symptoms may however remain
or occur de novo after LVAD implantation. Longitudinal in- and outpatient care is
therefore crucial for successful outcome and requires intensive involvement of patients
and caregivers. Patients may have abrupt LVAD mechanical failure leading to a sud-
den decrease in cardiac output and fatal outcome. On the other hand, LVAD may
continue to have adequate function while the patient develops other complications or
pathologies (e.g., infectious, embolic, renal). They will continue to work after the
patient is clinically brain dead, or they may prolong the dying process. Therefore,
patients and physicians must carefully weigh potential risks and benefits in the
patient’s specific situation before implementing LVAD as destination therapy. In the
follow-up they must also continue or initiate palliative care while implementing
LVADs. It is also crucial to address not only the important issue of advanced direc-
tives, but to extend such directives to what is called a “preparedness plan,” which adds
to the usual directives the specific issues related to the LVAD [32].
Communication in Advanced HF Patients
Communicating with an advanced HF patient and the patient’s loved ones can often
present multifaceted barriers, so much so that Momen in a recent literature review
called such communication the process of “addressing the elephant on the table” [33].
A survey conducted by McCarthy in 1997 among bereaved families of heart failure

patients with no sudden cardiac death showed that 37% only were aware of a poor
prognosis, 8% of patients and 44% of family members were told by a physician that
time was short, and 36% of these patients died alone [34]. We may imagine that
more emphasis is placed nowadays on accurate communication, but this is still a
challenging issue.
Criteria for Hospice Referrals of Advanced HF Patients
In the USA, patients are eligible for hospice care reimbursement under Medicare
regulations when they are likely to have a life expectancy of 6 months or less. Even
though, as discussed previously, it is difficult to predict this life expectancy in
patients with advanced HF, there are criteria to help the healthcare providers to
confirm hospice eligibility [35]. The list of these criteria can be downloaded from
several websites [36].
References
1. Tanner CE, Fromme EK, Goodlin SJ. Ethics in the treatment of advanced heart failure: palliative
care and end-of-life issues. Congest Heart Fail. 2011;17(5):235–40.
2. Hupcey JE, Penrod J, Fenstermacher K. Review article: a model of palliative care for heart
failure. Am J Hosp Palliat Care. 2009;26(5):399–404.
3. Teno JM, Weitzen S, Fennell ML, Mor V. Dying trajectory in the last year of life: does cancer
trajectory fit other diseases?J. Palliat Med. 2001;4(4):457–64.
4. Davis MP. Palliation of heart failure. Am J Hosp Palliat Care. 2005;22:211–22.
5. Doust JA, Pietrzak E, Sanders S, Glasziou P. How well does B-type natriuretic peptide predict
death and cardiac events in patients with heart failure: systematic review. BMJ.
2005;330(7492):625.
6. Mahon N, Blackstone E, Francis G, et al. The prognostic value of estimated creatinine clear-
ance alongside functional capacity in ambulatory patients with chronic congestive heart fail-
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7. Levi WC, Mozaraffian D, Linker DT, et al. The Seattle Heart Failure Model: prediction of
survival in heart failure. Circulation. 2006;113(11):1424–33.
8. Fonarow GC, Adamas Jr KF, Abraham WT, et al. Risk stratification for in-hospital mortality
in acutely decompensated heart failure: classification and regression tree analysis. JAMA.
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9. Adler ED, Goldfinger JZ, Kalman J, et al. Palliative care in the treatment of advanced heart
failure. Circulation. 2009;120(25):2597–606.
10. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline Update for the Diagnosis
and Management of Chronic Heart Failure in the Adult: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines (Writing
Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart
Failure): developed in collaboration with the American College of Chest Physicians and the
International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm
Society. Circulation. 2005;112(12):e154–235.
11. Connor SR, Pyenson B, Fitch K, et al. Comparing hospice and nonhospice patient survival
among patients who die within a three-year window. J Pain Symptom Manage.
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12. Emanuel EJ. Cost savings at the end of life. What do the data show? JAMA.
1996;275(24):1907–14.
13. Pyenson B, Connors S, Fitch K, Kinzbrunner B. Medicare cost in matched hospice and non-
hospice cohorts. J Pain Symptom Manage. 2004;28(3):200–10.
14. Goodlin SJ, Hauptman PJ, Arnold R, et al. Consensus statement: palliative and supportive care
in advanced heart failure. J Card Fail. 2004;10(3):200–9.
15. Sindone AP, Keogh AM, Macdonald PS, et al. Continuous home ambulatory intravenous inotropic
drug therapy in severe heart failure: safety and cost efficacy. Am Heart J. 1997;134(5 Pt 1):889–900.
16. Nauman DJ, Hershberger RE. The use of positive inotropes in end-of-life heart failure care.
Curr Heart Fail Rep. 2007;4(3):158–63.
17. Chua TP, Harrington D, Ponikowski P, et al. Effects of dihydrocodeine on chemosensitivity
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18. Johnson MJ, McDonagh TA, Harkness A, et al. Morphine for the relief of breathlessness in
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19. Williams SG, Cooke GA, Wright DJ, et al. Peak exercise cardiac power output; a direct indica-
tor of cardiac function strongly predictive of prognosis in chronic heart failure. Eur Heart
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in terminal illness. Cochrane Database Syst Rev. 2001;(4):CD002066.
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29. Fromme EK, Stewart TL, Jeppesen M, Tolle SW. Adverse experiences with implantable
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30. Wilson SR, Givertz MM, Stewart GC, Mudge Jr GH. Ventricular assist devices the challenges
of outpatient management. J Am Coll Cardiol. 2009;54(18):1647–59.
31. Lietz K, Long JW, Kfoury AG, et al. Outcomes of left ventricular assist device implantation as
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2007;116(5):497–505.
32. Swetz KM, Freeman MR, AbouEzzedine OF, et al. Palliative medicine consultation for
preparedness planning in patients receiving left ventricular assist devices as destination therapy.
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33. Momen NC, Barclay SI. Addressing ‘the elephant on the table’: barriers to end of life care
conversations in heart failure – a literature review and narrative synthesis. Curr Opin Support
Palliat Care. 2011;5(4):312–6.
34. McCarthy M, Hall JA, Ley M. Communication and choice in dying from heart disease. J R Soc
Med. 1997;90(3):128–31.
35. Stuart B, The NHO. Medical guidelines for non-cancer disease and local medical review pol-
icy: hospice access for patients with diseases other than cancer. Hosp
J. 1999;14(3–4):139–54.
36. http://www.lmhpco.org/professionals/diseases/heart.shtml.
Review Questions
1. Which is the global leading cause of death in the USA nowadays?

(a) Cancer
(b) Heart failure
(c) Suicide
(d) End-stage pulmonary diseases
2. What is the best tool to determinate an advanced HF patient prognosis?
(a) Single-item tools
(b) Multivariate models
(c) Prognosis factors
(d) All and none of them: prognosis in advanced HF remains difficult
3. What is the role of opioids in advanced HF?
(a) None, the risk of respiratory depression is too high
(b) Pain management only
(c) Pain management and dyspnea
(d) For dyspnea, it works only if associated with benzodiazepines
4. PM, ICD in patients who are referred to hospice:
(a) Both need to be discontinued
(b) PM needs to be discontinued
(c) ICD needs to be discontinued
(d) Both can be maintain and will improve the patient’s quality of life
5. LVAD as destination therapy:
(a) Do not improve the quality of life
(b) Do not present with severe complications
(c) Are rather cheap
(d) Can extend the duration of agony
Answers
1. (b)
2. (d)
3. (c)
4. (c)
5. (d)
Chapter 22
Palliative Care in Cardiac Electrophysiology
Eric Grubman
The field of clinical cardiac electrophysiology involves the management and

prevention of cardiac rhythm disturbances. If untreated, many of these rhythm
disturbances can rapidly prove fatal. Cardiac electrophysiology has grown dramatically
over the past 20 years, fueled largely by the advances in cardiac pacing, implantable
defibrillators, and cardiac ablation of arrhythmias. The results of this dramatic
expansion have resulted in a field that can provide invasive therapy to improve the
quality of life, as well as the duration of life.
Palliative care involves treatments designed to relieve or prevent suffering, rather
than cure the disease process. Many of these patients suffer from chronic illness, or
are nearing the end of life. Cardiac arrhythmias are far more common in these
patients than in the general population. Modern treatment of cardiac rhythm distur-
bances can often relieve or prevent symptoms, and should be considered for patients
undergoing palliative care.
This chapter first considers the treatment options available in cardiac electrophysiology,
followed by a consideration of the specific arrhythmias, as well as palliative care
decisions for each arrhythmia.
E. Grubman, M.D. (*)

Department of Internal Medicine, Yale University School of Medicine,
New Haven, CT, USA
e-mail: grubman@sbcglobal.net

DOI 10.1007/978-1-4614-5164-8_22,
386 E. Grubman
The Therapies
Devices
Cardiac Pacing
The modern era of cardiac pacing began in 1957, with the development of the
implantable pacemaker [1]. Since that time, advances in cardiac pacing have resulted
in a pacemaker that is smaller, lasts longer, and provides more physiologic heart rate
control. Modern pacemakers can automatically change pacing rates, automatically
change the pacing mode (i.e., both atria and ventricles or only one chamber), or pace
both ventricles synchronously (biventricular pacing) in an attempt to improve
functional status and survival.
Pacemakers are implanted for a variety of bradyarrhythmias, including
potentially life-threatening arrhythmias (i.e., complete heart block), as well as
arrhythmias that are symptomatic, but are not immediately life threatening (i.e.,
sinus node dysfunction). The implantation of cardiac pacemakers can be accom-
plished with minimal morbidity and mortality, and are frequently performed with
minimal sedation. The recovery period following pacemaker implantation is short,
and most patients require only a single overnight hospitalization.
After implantation, pacemaker function can be altered (reprogrammed) noninvasively,
using a specialized transceiver, which can communicate with the pacemaker.
Reprogramming of a pacemaker can activate, or deactivate, virtually any feature of the
pacemaker.
Implantable Defibrillators (ICDs)
Implantable cardioverter-defibrillators (ICDs) first became available in 1970 [2],

and have grown in clinical relevance since that time. Since their clinical introduc-
tion, ICDs have undergone multiple advances that have led to devices that are
extremely efficient at detecting and terminating rhythms associated with sudden
cardiac death (primarily ventricular fibrillation) [3]. In addition, currently available
ICDs offer full pacemaker capability, including biventricular pacing, which has
been shown to further improve both symptoms and survival in appropriate patients [4].
ICDs are implanted primarily to prevent sudden cardiac death in patients felt to
be at high risk for this disorder. Similar to cardiac pacemakers, implantation can be
accomplished with minimal morbidity and mortality, and are frequently performed
with minimal sedation. The recovery period following implantation is similar to that
of a cardiac pacemaker.
Reprogramming of an ICD can be accomplished noninvasively, much like that of a
pacemaker. It is possible to activate or deactivate virtually any feature of the ICD in
this manner. For example, it is possible to deactivate the therapies for ventricular
tachycardia/ventricular fibrillation, which leaving the pacemaker functions (which
treat bradyarrhythmias) intact.
22 Palliative Care in Cardiac Electrophysiology 387
If necessary, ICD therapy can be noninvasively deactivated. It is possible to “turn

off” the therapies for ventricular tachycardia/ventricular fibrillation, while leaving
pacing functions intact. It is also possible to deactivate pacing functions in these
devices as well, via the same noninvasive strategy.
Catheter Ablation of Arrhythmias
Catheter ablation of cardiac arrhythmias using radiofrequency energy has been

available since 1989 [5]. Since that time, it has been used to treat patients with a variety
of tachyarrhythmias, including Wolff–Parkinson–White syndrome, AV nodal
reentrant tachycardia, atrial tachycardia, and atrial flutter. It is associated with
success rates that are generally greater than 90% [6]. The procedure is generally
performed with minimal sedation, and, depending on the arrhythmia being
treated, is associated with low morbidity and mortality. The recovery period fol-
lowing ablation is quite short, and an overnight hospital stay is the norm.
The Arrhythmias
Tachyarrhythmias
Supraventricular Tachyarrhythmias
Atrial Fibrillation
Atrial fibrillation is the most common arrhythmia, occurring in approximately 10%

of patients over the age of 80 [7]. Although often asymptomatic, it can be associated
with a variety of symptoms, including fatigue, palpitations, exercise intolerance,
presyncope, and syncope. It is commonly associated with other chronic illnesses,
and, as such, is often a target for palliative care.
Treatment of atrial fibrillation is either aimed at restoring normal sinus rhythm,
or controlling the ventricular response to atrial fibrillation. Both of these strategies,
if effective, will eliminate symptomatic atrial fibrillation. Either therapy can be
quite intensive, involving complex medical regimens and invasive proceeders,
including ablation.
Rhythm control strategies in atrial fibrillation are designed to maintain normal
sinus rhythm. They frequently involve the use of antiarrhythmic drug therapy. These
drugs have a relatively high side effect profile and require invasive monitoring. If
palliative care is contemplated, it may be appropriate to change the focus of therapy
toward rate control in atrial fibrillation. This strategy has not been shown to be infe-
rior to a strategy of rhythm control [8].
In patients who are receiving a strategy of rate control, it is occasionally difficult
to achieve adequate rate control. The resulting rapid ventricular response in atrial
fibrillation can lead to worsening of symptoms, or in severe cases, exacerbations
388 E. Grubman
of congestive heart failure. In these cases, it is appropriate to consider an invasive

strategy to provide palliative care. Radiofrequency ablation of the AV node (with
concomitant permanent pacemaker implantation) will eliminate the need for rate
control medications, and will guarantee adequate rate control in atrial fibrillation.
Though invasive, this strategy is an appropriate palliative care in cases where rate
control in atrial fibrillation is difficult to achieve.
Atrial fibrillation is associated with an increased risk of embolic stroke. This risk is
increased in patients who are elderly, or patients with significant comorbidities (such as
hypertension or diabetes mellitus). A strategy of intensive anticoagulation, typically
with Coumadin, has been shown to decrease this risk dramatically. Coumadin therapy
does require occasional blood work, which does involve some mild discomfort.
The goal of palliative care in patients with atrial fibrillation is to minimize the
symptoms (palpitations, dizziness, syncope) as well as the risks (worsening congestive
heart failure, stroke) that can accompany the arrhythmia. Palliative care decisions in
atrial fibrillation may allow simplification of the medical regimen. Changing treat-
ment strategy from a strategy designed to maintain sinus rhythm to one that allows
atrial fibrillation, but provides adequate ventricular rate control, may simplify the
medical regimen and limit the repeated hospitalizations which often occur in patients
on antiarrhythmic drugs. Elimination of anticoagulation with coumadin will limit
blood drawing, but at the expense of a dramatically increased risk of stroke.
Supraventricular Tachycardia
Supraventricular tachycardia (SVT) can be caused by a variety of mechanisms.

They are not frequently life-threatening, but can be extremely symptomatic. They
are often associated with palpitations, dizziness, fatigue, and, in rare cases,
syncope.
SVT can often be prevented with medical therapy, including beta blockers, cal-
cium channel blockade, or antiarrhythmic therapy. If these therapies fail, ablation
has been very successful at eliminating these arrhythmias, with cure rates that are
frequently greater than 90% [6]. Though successful at eliminating these arrhyth-
mias, ablation is an invasive approach, which often requires some degree of seda-
tion, a procedure which can last several hours, and, quite frequently, an overnight
hospitalization.
Ventricular Tachycardia
Ventricular tachyarrhythmias are responsible for the majority of cases of sudden

cardiac death. It is estimated that there are greater than 300,000 cases of sudden
cardiac death annually in the USA [9]. These arrhythmias become more frequent as
underlying structural heart disease worsens. Traditional treatment of these arrhyth-
mias involved antiarrhythmic drug therapy, which was designed to prevent these
arrhythmias. In the early 1990s, several seminal trials demonstrated the inferiority
of antiarrhythmic drug therapy [10]. At the same time, the development of the
implantable defibrillator proved to be a transformative event. Rather than preventing
ventricular tachycardia/ventricular fibrillation, ICDs act rapidly to terminate these
arrhythmias, before they can become fatal. The efficacy of these devices in termi-
nating VT/VF is very high [3]. As a result, ICD implantation is extremely effective
at preventing sudden death in patients at high risk, and has largely replaced the use
of antiarrhythmic drug therapy in patients at high risk for ventricular arrhythmias
and sudden death.
If untreated, ventricular fibrillation will almost invariably lead to rapid, painless
death. Ventricular tachycardia is slightly less lethal, and can cause severe symptoms
(extreme dizziness, palpitations, and/or syncope), or sudden death. If they occur in
a patient with an ICD, the ICD will treat the arrhythmia, frequently by delivering a
high energy defibrillation shock (up to 700 V). In patients with palliative care goals,
it may be reasonable to deactivate ICD therapy, to eliminate the possibility of a
painful shock. Patients and their surrogates have the right to refuse life-saving treat-
ments, and deactivation of an ICD would fall directly into this category. Patients and
caregivers should understand that any ventricular tachyarrhythmias which occur
after the ICD has been deactivated, will likely prove fatal.
Bradyarrhythmias
Bradyarrhythmias are often associated with fatigue, dizziness, and syncope. Most
cases of conduction system disease are caused by degeneration of the cardiac con-
duction system, which ultimately results in bradycardia, and symptoms. In some
cases (i.e., complete heart block), the arrhythmia can prove rapidly fatal if untreated.
Pacemaker implantation can be expected to relieve the symptoms associated with
bradyarrhythmias entirely.
Whether patients with symptomatic bradyarrhythmias should undergo pace-
maker implantation is a reasonable consideration when palliative care is being
considered. The procedure, though minimal, is invasive, and requires a brief hospi-
talization and mild discomfort. It would be reasonable to consider pacemaker
implantation as palliative care for patients with severe symptoms, such as syncope
or dizziness, but it would also be reasonable to withhold pacemaker implantation in
patients whose only symptom was fatigue.
In patients who already have pacemakers implanted, it is reasonable to consider
deactivation of the pacemaker if requested by the patient or their surrogate. Patients
have the right to refuse life-sustained treatments, and deactivation of a pacemaker
(or ICD) would be considered to be refusal of a life-sustaining treatment. It is appro-
priate to do so in a palliative care situation, if requested by the patient or their
surrogate [11].
390 E. Grubman
Conclusion
Cardiac rhythm disturbances can be highly symptomatic, and are frequently associated
with significant morbidity and mortality. They often occur in patients with other
chronic illnesses. Treatments for the variety of cardiac rhythm disturbances has
improved dramatically over the past 25 years, and now offers a variety of therapies
for the vast majority of cardiac rhythm disturbances.
The field of palliative care is focused on the relief or prevention of suffering,
rather than the cure of disease. Cardiac electrophysiologic procedures can be used
to further these goals, and in many cases, is part of a palliative care strategy.
However, these treatments are invasive. Though they often serve to prolong life, the
treatments can lead to intermittent discomfort (i.e., ICD shocks). In these cases, it
may be reasonable to limit, or reverse therapy in an attempt to achieve the goals of
palliative care.
References
1. Weirich W, Gott V, Lillehei C. The treatment of complete heart block by the combined use of
a myocardial electrode and an artificial pacemaker. Surg Forum. 1957;8:360–3.
2. Mirowski M, Mower MM, Staewen WS. Standby automatic defibrillator: an approach to
prevention of sudden coronary death. Arch Intern Med. 1970;126:158–61.
3. Goldberger Z, Lampert R. Implantable cardioverter-defibrillators: expanding indications and
technologies. JAMA. 2006;295(7):809–18.
4. Bristow MR, Saxon LA, Boehmer J. Cardiac-resynchronization therapy with or without an implant-
able defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140–50.
5. Jackman WM, Wang X, Friday KJ. Catheter ablation of accessory atrioventricular pathways (Wolff-
Parkinson-White syndrome) by radiofrequency current. N Engl J Med. 1991;324:1605–11.
6. Calkins H, Yong P, Miller JM, Atakr Multicenter Investigators Group. Catheter ablation of
accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular
junction: final results of a prospective, multicenter clinical trial. Circulation.
1999;99:262–70.
7. Go AS, Hylek EM, Phillips KA. Prevalence of diagnosed atrial fibrillation in adults. JAMA.
2001;285(18):2370–5.
8. The AFFIRM Investigators. A comparison of rate control and rhythm control in patients with
atrial fibrillation. N Engl J Med. 2002;347:1825–33.
9. Mutchner L. The ABCs of CPR – again. Am J Nurs. 2007;107(1):60–9.
10. CAST Investigators. Preliminary report: effect on encainide and flecainide on mortality in a random-
ized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321:406–12.
11. Lampert R. HRS Expert Consensus Statement on the Management of Cardiovascular
Implantable Electronic Devices (CIEDs) in patients nearing end of life or requesting with-
drawal of therapy. Heart Rhythm. 2010;7(7):1008–26.
Review Questions
1. An 85-year-old woman with a previously implanted biventricular defibrillator is

receiving palliative care, due to metastatic colon cancer. She is competent to
make decisions regarding her care. She asks to have her ICD “turned off.” You
inform her that it would be appropriate to:
(a) Deactivate the defibrillation features of the device only
(b) Deactivation of biventricular pacing functions of the device only
(c) Deactivation of rate responsive pacing functions of the device only
(d) Deactivation of all pacing functions only
(e) All of the above are appropriate
2. A 75-year-old man with ALS is receiving palliative care. He develops complete
heart block, which results in recurrent syncope and severe dizziness. As his clini-
cian, you inform him that:
(a) Permanent pacemaker implantation is reasonable, given the symptomatic
nature of his bradyarrhythmia
(b) There is no role for pacemaker implantation in patients receiving palliative
care
(c) Temporary pacemaker implantation, which can be maintained for several
days, is the most appropriate therapy for his arrhythmia
(d) External pacing, though uncomfortable, is the most appropriate therapy for
his arrhythmia
3. A 68-year-old woman has a previously implanted pacemaker, for the treatment
of complete heart block. She would be asystolic without the pacemaker. She is
receiving palliative care for metastatic pancreatic cancer. Her pacemaker battery
has weakened to the point that the device should be changed. She is no longer
making her medical decisions, but her daughter, who has assumed this role, asks
that the pacemaker not be changed. She understands that this will likely lead to
the patient’s death. You should inform her that:
(a) Pacemaker generator change is minimally invasive, and must be performed,
as the therapy is vital
(b) Pacemaker generator change must be performed, as it is considered “con-
tinuation of existing therapy” and is not part of palliative care decisions
(c) It is appropriate not to replace the pacemaker, as long as the daughter under-
stands the implications
(d) Pacemaker generator change must be performed, as the decision not to
replace the pacemaker can only be made by the patient, not her daughter
4. A 90-year-old man is receiving palliative care, due to severe, advanced dementia.
He presents to the Emergency Room with newly a urinary tract infection. He is
incidentally noted to have atrial fibrillation. He is hemodynamically stable. The
most appropriate therapy for his atrial fibrillation would be:
392 E. Grubman
(a) Electrical cardioversion, followed by initiation of amiodarone therapy

(b) Electrical cardioversion, without long-term antiarrhythmic drug therapy
(c) Begin the patient on flecainide, with the hopes that it will restore normal
sinus rhythm, without the use of electrical cardioversion
(d) No further therapy is warranted, as the patient is asymptomatic
5. In patients receiving palliative care, ablation therapy for SVT:
(a) Is not appropriate
(b) Can be reasonable, if the arrhythmia is symptomatic and frequent
(c) Can be reasonable, if they can be accomplished with minimal risk
(d) Can be reasonable, only if they are likely to be life-saving
Answers
1. (e) All of the above are appropriate

2. (a) Permanent pacemaker implantation is reasonable, given the symptomatic
nature of his bradyarrhythmia
3. (c) It is appropriate not to replace the pacemaker, as long as the daughter
understands the implications
4. (d) No further therapy is warranted, as the patient is asymptomatic
5. (b) Can be reasonable, if the arrhythmia is symptomatic and frequent
Chapter 23
Palliation in Respiratory Disease
David R. Meek, Martin D. Knolle, and Thomas B. Pulimood
Introduction
Palliative care plays an important role in pulmonary disease; a common cause of

acute and chronic terminal illness. Its role is well recognised in lung cancer but less
so in other respiratory disease [1]. It can sometimes be difficult to differentiate
between what is considered palliation and what is considered routine care. It is
important therefore for the physician caring for patients with respiratory symptoms
or disease to be able to integrate restorative/curative management and palliative
measures as appropriate on an individual patient basis. This needs to be incorpo-
rated as part of their routine management plan. Similarly patients primarily receiv-
ing palliation benefit from curative and restorative measures such as treating
pneumonia or wheeze in terminal care. Hence patients benefit from a holistic, multi-
disciplinary team approach to their management which focuses on the patient and
their family’s needs, wishes and expectations. The American Thoracic Society
(ATS) have laid out a clinical policy statement related to palliative care for patients
with respiratory diseases alluding to this in some detail [2]. This chapter outlines a
symptom and disease-specific approach to palliation in respiratory disease.
D.R. Meek, M.R.C.P. (*) • T.B. Pulimood, M.B.B.S., F.R.C.P.

Department of Respiratory and General Internal Medicine,
West Suffolk Hospital, University of Cambridge Teaching Hospital,
Bury St Edmunds, Suffolk, UK
e-mail: dr_meek@hotmail.com; Thomas.pulimood@wsh.nhs.uk
M.D. Knolle, M.B., B.Chir., M.R.C.P.
Department of Respiratory Medicine,
Lister Hospital, Stevenage, UK

DOI 10.1007/978-1-4614-5164-8_23,
396 D.R. Meek et al.
Management of Symptoms
Breathlessness or Dyspnoea
Dyspnoea, a Greek word for “difficulty breathing”, has been defined by the ATS as
“a term used to characterize a subjective experience of breathing discomfort that is
comprised of qualitatively distinct sensations that vary in intensity. The experience
derives from interactions among multiple physiological, psychological, social, and
environmental factors; and may induce secondary physiological and behavioural
responses” [3].
Dyspnoea, together with pain, is one of the symptoms most common in and
feared by patients with terminal illness requiring palliation [4, 5]. The physiological
basis of the sensation of breathlessness is due to complex interactions between
respiratory centres within the brain (medullary, pontine and cortical), peripheral and
central chemoreceptor monitoring oxygen, carbon dioxide and pH levels, as well as,
mechano and pain receptors in the lung.
Breathlessness is a symptom of numerous conditions, two thirds of which are
primary respiratory or cardiac disease and in the other third it is multi-factorial [6].
Other causes include: anaemia, thyrotoxicosis, diabetic ketoacidosis, altitude sick-
ness, anxiety and other neurological illness. Symptoms of breathlessness are not
necessarily correlated to physiological parameters or underlying disease burden. It
is important to bear in mind other contributory factors, such as anxiety and pain.
The assessment of dyspnoea should include an assessment of its severity. A com-
monly used scale for this is the modified BORG score [7], which ranks dyspnoea
symptoms from 0 to 10. This provides an objective measure for comparison and
monitoring symptoms. However, more importantly, the extent of disability caused
by dyspnoea needs to be explored.
The first step in the treatment of dyspnoea is the diagnosis and treatment of any
underlying cause. For example, treatment of pneumonia or pulmonary emboli in
patients with terminal lung cancer might improve their symptoms sufficiently for
the patient to be comfortable. Should patients remain short of breath despite appro-
priate or optimal management of their underlying respiratory disease, other non-
pharmacological measures can be employed to help with dyspnoea [1]. Foremost
is patient education by physicians and nurses. Patients and their families need to be
aware of the level of dyspnoea and simple advice to control symptoms can go a
long way. In addition, patients, particularly those with end-stage chronic obstruc-
tive pulmonary disease (COPD), may benefit from keeping physically active with
pulmonary rehabilitation, which seeks to incorporate patient education, exercise
training and nutritional advice [8]. A dietician may provide support for the latter,
particularly if the labour of breathing increases calorie demands. Another simple
measure may be a fan providing cold air to the face to relieve the feeling of dysp-
noea. This provides facial cooling to the Vth cranial nerve region, i.e. mouth, nose
and cheeks.
23 Palliation in Respiratory Disease 397
Table 23.1 Management of breathlessness

Non-pharmaceutical Pharmaceutical
Morphinea
Physical activity and pulmonary Midazolamb
rehabilitation
Breathing training Lorazepamb
Relaxation and anxiety control Diazepamb
techniques
Symptom education Phenothiazinesb
Non-invasive ventilation
a
See ATS guideline [2]
b
Evidence limited
In terms of medical management (see Table 23.1), opiate treatment is still

considered the first line of treatment for palliation of breathlessness [9]. Opioids
tend to be effective and have not been shown to have an adverse effect on length of
life. These agents may be administered orally, subcutaneously, transdermally or
intravenously. Unfortunately, opioids do have a side effect profile that includes:
nausea, constipation and drowsiness. It is best to start with small doses of morphine
1–2.5 mg titrating up as required to a three times daily regime if needed. It can also
be part of an emergency breathlessness plan.
Oxygen supplementation tends to be particularly helpful in patients with
documented hypoxemia [10]; however, it does not tend to be effective in patients
with adequate oxygen saturations [11]. Heliox, which is a mix of helium and
oxygen (instead of nitrogen/oxygen in the normal atmosphere), is a less viscous gas,
allows for a smoother flow of oxygen and has been shown to alleviate dyspnoea in
patients with normal and low oxygen levels [12, 13]. This is particularly helpful
with large airway obstruction.
Benzodiazepines, in particular midazolam, are also commonly used to combat
terminal breathlessness. However, it should be noted that trial evidence does not
support their effectiveness [14]. Nevertheless, these medications may be useful as
adjuvant therapy [15] in combination with morphine. Midazolam is frequently used
in conjunction with morphine as a continuous infusion at the end of life.
Levomepromazine (previously known as methotrimeprazine), in a typical dose
range of 6.25–12.5 mg, is helpful if anxiety, nausea and vomiting are significant
associated symptoms.
Non-invasive ventilation (NIV) providing continuous positive airway pressure
(CPAP) or bi-level positive airway pressure (BIPAP) in inspiration and expiration
can also be employed in a palliative setting [16]. While some patients may not be
able to tolerate NIV, most commonly related to a feeling of claustrophobia from the
mask, it may relieve dyspnoea effectively without some of the undesirable effects of
drug therapy, such as opiate-induced drowsiness. However, it is important to explore
patient and family expectations before starting NIV and also outline clinical
scenarios in which NIV may be discontinued.
Chest Pain
Chest pain is a common emergency and chronic presentation, and needs to be

appropriately managed in patients with terminal illness. The initial assessment of
patients suffering terminal disease who present with chest pain should aim to establish
a diagnosis through history and investigations. However, investigations and
management may vary in patients with terminal illness from those without, in accor-
dance with the wishes of the patients and their families. If it is the patient’s wish to
be for active treatment of underlying causes of chest pain, this cause needs to be
identified and treated appropriately. If on the other hand, patients do not wish to
have active management of disease but rather symptom control, treatment of the
latter should be sought. Treatment of pain in the palliative setting requires a
multi-disciplinary, patient-centred approach. The palliative care team should be
involved early if pain control proves difficult.
The World Health Organization (WHO) analgesic ladder provides good gen-
eral guidance to pain control [17], starting with non-opioid analgesia such as acet-
aminophen/paracetamol or non-steroidal anti-inflammatory agents. This proceeds
to further steps that include opioids, initially weak agents such as codeine and
escalating to stronger medications, such as morphine or various alternatives. The
exact choice of opioid may vary from patient to patient and needs to take into
account the route of delivery. Different formulations are available and opioid
analgesia is available in oral, subcutaneous, intravenous, transdermal or sublin-
gual form. The right choice depends on the individual patient and their ability to
take medications. The dose requirements again may vary greatly between patients.
The starting doses of opioids should be equivalent to 2.5–10 mg of intravenous
morphine and titrated up appropriately. Further discussion of opioid-related top-
ics is described in Chap. 26 on “New Vistas in Pain Management”. Constipation
and nausea are common side effects of opioid treatment and should be pre-empted
by considering laxatives and anti-emetics. A further side effect of opioids may be
sedation. This should be frankly discussed with patients and family and may be
taken into consideration when titrating opioid doses. However, overall it is felt
that the treatment of pain is a priority, and that if sedation is a side effect, this may
simply need to be accepted and explained to the patient [18].
Additional treatments can be considered for pain from specific causes. Primary
or secondary tumours resulting in compression may be treated with high dose
steroids (dexamethasone). Neuropathic pain caused by nerve compression, either
secondary to tumours or pathological fractures may respond to treatment with gaba-
pentin or amitriptyline. A new once daily formulation of gabapentin, Gralise, has
similar efficacy with significant less side effects owing to its gastroretentive tech-
nology. Interventional procedures, described in Chap. 26, can provide significant
relief to patients for a variety of pain states. Bone pain from bone metastasis may
respond to treatment with bisphosphonate therapy and can be improved with single
fraction radiotherapy. Other pain options are described throughout this book.
Cough
A chronic cough is an accompanying feature of many pathophysiological states

affecting the airways, including diseases requiring palliative treatment such as lung
cancer or end-stage COPD. It is easy to underestimate the disabling effect a cough
may have on a patient’s life, but a persistent cough is considered unacceptable in
many social settings, such as movie theatres, concerts or restaurants. In addition,
cough may result in syncope or urinary incontinence, which may cause major
embarrassment and concerns for patients.
Cough is a symptom of different pathologies, which need to be explored. Cough
in the context of terminal illness may accompany different conditions, such as neu-
romuscular pathologies, be a side effect of treatment such as chemotherapy or radio-
therapy, or caused by a number of respiratory conditions such as tracheitis, acute
bronchitis, chronic bronchitis, bronchiectasis, pneumonia, pulmonary fibrosis, lung
cancer and pleural effusions amongst a wide range of respiratory pathology. Often,
cough present in end-stage COPD or lung cancer is due to direct irritation of the
airways and from accumulation of secretions in the airways. In order to relieve this,
several treatment strategies may be helpful. It is worth noting that there is almost a
dearth of credible evidence of management of cough in cancer patients [19]. This is
an area that clearly requires further work. Pancoast tumours, which are tumours
occurring in the lung apex can compress the recurrent laryngeal nerve, which results
in incomplete apposition of the vocal cords, and subsequently a hoarse voice and a
cough often described as a “bovine cough”. Treatment of the cough caused by
Pancoast tumours is through the treatment of the underlying malignancy.
Bronchodilation with inhaled or nebulised beta 2 agonists or muscarinic receptor
antagonists may be particularly helpful in treating cough in end-stage COPD or in
conditions with accompanying bronchospasm. In addition, inhaled or even oral glu-
cocorticoids may help dampen down airway inflammation, as such reducing airway
irritation and cough.
Secretions can be a problem in patients with terminal lung disease. For example,
an obstructing lung lesion, such as either a primary lung tumour or distant metasta-
sis can lead to accumulation of secretions behind the tumour and end-stage COPD
can often be accompanied by a degree of traction bronchiectasis. Facilitating spu-
tum clearance may alleviate the cough associated with these conditions. Methods
include: positional drainage exercises, chest physiotherapy and cough machines.
Treatments with mucolytic agents such as carbocysteine or nebulised saline to
loosen secretions are effective. Benzonate (Tessalon perles, Zonatuss) anesthetises
the stretch receptors and is effective in a number of cough states. Speech therapy
and vocal hygiene strategies have also been helpful to treat cough. Manoeuvres such
as pursed lip breathing, replacing cough with swallowing, avoiding smoking, avoid-
ing mouth breathing, minimising alcohol consumption and caffeine or increasing
water intake or steam inhalation are often simple measures used by these specialists
in their cough rehabilitation sessions. Evidence for these strategies, however, is
minimal but are worth considering when options are limited. With regards to symptom
relief, drugs that act centrally can be used to suppress cough. These include opioids
such as codeine and morphine, lidocaine and non-opioid agents such as
dextromethorphan [20, 21]. It is important to note suppression of cough can result
in pneumonia and therefore it is important to use cough suppressant drugs only after
careful assessment of risks and benefits.
Wheeze and Stridor
Wheeze and stridor are terms that describe the physical signs produced by turbulent
flow of air through narrowed airways. Stridor is a sign usually found in patients with
upper respiratory tract narrowing or obstruction. It is described as a high-pitched,
harsh, shrill, whistling or musical sound which can be present on inspiration and/or
expiration. Inspiratory stridor can be indicative of serious airflow airway obstruction.
It is therefore considered a medical emergency which necessitates urgent investigation
and intervention. It should be noted that a fall in oxygen saturations is considered to
be a late sign. Stridor can occasionally be intermittent if caused by a rapidly grow-
ing tumour that outgrows its blood supply resulting in repeated sloughing of necrotic
tissue. It can also be present polypoid masses that case intermittent obstruction.
Wheeze is described as a high pitched, continuous, coarse whistling sound and
can be present on inspiration, expiration or throughout the whole respiratory cycle.
The site and timing of the wheeze and presence of a monophonic or polyphonic
sound can help the examining physician differentiate between some pathologies.
These characteristics can help guide further investigations and subsequent treat-
ments. Examples of these would be a localised monophonic inspiratory and expira-
tory wheeze which can be associated with a discrete area of stenosis of the lower
airways such as that caused by a malignant lesion. This can be contrasted with the
diffuse polyphonic end expiratory wheeze heard in COPD or chronic asthma sug-
gesting obstruction in multiple airways. In the typical case of wheeze seen with
COPD, chronic asthma or lower respiratory tract infections, treatment should be
given with bronchodilator therapy, such as salbutamol or ipatropium bromide in the
nebulised or inhaled form and corticosteroids which help suppress inflammation
within the airways. Intravenous or oral aminophylline or salbutamol could also be
considered.
Emergency Management of Stridor
– Urgent assessment including concise history and examination

– Review of previous and current imaging for cause
– Attempt to ensure a calm and relaxing atmosphere in order to help relieve
distress
– Constant reassurance and encouragement should be given
– High flow oxygen therapy to relieve respiratory distress and dyspnoea

– High dose corticosteroids such as dexamethasone 8 mg i.v./PO twice daily can
be used to help reduce oedema although it should be remembered that this usu-
ally takes a number of hours to work
– Nebulised epinephrine can also help reduce airway oedema
– Heliox (mixed helium 70% and oxygen 30%) can be effective and occasionally
provide an immediate benefit. The principle behind this treatment is that the low
density and viscosity of helium reduces the turbulent flow through the airways,
thus improving delivery of oxygen
Long-Term Management of Stridor
The long term management of patients with stridor secondary to malignancy

includes pharmacological and physical interventions. Improvements in interven-
tional bronchoscopic techniques as well as chemotherapy and radiotherapy regimes
have meant that interventions can improve the patency of lumen of the airways,
leading to an improvement in oxygen delivery to the lungs. These interventions
include:
1. Tracheal and bronchial stenting.
– Stents are deployed using the bronchoscope and are self-expanding.
– Open up the airways and splint them open mechanically.
2. Cryotherapy “burns away” obstructing lesions and can lead to tumour necrosis
by freezing the tissue locally.
3. Chemotherapy especially in the case of small cell lung cancer and lymphoma
which are typically sensitive to current treatments.
4. Radiotherapy regimes leading to local tumour control and stopping further
tumour growth and in some cases tumour regression. It should be noted that
inflammation after radiotherapy can result in tissue expansion. A serious conse-
quence if the obstruction is critical. It may be necessary to empirically stent or
treat airways with other therapies prior to radiation therapy.
5. The consideration of tracheotomy in those patients with high tumours, e.g. at
vocal cords.
In reality, these measures are not usually performed in isolation and combinations
of therapies are typically used. To establish the most appropriate treatment, discus-
sions with patients and their family are warranted and considerations made regard-
ing the patients fitness to undergo invasive procedures or chemotherapy regimes. It
would also be appropriate to adopt a multi-disciplinary approach taking into account
the patient’s prognosis and life expectancy.
List 23.1 Pulmonary causes of hemoptysis

• Malignancy
– Bronchogenic carcinoma
– Lung metastases
– Kaposi’s sarcoma
– Carcinoid tumour
• Infections
– Pneumonia
– Lung abscess
– Tuberculosis
– Fungal infections
• Bronchiectasis
• Cystic fibrosis
• Vasculitis involving the lung
– Wegner’s granulomatosis
– Goodpasture’s syndrome
• Lung trauma/contusion
• Foreign body
• Pulmonary embolism
List 23.2 Non-pulmonary causes of “haemoptysis”

– Aspirated blood from nasal epistaxis or the upper respiratory tract. This could be precipi-
tated by nasal oxygen therapy which leads to drying of the nasal mucosa or from any other
cause for epistaxis
– Gastro-oesophageal reflux disease leading to irritation of the upper respiratory tract or
leading to aspiration from an upper gastrointestinal (GI) bleed. In the case of palliative care,
GI bleeds can be precipitated by the use of corticosteroid therapy as well as non-steroidal
anti-inflammatory agents. The concurrent use of anti-coagulants or anti-platelet therapies
can also worsen this process
– Trauma to the upper airways from, for example, following bronchoscopies or
tracheostomies
– Congestive cardiac failure and mitral stenosis can lead to the production of the typical pink,
frothy sputum described in textbooks although sputum in these diseases can often appear
similar to hemoptysis
Hemoptysis
Hemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum

which is invariably a very distressing symptom for patients. It can range from minor
blood streaking of sputum through to massive frank haemoptysis. Mild hemoptysis
can usually be investigated as an outpatient providing the patient is otherwise well
and haemodynamically stable with good respiratory function whereas massive hae-
moptysis is a medical emergency with a quoted mortality up to 80%. There is a
possibility for patients to have a small “sentinel” or “herald” bleed prior to massive
hemoptysis although this is a rare phenomenon.
The causes for haemoptysis are wide and a thorough history and examination
should be performed in order to narrow down the likely aetiology (List 23.1).
Decisions regarding appropriate use of imaging and invasive investigation tech-
niques should then be guided by the differential diagnosis. It should be noted that
some causes of hemoptysis may not be related to pulmonary pathology (List 23.2).
Investigations and Management
– Blood screening including: full blood count, coagulation and renal function tests.
Further blood tests should be arranged as necessary.
– Chest X-ray (CXR) is usually easy to arrange and interpret. It can be performed
quickly on the ward as a portable procedure, thus negating the need to transfer an
unstable patient out of a controlled environment. Although the CXR does not
give detailed information, it is usually required to plan further management. It
can help look for signs suggestive of malignancy, infection or pulmonary emboli
which are all potential causes of hemoptysis.
– Computer tomography (CT) imaging of the chest if the patient is stable allows a
more detailed view of the thoracic anatomy. It is important to discuss the details
of the clinical presentation so the radiologist can choose the right study protocol.
Many units have a standard hemoptysis protocol. It is usually performed as a CT
with contrast and contrast timings will vary depending on the main cause being
considered. This investigation can give information on the cause of hemoptysis
and also help exclude important negatives such as pulmonary emboli. The CT
images can also help plan for further management including the need for thera-
peutic bronchoscopy or bronchial artery embolisation.
– Treatment should be guided by the underlying cause. If the CT imaging suggests
infection, antibiotics or other therapeutic interventions should be given whereas
pulmonary emboli should be treated with anti-coagulation.
– It is important to inspect the upper airway carefully especially if frank hemopty-
sis is present as this is often the cause of fresh bleeding. An ear, nose and throat
specialist opinion is often helpful in this regard.
– Bronchial artery embolisation can be performed if the lesion/area bleeding is
directly fed by a rich vascular supply with evidence of bleeding on bronchial
angiography. The procedure is best performed in specialist centres due to the
required expertise and risk of failure or the need to proceed to further definitive
procedures if bleeding is not able to be controlled in this manner. The procedure
involves the injection of glues or insertion of coils to “block” supplying arteries.
It should be noted that the procedure carries a small risk of paraplegia (<1%) due
to an anatomical variable where the anterior spinal artery originates from the
bronchial arterial circulation [22, 23].
– Therapeutic bronchoscopy (as detailed below) [24].
– NB Hemoptysis of unknown cause is considered a contraindication to spirometry

as the effort required to do the forced manoeuvres of the procedure can promote
increased bleeding.
Massive Hemoptysis
A bleed of between 100 and 600 ml within a 24-h period is termed as massive
hemoptysis and is a life-threatening emergency. It is usually extremely distressing
for both the patient and their family or carers. As well as causing marked anxiety, it
is associated with a mortality rate of up to 80% even with active treatment [25]. Due
to the patient’s general condition and hemodynamic and respiratory symptoms,
investigations are usually difficult to perform and may be difficult to interpret.
Patients should be managed in the following way:
– High flow oxygen therapy.
– Cough suppressing agents such as opioids (oramorph, IM/IV morphine). If a
patient has an ongoing cough, they may dislodge any clot that may have already
formed.
– Tranexamic acid to aid coagulation.
– Intravenous access plus fluids (± blood) to maintain haemodynamic status.
– Positioning of patient in a lateral position with the affected side down. This prevents
blood draining into the non-affected lung whilst “sacrificing” the diseased lung.
– Bronchoscopy—ideally rigid bronchoscopy where local treatment can be given
directly to a bleeding lesion. Even flexible bronchoscopy can be beneficial with
the application of iced saline or vasoconstrictors such as epinephrine/adrenaline
or vasopressin onto a bleeding area to promote coagulation.
– In life-threatening cases, where appropriate, selective bronchial intubation can
be used with the affected lung “blocked off” and single lung ventilation
performed.
– Bronchial angiogram followed by bronchial artery embolisation can be per-
formed by interventional radiologists if a specific bleeding area is identified.
– Surgical option is considered the last resort with lobectomy or pneumonectomy.
This should obviously only be performed in selected cases where appropriate.
Infections
Lung infections can be the terminal event in many chronic lung conditions. In con-
ditions such as cystic fibrosis, bronchiectasis and COPD, patients are particularly
susceptible to developing recurrent lower respiratory tract infections, which can
lead to progressive decline in lung function [26]. Recurrent infections can also lead
to resistance to antibiotics due to repeated courses of antibiotics [27] and the

presence of increasingly difficult to treat organisms such as Pseudomonas aeruginosa.
Whereas these organisms are all treatable within the general population, the pres-
ence of nutritional deficiencies and relative immunodeficiency associated with some
of these conditions leads to an increase in morbidity and mortality [28]. Furthermore,
patients with malignancy can be more prone to lower respiratory tract infections due
to partial/total obstruction of airways leading to post-obstructive pneumonias caused
by an inability to clear out mucous. Combined with the immunosuppression caused
by chemotherapy and radiotherapy, infections can be a major problem for these
patients. As with the general population, it is important to review previous micro-
biological results in order to gain information on previously found organisms and
their sensitivities. Many patients will already have sputum cultures or bronchoal-
veolar washing results available and antibiotic therapy should be targeted to these
results. Further cultures should be sent prior to antibiotic therapy if possible and if
the patient is stable enough to wait; otherwise, antibiotic therapy should be com-
menced as soon as possible. In the absence of previous positive cultures, broad
spectrum antibiotics should be commenced which can be rationalised to targeted
therapy depending on response and available results. In association with antibiotics,
supportive therapy in the form of intravenous fluids should be given alongside spu-
tum clearance techniques, which may include chest physiotherapy, humidified oxy-
gen therapy or saline nebulisers and mucolytic therapy such as carbocysteine
(mucodyne). Other treatments may include: steroid therapy and bronchodilator
therapy plus prophylactic anti-coagulant therapy to prevent venous thromboembolic
events. These should be decided on a case-by-case basis.
COPD
Chronic obstructive pulmonary disease (COPD) is a disease entity encompassing

chronic bronchitis and/or emphysema, commonly caused by smoking and charac-
terised by airflow limitation that is not fully reversible. The hallmark test for the
diagnosis of COPD is spirometry and a forced expiratory volume in 1 second
(FEV1) over a forced vital capacity (FVC) ratio of 0.7 or lower in the presence of
symptoms or radiographic investigations suggestive of COPD and absence of an
alternative explanation for the reduced FEV1/FVC ratio. COPD encompasses a
spectrum that can range from a mild illness to a severe, life-threatening disease.
However, as lung function declines with age COPD tends to get worse over time
[29].
Globally, COPD is responsible for an increasing proportion of deaths. Cancer-
based palliative care services are being extended to include non-malignant diseases
such as COPD. About half of patients discharged from hospital after a COPD exac-
erbation will die within 2 years. In these patients with COPD, several indicators
carry a poor prognosis. These include: poor nutritional status (low body-mass index),
co-morbid heart disease, depression, continued smoking and older age. A low FEV1,
poor exercise tolerance, frequent exacerbations and complications such as respira-

tory failure and cor pulmonale also affect prognosis [30]. Respiratory failure is
defined as hypoxia with a PaO2 < 60 mmHg, while cor pulmonale is right-sided heart
failure secondary to pulmonary disease. A combined tool to measure mortality in
COPD is the BODE index, which combines measures of body-mass index, airway
obstruction, dyspnoea and exercise capacity [31]. Accurate predictions, however,
are extremely difficult and doctors familiar with these patients tending to overesti-
mate survival. The only other condition where prognosis is less accurate is demen-
tia. A policy focus on identifying a time point for transition to palliative care has
little resonance from accounts of patients, professional and informal carers in a
small qualitative study looking into this. COPD appears to be perceived as a way of
life. A holistic assessment of needs could be linked with milestones such as hospital
admission [32].
Treatment of patients with terminal COPD encompasses optimisation of their
treatment. This employs inhaled or nebulised Beta-2 adrenergic agonists, inhaled or
nebulised muscarinic antagonists, inhaled corticosteroids, oral theophylline or
phospho-diesterase 4 inhibitors. In addition to medical therapy, smoking cessation
therapy and vaccination (pneumococcal and influenza) should be offered to appro-
priate patients with COPD.
Additional therapy for COPD follows much along the same principles as treat-
ment of dyspnoea, with a focus on patient education and pulmonary rehabilitation.
Patients benefit from long-term oxygen therapy in terms of symptoms and survival
if they develop hypoxemia (PaO2 less than 55 mmHg, or PaO2 less than 59 mmHg
in the presence of pulmonary hypertension or polycythemia). Short burst oxygen
therapy (2 h/day) may be beneficial in symptom control, as it may improve exer-
tional dyspnoea and exercise tolerance. Patients suffering from hypercapnia may
benefit from non-invasive ventilation, if tolerated. Please also see the sections above
on “Cough”, “Breathlessness or Dyspnea”, and “Wheeze and Stridor.”
Neurological Cases
Respiratory problems are commonly found in the neurological patient. More impor-
tantly, they are also a common cause of mortality within this patient population.
From an increased risk of pulmonary embolism in the immobile patient, to recurrent
aspiration, and ventilatory failure from bulbar and respiratory muscle weakness, the
respiratory problems experienced within this patient subgroup are numerous. It
should therefore be suggested that the respiratory physician should play a role in the
management of patients suffering from long-term chronic neurological conditions.
Many neurological conditions are associated with bulbar weakness leading to
dysfunction of swallow and the possibility of recurrent aspiration with repeated
lower respiratory tract infections and aspiration pneumonia. These patients are usu-
ally further compromised by having a weak cough so limiting their ability to clear
secretions from their chest. Management should therefore include active monitoring
and aggressive treatment of the chest with involvement of a physiotherapist specialising
List 23.3 Causes of diaphragmatic weakness

• Brainstem CVAs and lesions
• Phrenic nerve injury/idiopathic dysfunction
• Guillan–Barre syndrome
• Lou Gehrig’s disease (motor neurone disease)
• Muscular dystrophy
• Myotonic dystrophy
in chest conditions, a speech and language therapist and the respiratory physician. The
patient’s swallow should be examined and monitored for evidence of deterioration
and the chest for evidence of aspiration. Infections should be treated early as the
neurological patient tends to have a poor respiratory reserve and can decompensate
quickly into ventilatory failure with a need for consideration for respiratory
support.
A further problem with many neurological conditions is diaphragmatic weakness
which can rapidly lead to ventilatory respiratory failure (List 23.3). The importance of
the diaphragms is best seen during sleep, specifically the rapid eye movement (REM)
stage of sleep. A feature of REM sleep is the presence of REM “paralysis” where the
muscles, including the muscles of respiration become flaccid leading the body to rely
on the diaphragms to maintain respiration. When the diaphragms are weak or paraly-
sed the patient loses this respiratory mechanism leading to nocturnal hypoventilation
which, with progression of the underlying disease leads to type II (hypercapnic, ven-
tilatory) respiratory failure. It is very important to identify and prepare for this early
particularly in patients with motor neurone disease as their progression to death is
very rapid from the time of diagnosis of type II respiratory failure.
Where appropriate, early discussions should take place with the patient and their
family or carers. The patient should be given information regarding their underlying
condition and the likely future prognosis plus treatment options. Discussions should
include the use of artificial nutrition and potential future need for respiratory support.
Having an open discussion early in the disease process allows the patient to express
their wishes for future treatment and also to express what they feel to be the limits of
treatment that they would accept. In many neurological conditions with bulbar involve-
ment, communication becomes progressively more difficult and it may become more
difficult to appreciate a patient’s decisions. It should be remembered that in many
cases, neurological conditions are not curable and the role of artificial nutrition and
respiratory support is to prolong life—thus, the decisions should involve what is con-
sidered by the patient to be an appropriate quality of life.
Treatment Options
Centres specialising in ventilatory failure in patients with neurological conditions

are increasing. In early stages, oxygen therapy may be sufficient to control a patient’s
symptoms and respiratory difficulties. As the underlying disease progresses,
neuromuscular function becomes further impaired and nocturnal hypoventilation

can occur. This can be easily tested on simple overnight oximetry studies. Initially,
these studies may show REM-related episodes of desaturation which typically occur
every ~90 min through the night and become more frequent towards the end of the
night where the proportion of REM sleep increases. Providing there is no evidence
of ventilatory failure on arterial blood gas sampling or clinically (List 23.3), the
patient can be followed up with serial overnight oximetry. If type II respiratory
(ventilatory, hypercapnic) failure develops, non-invasive ventilation (NIV) can be
commenced at night to improve oxygenation and carbon dioxide clearance [33]. As
the muscles become weaker, NIV may be required for longer periods of time includ-
ing daytime “top-ups”. With further progression, tracheostomy and full-time inva-
sive ventilation has been used. This is obviously a supportive measure with an aim
to prolong a patient’s life. It should therefore be established whether this is an
acceptable quality of life for the patient and allow him or her to make up their own
decisions regarding these treatments.
Lung Cancer
Lung cancer is the most common form of malignancy worldwide. It is by far the
most common cause of cancer in male populations and although it is the fourth most
common in females (behind breast, colorectal and cervix/uterus), its incidence is
increasing with time. In 2008, the World Health Organisation via the International
Agency for Research on Cancer released figures on the GLOBOCAN network with
“the aim of providing estimates of the incidence of and mortality from major can-
cers, at national level, for all countries of the world”. GLOBOCAN estimates that
the annual incidence for all cancers in 2008 worldwide was 12.66 million. Of these,
1.6 million are thought to be from lung primary with 1.1 million cases being male
and 500,000 females. Despite advances in the treatment of many forms of malig-
nancy, lung cancer is still associated with a high mortality rate with 1.38 million
deaths worldwide attributed to the disease. In 2008, GLOBOCAN estimates that
there were 215,021 new diagnoses of lung cancer with 161,841 deaths in the USA.
When compared with breast cancer (182,460 diagnoses and 40,481 deaths) and pro-
static cancer (186,320 diagnoses and 28,660 deaths), it is clear that not only is lung
cancer the most common malignancy, it also carries the worst prognosis.
The reason for the high mortality rate in lung cancer is usually seen as the late
presentation. At present there are no national screening programmes in operation
and the typical symptoms of lung cancer are usually fairly non-specific (List 23.4).
Lung cancers are also typically aggressive with early local and metastatic spread
often present at the time of diagnosis. Another factor is that patients are often found
to have other co-morbidities such as ischemic heart disease and chronic obstructive
pulmonary disease (COPD) due to their common risk factor of smoking. These
underlying illnesses can mean that patients with cancer staged as being potentially
resectable are not offered operative procedures due to the high risks associated with
List 23.4 Symptoms and signs in patients at risk of ventilatory failure

• Diaphragmatic weakness
– Suggested by paradoxical (see-saw) respiration on lying supine
– A decrease of 20% in FVC on supine spirometry as compared to erect spirometry
• FVC < 1L
• Orthopnea
• Paroxysmal nocturnal dyspnoea
• Nocturnal hypoventilation as seen on overnight oximetry
• Early morning headaches, drowsiness, excessive daytime somnolence, worsening concen-
tration levels
List 23.5 Symptoms of SVC obstruction

1. Facial oedema
2. Facial flushing
3. Headache
4. Distended veins in upper limb, upper body, head and neck
5. Dizziness
6. Inspiratory stridor
7. Dyspnoea
surgery. Poor lung function would also make radiotherapy to the chest difficult due
to the likely damage to surrounding normal tissue, potentially further depleting an
already limited physiological reserve. It should be noted that active treatments can
be interwoven with palliative care strategies. This includes the use of radiotherapy
to help with pain control from metastases and to help with symptoms from spinal
cord compression. Radiotherapy and superior vena caval stenting can be performed
to help with the symptoms of superior vena caval obstruction (List 23.5).
In summary, it is therefore important that respiratory physicians and palliative
care teams work closely to ensure the best possible outcomes for patients. It is esti-
mated that palliative care involvement can lead to relief from physical, psychosocial
and spiritual problems in over 90% of patients with advanced cancer. It has also
been shown that the early involvement of palliative care services in patients with
advanced non-small lung cancer led to not only an improvement in quality of life,
well-being and mood, but also showed that these patients had a longer survival even
with less aggressive care at the end of life [34].
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Review Questions
1. Treatments of proven benefit in dyspnoea do not include:

(a) Opioids
(b) Oxygen for patients with hypoxia
(c) Benzodiazepines
(d) Heliox
2. Treatment of symptomatic cough includes:
(a) Bronchodilator therapy
(b) Physiotherapy
(c) Dextromethorphan
3. Patients with hemoptysis:
(a) Suffer underlying lung conditions
(b) Need to be managed as inpatients
(c) Have massive hemoptysis if they exporate > 50 ml of blood over 24 h
(d) If massive, may have up to 80% mortality
4. For the effective treatment of dyspnoea, opioids may be give
(a) Orally
(b) Intravenously
(c) Transdermally
5. Stridor:
(a) Is a medical emergency
(b) Can be alleviated quickly by i.v steroids
(c) Can only be treated by physical means, e.g. stenting/tracheostomy
(d) Should be treated by administering back to back salbutamol nebulisers
6. In haemoptysis:
(a) A CXR is usually sufficient to diagnose cause and aetiology
(b) Patients should receive high flow oxygen therapy
(c) “Massive” bleeds are defined as blood loss > 50 ml
(d) Patients should receive nebulised therapy
7. The treatment of lung infections in immunosuppressed patients should include:
(a) Broad spectrum antibiotics
(b) The use of mucolytics
(c) Physiotherapy
8. Patients with respiratory muscle weakness are most likely to hypoventilate:

(a) When awake
(b) In Stage 1 + 2 sleep
(c) In Stage 3 + 4 sleep
(d) In REM sleep
9. Poor prognosis in lung cancer compared to other malignancies is typically due to:
(a) Late presentation of disease
(b) Advanced stage of disease at presentation
(c) Poor performance status of patients due to co-existing medical conditions
Answers
1. (c). While opioids have been shown to be effective in a number of trials, as have
oxygen for hypoxic patients or heliox, particularly for patients with large airway
obstruction, there is little evidence for the use of benzodiazepines. However,
treatment of dyspnoea often includes benzodiazepines such as midazolam, as it
is felt that patients may still benefit.
2. (d). Treatment of symptomatic cough is important as it can be a disabling feature
of many illnesses. Treatment of cough requires the diagnosis and management of
the underlying condition—which may be pulmonary or extra-pulmonary, such as
post-nasal drip and gastro-esophageal reflux disease. Cough, particularly caused
by airways disease such as asthma or COPD may respond to bronchodilator ther-
apy. Physiotherapy can be important in teaching cough suppression techniques.
Dextromethorphan is a pharmacological cough suppressant.
3. (d). In patients presenting with hemoptysis, it is important to rule out bleeding
from other sites, such as the oral cavity or nose, which can present as hemoptysis
without any overt epistaxis or pooling of blood in the mouth. Not all hemoptysis
needs to be managed as an inpatient, and patients with mild hemoptysis who are
haemodynamically stable and have little co-morbidities may be managed as out-
patients after thorough assessment. Massive hemoptysis is defined as expectora-
tion over 100 ml of blood over 24 h. Massive hemoptysis may be fatal and
requires intensive management and resuscitation, if appropriate. However, the
mortality of massive hemoptysis may approach 80%.
4. (d). In terms of pharmacological treatment of dyspnoea, opioids are still consid-
ered first line. Opioids may be administered in a number of different routes,
including orally, subcutaneously, transdermally or intravenously. However, it is
important that in the treatment of dyspnoea a patient centred multi-disciplinary
team approach is taken. This will include the treatment of patients with non-
pharmacological methods such as psychological support, exercise, nutritional
advice and other methods, such as cooling fans.
5. (a). Stridor is considered to be a medical emergency which can rapidly progress
to death due to complete airway obstruction. Although steroids are beneficial,
their mode of action means that they usually take a few hours to work. Treatment
of stridor is dependent on the cause, i.e. small cell lung cancer or lymphoma
causing airway obstruction due to mediastinal lymphadenopathy may respond to
chemotherapy agents. Tracheostomy is only helpful in high tumours, i.e. those
above the vocal cords. Nebulised therapy with epinephrine has been shown to be
beneficial.
6. (b). A CXR is often quick and easy to arrange. However, more detailed radiol-
ogy such as CT scanning is often necessary in order to determine the cause for
haemoptysis. Patients with haemoptysis should be treated with high flow oxy-
gen and cough suppressant medications such as opiates. They should be man-
aged in a calm, relaxed manner, positioned lying on the side of the diseased
lung, so protecting the “good” lung. Nebulised therapy can lead to coughing
which can precipitate further bleeding. Massive haemotysis is defined as blood

loss of 100–600 ml in a 24-h period.
7. (d). All of the above are suggested. Physiotherapy can help clear secretions.
Mucolytics such as carbocysteine and nebulised saline can help loosen secretions
to help expectoration. Infections in immunosuppressed patients maybe due to
atypical or unusual pathogens, therefore, initial treatment with broad spectrum
antibiotics is recommended whilst culture results are awaited.
8. (d). During REM sleep flaccid paralysis occurs meaning breathing is via the
diaphragm only. If a patient has a neuromuscular weakness affecting the dia-
phragms, they will breathe less effectively during this phase of sleep. Stage 1 + 2
is defined as light sleep, Stage 3 + 4 is defined as deep sleep.
9. (d). Patients with lung cancer often present late and with advanced disease. They
often have co-existent COPD and cardiac disease due to their shared aetiology
(i.e. smoking).
Chapter 24
Palliative Care in Critical Care Units
Rita Agarwala, Ben Singer, and Sreekumar Kunnumpurath
Introduction
Modern Critical Care Units admit increasingly more complex cases and are able to
offer novel, often very invasive, interventions in order to achieve favourable out-
comes. Despite this over 20% of deaths in the USA occur in critical care units and
over half of those who die in hospital are cared for in critical care units within 3 days
of their death [1]. It is, therefore, essential to appreciate the integral role of palliative
care within this environment.
The majority of patients admitted to the critical care unit are treated aggres-
sively for acute, potentially reversible diseases [1]. However, palliative care within
this group should not be ignored. These patients will still experience pain, dis-
comfort, fear and confusion [2]. Also, a subset of these patients will fail to respond
to treatment and further aggressive management will no longer be in their best
interests. Palliative care in these patients then becomes the main focus of therapy
in the critical care unit.
There is also a group of patients with chronic conditions such as chronic obstruc-
tive pulmonary disease or lung fibrosis who are admitted to the critical care unit
with the hope of reversing an acute exacerbation or treating a complication of their
condition. Palliative care in this group plays a more significant role. Again, a pro-
portion of these patients will continue to deteriorate and symptom control becomes
the main goal of treatment.
Many of the principles of palliative care discussed throughout this book, particu-
larly those relating to terminal care, still apply to patients within critical care.
R. Agarwala, B.M., B.Sc. • B. Singer, M.B.B.S., F.R.C.A. (*)

S. Kunnumpurath, M.B.B.S., M.D.
Department of Anesthetics, Epsom and St Helier University Hospitals NHS Trust,
Carshalton, Surrey, UK
e-mail: b.singer@doctors.org.uk

DOI 10.1007/978-1-4614-5164-8_24,
418 R. Agarwala et al.
Maintaining dignity, good communication, ensuring adequate pain management,

providing treatment for anxiety, dyspnoea and secretions should not be forgotten.
This chapter, however, will focus on palliative care issues and diseases often seen in
the critical care unit.
Non-invasive Ventilation
Non-invasive positive pressure ventilation (NIPPV) is one method of assisting ven-
tilation without an endotracheal tube. Pressurised gas is delivered to the airways via
a mask, inflating the lungs. Exhalation then occurs by the passive elastic recoil of
the lungs and the active contraction of the expiratory muscles [3]. The mask is tight
fitting and is applied over the mouth and nose, or in some circumstances, just the
nose alone. It is then held in place with elasticated straps (Fig. 24.1). The patient
breathes spontaneously and each breath is supported. There are two forms of NIPPV,
continuous positive pressure ventilation (CPAP) and bilevel inspiratory positive
pressure ventilation (BIPAP).
In CPAP, a constant pressure is delivered during both inspiration and expiration.
By doing so, collapsed or underventilated alveoli are opened up, increasing func-
tional residual capacity and improving oxygenation. CPAP also helps improve lung
compliance and decreases the work of breathing [4]. In pulmonary oedema, excess
alveolar fluid weighs down the closed alveoli. At the end of expiration the energy
required to re-open the alveoli for gas exchange is high. This can lead to rapid
fatigue and worsening in the patient’s condition. The application of CPAP splints
the alveoli open and reduces the energy expenditure making breathing much easier
for the patient. It also causes a reduction in afterload making CPAP an attractive
treatment for pulmonary oedema [3].
In some conditions, CPAP would fail to provide adequate respiratory support
and BiPAP may be more appropriate. In BiPAP, two levels of pressure are delivered
to the patient. The first, as in CPAP, is a constant pressure delivered throughout the
respiratory cycle and is known as expiratory positive airway pressure or EPAP. The
second is the inspiratory positive airway pressure, IPAP. When the ventilator
detects the negative pressure generated by the patient breathing in it delivers a pre-
set pressure (the IPAP) of oxygen/air mix above the pressure already being deliv-
ered by the EPAP. This not only reduces the work of breathing but also increases
ventilation [3].
NIPPV is now regularly used to reverse and cure acute respiratory failure [3].
Studies have proven its benefit in chronic obstructive airway disease (COAD) [5],
respiratory failure in immunocompromised hosts [6] and in cardiogenic pulmonary
oedema [7]. A consensus statement in 2001 on non-invasive ventilation for acute
respiratory failure also supported the use of palliative NIPPV in selected patients.
The consensus suggested palliative NIPPV could be used when endotracheal intu-
bation was inappropriate provided the cause of respiratory failure was known to be
reversible and that the NIPPV helped to improve patient comfort [8]. A society for
24 Palliative Care in Critical Care Units 419
Fig. 24.1 Examples of masks

used for non-invasive
ventilation (a) oronasal mask.
(b) Nasal mask
critical care medicine task force built on this and provided one approach to
categorise the use of NIPPV [4]: Those without preset limits on the provision of
advanced life support; NIPPV for patients who decline endotracheal intubation and
invasive mechanical ventilation; NIPPV as a comfort measure for patients who
decline endotracheal intubation [4]. The latter two categories describe palliative
NIPPV.
In the second category, NIPPV is being used to help support ventilation whilst
the underlying cause of acute respiratory failure is treated. It is commonly used in
patients with a chronic condition with the hope of reversing an acute exacerbation
or treating a complication of their illness. Though the patient should be comfortable
on NIPPV, some discomfort may be tolerated if oxygenation or ventilation is
improving. If NIPPV, however, is not tolerated or not improving the patient’s acute
illness, then comfort measures should be adopted after discussion between the
patient, family and the healthcare team [4].
Table 24.1 Adverse side effects of NIPPV [3]

Adverse effect Possible solution
Discomfort from the mask New type of mask, check fit

Facial skin erythema Loosen straps
Nasal Bridge ulceration Loosen straps, artificial skin
Nasal congestion Nasal decongestant, antihistamine
Eye irritation Check mask fits
Gastric insufflations Reduce pressure, Reassure
Air leaks New mask type, encourage mouth closure
Aspiration pneumonia Careful patient selection, adequate
consciousness
Hypotension Reduce pressures
Pneumothorax Stop NIPPV if possible. Chest drain if indicated
NIPPV can be used as a comfort measure. Though limited, evidence suggests

that NIPPV can reduce the sensation of dyspnoea [9, 10]. This may allow a
reduction in the amount of opiate and anxiolytic required to treat this distressing
symptom and thus reduce side effects (such as reduced consciousness) associ-
ated with these drugs. Though the mask itself may hinder speech, the relief of
dyspnoea and the improved consciousness may help maintain communication for
longer.
However, NIPPV is associated with adverse side effects. One side effect is dis-
comfort [3], not only associated with the very tight fitting mask, but also due to the
high pressures giving an initial sensation of trying to breathe through a strong wind
tunnel. Some strategies exist for circumventing these problems such as using differ-
ent masks [3] (hood masks, nasal masks), or starting on low pressures and increas-
ing gradually. Another approach is to use light sedation to reduce patient anxiety but
this carries significant risks of reducing the patient’s respiratory drive and conscious
level and may negate the original reasons for using NIPPV. Other adverse effects are
listed in Table 24.1 [3].These effects may be unacceptable to the patient and out-
weigh the relief of dyspnoea NIPPV may provide. For this reason, for patients in the
third category in particular, it is vital they are able to communicate the decision to
start or continue support as any discomfort is this group should not be tolerated
[4].
There are also several relative contraindications for starting NIPPV. These
include patients actively or at high risk of vomiting (i.e. bowel obstruction), reduced
consciousness, untreated significant pneumothorax and oral–facial abnormalities
[11].
The use of palliative NIPPV still remains a controversial issue. The concern is
the inadvertent prolongation of the dying process [12]. There is no data currently
which supports or refutes this. Also, data proving NIPPV in the dying patient
improves the quality of end-of-life care or the family experience does not exist
either.
Diabetic Ketoacidosis
A potentially life-threatening complication seen in patients with diabetes is diabetic

ketoacidosis (DKA). Mortality rates have improved greatly due to the improved
management over the past 20 years and have fallen from close to 8% to now just
0.67% [13]. It remains high in developing countries and those not hospitalised indi-
cating the importance of early diagnosis, prompt treatment and disease prevention
[14].
DKA occurs due to absolute or relative insulin deficiency and excessive counter-
regulatory hormones such as glucagon, cortisol and growth hormone. This imbal-
ance leads to severe hyperglycaemia, acidosis and ketonaemia [15]. The deficiency
of insulin within the body enhances hepatic glucose production causing the hyperg-
lycaemia. The high blood glucose levels trigger an osmotic diuresis resulting in
severe dehydration. The dehydration is then exacerbated by the vomiting associated
with the disease process and the reduced fluid intake secondary to the decreased
level of consciousness. With such severe dehydration, electrolyte shifts occur which
can also be life threatening.
Hepatic glucose production is increased by the breakdown of fat and protein.
When fat is metabolised like this it produces large amounts of fatty acids. These
fatty acids are then converted to ketones (mainly acetone, 3 beta hydroxybutyrate
and acetoacetate) resulting in the ketonaemia and acidosis [16].
As soon as a diagnosis of DKA is made a rapid assessment of airway, breathing
and circulation should be done. If the dehydration is severe enough to cause a
decreased level of consciousness and airway compromise this must be dealt with
first, often requiring intubation and ventilation. After this initial assessment, large
bore intravenous cannula should be inserted and intravenous fluids commenced.
A medical history should be elicited and a clinical examination performed to help
identify potential triggers such as infection and non-compliance with medications.
Initial investigations, such as those listed in Table 24.2 [15], should also be com-
pleted to aid diagnosis and management. Intravenous fluids must also be started
promptly to restore the circulating blood volume. Initially, one litre of 0.9% saline
is infused over an hour. Subsequent litre bags of 0.9% saline containing potassium
chloride are then infused over 2, 4 and 6 h. If a patient is haemodynamically unsta-
ble (hypotensive and tachycardic) then these fluids must be given faster without any
additional potassium. Due to the greater risk of complications from DKA and its
treatment, caution in the rate of fluid resuscitation must be exercised in the elderly,
those aged 18–25, in pregnancy and in patients with heart or kidney failure. In these
patients fluid should be replaced cautiously and guided by central venous pressure
measurements.
Potassium chloride is often added to the second and subsequent bags of fluid
because treatment of DKA often drives potassium back into cells causing a hypoka-
laemia. It is not added to the first litre of fluid in case the DKA has caused a renal
failure and an associated hyperkalaemia. In fact, hyperkalaemia is often seen in
patients with DKA at presentation due to the acidosis and potassium should not be
Table 24.2 Suggested initial investigations when managing DKA

Blood ketones
Capillary blood glucose
Venous plasma glucose, urea and electrolytes, full blood count
Blood cultures
Venous blood gas
Electrocardiogram
Chest radiograph
Urinalysis and culture
added if the level is greater than 5.5 mmol/l. Once fluid has been initiated a fixed
rate intravenous insulin infusion should be commenced at 0.1 unit of fast acting
soluble insulin per kilogramme per hour. If there will be a delay in starting the infu-
sion a once only dose of intramuscular fast acting insulin can be given at 0.1 unit/
kg. Continue any long acting insulin the patient normally takes at the usual dose and
time [15].
Once treatment has been initiated reassessment of the patient and the metabolic
parameters is required. A catheter should be considered if the patient is anuric,
oliguric or incontinent as this aids assessment of the response to treatment. Also a
nasogastric tube may be beneficial in patients who are persistently vomiting and
again will help quantify fluid loss. Metabolic parameters should also be reviewed
and if a fall in blood ketones by at least 0.5 mmol/l/h or, a fall in blood glucose by
3 mmol/l/h or, a rise in venous bicarbonate of 3 mmol/l/h is not achieved the insulin
infusion rate should be increased by 1 unit/h until these rates of improvement are
seen. Once the blood glucose is below 14 mmol/l, 10% dextrose fluid infusion at
125 ml/h should be started alongside the 0.9% saline. Again caution in fluid vol-
umes must be taken in high-risk patients and should be adjusted to the patient’s
clinical condition and the measured variables. The glucose fluid is added to prevent
hypoglycaemia as the insulin infusion must continue to suppress the production of
ketones. Serum potassium must also be measured frequently and potassium replace-
ment within the fluids continued if the potassium remains between 3.5 and 5.5 mmol/l
and the patient continues to pass urine. Again, above this range potassium should
not be added and below this further potassium may need to be given. Additional
potassium can be given in concentrated volumes via central venous access and in
the presence of close cardiac monitoring.
After 24 h the acidosis and ketonaemia is likely to have resolved. Resolution is
defined as ketones less than 0.3 mmol/l and pH more than 7.3. The precipitating
factor should continue to be treated but if the patient is eating and drinking normally
they can be transferred to a subcutaneous insulin regime. A dose of fast acting insu-
lin should be given subcutaneously before a meal and then the intravenous infusion
stopped 1 h later. This transfer to subcutaneous insulin is ideally managed by the
specialist diabetes team and the team should be involved in the care of DKA patients
from a very early stage [15]. Their involvement has been shown to reduce length of
hospital stay [17].
The management of DKA involves aggressive fluid management. This has

consequences including hyperchloraemic acidosis, due to the large volumes of 0.9%
saline used, and more significantly pulmonary and cerebral oedema. The hyperchlo-
raemic acidosis has not been shown to cause significant morbidity or increase length
of stay in hospital. However, it is the reason why bicarbonate is not used to define
resolution of DKA. Cerebral and pulmonary oedema are uncommon in DKA. They
occur within a few hours of treatment and are thought to be iatrogenic though this
has been disputed [15]. Cerebral oedema is more likely to occur in the younger
population whereas pulmonary oedema is more likely to be seen in the elderly and
in those with cardiac and renal dysfunction [15].
The treatment of DKA involves numerous blood tests to assess progress and can
be distressing for the patient. Though central venous access will reduce the number
of needle pricks, its insertion can be difficult, painful and associated with complica-
tions. Response to treatment can be assessed using venous blood and arterial punc-
ture or arterial catheter insertion is not required unless there is any concern regarding
oxygenation, ventilation or haemodynamic stability in severe DKA. Arterial punc-
ture is again very painful. Whatever method is used for venesection, the distress it
can cause the patient should be considered and local anaesthetic should be thought
about with each attempt.
Hyperkalaemia
Potassium is the most abundant cation in the body, the majority of which lies intra-
cellularly. Despite variable daily potassium intake the serum potassium levels
remain within a very narrow normal range. This is due to strict regulation of potas-
sium excretion at the kidney, gastrointestinal losses and the transfer between the
extracellular and intracellular compartments. Potassium plays a key role in the
excitability of cells and therefore, abnormalities in the potassium level can result in
life-threatening arrhythmias and cardiac arrest [18].
Causes of hyperkalaemia are listed in Table 24.3 [18]. No exact definition for
mild, moderate and severe hyperkalaemia exist, however most authorities advise
treatment if the potassium is more than 6 mmol/l. Often multiple factors are involved
in causing hyperkalaemia which leads to either decreased excretion of potassium or
increased release from cells. Increased potassium intake can also cause hyperkalae-
mia especially in the presence of renal failure. Intake can be dietary, secondary to a
blood transfusion as potassium is released from haemolysis and iatrogenic when too
much potassium is given via intravenous fluids or total parenteral nutrition. Spurious
results must be excluded first before other causes are searched for. Though over
75% of severe hyperkalaemia cases are due to renal failure, potassium excretion is
relatively well preserved in chronic renal disease until the renal dysfunction is
advanced. There are a group of patients in whom hyperkalaemia occurs without
severe renal failure due to damage of the juxtoglomerulus apparatus in the kidney.
The main cause of this is diabetes and it results in a reduced renin production and
therefore reduced aldosterone production. Aldosterone is key in regulating
Table 24.3 Causes of

hyperkalaemia [18] Spurious result
Lab error
Excessive tourniquet
Traumatic venipuncture
Ingestion of foods with high potassium content
Figs
Chocolate
Banana/kiwi
Spinach/tomatoes
Tissue breakdown
Rhabdomyolysis
Tumour lysis syndrome
Severe burns
Insulin deficiency
Metabolic acidosis
Renal failure
Addisons disease
Hyporeninaemic hypoaldosteronism
End organ insensitivity to aldosterone
Sickle cell disease
Amyloidosis
Drugs
Beta blockers
Suxamethonium
Potassium supplements
Angiotensin converting enzyme inhibitors
Angiotensin II receptor blockers
Non-steroidal anti-inflammatory drugs
Potassium sparing diuretics
potassium excretion and with reduced aldosterone there is reduced potassium excre-
tion by the kidney. There are also diseases and drugs which can cause an absolute or
relative aldosterone deficiency [18].
One of the main contributors to the development of hyperkalaemia is drug ther-
apy. Angiotensin Converting Enzyme Inhibitors and angiotensin receptor blockers
are being increasingly used for its reno- and cardioprotective properties in particular
groups of patients. Not only do they reduce renal perfusion but they also impair
aldosterone release thus reducing potassium excretion by the kidney. In patients
with normal renal function, this reduction in potassium excretion is rarely sufficient
to cause a hyperkalaemia. However, these drugs are often targeted at those with
underlying co-morbidities such as the elderly, those with diabetes, renal disease and
cardiovascular dysfunction who are therefore at high risk of developing hyperkalae-
mia. Drugs like this must be started cautiously in these patients and slowly titrated
with potassium being checked within a week of any dose change [18].
In the majority of cases, hyperkalaemia is asymptomatic. Palpitations, lethargy
and muscle weakness are often described when symptoms are present due to the
Fig. 24.2 Electrocardiogram changes in (a) hyperkalaemia and (b) hypokalaemia
cardiac arrhythmias and abnormal muscle function that can occur when high
potassium levels exist. When hyperkalaemia is identified on laboratory results an
electrocardiogram should be performed as specific changes may be seen as shown
in Fig. 24.2a. A medical history and examination must also be performed to help
identify potential causes so that further investigations can be directed [18] to pin-
pointing the disorder.
Mild to moderate hyperkalaemia may be managed by a loop diuretic to increase
potassium excretion, though this may be ineffective in patients with renal failure.
Dietary potassium should be restricted and contributing drugs should be stopped or
reduced where possible [18].
Severe hyperkalaemia is life threatening and requires prompt and aggressive
management. Initial treatment involves stabilisation of the myocardium with cal-
cium (10 ml of 10% calcium gluconate infused over 3–5 min). Though this does not
reduce the serum potassium level it does protect the heart, reducing the risk of fatal
arrhythmias and resolution of electrocardiogram changes can be seen. Once the
myocardium has been stabilised, the hyperkalaemia itself must be corrected. This is
done by driving potassium from the extracellular compartment, intracellularly. Both
insulin and beta-2 agonists activate the sodium–potassium pump, thus shifting
potassium into cells [19]. Beta-2 agonists can be given via a nebuliser or intrave-
nously. Both produce a response within 30 min but the intravenous route is thought
to achieve a maximal response more rapidly [20]. However, due to the ease to set up,
the nebulised route is often used and complements the effect of insulin. Insulin is
given as a rapid intravenous infusion with glucose to minimise potential hypogly-
caemia. It has been shown to have a more rapid effect on serum potassium levels
than beta-2 agonists and sodium bicarbonate though the overall maximal effect is
similar [21]. The use of sodium bicarbonate for treatment of hyperkalaemia remains
controversial as evidence supporting its use remains inconclusive [18, 21]. It may
have a role in the acidotic hyperkalaemic patient or the patient in cardiac arrest.
When the above interventions have failed, urgent renal replacement therapy (RRT)
is required to remove the potassium from the body. RRT is the process by which
blood is removed from the body, filtered via a semipermeable membrane to remove
unwanted solutes and then returned back to patient in a continuous cycle. The
difficulty is that RRT is time consuming to set up, requires a specialised catheter
for intravenous access and can cause haemodynamic instability. Though it is the
definitive treatment for hyperkalaemia it is not therefore the first-line manage-
ment option. Removal of potassium from the body can also be promoted by drug
therapy such as diuretics in those with normal renal function or cation exchange
resins [18].
Once the acute severe hyperkalaemia has been managed, the cause must be
identified and treated to prevent reoccurrence.
Hypokalaemia
The majority of cases of hypokalaemia are mild (between 3.0 and 3.5 mmol/l) and
are often iatrogenic as a consequence of prescribed drugs. Though it is mostly
asymptomatic, hypokalaemia can cause fatal arrhythmias and cardiac arrest. If
symptoms are present, they are often non-specific such as muscle weakness, cramps
and palpitations [22]. As with hyperkalaemia, if low potassium is identified on labo-
ratory tests, an electrocardiogram should be performed as characteristic changes of
hypokalaemia can be seen and are shown in Fig. 24.2b.
Table 24.4 [22, 23] lists some of the causes of hypokalaemia which can essen-
tially be divided into those that cause potassium to shift into cells and those that
increase potassium loss from the body [22]. The cause should be investigated, start-
ing with history and examination followed by laboratory tests.
By establishing the cause the underlying disorder can be treated and the hypoka-
laemia resolved. In the majority of cases, this approach is adequate at correcting the
potassium deficiency. If potassium replacement is required it can be given orally or
intravenously. Oral preparations are associated with an increased risk of gastrointesti-
nal ulceration and so should always be given with plenty of fluid. Ingestion of foods
with high potassium content such as bananas, pineapples and avocados can also be
used to raise the serum potassium. Intravenous potassium is required to treat severe
hypokalaemia (serum potassium less than 2.5 mmol/l) but should not be given at a rate
greater than 20 mmol/h and should not be concentrated more than 40 mmol in 1 l
Table 24.4 Causes of hypokalaemia Diuretics

Vomiting and diarrhoea
Pyloric stenosis
Rectal villous adenoma
Intestinal fistula
Hypomagnesaemia
Hyperaldosteronism
Conns syndrome
Cushings disease
Renal tubular acidosis
Excess liquorice ingestion
Transcellular shifts
Alkalosis
Insulin administration
Catecholamines
Phosphodiesterase inhibitors
Activation of the renin–angiotensin pathway
Bartter syndrome
Gitelman syndrome
Malnutrition
as it is irritant to veins [22, 23]. If faster replacement or more concentrated solutions

are required, for example in symptomatic severe hypokalaemia or patients with heart
failure who cannot tolerate large fluid volumes, then potassium must be given via a
central venous catheter with close cardiac monitoring. In all patients having potassium
replacement, levels must be frequently checked to avoid the danger of rebound hyper-
kalaemia. As the risk of hyperkalaemia is so high in oliguric patients, potassium
should not be replaced without expert advice [22].
The treatment of acute hypokalaemia is more urgent than the treatment of chronic
hypokalaemia which can often be resolved by treating the cause alone. Chronic hypoka-
laemia may also be treated with potassium sparing diuretics, though again the risk of
rebound hyperkalaemia, especially in those with chronic kidney disease, is high [22].
Hyponatremia
Sodium is the primary extracellular cation and it plays a significant role in determin-
ing the extracellular fluid volume. Low serum sodium levels can be seen in 15–30%
of hospitalised patients [24] and has been shown to be a predictor of mortality in
critically unwell patients [25].
If hyponatremia is identified on laboratory tests, a detailed history and examina-
tion will help guide the clinician to the most likely cause. By determining the extra-
cellular volume status of the patient, the hyponatremia can be classified into three
categories: hypovolemic, euvolemic and hypervolemic hyponatraemia [26].
Table 24.5 Causes and management options of hyponatremia [26]

Hyponatraemia Causes Urinary sodium Treatment
Hypovolemic Renal losses Urinary sodium Isotonic saline
hyponatra- Diuretic excess concentration more
emia Mineralocorticoid deficiency than 20 mmol/l
Polycystic kidney disease
Interstial nephritis
Renal tubular acidosis
Osmotic diuresis
Extrarenal loss Urinary sodium
Gastrointestinal (vomiting, concentration less
diarrhoea, peritonitis, than 10 mmol/l
pancreatitis, ileus)
Burns
Haemorrhage
Euvolaemic Glucocorticoid deficiency Urinary sodium Water restriction
hyponatra- Hypothyroidism concentration more
emia Hypopituitarism than 20 mmol/l
Primary polydipsia
Pain
Psychiatric disorders
SIADH
Hypervolemic Nephrotic syndrome Urinary sodium Sodium and water
hyponatremia Cardiac failure concentration less restriction
Cirrhosis than 10 mmol/l
Acute renal failure Urinary sodium
Chronic renal failure concentration more
than 20 mmol/l
In hypovolemic hyponatremia there is a deficit of both total body water and

total body sodium. The patient may be hypotensive or complain of orthostatic
hypotension, be tachycardic, have a low jugular venous pressure and be peripher-
ally vasoconstricted with increased capillary refill time. The cause can then be
further classified into renal losses and extra renal losses which are explored in
Table 24.5 [26].
In euvolemic hyponatremia, the total body sodium content is normal but
there is a gain of water due to excessive amounts of antidiuretic hormone (ADH)
which impairs water excretion. The ADH may be produced in excess from the
pituitary itself by inappropriate stimulation or it may come from an ectopic
source. This is called SIADH or syndrome of inappropriate ADH secretion, the
causes of which are extensive and listed in Table 24.6. Before SIADH is consid-
ered however, other causes of euvolemic hyponatremia must be excluded and
are listed in Table 24.5 [26].
In hypervolemic hyponatremia, though both are raised, the total body water is
increased to a greater extent than the total body sodium causing a relative hyponatremia.
Table 24.6 Causes of SIADH (this list is Malignant disease

by no means complete) Small cell carcinoma
Pancreatic carcinoma
Bladder cancer
Prostate cancer
Lymphoma
Pulmonary disorders
Pneumonia
Tuberculosis
Cystic fibrosis
Central nervous system
Infection—AIDS, meningitis, abscess
Masses—subdural haematoma, subarachnoid
haemorrhage, brain tumour, hydrocephalus
Multiple sclerosis
Guillain–Barre syndrome
Drugs
Tricyclic antidepressants
Serotonin selective receptor inhibitors
Nicotine
Non-steroidal anti-inflammatory drugs
Desmopressin
Vasopressin
Oxytocin
Pain
Stress
General anaesthesia
The patient may present with ascites, peripheral oedema or pulmonary oedema. Again
causes and management options are listed in Table 24.5 [26].
Low serum sodium levels can be acute or chronic. When acute it can present as
a life-threatening event due to swelling of the brain causing herniation and cardio-
pulmonary arrest. Other neurological signs may precede this such as acute psycho-
sis, hallucinations, tremor, hemiparesis and seizures. Some patients may present
with more non-specific symptoms such as lethargy, agitation, nausea and anorexia.
In chronic hyponatremia, the neurological findings tend to be mild as the brain has
time to adapt to changes in sodium concentration [26].
The management of hyponatremia is influenced by many factors including, the
rate of onset, the severity and the presence of symptoms. In severe, life-threatening
acute hyponatremia, presenting with seizures or coma, immediate treatment with
3% hypertonic saline should be started at 100 ml/h. This will increase the serum
sodium concentration by 2 mmol/l/h and should be continued until improvement is
seen in the patient’s signs and symptoms [26]. However, if correction of the hypona-
tremia is too rapid, especially in those with chronic hyponatremia, damage to the
brain will occur, called osmotic demyelination, with pontine and extrapontine sites
being most vulnerable. This can present as a delayed onset of neurological signs
following treatment [27]. To avoid osmotic demyelination in chronic hyponatremia,
correction should be limited to less that 12 mmol in 24 h and less than 18 mmol in
48 h [28]. However in high-risk patients with malnutrition, hypokalaemia, alcohol-
ism and liver disease, correction should be slower than this [26].
The management of hyponatremia is also determined by the category it falls in
to. Hypovolemic hyponatremia is treated by volume expansion. The underlying
cause must also be addressed such as discontinuation of the offending medication or
hormone replacement if hypothyroidism or glucocorticoid deficiency is suspected.
In euvolemic and hypervolemic hyponatremia fluid restriction may resolve the low
serum sodium concentration. However, fluid intake must be less than daily urine
output and insensible losses which many patients find difficult to adhere to.
Demeclocycline is another approach which induces a nephrogenic diabetes insipi-
dus so that the kidney can no longer conserve water. It can cause nephrotoxicity and
caution must be taken when using in patients with liver disease or congestive car-
diac failure. Lithium has also been used to induce a nephrogenic diabetes insipidus
but the effect is inconsistent and its narrow therapeutic window makes risk–benefit
ratio high [26]. Recently, V2 vasopressin receptor antagonists and dual V1/V2
receptor antagonists have been developed. They are still in the early stages of clini-
cal use but certain types have been approved for use in both America and Europe in
specific conditions. Their effect is to increase solute free water excretion and thus
they are well suited for the treatment of hypervolemic and euvolemic hyponatremia.
At the time of writing this chapter, data supporting their use are promising but studies
are small [26, 29].
Hypercalcaemia
The majority of the body’s calcium is stored in bone, however only a very
small proportion of it is readily exchangeable with extracellular calcium. The
extracellular calcium may be either bound (to mostly protein but also to phos-
phorous and lactate) or free. It is this free calcium that is tightly regulated and
when abnormal causes the symptoms of hyper- or hypocalcaemia [30].
Symptoms of hypercalcaemia are non-specific and include muscle weakness,
fatigue, confusion, abdominal pain and arrhythmias. A more complete list, as
well as a list of causes of hypercalcaemia, is provided in Table 24.7 [31].
Within the outpatient setting, primary hyperparathyroidism is the most com-
mon cause of hypercalcaemia; however, this is superseded by malignancy in
the inpatient population [31].
Twenty per cent of patients with a malignancy will develop hypercalcaemia
at some point during their disease process [ 32] and the pathological process
can be classified into four types. Local osteolytic hypercalcaemia occurs in
malignancies with extensive bone involvement such as breast cancer. The
tumour cells enter the bone’s microenvironment, release factors that stimulate
Table 24.7 Causes and clinical features of hypercalcaemia [31]

Causes Clinical features
Malignancy associated hypercalcaemia Muscle weakness
Primary and tertiary hyperparathyroidism Fatigue and lethargy
Headache
Parathyroid carcinoma Confusion and psychosis
Familial benign hypocalciuric hypercalcaemia Coma
Abdominal pain
Granulomatous disorders Constipation
Sarcoidosis Nausea and vomiting
Crohns disease Pancreatitis
Tuberculosis Polyuria and polydipsia
Drugs Nephrocalcinosis and nephrolithiasis
Thiazides Arrhythmias
Lithium Short QT interval
Vitamin D Cardiac arrest
Thyrotoxicosis Bone pain
Adrenal insufficiency
Milk-alkali syndrome
Renal failure
osteoclasts and thus increase bone resorption. Humoral hypercalcaemia of

malignancy occurs due to the secretion of parathyroid hormone related pep-
tide (PTHrP) by the tumour cells. The PTHrP increases osteoclastic activity in
the bone as well as increasing calcium reabsorption by the kidney. Vitamin D
mediated hypercalcaemia is rare but it is due to the production of 1,25-dihy-
droxyvitamin D by the malignant cells. It is also the process by which granu-
lomatous disorders cause hypercalcaemia. The vitamin D increases calcium
reabsorption from the gut. The forth pathological process responsible for
hypercalcaemia of malignancy is the ectopic production of parathyroid hor-
mone (PTH) by the cancerous cells and is again very rare [30, 31 ] .
Hypercalcaemia has a potent diuretic effect and, therefore, the initial manage-
ment of hypercalcaemia of malignancy is fluid replacement with 0.9% saline. Loop
diuretics increase renal calcium excretion; however, if they are given to patients
who are not volume replete they could worsen the hypercalcaemia. In dehydration
the kidney increases tubular absorption to prevent sodium loss but calcium reab-
sorption is also increased during this process. Bisphosphonates inhibit bone resorp-
tion so are frequently used to treat the high calcium in malignancy. The effect on
serum calcium concentrations, however, is not seen until 24–48 h later. They also
cause an acute phase reaction causing flu-like symptoms, can affect renal function
so must be used in caution in patients with renal disease and can cause transient
hypocalcaemia and hypophosphataemia [31, 32]. Glucocorticoids are sometimes
used to treat vitamin D mediated hypercalcaemia with reductions in serum calcium
concentration occurring 3 days later [33]. RRT using a dialysate containing no
calcium would also be effective in reducing serum calcium concentrations and may
be appropriate in patients with severe hypercalcaemia and renal dysfunction when
aggressive fluid replacement and bisphosphonates are contraindicated. All the above
management options only have a temporary effect, but they may provide enough
time for treatment of the underlying malignancy [31].
Parathyroid hormone secretion is normally stimulated by hyperphosphataemia
and hypocalcaemia. It increases bone resorption, enhances renal absorption of
calcium and excretion of phosphate and aids the formation of active vitamin D
which increases calcium absorption from the gastrointestinal tract. Primary hyper-
parathyroidism (PHPT) affects 1 in 1,000 people, mostly female and most fre-
quently in the 6th decade of life [30]. If diagnosed at a younger age, multiple
endocrine neoplasia (MEN) must be investigated and ruled out. Eighty per cent of
PHPT cases are due to a single benign adenoma with the remaining cases due to
four gland hyperplasia. Parathyroid cancers are rare, responsible for less than
0.5% of cases [31].
PHPT is a curable disease by excision of the gland and guidelines were devel-
oped to direct the timing of surgery. In symptomatic PHPT with overt renal or bone
disease and episodes of life-threatening hypercalcaemia, surgical excision of the
parathyroid tissue is the appropriate treatment. In asymptomatic PHPT, surgery
should be performed when the serum calcium is more than 1 mg/dl above the local
reference range; the creatinine clearance is less than 60 ml/min; the patient is under
50 years old and the bone mineral density T-score is less than −2.5 [34]. Those that
do not meet the criteria for surgery should be managed medically with yearly bone
mineral density scans, blood tests every 6 months and advice including the impor-
tance of hydration and the avoidance of drugs that increase serum calcium such as
thiazides and lithium [31]. Bisphosphonates are also used in the medical manage-
ment of PHPT. Alendronate has been the most extensively studied and though it
does not reduce serum calcium or PTH concentration, it does reduce bone turnover
and improve bone mineral density [35]. Intravenous bisphosphonates should only
be used in life-threatening hypercalcaemia.
Cinacalcet is an oral calcimimetic that increases the sensitivity of the calcium
sensing receptor found in both the kidney and the parathyroid gland. In PHPT, this
receptor fails to respond to the high circulating calcium levels and thus fails to
suppress PTH secretion [36]. Initial studies of cinacalcet in the treatment of PHPT
are promising achieving normocalcaemia in the majority of patients [36]; how-
ever, it is not yet licenced for routine use in these patients. It may be used in
patients with parathyroid carcinoma and persistent hypercalcaemia when surgery
is not an option [31].
Familial Benign Hypercalcaemia is an autosomal dominant inherited disorder of
the calcium sensing receptor. The PTH levels may be inappropriately normal or
even raised and therefore this disorder should always be considered as part of the
differential diagnosis of PHPT. Surgical excision of the parathyroid gland is reserved
for those with severe hypercalcaemia and recurrent pancreatitis as parathyroidec-
tomy is rarely successful with rebound hypercalcaemia occurring within 1 week
despite the operation [37].
Hypocalcaemia
Hypocalcaemia can be as high as 85% in the critical care population but can also be
seen in the outpatient setting [38]. When it develops gradually it can be completely
asymptomatic but those with acute reductions in their serum calcium levels will
experience severe symptoms including muscle spasms and cardiac arrhythmias. The
extracellular calcium concentration plays an important role in the functioning of
nerves and muscles. When hypocalcaemia develops, neuromuscular excitability
occurs, causing muscle twitching, tingling sensations, carpopedal spasm, seizures
and tetany. The neuromuscular excitability can also be provoked if the above signs
are not evident by Chvosteks test (tapping the parotid gland over the facial nerve to
cause facial twitch) or Trousseau’s test (inducing carpopedal spasm by inflation of
a blood pressure cuff) [39].
The causes of hypocalcaemia are listed in Table 24.8 [39]. Vitamin D acts on the
gastrointestinal tract to promote calcium absorption. Though a small proportion is
taken by diet, the majority of vitamin D is synthesised in the skin and then activated
by the liver and finally the kidney. Synthesis in the skin requires exposure to sun-
light and this process is reduced by pigmented skin [39].
Hypoparathyroidism, often iatrogenic after thyroid or parathyroid surgery, can
also be idiopathic or due to an autoimmune process. With reduced PTH, renal cal-
cium excretion is increased, there is reduced calcium absorption from the gut due to
reduced production of active vitamin D and bone resorption slows.
Pseudohypoparathyroidism produces a similar picture but occurs due to tissue resis-
tance to the PTH. Though the PTH levels are high, the hypocalcaemia persists. It is
a genetic disease often associated with skeletal abnormalities such as shortening of
the metacarpal bones. There are a group of patients that exhibit these same skeletal
abnormalities but have no biochemical irregularities and they are said to have
pseudohypoparathyroidism.
The treatment of hypocalcaemia very much depends on the speed of onset, the
signs, symptoms and the severity. In acute hypocalcaemia with neuromuscular
excitability, calcium must be replaced intravenously. Even if patients are asymp-
tomatic with a corrected serum calcium concentration of 1.9 mmol/l or less, cal-
cium should be replaced [40]. With electrocardiographic monitoring, 10 ml of
10% calcium gluconate (can be diluted in 5% dextrose to larger volumes) should
be infused slowly over 10 min. If correction is too rapid cardiac arrhythmias can
occur but as long as done slowly, the treatment can be repeated until symptoms
have resolved. Calcium chloride can also be used but is associated with more
local irritation. Oral calcium replacement should also be commenced.
Occasionally, a continuous infusion of a dilute calcium solution may be required
to maintain the serum calcium within the normal range. Calcitriol may also need
to be given if the cause of the hypocalcaemia is due to a relative or absolute
deficiency in PTH.
When the hypocalcaemia is mild, treatment is directed towards the underlying
cause. For example, in vitamin D deficiency, vitamin D can be replaced either
Table 24.8 Causes or Vitamin D deficiency

hypocalcaemia
Hypoparathyroidism
Renal disease
Parathyroid hormone resistance
Hypomagnesaemia
Infusion of phosphate or calcium chelators such as
citrate
Critical illness
orally or intramuscularly. In hypoparathyroidism, treatment can either be with

active vitamin D (calcitriol or alfacalcidol) or with synthetic parathyroid hormone
[39, 40].
Conclusion
The critical care unit can offer respiratory, cardiac and renal support and is also well
placed to aid correction of biochemical and metabolic disturbances. The intensive
monitoring, organ support and increased nursing care that critical care units provide
makes the management of complex chronic diseases possible.
However, investigation and treatment must be directed to the individual patient.
There will be circumstances when aggressive management of the disease process is
no longer in the patient’s best interest. When this occurs comfort becomes the main
goal of therapy.
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Review Questions
1. In hyperkalaemia which one of the following ECG changes does not occur?
(a) Tall tented T waves
(b) Loss of p wave
(c) Appearance of u wave
(d) Widened QRS complexes
(e) Normal ECG
2. Which one of the following is a cause for hypokalaemia?
(a) Spironolactone
(b) Addisons disease
(c) Conns syndrome
(d) Rhabdomyolysis
(e) Metabolic acidosis
3. Which one of the following statements is false?
(a) Continuous positive pressure ventilation opens up underventilated alveoli
(b) Continuous positive pressure ventilation delivers two levels of pressure to
the patient
(c) Non-invasive ventilation can be used as a comfort measure
(d) Non-invasive ventilation should not be used in those at high risk of
vomiting
(e) Non-invasive ventilation can cause hypotension
4. Which one of the following statements about diabetic ketoacidosis is false?
(a) The breakdown of proteins results in the excessive production of ketones
(b) Diabetic ketoacidosis causes severe dehydration and requires prompt fluid
resuscitation
(c) Treatment of diabetic ketoacidosis may cause hypokalaemia
(d) Treatment of diabetic ketoacidosis may cause a hyperchloraemic acidosis
(e) Resolution of acidosis and ketonaemia usually occurs within 24 h
5. Which one is not a cause of hyponatraemia?
(a) Pain
(b) Hyperthyroidism
(c) Vomiting
(d) Renal tubular acidosis
(e) Nephrotic syndrome
6. Which one of the following statements about calcium is false?
(a) The majority of the bodies calcium is stored in bone
(b) Vitamin D aids calcium absorption from the gut
(c) It is the amount of bound calcium that causes symptoms of hyper- or

hypocalcaemia
(d) Normally, parathyroid hormone increases the renal absorption of calcium
(e) The extracellular calcium concentration plays an important role in the
functioning of nerves and muscles
7. Which one of the following causes hypocalcaemia
(a) Primary hyperparathyroidism
(b) Sarcoidosis
(c) Thiazide diuretic drugs
(d) Pseudohypoparathyroidism
(e) Lithium therapy
8. Which one of the following regarding treatment of hyponatraemia is false?
(a) If hyponatraemia is corrected too quickly it may result in osmotic
demyelination
(b) Hypovolaemic hyponatraemia should be treated with water restriction
(c) Hypertonic Saline should be considered if hyponatraemia presents with
seizures
(d) Vasopressin receptor antagonists have recently been developed for the
treatment of hyponatraemia
(e) Demeclocycline may cause nephrotoxicity
9. Which one of the following is a cause of hyperkalaemia
(a) Hypomagnesaemia
(b) Alkalosis
(c) Gitelman syndrome
(d) Rhabdomyolysis
(e) Phosphodiesterase inhibitors
10. Which one of the following is not a sign or symptom of hypercalcaemia
(a) Short QT interval on electrocardiogram
(b) Pancreatitis
(c) Nephrocalcinosis
(d) Constipation
(e) Chvosteks test
Answers
1. (c)
2. (c)
3. (b)
4. (a)
5. (b)
6. (c)
7. (d)
8. (b)
9. (d)
10. (e)
Chapter 25
Pediatric Palliative Care
Shu-Ming Wang, Paul B. Yost, and Leonard Sender
Introduction
Many people confuse palliative care with hospice care. However, the two approaches
are very different. Hospice care specifically is end-of-life care. The World Health
Organization (WHO) defines palliative care and pediatric palliative care in the fol-
lowing way:
Palliative care is an approach that improves the quality of life of patients and
their families facing the problems associated with life-threatening illness, through
the prevention and relief of suffering by means of early identification and impec-
cable assessment and treatment of pain and other problems: physical, psychosocial,
and spiritual. Palliative care:
• Provides relief from pain and other distressing symptoms
• Affirms life and regards dying as a normal process
• Intends neither to hasten or postpone death
• Integrates the psychological and spiritual aspects of patient care
• Offers a support system to help patients live as actively as possible until death
• Offers a support system to help the family cope during the patient’s illness and in
their own bereavement
S.-M. Wang, M.D. (*)

Department of Anesthesiology and Perioperative Care, University of California,
e-mail: Shuminw1@uci.edu; smwang800@gmail.com
P.B. Yost, M.D., F.A.A.P.
Department of Anesthesiology, St. Joseph’s of Orange, Orange, CA, USA
L. Sender, M.D.
Department of Medicine, University of California, Irvine School of Medicine,
Irvine, CA, USA

DOI 10.1007/978-1-4614-5164-8_25,
442 S.-M. Wang et al.
• Uses a team approach to address the needs of patients and their families, including
bereavement counseling, if indicated
• Will enhance quality of life, and may also positively influence the course of
illness
• Is applicable early in the course of illness, in conjunction with other therapies
that are intended to prolong life, such as chemotherapy or radiation therapy, and
includes those investigations needed to better understand and manage distressing
clinical complications
WHO Definition of Palliative Care for Children
Palliative care for children represents a special, albeit closely related field to adult
palliative care. WHO’s definition of palliative care appropriate for children and
their families is as follows; the principles apply to other pediatric chronic disorders
[1]:
• Palliative care for children is the active total care of the child’s body, mind, and
spirit, and also involves giving support to the family.
• It begins when illness is diagnosed and continues regardless of whether or not a
child receives treatment directed at the disease.
• Health providers must evaluate and alleviate a child’s physical, psychological,
and social distress.
• Effective palliative care requires a broad multidisciplinary approach that includes
the family and makes use of available community resources; it can be success-
fully implemented even if resources are limited.
• It can be provided in tertiary care facilities, in community health centers, and
even in children’s homes.
This chapter includes the demographics of children who would benefit from pal-
liative care, description of pediatric palliative care, the barriers why pediatric pallia-
tive care has not been fully accepted and implemented, as well as discussion of
death with children at various stages of development, issues related to palliative care
in special situations such as neonatal ICU, and information regarding the well-being
of health care providers and caregivers.
Background and Demographics
Each year in the United States more than 50,000 children die, with around 50% of the
deaths occurring in the first year of life. The common causes of death in infants and
children are summarized in Table 25.1 [2]. Congenital malformations and chromo-
some abnormalities are the number one cause of death in infants. For children (age
25 Pediatric Palliative Care 443
Table 25.1 Causes of death

Infant
1. Congenital malformations (20.1%)
2. Prematurity/low birth weight (16.9%)
3. Sudden infant death syndrome (8.2%)
4. Maternal complication (6.3%)
5. Unintentional/accidental injury (4.6%)
6. Complications caused by placenta, cord, or membrane (3.8%)
7. Bacterial sepsis (2.5%)
8. Respiratory distress (2.2%)
9. Diseases of circulatory system (2.1%)
10. Neonatal hemorrhage (2.0%)
Infant with chronic complex conditions
1. Cardiovascular (32%)
2. Congenital/genetic (26%)
3. Respiratory (17%)
4. Neuromuscular (14%)
All children (1–19 years)
1. Accident (38.8%)
2. Assault (12.4%)
3. Malignancy (8.6%)
4. Suicide (8.0%)
5. Congenital malformation, deformity, and chromosomal diseases (4.7%)
6. Heart disease (3.4%)
7. Cerebrovascular disease (1.9%)
All children with chronic complex conditions (1–19 years)
1. Malignancy (43%)
2. Neuromuscular (23%)
3. Cardiovascular (17%)
1–19 years) the number one cause of death is accidental/unintentional injury. The
second leading cause of death for children for ages 1–4 is congenital malformations,
deformities, and chromosomal abnormalities; for ages 5–14: malignancy and for ages
15–19: homicide [3]. Three-fourth of pediatric deaths occur in hospitals each year,
mostly in the ICUs where aggressive, life-sustaining, medical therapy is typically
provided. Of the deaths that occur in children, around 25% are due to Chronic Complex
Conditions [4–7]. Chronic complex conditions (CCC) were defined by Feudtner et al.
[4] as “any medical condition that can be reasonably expected to last at least 12 months
(unless death intervenes) and to involve either several different organ systems or one
organ system severely enough to require specialty pediatric care and probably some
period of hospitalization in a tertiary care center.” In 2007, the American Academy of
Pediatrics issued recommendation for an integrated palliative care model. In this
model, the integrated palliative care emphases the provision of curative therapies and
comfort measures should be initiated at the time of disease diagnosis [8]. More
importantly, a recent study suggests that a high-volume specialist palliative care unit
and team may reduce in-hospital end-of-life care cost [9].
Pediatric Palliative Care [10–14], (Himelstein 2005, 2006)
Pediatric palliative care is about helping children and families to live their fullest
while facing a life-limiting or complex medical condition. It is an interdisciplinary
practice that includes inputs from physicians, social workers, pastoral care provid-
ers, and nurses. The principles of palliative care are based on open, honest discus-
sions earlier in the disease trajectory, and allow patients and families participate in
decision-making process.
The pediatric palliative care should be:
• Child-focused, family-oriented, and relationship-centered
• Focusing on relief of suffering and enhancing quality of life for the child and
family, not to shorten life
• Incorporated into mainstream of medical care regardless of the curative intent of
therapy
• Coordinated across all sites of care delivery
• Goal directed and consistent with the beliefs and values of the child and
caregivers
All children suffering from chronic, life threatening, and terminal illnesses
should be eligible to receive palliative care. Successful pediatric palliative care
should give patients and their family the opportunities to express their feelings and
concerns as well as actively incorporate their concerns into the care that address the
physical, psychological, and spiritual aspects of patients as individuals and family
as a unit.
Barriers to Implementation of Pediatric Palliative Care [15, 16]
• Uncertain prognosis
• Communication problems: readiness of the family, cultural differences, religious
beliefs, etc.
• False hope for cure
• Inappropriate use of advanced life-saving technology
• Ethical and legal issues
• Inappropriate eligibility criteria
• Inadequate assessment and management of symptoms
• Lack of training and expertise to approach the parents and patient regarding the
trajectory of disease process.
• Fragmented care, limited access to specialty care in rural areas

• Lack of adequate data and scientific knowledge to deliver effective care and to
design supportive public policies
• Limited financial resources for specialized pediatric care
Clearly, the problem of pediatric palliative care is a multifaceted one that will
need to be addressed through multiple reinforcing strategies: medical education,
regulatory reform, changes in health care financing, and hospital quality improve-
ment efforts, as well as broad social changes in the ways in which our society views
children, families, death, and dying. Lastly, the advances in pediatric medical/surgi-
cal care have steadily decreased the overall number of deaths in children with CCC
from 1989 to 2003 [17]. In other words, children with CCC are living longer.
Therefore, it is important to establish the delivery of comprehensive care early on
and find creative ways to provide and coordinate care over a longer period [3].
While previous analysis reveals that most CCC do not lead to death in childhood,
the death rate is more than twice that of an age-matched unaffected population and
death could potentially occur at any time [5].
Issues Related to the Delivery of Pediatric

Palliative Care [18, 19]
Initiation and Formation of Team
Which of the healthcare practitioners is best suited to supervise the medical care of
children with CCC and life-threatening illnesses? Pediatricians often have strong
relationships with the child and his/her family and they play an important role in
influencing the acceptance of palliative care services for the patient and family. The
increased awareness of the need of palliative care has reorganized the curriculum
during pediatric residency training. However, not every pediatrician feels comfort-
able in disclosing the potential impending death or shouldering the palliative care
alone, and most pediatricians may not be aware of the many services available to
alleviate the suffering of a CCC or dying child and their family. A team approach
between various specialists, therapists, and religious leaders provides the best com-
prehensive care of the patient with CCC, with the care coordinator being a practitio-
ner of pediatric palliative care.
Physical and Emotional Suffering
Pain is a common symptom associated with children with life-limiting illness. Pain
is unique to an individual. Based on the age and developmental stage of the patient,
Table 25.2 Pain assessment scales

Child’s age
Objective pain assessment scale
Premature Infant Pain Scale (PIPP) >36 weeks gestational age
Neonatal Infant Pain Scale (NIPS) <1 year of age
Face, Leg, Activity, Cary, Consolability Scale (FLACC) 2 months–7 years of age
Children’s Hospital Eastern Ontario Pain Scale (CHEOPS) 1–7 years of age
Subjective pain assessment scale
Wong-Baker FACE Rating Scale >3 years of age
OUCHER 3–13 years of age
Numerical Rating Scale (NR-22, NRS-101) >9 years of age
Visual Analog Scale >7 years of age
the level of pain can be assessed through observation or asking the caregiver and
patient using a pain rating scale as listed in Table 25.2. For a nonverbal child, one
can evaluate the patient’s behavior and physiological signs. Most importantly, fam-
ily members should be included early on in the treatment process. Various pain
medications can be prescribed based on the recommendation of WHO’s pain relief.
Prior to prescribing the pain medication, several considerations should be taken: (1)
Whether the child can and will take medication by mouth. (2) Routes of administer-
ing the pain medication. (3) Dose adjustment based on the maturity of organs and
co-existing diseases. (4) May consider long-acting analgesics. (5) Consider adding
alternative interventions such as acupressure, music, guided imagery, hypnosis, etc.
Once the analgesic medications are prescribed, the assessment should be obtained
from the child and/or caregivers regularly to assess the effectiveness of therapy.
Other symptoms which may be associated with the last phase of a child with
chronic complex condition, e.g., anxiety, dyspnea, nausea, vomiting, etc. Anxiety
and dyspnea may be difficult to assess, but once it is identified, the underlying
causes should be addressed. If there is no acute process, but is a progression of ill-
ness, benzodiazepine and supplemental oxygen should be provided. Similarly, if the
child experiences nausea and vomiting, antiemetics should be administered with or
without the adjunctive alternative treatments to decrease the frequency and symp-
toms should be considered. Many children who suffer with CCC also have problems
with anxiety and depression; however, the emotional/psychological suffering is an
experience that results from a threat to any part of an individual’s personhood; how-
ever, it is poorly understood especially for those children who are very young and
nonverbal. Through the Mandela technique such as drawings, the depth and com-
plexity of cognition and emotion of a very young child might be appreciated, thus
the appropriate intervention and guidance can be provided. Having a specialist in
child psychology, psychiatry, child life, play therapy, music therapy, pet therapy,
and social workers available are important aspects of the team approach to pallia-
tive care. Some children may benefit from antidepressant and/or sedative medica-
tions as well. Palliative care is not only providing medical support, but also providing
the support for the emotional needs of the patient and the emotional support and
needs of patient’s family members. Team approach and group meetings should be
initiated early on to identify specific needs and interventions to prevent emotional
fatigue of the family.
Spiritual Care
Last, but certainly not least, spiritual care. Robinson et al. [20] conducted a survey on
parents of 56 children who died in three pediatric intensive care units in Boston,
Massachusetts. The survey results indicated that 73% of parents reported that prayers,
faith, access to and care from clergy, and belief that the parent–child relationship
transcends death, help them the most in dealing with their child’ last phase of life.
Spiritual care should be an integral part of the team approach to palliative care.
Clergy and leaders from the faith of the family should be included in the process.
The Understanding and Discussion About Death
Similar to adults, the past experiences with death for the terminally ill child, as well
as his/her age, emotional development, and surrounding have significant impact on
how he/she perceive death. Every child, at any age, has his/her own unique concept
of death. Adult’s misconceptions and fear about death are often transferred to his/
her children. Treating death as part of life is difficult for children with CCCs or life-
threatening illnesses, but treating death in this way may alleviate some of the fear
and confusion associated with it. When managing a terminally ill child and his/her
siblings, the age and development will be an important factor.
Infant
Death is not a concept but a terminally ill infant will require care and comforting
both physically and emotionally to maintain a consistent routine because he/she
does react to the separation of parent, painful procedures, and any alteration of his/
her routine.
Toddler
Death bears little meaning. Instead he/she may receive the most anxiety from the
emotion of those around him/her. The words “death” or “forever” or “permanent”
may not have any real value to him/her. Even with previous experiences with death,
the toddler may not understand the relationship between life and death.
Preschool Children
Children of the age group may begin to understand that death is something feared
by adults but they do not understand that death is permanent and every living thing
will eventually die. People around this group of children can influence their
experience with death. They may ask questions about “why?” and “how?” death
occurs. The preschool children may feel shame and guilt. It is not uncommon for
this age group of children to believe that becoming seriously ill is a form of punish-
ment for something they did or thought about. When handling children at this age,
death should not be explained as “sleep” to prevent the possible development of a
sleep disorder. At times, they do not understand how their parents could not protect
them from their illnesses. If siblings of a dying child are at this age group, they may
feel as if they are the cause of illness and death. Therefore, a preschool sibling of a
dying child also requires reassuring and comforting.
School Age Children
When children reach this stage of development, they may have a more realistic
understanding about death and frequently death is personified as an angel, skeleton,
or ghost. They may start to understand death as permanent, universal, and inevita-
ble. They may be interested in the physical process of death and what happens after
a person dies. They may fear their own death because of uncertainty of what hap-
pens to them after they die. Children in the age range tend to mirror the emotions of
their parents. When the parents are scared and anxious, the kids may feel similarly.
Adolescent
Adolescents understand the concept that death is permanent. Past experience and
emotional development greatly affect the adolescent’s concept of death. Similar to
adults, adolescents may want to observe their religious or cultural ritual. In spite of
the predominant theme in adolescence is a feeling of immortality or being exempt
from death. Their realization of their own death threatens all of these objectives.
Denial and defiant attitudes may suddenly change the personality of a teenager fac-
ing death. An adolescent may feel as if they no longer belong or fit in with their
peers or feel an inability to communicate with his/her parents. The adolescent may
feel alone in their struggle, scared, and angry.
Issues Related to Palliative Care in the NICU [21, 22]
Few health care environments or patient populations present more challenges than
neonates dying in the Neonatal Intensive Care Unit. However, 50% of children die
in the first year of life and 25% die in the first month. Palliative care can be very
helpful in defining the goals and limits of care, and can help parents and the health
care team make good decisions on behalf of the neonate when crises occur. Three
unique situations have been identified in newborn ICU in which palliative care team
should intervene and offer the support in decision making and comfort for the
neonate and parents. These scenarios are described as following [23]:
• When a serious health issue is identified prenatally by ultrasound, amniocentesis,
or other prenatal exam.
• When a very premature infant is born or an infant is born with a life-threatening
condition diagnosed in the delivery room.
• When a very ill neonate develops multiorgan system failure and care becomes
futile.
While supporting neonates through the use of ECMO, high-frequency oscilla-
tory ventilation and other new technologies, one fact is that neonates do feel pain,
and every effort should be made to ensure the baby is comfortable and free of physi-
cal suffering during painful procedures. Care should be taken to ensure sedative and
analgesic agents are given when any paralyzing agents are used. It is always difficult
to discuss with parents of infant with terminal illness because of their emotions.
Regardless of level of education, religion, socioeconomic, and age factors, it is
important for them to understand the issues surrounding the care of their critically
ill neonate who cannot speak for him- or herself. It is important to know that pallia-
tive care of newborns is holistic and extensive care for an infant who is not going to
“get better” or having decent quality of life. The focus of palliative care in NICU is
for both the infant and his/her family and may be initially combined with cure-ori-
ented, disease-modifying care; then modify accordingly based on the condition of
infant. Its goals are to prevent and relieve infant suffering and to improve the condi-
tion of the infant’s living or dying and well-being of the family [23].
Issues Related to Health Care Practitioners and Care Givers
Stress and Burnout in Health Care Practitioners
Caring for children with life-limiting conditions is a stressful task not only for
patient’s family, friends, and siblings, but also for health care providers. Although
little is known about how health care professionals cope with the challenges of chil-
dren with life-threatening and life-limiting disease, studies suggest that they are at
risk for developing compassion fatigue and burnout. Difficulties in communications
with young patients and parents and inadequate support system were listed as com-
mon issues for health care providers in many countries. In addition, the uncertainty
of most childhood life-threatening conditions and the continued hope for survival
make decisions to shift from cure to palliation difficult and distressing for many
health care providers. The emotional impact of the dying process and death of a
child and grieving of health care providers are frequently hidden and disenfranchised.
The society expects health care providers remain strong and stoic in the face of
death. Papadatou et al. [24] demonstrated that even though health care providers
work in different environments and cultures, the grieving process of health care
providers has unique characteristics. Some may grieve over the loss of a personal
bond they have developed with a child, some over the nonrealization of their efforts
to cure or control the disease, and others over unresolved personal loss that surface
with the death of a child. Nevertheless, health care professional’s grieving process
is an ongoing fluctuation between experiencing grief by focusing on the loss, and
avoiding or repressing grief by moving away from it. When healthcare providers do
not have fluctuating feelings, suppress and deny the feelings, or submerge in their
grief, complications occur. Frequently, the health care professionals rely on their
colleagues for support, not their family members. Through information exchanges,
clinical collaboration, and sharing personal experiences, the healthcare providers
try to cope with their loss.
Bereavement
Suffering from CCC and life-threatening illnesses does not end with the wake or
funeral. Pediatric palliative care should extend beyond the patient’s death.
Communication with the family should continue not only to offer support for the
family, but to monitor siblings and the parents for signs of difficulty adjusting to life
without their son, daughter, sister, or brother. A simple note or phone call may mean
a lot to the family, and a referral to a psychologist or therapist may help the grieving
process.
Summary
Pediatric Palliative care is systematic coordinated care of patients with CCCs and
life-threatening illnesses. Palliative care is not specifically end-of-life care. Pediatric
Palliative Care should be initiated early in the disease process and it should extend
beyond the patient’s death. The goal of pediatric palliative care is to alleviate the
physical, emotional, psychosocial, and spiritual suffering of children and their fami-
lies suffering CCCs and life-threatening illness. The hallmark of successful care of
the patient with a CCC is open, straightforward communication with the patient,
their families, and amongst those taking care of the patient. Successful palliative
care is usually multifaceted and includes the expertise of many specialties including
but not limited to social work, psychology, psychiatry, pain and symptom manage-
ment, child life, play therapy, music therapy, and pet therapy. Care should include
clergy and spiritual leaders. Pediatric palliative care is the multidisciplinary approach
to the pediatric patient with a CCC and life-threatening illnesses and it can make all
the difference in the world.
References
1. http://www.who.int/cancer/palliative/definition/en/.
2. Feudtner CF, DiGiuseppe DL, Neff JM. Hospital care for children and young adults in the last
year of the life: a population-base study. BMC Med. 2003;1:3.
3. Friebert S. NHPCO Facts and Figures – pediatric palliative and hospice care in America. 2009.
http//www.nhpco.org/files/public/quality/Pediatric_Facts-Figures.pdf.
4. Feudtner C, Silveria MJ, Christakis DA. Where do children with complex chronic conditions
die? Patterns in Washington State, 1980–1998. Pediatrics. 2002;109:656–60.
5. US Department of Health and Human Service, Health Resources and Service Administration,
Maternal and Child Health Bureau. The National Survey of Children with Special Health Care
Needs Chartbook 2005–2006. Rockville, MD: US Department of Health and Human Service;
2007.
6. Simon TD, Feudtner C, Stone BL, Sheng X, Bratton SL, Dean M, Srivastava R. Children with
complex chronic conditions in patient hospital settings in the United States. Pediatrics.
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7. Mathews TJ, Miniño AM, Osterman MJK, Strobino DM, Guyer B. Annual summary of vital
statistics: 2008. Pediatrics. 2011;127:146–57.
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rics;106/2/351.pdf.
9. Smith TJ, Coyne P, Cassel B, Penberthy L, Hopson A, Hager MA. A high-volume specialist
palliative care unit and team may reduce in-hospital end-of life care cost. J Palliat Med.
2003;6:699–705.
10. Feudtner CF, Hays RM, Haynes G, Geyer R, Neff J, Koepsell TD. Death attributed to pediatric
complex chronic condition: national trends and implications for supportive care services.
Pediatrics. 2001;107:e99.
11. Korones DN. Pediatric palliative care. Pediatr Rev. 2007;28:e46.
12. Himelstein BP, Hilden JM, Boldt AM, Weissman D. Pediatric palliative care. N Eng J Med.
2004;350:1752–62.
13. Himelstein BP. Palliative care in pediatrics. Anesthesiol Clin N Am. 2005;23:837–56.
14. Himelstein BP. Palliative care for infants, children, adolescents and their families. J Palliat
Med. 2006;9:163–81.
15. Davies B, Sehring SA, Partridge JC, Cooper BA, Hughes A, Philp JC, et al. Barriers to pallia-
tive care for children: perceptions of pediatric health care providers. Pediatrics.
2008;121:282–8.
16. Liben S, Papadatou D, Wolfe J. Paediatric palliative care: challenges and emergence ideas.
Lancet. 2008;371:852–64.
17. Feudtner CF, Feinstein JA, Satchell M, Zhao H, Kang TI. Shifting place of death among chil-
dren with complex chronic conditions in the United States, 1989–2003. JAMA.
2007;297:2725–32.
18. Masera G. Who can decide what is in a child’s best interest? A problem-solving approach.
Med Pediatr Oncol. 2001;36:649–51.
19. Hynson JL, Sawyer SM. Paediatric palliative care: distinctive needs and emerging issues.
J Paediatr Child Health. 2001;37:323–5.
20. Robinson MR, Thiel MT, Backus MM, Meyer EC. Matters of spirituality at the end of life in
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Review Questions
1. What is the palliative care?

(a) Supportive care only
(b) Only those who is terminally ill can receive it
(c) Both supportive care and curative care together
(d) Only being administered in hospice
(e) The goal is to make patient comfortable
2. Which statement is true?
(a) Palliative care can only be delivered in hospital
(b) Hospice care and palliative care are the same
(c) Palliative care requires multiple disciplinary service
(d) Palliative care can only be delivered in hospice
(e) Every case for palliative care should be treated uniformly
3. What are the barriers of pediatric palliative care?
(a) Inadequate education and exposure
(b) Uncomfortable in discussing the issue related to death
(c) Cultural and religious differences
(d) Uncertainty of disease progression
4. Which one is not included in pediatric palliative care?
(a) Spiritual consultation
(b) Social support, family consultation
(c) Curative treatments
(d) All services are covered by insurance and Medicaid
(e) Symptomatic treatments
5. Pediatric palliative care should include the following service
(a) Religious clergy or cultural leader
(b) Social worker
(c) Nursing
(d) Doctor
6. The similarities between hospice and palliative care are except
(a) Symptomatic treatments
(b) Curative treatment
(c) Majority of services are covered by Insurance
(d) Both types of care can be delivered at home
(e) Both types of care can be delivered in the hospital
7. The pediatric palliative care is as described below except

(a) Mainly delivered through one person
(b) Deliver at home, hospital, or nursing facility
(c) Doctor, nurse, social worker, chaplain, home health aide are included in the
team
(d) Patients with chronic complex illness can benefit from it
(e) Provide support to the whole family
8. What are symptomatic treatments?
(a) Pain management
(b) Anxiety treatment
(c) Spiritual consultation
(d) None of the above
9. The barriers to establish neonatal palliative care are all except
(a) The advancement of surgical techniques and life-support technology
(b) The prognosis of the illness is undetermined
(c) Social circumstance when the neonate was conceived, e.g., unplanned or
IVF
(d) The decision of palliative care should be made prenatally or immediately
when resuscitation is warranted
(e) None of the above
10. Pediatric palliative care
(a) The goal of palliative care is to provide most aggressive treatment for pedi-
atric patients
(b) All neonates need palliative care
(c) The advancement of technology and surgical interventions warrant excel-
lent overall outcomes
(d) The person who has the best interest of the child should make the decision
regarding the care for the child
Answers
1. (c)
2. (c)
3. (e)
4. (d)
5. (e)
6. (b)
7. (a)
8. (e)
9. (d)
10. (e)
Chapter 26
New Pain Management Vistas in Palliative Care
Christopher K. Merritt, Lien B. Tran, Rinoo V. Shah, and Alan David Kaye
Palliative care medicine is an evolving field, unique with respect to the diverse
patients that it treats and drawing from all fields of medicine. Within the field of
palliative care, new treatment modalities are continuously under development, and
existing modalities are increasingly being applied to ease the suffering patients.
This chapter will look toward some of the new treatments under development that
may shape the future of palliative care, including new pharmacologic agents, new
methods of drug delivery, and the application of regional anesthesia to control pain
in palliative care patients.
Novel Agents in Pain Management
Anti-nerve Growth Factor Agents
Nerve growth factor (NGF) is a neurotrophic agent that acts through binding to the
tropomyosin-related kinase A receptor (TrkA). Patients with mutations in the gene
encoding the TrkA receptor demonstrate congenital analgesia and anhidrosis but
few additional adverse effects [1]. Through the interaction with TrkA, NGF func-
tions not only in the growth of nerve fibers, but it also enhances acute nociceptive
pain and is also involved in pathologic chronic pain states and hyperalgesia [2].
NGF is released in response to tissue injury by mast cells, eosinophils, macrophages,
and others, and in turn stimulates the release of additional inflammatory mediators
C.K. Merritt, M.D. (*) • L.B. Tran, M.D. • A.D. Kaye, M.D., Ph.D.
Department of Anesthesiology, Louisiana State University School of Medicine,
e-mail: cmerr2@lsuhsc.edu; alankaye44@hotmail.com
R.V. Shah, M.D., M.B.A.
Department of Anesthesiology, Guthrie Clinic-Big Flats,
Horseheads, NY, USA

DOI 10.1007/978-1-4614-5164-8_26,
458 C.K. Merritt et al.
that enhance the nociceptive response. In addition, the NGF–TrkA complex

undergoes retrograde transport to the dorsal root ganglion, where it induces tran-
scriptional changes that increase nociceptive sensitivity and contribute to hyperal-
gesia [2]. Novel anti-NGF agents have shown significant promise in animal models
attenuating both acute inflammatory pain in addition to chronic pain and hyperalge-
sia. Three monoclonal antibodies are under development by Pfizer (tanezumab),
Janssen (fulranumab), and Regeneron (REGN475) with promising analgesic results.
Concerns exist about the possibility of rapidly progressive osteoarthritis with at
least one of these agents, tanezumab. Nevertheless, the potential benefit of anti-
NGF agents for patients suffering with chronic pain led the FDA to endorse the
continued development of these drugs [3].
Nav1.7 Blocking Agents
The role of the sodium channel subunit, Nav1.7, has recently come to light as a
promising potential analgesic target. In 2006, Cox et al. identified three families
with congenital analgesia, mapped the chromosomal location of their mutation, and
identified their mutation in the SCN9A gene [4]. This results in loss of function of
the Nav1.7 subunit of the voltage-gated sodium channel. Although voltage-gated
sodium channels are ubiquitous in neurons, the Nav1.7 subunit is highly expressed
in nociceptive fibers. Loss of function of the Nav1.7 subunit results in congenital
analgesia but few additional effects [4]. Sodium channel blockade is widely utilized
in local anesthetics as well as antiarrhythmic agents such as mexiletine. However,
no currently available sodium channel blocking agents are specific to the Nav1.7
subunit [5]. A selective Nav1.7 blocking agent could potentially stop nociceptive
pain without otherwise interrupting nerve transmission. Such an agent would pres-
ent a very attractive analgesic and is the subject of ongoing investigation.
High Dose Topical Capsaicin
Topical capsaicin has long been used as a treatment for neuropathic pain syndromes
including painful diabetic neuropathy, HIV-associated peripheral neuropathy, pos-
therpetic neuralgia, as well as in over-the-counter formulations [6]. Capsaicin acti-
vates the TRPV1 receptor on nociceptive fibers resulting in calcium influx into
cells, depolarization, and the sensation of heat and pain. Repeated applications can
cause a decrease in sensitivity to pain and hyperalgesia. It was previously believed
that topical capsaicin resulted in analgesia by causing depletion of substance P in
the spinal cord. More recent evidence, however, points to “defunctionalization” of
nociceptive fibers by topical capsaicin, a multifactorial effect signaling ability of
nociceptive pathways [7]. Although successful, the benefits of formulations ranging
from 0.025 to 0.075% are limited with respect to the duration of their effect and the
26 New Pain Management Vistas in Palliative Care 459
ceiling of their benefit [7]. Eight percent capsaicin for topical application (Qutenza™
patch) has recently been FDA approved for the treatment of HIV-associated periph-
eral neuropathy and postherpetic neuralgia. A single 60-min treatment results in a
significant decrease in pain for 12 weeks [8–11]. Temporary pain and local irritation
were the most common adverse events and rarely resulted in inability to complete
treatment [12, 13].
Voltage-Gated Calcium Channel Blocking Agents
Voltage-gated calcium channels (VGCCs) function in diverse physiologic roles in

many neurological systems. Activation of these channels affects the membrane
potential of neurons and their depolarization, release of neurotransmitters, as well
as affecting the enzymatic activity and genetic transcription of neurons [14].
Through these effects, VGCCs have been implicated in physiologic nociception, as
well as pathologic pain conditions. The high voltage activated N-Type calcium
channel is highly expressed in dorsal root ganglion cells bodies and at the synapse
of afferent nociceptive fibers and dorsal horn neurons. At these sites, N-Type VGCC
function in both the transmission and modulation of pain. Currently, one N-Type
VGCC blocking agent is available clinically, ziconotide (Prialt™). Ziconotide is a
peptide first isolated from the poison of a marine cone snail. The peptide structure
of ziconotide necessitates intrathecal administration to reach its site of action in the
spinal cord. Ziconotide is indicated for the treatment of patients with severe chronic
pain of various etiologies in those who are refractory to or unable to take first-line
systemic analgesics, adjunctive therapies, or IT morphine. Studies of intrathecal
ziconotide infusion reduced pain scores in chronic pain patients approximately
30–50% including those with HIV-associated chronic pain, cancer-related pain, as
well as patients with nonmalignant chronic pain. Although generally well tolerated,
ziconotide can cause neuropsychiatric side effects including confusion, dizziness,
and somnolence. Despite ziconotide’s significant benefit, its clinical utility remains
limited by cost and the need for delivery by intrathecal microinfusion catheters.
Cannabinoids
Smoked or ingested cannabis has long been used both recreationally, as well as for
medical purposes to treat symptoms such as pain, nausea, cachexia, and glaucoma.
As a pharmacologic agent, however, the potential benefit of cannabis has been com-
plicated by psychotropic side effects, legal restrictions, inconsistency in regulation
and potency, and risks of smoke inhalation [15–17]. Currently, the US Drug
Enforcement Agency classifies cannabis as a Schedule I agent with high potential
for abuse, no currently accepted medical use, and a lack of accepted safety for use
even under medical supervision [18]. Despite this, 14 states have enacted laws allow-
ing the use of cannabis for medical purposes under physician supervision [16].
The primary active agent in cannabis, delta-9-tetrahydrocannabinol, acts via the

cannabinoid receptors CB1 and CB2 to produce its varied psychotropic and thera-
peutic effects, with the majority of psychotropic effects occurring via CB1 signaling
[15]. Synthetic preparations of delta-9-tetrahydrocannabinol or dronabinol
(Marinol™) have been classified by the DEA as a Schedule III agent and are FDA
approved for the treatment of anorexia in patients with AIDS-associated wasting as
well as nausea associated with cancer chemotherapy that has failed conventional
treatment [19]. Small studies have also suggested that dronabinol also significantly
reduces pain scores in patients with central pain due to multiple sclerosis as well as
in patients with chronic pain syndromes using opioids [20, 21].
Recently, improved understanding of cannabinoid pharmacology has created the
potential for new pharmacologic agents for symptom management. The CB2 recep-
tor is primarily expressed in peripheral immune and inflammatory cells, though it
may also be expressed in the central nervous system, particularly in pathologic pain
states [15]. In these two locations, the CB2 receptor is thought to modulate nocicep-
tion in both inflammatory as well as neuropathic and central pain states [15, 22]. In
animal models selective CB2 receptor agonists attenuated both acute and chronic
pain. In addition, rats subjected to painful nerve injury self-administered the CB2
receptor agonist more than control rats [15]. This may suggest that action at the CB2
receptor possesses more analgesic effects than psychotropic effects, and therefore
future selective CB2 receptor agonists may provide analgesia with limited abuse
potential [15].
Fatty-Acid Amide Hydrolase Inhibitors
In addition to these exogenous cannabinoids, endogenous cannabinoids exert effects

via the CB1 and CB2 receptors, and modulation of these endogenous cannabinoids
presents an attractive target for future analgesics. The two best-characterized can-
nabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and these are
thought to be the primary endogenous ligands of the CB1 and CB2 receptors, respec-
tively [22]. AEA and 2-AG are hydrolyzed and inactivated via the intracellular
enzyme fatty-acid amide hydrolase (FAAH) [22, 23]. FAAH knockout mice demon-
strate reduced sensitivity to painful stimuli and increased levels of endogenous can-
nabinoids presumably due to decreased endocannabinoid hydrolysis [24]. This
suggests that inhibition of FAAH could be a viable strategy to therapeutically
increase endogenous cannabinoids, and preliminary data supports this. URB597 is
an experimental specific FAAH inhibitor that enters the CNS, and in animal models
results in anxiolysis, reduced sensitivity to pain and antidepressant activity [23,
25–27]. URB937 is another specific FAAH inhibitor; however, it only functions in
peripheral tissues since it is actively transported out of the CNS [23]. Interestingly,
in animal models, this purely peripheral FAAH inhibition results in significant
reduction in inflammatory mediated as well as neuropathic pain [23]. FAAH
inhibition, particularly if limited to peripheral tissues, holds significant promise to

maximize the analgesic benefits of the cannabinoid system while minimizing psy-
chotropic side effects and potential for abuse.
AMPA and Kainate Ionotropic Glutamate Receptor Antagonists
Glutamate is the primary excitatory neurotransmitter, and glutamate signaling has

been indicated in a wide variety of disease states including neuronal injury after cere-
bral ischemia, epilepsy, Parkinson’s disease, Alzheimer’s disease, chronic pain, and
hyperalgesia [28, 29]. Excessive glutamate signaling can damage neurons through
elevated intracellular calcium release, although enhancing glutamate excitation may
have benefits in promoting synaptic connections in learning disorders or neurodegen-
erative conditions. AMPA and Kainate subclasses of ionotropic glutamate receptors
(iGluRs) serve different functions in the CNS and may be expressed peripherally;
AMPA iGluRs are responsible for the majority of glutamate signaling, where Kainate
iGluRs perform more modulatory functions [28, 29]. AMPA agonists such as CX717
increase excitatory transmission and may encourage synaptic connections and learn-
ing. CX717 has shown success for the treatment of ADHD, though it did not receive
FDA approval. AMPA agonists continue to be investigated to enhance learning in
Alzheimer’s disease as well as prevention of opiate-induced respiratory depression,
both with preliminary evidence of promise in animal studies [30, 31].
In contrast, AMPA and AMPA/Kainate antagonists such as talampanel, peram-
panel, and tezampanel decrease excitatory glutamate signaling and have been inves-
tigated for prevention of neurodegeneration in Alzheimer’s, as adjunctive
antiepileptic medications, and may decrease pain in patients with painful diabetic
neuropathy [29]. In addition, AMPA/Kainate receptor antagonists have shown pre-
liminary benefit in the treatment of migraines and postoperative pain in animal stud-
ies [32–34]. Excitatory glutamate serves myriad and complex roles in normal
physiology and both excessive and inadequate glutamate signaling function in path-
ological conditions and have the potential to be modulated for therapeutic benefit.
Human Chorionic Gonadotropin
Human chorionic gonadotropin (hCG) is an endogenous hormone which stimulates

the production of testosterone, thyroid hormones, estradiol, and progesterone [35].
Exogenous subcutaneous recombinant hCG (Ovidrel™/Novarel™) is currently
indicated for the treatment of prepubertal cryptorchidism, hypogonadotropinism
and hypogonadism, and for the induction of ovulation and pregnancy in anovula-
tory women [36]. Emerging case reports suggest that hCG may have analgesic
benefits to patients with chronic pain particularly those on chronic opioid therapy
[37]. Opioids can cause suppression of pituitary gonadotropin release and produce
a state of relative hypogonadotropinism and hypogonadism [38–40]. Androgen

replacement in male patients with testosterone deficiency improves mood, sleep,
and energy, though without consistent improvement in pain scores [39]. However,
in patients with hypogonadotropinism, subcutaneous injection of hCG 500–
1,000 units one to three times per week has been reported to significantly improve
pain control in addition to energy, mood, and libido [37].
Somatropin/Human Growth Hormone
Somatotropin [human growth hormone (hGH)] is another endogenous anabolic hor-

mone that promotes muscle and bone growth, lipolysis, gluconeogenesis, and organ
growth [35]. Exogenous recombinant hGH (somatropin) has been widely reported
in the popular media due to its frequent abuse by athletes and celebrities for its ana-
bolic properties. Nevertheless, FDA indicated for the treatment of documented hGH
deficiency, pediatric chronic kidney disease, and pediatric disorders associated with
significant short stature [35, 41]. More recently and relevant to palliative care, rhGH
has been indicated for the treatment of HIV-associated wasting syndrome and par-
enteral nutrition-dependent short bowel syndrome. In these situations, rhGH has
been shown to increase body weight, muscle mass, and improve physical endur-
ance. Research is ongoing into the use of rhGH in the treatment of cachexia related
to other syndromes such as CHF, COPD, and cancer-related wasting with some
evidence of benefit [42–51].
In addition to rhGH, the peptide hormone ghrelin, a hGH secretagogue released
by the stomach in response to fasting, has shown promise for patients with wasting
disorders. Ghrelin stimulates the release of hGH and other orexigenic hormones.
Exogenous administration of ghrelin increases appetite and food intake, and pre-
liminary studies have examined ghrelin administration to patients with cancer
cachexia or protein malnutrition related to dialysis-dependent kidney disease. These
data suggests that ghrelin may increase food intake and lean body mass in [41, 47,
52–57]. Concerns exist, however, with both ghrelin and rhGH that these agents
could potentially stimulate tumor growth in patients with malignancy. In addition, a
randomized controlled trial of hGH administration to acutely and critically ill
patients demonstrated a significantly increased mortality rate in those patients who
received hGH [58].
New Directions in Drug Delivery
Advances in the delivery of medications have allowed for improvements in the

pharmacokinetic profile of medications and the minimization of unwanted side
effects. These advances have been particularly important in expanding the utility of
existing medications to better serve a variety of patients.
Extended Release Enteral Formulations
Extended release formulations of medications allow for simpler dosing regimens,

improved patient satisfaction, and improved patient compliance [59, 60]. In addi-
tion, they can provide more stable blood concentrations of therapeutic agents and
may avoid the peaks and troughs of immediate release drugs. This may result in
fewer adverse effects that occur at high peak concentrations and fewer periods of
inadequate treatment due to low drug concentrations at trough points.
Extended release medications use a variety of drug delivery strategies. Early
extended release formulations mixed the active agent within an insoluble matrix
that slowed the dissolution of the drug. Newer formulations, for example Exalgo™
(hydromorphone extended release), is based on the osmotic-controlled release oral
delivery system (OROS). In OROS delivery systems, the active agent is encapsu-
lated in an insoluble shell with a laser-drilled hole. The osmotic pressure of gastro-
intestinal fluids dissolving into the tablet generates the driving force for a slow,
predictable release of active medication.
Some newer extended release formulations use a polymer matrix to both delay
release of agent and slow gastric transit. Gralise™ (gabapentin extended-release)
represents a newer class of extended release formulations that uses a polymeric
system to delay transit of the tablet from the stomach [61]. Gabapentin has been
successfully used to treat a variety of neuropathic pain states including diabetic
neuropathy and postherpetic neuralgia with few adverse effects [62–64]. In contrast
to traditional immediate release formulations of gabapentin, Gralise™ tablets
expand in the stomach when taken with food. Gabapentin is slowly released from a
polymeric matrix where it is subsequently absorbed in the small intestine. This
allows not only for more convenient once-daily dosing, but it also decreases the
peaks and troughs of thrice-daily gabapentin dosing. Furthermore, Gralise™ allows
for a peak plasma gabapentin concentration at night when the undesired side effect
of somnolence is unnoticed.
Parenteral Formulations
Transdermal and transmucosal delivery systems present attractive options for pal-
liative care patients in whom enteral delivery may be limited by nausea, malabsorp-
tion, or dysphagia, as well for drugs with poor oral bioavailability in which enteral
formulations are unavailable. The potent opioid fentanyl is a prototypical example
of a medication with poor oral bioavailability whose utility has been greatly
enhanced by the development of transmucosal (Actiq™, Fentora™) and transder-
mal formulations (Duragesic™). Transmucosal fentanyl allows for rapid treatment
of breakthrough pain, while Duragesic™ patches deliver a basal rate of fentanyl to
the patient to treat chronic pain, but cannot be used to treat breakthrough pain. In
contrast, Ionsys is an iontophoretic transdermal fentanyl delivery system under
Fig. 26.1 The Sufentanil

NanoTab® PCA System (with
permission from AcelRx
Pharmaceuticals, Inc.)
development that would allow patient controlled analgesia (PCA) through the active
delivery of transdermal fentanyl on patient demand with the added safety of timing
lockouts [65].
Newer transmucosal formulations of the opioid sufentanil may be able to provide
rapid and enduring pain control through dosing as a sublingual patient controlled
analgesia (PCA) system, the Sufentanil NanoTab® PCA System [66]. The system is
shown in Fig. 26.1. Sufentanil is an analog of fentanyl that is approximately 10
times more potent than fentanyl and 1,000 times more potent than morphine [67].
Sufentanil provides superior analgesia with lower rates of respiratory depression
than fentanyl or morphine after intravenous administration [67]. However, it is
extremely lipophilic resulting in a short duration of action due to rapid redistribution
into lipid-rich tissues in the body. Transmucosal absorption of sufentanil results in a
longer plasma half-life, which may expand its clinical utility [66–72]. The Sufentanil
NanoTab® PCA System delivers a 3-mm tablet on demand under the patient’s tongue
with programmed timing lockouts [72]. The advantage of this technology is that
there is no need for the placement of an iv or classic PCA equipment for the system
to be effective. Clinical data, thus far, has been quite positive with this innovative
system that has been developed through AcelRx Pharmaceuticals, Inc.
In addition to opioids, transdermal delivery systems of NSAIDs such as diclofenac
are being prescribed to treat localized pain and inflammation. Delivery systems
such as the Flector™ patch and Voltaren™ gel allow targeted application of anti-
inflammatory agents. Systemic absorption of diclofenac gel is approximately 94%
less than an equivalent oral dose of diclofenac [73]. This decreased systemic
absorption may result in an improved safety profile with fewer side effects.
Transdermal lidocaine (Lidoderm™) has been previously discussed in this text and
represents an additional safe localized analgesic adjunct. In addition to these trans-
dermal and sublingual delivery systems, intranasal delivery systems of morphine
(Rylomine™) and fentanyl are being investigated, as are intranasal, oral, and sub-
lingual formulations of medications such as ketamine, which are currently commer-
cially available only for intravenous administration [74]. The ever-expanding
complement of new drug delivery systems promises to greatly improve the safety
and utility of medications available for symptom management in palliative care.
Regional Anesthesia and Palliative Care
Introduction to Regional Anesthesia
Regional anesthesia consists of the application of local anesthetic agents to nerve

roots or peripheral nerves to provide anesthesia or analgesia to a portion of the body.
Regional anesthesia provides targeted analgesia while not affecting a person’s con-
sciousness or resulting in physiologic impairment of vital organ systems. Local and
regional anesthesia has long been used within the fields of obstetrics, dentistry, and
anesthesiology to provide pain control during and after surgical procedures. In addi-
tion to perioperative pain control, neuraxial (intrathecal and epidural) blockade and
peripheral nerve blockade have proven useful in the treatment of diverse pain condi-
tions. These include cancer pain, complex regional pain syndromes, radicular pain
from herniated vertebral discs, ischemic pain, sickle-cell crises, posttraumatic pain,
neuropathy, and/or the complications of treatments such as postradiation pain and
lymphedema.
Regional blockade can provide rapid and complete control of existing pain but
can also form a component of preemptive analgesia to ameliorate anticipated acute
pain. Regional anesthesia may have benefits in interrupting the neurophysiological
and psychophysiological response to pain thereby improve control chronic pain
through psychological relief [75]. As these benefits have become apparent, the
safety of regional anesthesia has also improved through newer medications and
ultrasound-guided nerve localization. The utility of regional anesthesia has expanded
from single injections lasting hours to indwelling peripheral nerve catheters that can
provide analgesia for many days.
The increasing utility and safety of regional anesthesia make it an attractive
future tool for palliative care medicine. However, patients with advanced systemic
disease may present challenges for the use of regional anesthesia, particularly with
the insertion of indwelling catheters. Patients receiving palliative care often have
pain in multiple portions of their body, may have coagulopathies, or may present
anatomical challenges due to the presence of edema, contractures, scar tissue, or
absence of peripheral pulses and normal anatomic landmarks [76].
Local Anesthetic Agents
Local anesthetics (LAs) are the key agents used to achieve neural blockade in
regional anesthesia. The basic structure of LAs consists of an aromatic end and an
amine end connected to each other through an ester or and amide chain [77]. These
molecules act primarily via targets on neuronal sodium channels thereby blocking
the conduction of action potentials along the course of nerves.
Na Channel Blockade
The susceptibility of a nerve to blockade by LAs depends on characteristics of the

individual drug (e.g., potency, pKa, buffering), characteristics of the tissue (e.g., pres-
ence of local inflammation and acidosis), and characteristics of individual nerve fibers
(e.g., diameter, myelination, activity). LAs tend to block small nerve fibers both ear-
lier and at lower concentrations than large nerve fibers, and blockade resolves in the
reverse order. For example, blockade of 0.15-mm C-fibers (postganglionic autonomic,
pressure, dull pain, and temperature) occurs before 1.5-mm Ad fibers (sharp pain), and
blockade of 15-mm Aa (motor) is the last to occur [77]. In addition to blocking Na
channels on sensory and motor fibers, at high doses or after inadvertent intravascular
injection, LAs can block Na channels in the brain and heart potentially resulting in
loss of consciousness, seizures, myocardial depression, and even cardiac arrest.
Ester and Amide LAs
LAs can be broadly divided into two categories: those with an amide linking chain
and those with an ester linking chain. Ester LAs can generally be identified as those
with only one “i” in their names, and they include the first clinically utilized LA,
cocaine, as well as procaine, chloroprocaine, and tetracaine. Amide LAs can gener-
ally be identified as those with two “i’s.” Amides are more commonly available, and
include lidocaine, mepivacaine, bupivacaine, and ropivacaine. Allergy to ester LAs is
much more common than amide LAs, due to the metabolism of ester LAs to the com-
mon allergen para-aminobenzoicacid (PABA). Amide LAs can generally be safely
used in patients with a history of allergy to ester LAs. Ester LAs are primarily metab-
olized by pseudocholinesterase, whereas amide LAs undergo hepatic metabolism.
Lidocaine is an intermediate-duration amide local anesthetic with significant
potency, fast onset, good tissue penetration, and low cardiac toxicity. The concen-
tration of lidocaine used for regional anesthesia ranges from 1 to 2%, and a single
injection can provide up to approximately 6 h of analgesia. Lidocaine is often used
in combination with a long-acting local anesthetic, such as bupivacaine or ropivacaine
in order to achieve both rapid and enduring analgesia. The duration of analgesia
with this technique may be less compared to a long-acting local anesthetic such as
ropivacaine or bupivacaine used alone [78].
Bupivacaine was the first long-acting amide local anesthetic created. The con-
centration of bupivacaine used for peripheral nerve blockade ranges from 0.25 to
0.5%, and a single injection can provide up to approximately 16–24 h of analgesia.
It is more hydrophobic than lidocaine and has a slower onset. Bupivacaine is highly
protein bound which allows for a longer duration; however, this also contributes to
the potential for cardiotoxicity. Due to its narrow therapeutic index, bupivacaine has
greatly been replaced by ropivacaine.
Levobupivacaine is the levorotatory enantiomer of bupivacaine. Commercial
bupivacaine is a racemic mixture of both enantiomers (R and S). Levobupivacaine
is approximately equivalent to its racemic bupivacaine with respect to onset, dura-
tion, and dosing in regional anesthesia. However, cardiac and CNS toxicity of
levobupivacaine is approximately 35% less than racemic bupivacaine.
Exparel™ is a bupivacaine liposome injectable suspension (1.3% 266 mg/20 ml
or 13.3 mg/ml). DepoFoam, which is a multivesicular liposome, consists of tiny
10–30 mm in diameter lipid-based particles which contain discrete water-filled
chambers of bupivacaine dispersed through a lipid matrix. This novel preparation
allows for increased duration of efficacy and pain relief up to 72 h after injection.
This drug preparation recently came to market in early 2012.
Ropivacaine is a long-acting amide local anesthetic derived from mepivacaine
and is a structural analog of bupivacaine. Ropivacaine differs from bupivacaine in
that it exists as a pure S enantiomer, and it demonstrates reduced cardiac and CNS
toxicity and may result in reduced motor blockade [79]. Concentrations of ropiva-
caine ranging from 0.2 to 1% are used for regional anesthesia, and a single injection
can provide up to approximately 16 h of analgesia.
Mixtures of lidocaine with a long-acting local anesthetic such as bupivacaine or
ropivacaine are commonly used for peripheral nerve blocks. This combination does
achieve a quicker onset of analgesia; however, the plasma levels of the long-acting
local anesthetics are lower than when using only long-acting local anesthetics.
Additives to LAs
Vasoconstrictors such as epinephrine or phenylephrine are often added to LAs to

improve the duration and quality of neural blockade. Vasoconstriction slows the rate
of systemic absorption, which can allow for the administration of higher doses of
LAs before encountering toxicity. The addition of epinephrine to LAs can also serve
as a marker of intravascular injection. If LA with epinephrine is injected intravascu-
larly, the patient will demonstrate signs of tachycardia, hypertension, or T-wave
peaking on EKG. Epinephrine may also improve the quality of neuraxial LA block-
ade independent of vasoconstriction through a-2 adrenergic activity [80].
Sodium bicarbonate is frequently added to LAs to increase the speed of onset of
some LAs. LAs are weak bases and are often packaged as their water-soluble salt
forms at an acidic pH. The addition of sodium bicarbonate raises the pH of the
solution and increases the fraction of LA that exists in its unionized form. LAs must
cross the cell membrane in this unionized form to gain access to the intracellular
receptor site of the Na channel. By favoring this unionized state, sodium bicarbon-
ate can hasten onset of blockade. The correct ratio is 1 ml of sodium bicarbonate per
10 ml of lidocaine or 30 ml of bupivacaine.
Additional adjuncts are occasionally added to LA solutions in certain clinical
scenarios. Opioids such as fentanyl, morphine, or hydromorphone are commonly
added to solutions of neuraxial LAs in epidural infusions or spinals. They improve
pain control while minimizing the systemic side effects of opioids and decrease the
necessary concentration of LA to achieve similar pain control. This decreased con-
centration of LA may allow for decreased motor block; however, risks of respiratory
depression must be considered when administering neuraxial narcotics. a-2 adren-
ergic agonists such as clonidine or dexmedetomidine can also be added to mixtures
of LAs for neuraxial administration. They improve pain control, but may result in
hypotension and bradycardia. The NMDA-antagonist ketamine has also been added
to mixtures of LAs for neuraxial administration with improved analgesia, but this is
uncommonly used in the USA [81]. Steroids such as dexamethasone have been
added to LAs for peripheral nerve blockade with reports of improved duration and
quality of blockade. Any medication administered perineurally should be preserva-
tive free, as some preservative preparations contain the neurotoxic agent phenol.
This is particularly critical for neuraxial administration where neurotoxicity could
result in devastating cauda equina syndrome or paraplegia.
Toxicity of LAs
The primary concern in the administration of LAs is the risk of systemic LA absorp-
tion resulting in CNS and cardiac toxicity. This can occur from inadvertent intravas-
cular injection of LA or from systemic absorption of LA. The risk of systemic
toxicity depends on the LA agent and the site of administration. For example, even
a very small dose of lidocaine can rapidly cause unconsciousness and seizure if
inadvertently injected into the vertebral artery. Even without intravascular injection,
rates of absorption and risk of systemic toxicity vary by location of administration.
For example, rates of systemic absorption are highest with interpleural or intercos-
tal injection, lowest with subcutaneous infiltration, and lower still with the addition
of vasoconstrictors. Toxicity also varies with specific LA agents. The potent, lipo-
philic, long-acting amide agent bupivacaine presents much higher risk of cardiotox-
icity than the less potent, rapidly metabolized ester agent chloroprocaine.
CNS Toxicity
At sufficient doses or after intravascular injection, LAs cause CNS stimulation.

Early symptoms can include lightheadedness, metallic taste, tinnitus, and circumoral
numbness. This can progress to restlessness, unconsciousness, and tonic–clonic

seizures. At higher doses, CNS depression occurs which can result in respiratory
failure and death.
Cardiovascular Toxicity
LAs can additionally cause cardiovascular toxicity, though this generally occurs at
doses higher than those causing CNS symptoms. LAs act on the myocardium,
decreasing electrical excitability, conduction rate, and contractile force. On rare
occasions LAs have caused cardiovascular collapse and death without preceding
CNS symptoms. This may be due to either an action on the pacemaker or the sudden
onset of ventricular fibrillation. Ventricular tachycardia and fibrillation are relatively
uncommon consequences of local anesthetics but can occur, particularly with bupi-
vacaine. Bupivacaine-associated cardiotoxicity is very resistant to resuscitation and
defibrillation. In addition to ACLS, treatment should include rapid administration of
lipid emulsion bolus and infusion [82].
Methemoglobinemia
Clinically significant methemoglobinemia may occur with the local anesthetics

benzocaine and priolocaine [83]. Benzocaine is commonly available in a spray form
for topical anesthesia to mucous membranes (Hurricaine™ Spray), and prilocaine is
a component in eutectic mixture of local anesthetic (EMLA) cream often used to
provide topical anesthesia prior to intravenous line placement in children.
Performing Regional Nerve Blocks
Any patient considering regional anesthesia should be advised of the risks of the pro-
cedure (infection, bleeding, damage to nerves, damage to adjacent structures, local
anesthetic toxicity, etc.). They should also be forewarned of side effects of nerve block-
ade such as motor block that may present a risk of falls and care of the numb limb. In
addition, patients with continuous catheters should be evaluated in person or via tele-
phone to assess for any signs or symptoms of infection or local anesthetic toxicity.
Strict sterile technique including antibiotic skin preparation, sterile gloves, hat,
and mask should be used for all peripheral nerve blocks, and asepsis is especially
critical with peripheral nerve catheters. Monitoring patients for regional anesthesia
is additionally important, as patients may require procedural sedation, and compli-
cations such as local anesthetic toxicity, pneumothorax, nerve injury, vascular punc-
ture, and bleeding can occur. Standard monitoring should include pulse oximetry,
electrocardiography, and blood pressure monitoring. Some centers use capnography
to ensure adequate ventilation, but pulse oximetry and frequent verbal communica-
tion with the patient are often sufficient [84].
Resuscitation equipment should also be available, including a self-inflating bag-
valve-mask, oxygen source with face-mask, suction, intravenous access, laryngo-
scope, and endotracheal tubes. Resuscitation medications such as vasopressors and
lipid emulsion should also be readily available.
Single-Shot Peripheral Nerve Blocks and Peripheral Nerve

Catheters
Single shot peripheral nerve blocks are intended for the treatment of acute pain.
They provide rapid analgesia, but even with long-acting local anesthetics, single
shot blockade can provide analgesia for only up to 24 h. In order to provide more
enduring analgesia, continuous peripheral nerve catheters can be placed near the
target nerve to deliver a continuous infusion of local anesthetic and extend the dura-
tion of analgesia for days. Initial use of continuous peripheral nerve blockade was
limited to the inpatient population, but increasingly patients are being sent home
with peripheral nerve catheters. Despite the benefits and widespread use of continu-
ous peripheral nerve catheters, few studies exist regarding the prevention of compli-
cations during peripheral nerve catheter placement, management, and removal. In a
series of 620 outpatients treated with continuous peripheral nerve blocks, there were
surprisingly few interventions requiring an anesthesiologist. Patients were able to
manage and remove their catheters at home without additional follow-up. This sug-
gests that with adequate instruction and telephone access to health care providers,
patients are comfortable with managing and removing continuous peripheral nerve
catheters at home [85].
The duration of continuous peripheral nerve blocks is limited primarily by the
risk of infection, which increases with the duration of infusion. Most clinicians
remove catheters after approximately 3–7 days, though case series have been pub-
lished with duration greater than 2 weeks [86, 87]. Additional challenges with
peripheral nerve catheters include more difficult placement, possibility of malposi-
tioning resulting in failure or complication.
Specific Regional Techniques
Common blocks for the upper and lower extremities will be discussed, with ultra-
sound-guided techniques described when possible. Although far from exhaustive,
these techniques allow for analgesia to all or part of the upper and lower extremities
with either single shot or continuous catheter techniques. All regional anesthesia
techniques carry risks of vascular injury and bleeding, local anesthetic toxicity, and
Fig. 26.2 Position of an ultrasound

probe for interscalene brachial
plexus block, obtained with
permission from Essentials of
Regional Anesthesia, Tran De QH,
Dugani S, Asenjo J. Kaye AD,
Urman R, Vadivelu N (editors),
Springer, Chap. 13, p. 345
Fig. 26.3 Ultrasonographic appearance of the interscalene and cervical paravertebral brachial
plexus (A carotid artery, AS anterior scalene muscle, MS middle scalene muscle, SCM sterno-
cleidomastoid muscle, V internal jugular vein, obtained with permission from Essentials of
Regional Anesthesia, Tran De QH, Dugani S, Asenjo J. Kaye AD, Urman R, Vadivelu N (editors),
Springer, Chap. 13, p. 346
nerve injury from intraneural injection or neurotoxicity of local anesthetics and

additives. Upper extremity nerve blocks carry additional risks, such as pneumotho-
rax, injury or blockade of the recurrent laryngeal and phrenic nerves, and inadver-
tent intrathecal or epidural injections. Among others, relative contraindications to
all peripheral nerve blocks include pathologic coagulopathy, blood thinning agents,
infection at the site, systemic infection, and preexisting nerve damage. Figure 26.2
shows a typical probe utilized for ultrasound guided regional techniques. Figure 26.3
demonstrates imaging from an ultrasound guided regional block.
Peripheral Nerve Blocks of the Upper Extremity
Interscalene Brachial Plexus Block
The interscalene nerve block is the most proximal approach to the brachial plexus,
anesthetizing the shoulder, clavicle, and proximal humerus innervated by roots and
trunks. This block typically spares the C8-T1 nerve roots (ulnar nerve.) Using the in-
plane ultrasound approach, the subclavian artery is first identified. The brachial plexus
should appear as a cluster of hypoechoic circles superior and posterolateral to the artery.
When it is followed in the cephalad direction, the cluster takes on a stacked “stop-light”
appearance between the anterior and middle scalene muscles. Approximately 30 ml of
local anesthetic is typically deposited between the first and second or second and third
nodules, which are likely the nerve roots of C5, C6, and C7 [84].
Interscalene brachial plexus blockade can cause recurrent laryngeal nerve injury,
pneumothorax, vertebral artery injury or injection, neuraxial injection, and Horner’s
syndrome by injuring the cervical sympathetic chain. Interscalene brachial plexus
blockade results in nearly universal blockade of the ipsilateral phrenic nerve.
Therefore, interscalene block may be contraindicated in patients with significant
respiratory insufficiency, contralateral hemidiaphragmatic paralysis, contralateral
pneumonectomy, etc.
Supraclavicular Brachial Plexus Block
The supraclavicular block anesthetizes the distal clavicle, humerus, forearm, and
hand through blockade at the trunks and divisions of the brachial plexus. It is
identified by ultrasound as the hypoechoic cluster that appears superior and postero-
lateral to the subclavian artery as described in the interscalene brachial plexus block
above. Local anesthetic is injected toward the “corner pocket,” i.e., the intersection
between the subclavian artery and the first rib.
As with the interscalene nerve block, Horner’s syndrome, recurrent laryngeal
nerve injury can occur. Phrenic nerve blockade occurs approximately 30% of the
time with the supraclavicular nerve block due to cephalad spread of local anesthetic.
The close proximity of the brachial plexus to the subclavian artery and the apex of
the lung make pneumothorax, intravascular injection, and vascular injury the most
common complications of supraclavicular blockade.
Infraclavicular Brachial Plexus Block
The infraclavicular approach blocks the brachial plexus at the level of the lateral,
medial, and posterior cords, providing anesthesia to the humerus, forearm, and
hand. Placing the ultrasound probe sagitally in the infraclavicular fossa, medial to
the coracoid process will obtain a short-axis view of the axillary vessels. Using an
in-plane technique and a cephalad to caudad direction, a 10-cm block needle is
advanced until the tip lies just deep to the artery, where local anesthetics can be
injected.
Vascular puncture is the primary concern during an infraclavicular block.
External compression can be difficult to achieve due to the depth of the vessels.
Caution should be taken in coagulopathic patients, and perhaps a different approach
should be considered. There have also been anecdotal reports of Horner’s syndrome,
phrenic nerve paralysis, and pneumothorax associated with infraclavicular blocks.
Axillary Brachial Plexus Block
The axillary brachial plexus block anesthetizes the terminal branches of the brachial
plexus (musculocutaneous, median, radial, and ulnar nerves.) The musculocutane-
ous and median nerves are situated ventral relative to the artery. The musculocuta-
neous nerve has generally split away from the rest of the branches and may need to
be individually targeted a few centimeters ventrolateral to the artery. The radial and
ulnar nerves are located dorsal relative to the artery. Using an in-plane technique
and puncture sites above or below the artery, a 5-cm block needle is directed toward
each of the four neural structures. Care must be taken to visualize the entire length
of the needle during the advancement process. Local anesthetic is injected until
circumferential spread is achieved for each nerve.
The overall safety margin for this block is extremely high. The biggest risk is
vascular puncture. Continuous block catheters in the axilla are generally avoided
due to higher rates of infection.
Peripheral Nerve Blocks of the Lower Extremity
Sciatic Nerve Block
The sciatic nerve is the largest nerve in the human body and provides sensory and
motor innervation to the posterior thigh and lower leg. It arises from the lumbosacral
plexus (ventral rami of L4–5 and S1–3). There are many approaches to the sciatic
nerve block. Here, the classic approach and an ultrasound-guided approach will be
discussed [84].
The classic or Labat approach utilizes the nerve stimulator to verify plantar flexion
at the ankle, which is the desired response. The patient is placed in the lateral position
with the targeted side up, slightly flexed at the hip and knee. This position will bring
the sciatic nerve into a more superficial position. The unaffected or dependent leg is
positioned down and straightened. The landmarks include the posterior superior iliac
spine (PSIS), greater trochanter, and sacral hiatus. A first line is drawn between the
greater trochanter and PSIS. A second line is drawn from the sacral hiatus to the
greater trochanter. A third line is drawn perpendicular to the first at its midpoint and
will intersect the second line. The needle insertion point is where lines two and three
intersect. Insert the needle perpendicular to all planes. Stimulation of the gluteus max-
imus muscle is often encountered just before the sciatic nerve stimulation which is
seen as plantar or dorsiflexion at the ankle or toes. Plantar flexion indicates stimula-
tion of the tibial component of the nerve and is associated with greater block
success.
The subgluteal approach is one of several ways to block the sciatic nerve under
ultrasound guidance. The patient is again placed in the lateral position with the tar-
geted leg up. The landmarks are the greater trochanter and ischial tuberosity. A line
is drawn between these two structures, and a low frequency ultrasound probe is
placed at the midpoint of the line. The sciatic nerve can be identified as a hyperechoic
structure (wide, flat, or triangular) beneath the gluteus maximus muscle and between
the greater trochanter and ischial tuberosity. Using an in-plane technique, 20–30 ml
of local anesthetic can be injected around the nerve.
Sciatic blockade is fairly safe with complications including intravascular injec-
tion and damage to the sciatic nerve.
Popliteal Sciatic Nerve Block
The sciatic nerve can be blocked lower in the leg as it splits into the common per-
oneal and tibial nerves for anesthesia of the entire lower leg, foot, and ankle with the
exception of the medial saphenous distribution. The patient can be either in the
supine or lateral position. If in the supine position, the leg will need to be elevated
so that the ultrasound probe can be placed under the leg. The ultrasound probe is
first placed in the popliteal crease to identify the popliteal artery (deep) and tibial
nerve (superficial). Once these structures have been identified, follow the tibial
nerve cephalad until the common peroneal nerve can be seen coming in laterally to
join the tibial nerve forming the sciatic nerve. This junction usually occurs approxi-
mately eight centimeters cephalad from the popliteal crease but may vary among
patients. Using an in-plane technique from a lateral direction, inject local anesthetic
around the nerve. The proximity of the sciatic nerve to the popliteal artery and vein
makes intravascular injection the primary concern.
Femoral Nerve Block
The femoral nerve is derived from the L2–L4 nerve roots in the lumbar plexus. It
provides sensory innervation to the anterior thigh, anterior knee, and medial lower leg,
as well as motor innervation to the quadriceps. This nerve can be easily blocked using
a nerve stimulator or by ultrasound. The patient is placed in the supine position. The
inguinal ligament is identified by drawing a line from the pubic tubercle to the anterior
superior iliac spine. The femoral artery can be palpated just distal to the ligament, and
the femoral nerve should be about 1–1.5 cm lateral to the femoral artery. With a nerve
stimulator technique, insert the needle in a cephalad direction at a 45–60° angle to the
skin and monitor for contraction of the rectus femoris (patellar snap). Under ultra-
sound, locate the femoral artery and vein. The femoral nerve is the hyperechoic bundle
about 1 cm lateral to the femoral artery. Using an in-plane technique, approach the
nerve from a lateral direction, carefully visualizing the needle tip to avoid puncture
and injection into the femoral artery. The proximity of the femoral nerve to the femo-
ral artery and vein makes intravascular injection the primary concern.
Saphenous Nerve Block
The saphenous nerve is a terminal branch of the posterior division of the femoral
nerve (L3–L4). It provides sensory innervation to the medial aspect of the upper
thigh, lower leg, ankle, and foot. It is the only nerve that innervates the lower leg
that is not derived from the sciatic nerve, and below the knee it has no motor com-
ponent. The patient is placed in the supine position, and the ultrasound probe is
placed in the transverse fashion on the anterior thigh. The sartorius muscle will be
most superficial and medial, and the vastus medialus laterally and deeper. The
saphenous nerve can be found deep to the sartorius muscle and travelling with the
deep genicular artery, a branch of the superficial femoral artery. An in-plane approach
is used from the lateral edge of the ultrasound probe. Inject 8–15 ml of local anes-
thetic with intermittent aspiration to exclude vascular injection.
In summary, drug development and technology advances have given the practi-
tioner additional tools to manage pain. This is particularly good news in palliative
care. Though the drugs and technologies are not perfect, it is an exciting time and
the future appears quite exciting in that our patients should be afforded greater
opportunity for excellent patient care and comfort.
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Review Questions
1. Members of which of the following classes of agents are currently available for
clinical use (select all that apply):
(a) Anti-NGF agents
(b) VGCC blocking agents
(c) High-dose topical capsaicin
(d) FAAH inhibitors
2. Extended release enteral formulations may allow for all of the following
except:
(a) Improved compliance
(b) Reduced adverse effects
(c) Improved rapidity of effect onset
(d) Simpler dosing regimen
3. Which of the following parenteral analgesics would be least suited to rapid con-
trol of breakthrough pain?
(a) Sufentanil NanoTab® PCA System
(b) Transdermal fentanyl patch
(c) Buccal fentanyl lozenge
(d) Ionsys® iontophoretic transdermal fentanyl
4. Monitoring for regional anesthesia under moderate sedation include all of the
following except:
(a) Electrocardiography
(b) Pulse oximetry
(c) Neurological checks every 1 h
(d) End-tidal CO2 monitoring
5. Regional anesthesia:
(a) May not be feasible in patients with severe edema or contractures
(b) Can be used in any patient suffering from chronic pain
(c) Is more effective than opioids and should be the first-line treatment for
chronic pain
(d) Is not recommended for patients experiencing a sickle cell crisis
6. Risks of continuous catheter regional nerve blocks include which of the following?
(a) Infection at the site of catheter insertion
(b) Cardiovascular collapse from local anesthetic toxicity
(c) Falls from lower extremity nerve blocks
Answers
1. (b, c)
2. (c)
3. (b)
4. (c)
5. (a)
6. (d)
Chapter 27
Ethics in Palliative and End-of-Life Care
Jack M. Berger
Introduction
“Do the kind thing, and do it first,” said William Osler as advice to physicians (circa
1904) [1]. But in 1904 there were limited things that physicians could do for their
patients with chronic pain or who were in need of care at the end of life. William
Osler in his Ingersoll Lecture 1904 entitled Science and Immortality (Houghton,
Mifflin and Comp., Riverside Press, Cambridge 1904) stated: “I have careful
records of about five hundred death-beds, studied particularly with reference to the
modes of death and the sensations of the dying…” “Ninety suffered bodily pain or
distress of one sort or another…” (This is about 20%) [1].
Osler continued, “…eleven showed mental apprehension, two showed positive
terror, while one expressed spiritual exaltation, and one expressed bitter remorse.
The great majority gave no sign one way or the other; like their births, their deaths
were as a sleep and a forgetting….” “As a rule, man dies as he has lived, uninfluenced
practically by the thought of a future life…wondering but uncertain, generally
unconscious and unconcerned” [1].
In Osler’s time, that’s how people died… a doctor could visit a patient and could
tell the patient’s family that death was imminent. The doctor’s duty was then to
provide comfort to the patient and the family, and to diminish suffering. The patient
got plenty of Laudanum® and humane care.
J.M. Berger, M.S., M.D., Ph.D. (*)

University of Southern California,
e-mail: jmberger@usc.edu

DOI 10.1007/978-1-4614-5164-8_27,
484 J.M. Berger
Extent of the Problem
Weiss et al. report that the number of seriously ill patients who experience “substan-
tial” pain ranges from 36 to 75% [2]. And according to Jennings and his associates
“…too many Americans die unnecessarily bad deaths—deaths with inadequate
palliative support, inadequate compassion, and inadequate human presence and
witness. These deaths are preceded by a dying marked by fear, anxiety, loneliness,
and isolation; deaths that efface dignity and deny individual self-control and
choice” [3]. So, we are not even doing as well as Osler over 100 years ago.
Defining Death
With advances in life support, the line between who is alive and who is dead has
become blurred [4]. Thus, we need to define death in order to be able to declare a
person physically and legally dead. In the first edition of Encyclopaedia Britannica
“DEATH” was defined as the separation of the soul and body; in this sense death
stood opposed to life, which consisted in the union of the soul and body [5].
The Uniform Determination of Death Act (UDDA), written by the President’s
Commission on Bioethics in 1981, confronts the complexities concerning the dec-
laration of death [6]. The UDDA wording specifically states: “An individual who
has sustained either (1) irreversible cessation of circulatory and respiratory func-
tions, or (2) irreversible cessation of all the functions of the entire brain, including
the brain stem, is dead.” In other words, the UDDA states that a person can be
declared dead when either the heart and lungs or the brain and brain stem stop func-
tioning permanently [7].
The problem today is not so much determining death but rather with our modern
interventions, we can prolong the dying process (dialysis, ventilators, intravenous
fluids, antibiotics, furosemide, etc.) and therefore, we are unable to recognize when
death will occur. It appears that we health care providers and physicians suffer from
“Mural Dyslexia” defined as the inability to read the handwriting on the wall [8].
In their article, “Care of the dying: An ethical and historical perspective” pub-
lished in Critical Care Medicine in 1992, Cowley, Young, and Raffin conclude that:
“Despite the miraculous advances in medical theory and medical practice, the eth-
ics surrounding medical care for the dying are more troubling today than they were
in ancient Athens at the time of Plato [9]. In classical antiquity, the primary con-
cerns were for health and living well. The ‘Middle Ages’ saw the emergence of the
principle of sanctity of life. To these basic ideals, the ‘Renaissance’ and the
‘Enlightenment’ added the aspiration to prolong life. Finally, in the twentieth cen-
tury, modern science has rendered this aspiration a reality of unclear merit” [9]. And
we can expand that to include the twenty-first century now.
In making end-of-life decisions regarding symptom management and palliative
care, one must have the ability to estimate accurately a patient’s length of survival
27 Ethics in Palliative and End-of-Life Care 485
(LOS) and improved quality of life. In 1994, Daas wrote that “we do not have the
ability to accurately estimate LOS and that we have little knowledge or understand-
ing of the end-stage illness experience” [10]. It is known that anorexia/cachexia in
association with increased heart rate does correlate with the terminal cancer syn-
drome. Dysphagia, cognitive failure, and weight loss are highly correlated with
shorter LOS, <4 weeks. The presence of pain, although producing poor quality of
life, does not contribute to decreased LOS in terminal illness [10].
According to Spiegel, Stroud, and Fyfe, here at the end of the twentieth century,
the old adage, to “cure rarely, relieve suffering often, and comfort always,”
(Hippocrates) has been rewritten: The doctor’s job has become to “cure always,
relieve suffering if one has the time, and leave the comforting to someone else”
[11]. They further state that the acute disease model, which emphasizes diagnosis,
definitive treatment, and cure, works in many situations, but the leading killers of
Americans—heart disease, stroke, and cancer—are by and large chronic and pro-
gressive rather than acute and curable [11]. Western Medicine’s success is also its
weakness. The application of a curative model when disease management is all that
can be given leaves doctors and patients dissatisfied [11].
Ethical Principles
In providing palliative and end-of-life care, one must consider Medical Ethics and
Ethical Conduct, Moral Obligations, and Legal Responsibilities.
In end-of-life care, there are four guiding ethical principles which govern our
decision making and care of patients. These are the same principles that guide us in
the conduct of medicine in general.
• Nonmaleficence [11] (minimize harm) (Hippocratic oath)
• Beneficence [12] (do good if you can) (St. Thomas Aquinas thirteenth century)
• Patient autonomy [13] (respect for the patient as a person, informed consent)
(Nuremberg trial of Nazis physicians who performed experiments on humans
without consent)
• Justice [14] (fair distribution of available resources) (not everyone is entitled to
everything that medicine has to offer when resources are limited)
In implementing the above principles the physician has to balance “Three
Dichotomies.”
• The potential benefits of treatment must be balanced against the potential burdens.
• Striving to preserve life but, when biologically futile, providing comfort in
dying.
• Individual needs are balanced against those of society.
Eric J. Casssel, in his article the “Nature of suffering and the goals of medicine,”
stated “…The relief of suffering and the cure of disease must be seen as twin obliga-
tions of a medical profession that is truly dedicated to care of the sick. Physicians’
486 J.M. Berger
failure to understand the nature of suffering can result in medical intervention that
(though technically adequate) not only fails to relieve suffering, but becomes a
source of suffering itself” [15].
Rule of Double Effect
At the end of life, providing pain relief can present a dilemma for physicians who
operate under misconceptions of both the law and ethics. The “Rule of Double Effect”
which is the moral doctrine taken from the teachings of St. Thomas Aquinas of the
thirteenth century gives physicians the ethical duty and moral obligation to relieve
pain and suffering [12]. Yet these philosophical arguments do not provide insight into
the ambivalence that practitioners feel when they legitimately engage in these prac-
tices. Why should a physician feel ambivalence about doing the “right thing?”
With regard to palliation and comfort care, many clinicians are unaware of the
current ethical and legal consensus regarding palliative care at the end of life. This
consensus is built around the principle of the double effect. The thrust of the prin-
ciple is to focus on the intention of the caregiver in seeking to provide comfort to
terminally ill patients, even if the clinician realizes that a side effect of the therapy
could be an earlier death [14].
The principle of double effect continues to be an area of lively debate in bioeth-
ics, in part because of the ambiguous intentions of caregivers in treating patients at
the end of life. For example, even when a physician has no desire to hasten the
patient’s death, the death of the patient may nevertheless be seen as a good or desir-
able outcome. Despite these ambiguities, however, the principle remains an ethical
and legal touchstone around treatment of the terminally ill [14].
The US Supreme Court in Vacco v. Quill, validated the rule of double effect
when Justice Rehnquist stated that “It is widely recognized that the provision of
pain medication is ethically and professionally acceptable even when the treatment
may hasten the patient’s death if the medication is intended to alleviate pain and
severe discomfort, and not to cause death” [16].
In the Vacco v. Quill case, a landmark decision was reached by the Supreme
Court of the United States regarding the right to die [16]. It ruled that a New York
ban on physician-assisted suicide was constitutional and preventing doctors from
assisting their patients in bringing about death, even those terminally ill and/or in
great pain, was a legitimate State interest that was well within the authority of the
State to regulate [16]. In brief, this decision established that, as a matter of law, there
was no constitutional guarantee of a “right to die” [16]. But it also affirmed that a
patient retains the Right to choose not to continue treatment, even life sustaining
treatment, and that choosing to discontinue treatment or declining treatment is not
equivalent in the eyes of the law to requesting a treatment to end life [16].
Not only is the rule of Double Effect well ensconced in the law, but also all of the
major religions have doctrines that support this approach. The principle of double
effect was initially developed in the Catholic tradition, from the teachings of St. Thomas
Aquinas in the thirteenth century [12]. Clinicians should, therefore, never withhold
needed pain medications from terminally ill patients for fear of hastening their death
through respiratory depression or other complications [12, 15].
The “Rule of Double Effect” states that an action having two effects, one good
and one bad is permissible if five conditions are fulfilled:
1. The act itself is good or at least morally neutral, e.g., giving morphine to relieve
pain.
2. Only the good effect is intended (relieving pain) and not the bad effect (ending
the patient’s life).
3. The good effect is not achieved through the bad effect (pain relief does not
depend on hastening death).
4. There is no alternative way to attain the good effect (pain relief).
5. There is a proportionately grave reason for running the risk, e.g., relief of intoler-
able pain and suffering.
Clearly, to justify use of this rule, the patient or surrogate decision maker would
need to be informed of the risks and give valid consent (Principle of Autonomy). It
is clear that any patient coming for surgery is expecting that his/her physician will
attend to the pain which results from the surgery including the use of opioids. If
other forms of pain relief are to be used, such as epidural analgesia or peripheral
nerve blockade, then additional consent discussions should be undertaken so that
patients can make informed decisions about their pain management care.
According to the Rule of Double Effect, it is clear in end-of-life care that there
are ethical and legal sanctions for the use of whatever doses of opioids that are nec-
essary so long as death is not directly intended. If the doses of the opioids necessary
to relieve pain are large enough to produce deep sedation, this too would be permis-
sible, if suffering can be relieved in no other way.
Thorn and Sykes studied 238 consecutive dying patients [17]. In a retrospective
study they found that there was no difference in survival between those patients
requiring escalating doses of opioids versus those patients that were on stable doses
of opioids [17]. Because of this finding, they concluded that the rule of double effect
was not even needed to justify the use of opioids for the control of pain at the end
of life, and this could be that the first two principles of ethical conduct, nonmaleficence
and beneficence, are maintained [17].
Ethics and the Use of Opioids
Much of inadequate pain management, particularly in end-of-life care can be traced

to lack of knowledge on the part of physicians. In a typical example, a physician was
managing an end-stage AIDS patient who had a DNR status and a documented pain
scores of 6/10 (10/10 on the verbal analogue scale is the worst possible pain imagin-
able). The patient was receiving 3 mg/h IV morphine infusion from which the phy-
sician stated, “We must wean off the morphine. We’re killing him.” The physician
488 J.M. Berger
wanted to give naloxone to reverse the effects of the morphine and then remedicate
the patient with 25 mg Meperidine IV q4 h PRN for pain control. What’s wrong
with this scenario?
• 3 mg/h of IV Morphine = 72 mg/day
• 1 mg Morphine IV = 10 mg Meperidine IV
• 72 mg Morphine = 720 mg Meperidine
• 25 mg Meperidine q4 h = 150 mg/day
• The patient was already in moderate to severe pain at the current dosage
which was already inadequate, and the Physician was reducing the dose by
80%. Further, by writing a PRN order, the physician was insuring that the
patient would not even receive the 25 mg of Meperidine q4 h
This is a classic case of “Opiophobia”—“the unreasonable fear of opioid use,
based on an inaccurate assessment of its dangers.” It affects patients as well as
physicians and may be one of the greatest barriers to the provision of effective pain
medication [18]. The 1993 California Medical Board Statement on the Prescribing
of Controlled Substances stated that…Concerns about regulatory scrutiny should
not make physicians who follow appropriate guidelines reluctant to prescribe or
administer controlled substances, including Schedule II drugs, for patients with a
legitimate medical need for them [19].
Likewise, the Federal Controlled Substances Act (CSA) does NOT address med-
ical treatment issues such as the selection or quantity of prescribed drugs [20]. The
US Supreme Court addressed these issues in the 1990s [21]. While the Court did not
support either using drugs to terminate life or the legalization of drugs and con-
trolled substances, it fully encouraged and supported adequate pain and symptom
management, as reported in the New England Journal of Medicine in 1997: A
[United States Supreme] Court majority effectively required all states to ensure that
their laws do not obstruct the provision of adequate palliative care, especially for
the alleviation of pain and other physical symptoms of people facing death [21].
The CSA regulates drugs, not the practice of medicine. The practitioner’s judg-
ment, based upon training, medical specialty, and practice guidelines deter-
mines what may be considered legitimate medical purpose, (DEA Policy
Statement) [22]. According to the federal CSA, in order for a prescription to be
valid, it must be issued for a legitimate medical purpose by an individual practitioner
acting in the usual course of professional practice. A dentist, for example, cannot
prescribe opioids for gynecological pain even though he/she has a DEA number.
Model guidelines for the use of controlled substances for the treatment of pain
were developed jointly by the DEA and Federation of State Medical Boards of the
United States and adopted May 2, 1998 [23, 24]. The purpose was: (to) protect
legitimate medical uses of controlled substances while preventing drug diversion
and eliminating inappropriate prescribing practices. Simply put, you have a
license to drive your car but you have to recognize stop signs and traffic lights.
Good faith prescribing requires an equally good faith history, physical exami-
nation and documentation {of benefit}. One can always be sued by a patient or the
family claiming injury or the patient becoming addicted to opioids. One can always
be manipulated or deceived by individual patients seeking to abuse opioid medica-

tions. But careful monitoring and particularly documentation of benefit will reduce
these risks to both the physician and patient to a minimum.
Ethics in Decision Making
In providing symptom management and palliative care at the end of life, difficult
decisions have to be made with respect to initiating therapeutic interventions or
discontinuing interventions. There appears to be a great deal of discrepancy between
what physicians state as to their biases for withdrawing life support measures and
what they actually practice in real life. Asthenia, malnutrition, and cachexia are
common in dying patients with advanced cancer. They may in fact be adaptive
mechanisms which do not require intervention [25].
Enteral feedings can lead to pneumonia from aspiration or diarrhea from poor
absorption. Parenteral feeding requires intravenous access, and there is no evidence
for improved survival, no evidence for improved tumor response to chemotherapy,
and no evidence of decreased chemotherapy toxicity. Decreased surgical complica-
tions with the use of total parenteral nutrition are debatable. In animal studies, there
is evidence of actual enhanced tumor growth, and there is no evidence for enhanced
quality of life or satisfaction of hunger [26].
Withdrawing Supportive Measures
In their study on “Biases in how physicians choose to withdraw life support,”

Christakis et al. reported that in order of preference, physicians find it easier to
withdraw or withhold treatments in the following order: blood products, hemodialy-
sis, intravenous vasopressors, total parenteral nutrition, antibiotics, mechanical ven-
tilation, tube feedings, and finally intravenous fluids [27].
These therapies correlate with the preferences to withdraw forms of therapy sup-
porting organs that failed for natural rather than iatrogenic reasons, to withdraw
recently instituted rather than long-standing interventions, to withdraw forms of
therapy resulting in immediate death rather than delayed death, and to withdraw
forms of therapy resulting in delayed death when confronted with diagnostic uncer-
tainty [27].
In their report entitled Outcome of Cancer Patients Receiving Home Parenteral
Nutrition, Cozzaglio et al. retrospectively studied patients with metastatic cancer
who were treated with home parenteral nutrition [28]. They note that the use of
parenteral nutrition in end-stage cancer patients varies from country to country [28].
In the USA, Japan, and Italy, 40–60% of all patients getting home parenteral nutri-
tion have cancer while only 18% in France and 5% in the UK [8]. Cozzaglio et al.
state that “the variance reflects a difference in cultural, ethical, social, and economic
490 J.M. Berger
approaches to the problem, with a lack of a scientific basis resulting from the scar-
city of specific literature” [28]. Cozzaglio et al. conclude that home parenteral nutri-
tion does not benefit cancer patients with a Karnofsky score of <50 [28]. In those
patients who were treated less than 3 months (Karnofsky <50) there was no benefit
in quality of life improvement [28].
Since dyspnea is a subjective experience like pain, it has a complicated pathophys-
iology that is affected by physical, psychological, social, and spiritual factors. The
involvement of the entire interdisciplinary team is essential for treating dyspnea
effectively, particularly in the terminal stages of disease.
Hydration is another area that presents ethical problems for physicians in the
dying patient. Too much hydration in a patient who is unable to eliminate the fluid
can lead to pulmonary congestion and dyspnea, edema around encapsulated tumors
leading to pain. Yet withholding fluids may make the family members uncomfort-
able or suspicious. One must explain to the family about the harmful effects of
excess fluid and that if the patient is thirsty, he/she will tell the doctor or nurse. In
dealing with pain or end-of-life care, we must make every effort to control pain,
being mindful of the risks of our interventions, but at the same time not be afraid to
take action.
Futility
Luce [29] discussed in detail the Consensus report on the “Ethics of Foregoing Life-
Sustaining Treatments in the Critically Ill” prepared by the Task Force on Ethics of
the Society of Critical Care Medicine and published in 1990 [30]. Much of Luce’s
discussion centers on the definition of futility of care. This term generally conveys
the idea that a patient cannot benefit from treatment, that the patient’s acute disorder
is not reversible, that the patient will not survive the current hospital stay, or that the
quality of the patient’s life following discharge will be poor [31].
Many barriers to decision making center on misunderstandings of the legal
aspects of withholding and withdrawing life support measures. As a result (accord-
ing to Luce) the courts in recent years have underscored the right of patients to
refuse treatment, affirmed the concept that human life is more than a biologic pro-
cess that must be continued in all circumstances, defined how therapeutics may or
may not benefit patients, argued against a distinction between the withholding and
withdrawing of life support, established guidelines for limiting life-sustaining treat-
ments, and approached the resolution of disagreements among physicians and
patients or their surrogates [16, 31].
Generally the courts have ruled that most patients would accept or refuse medical
therapy based on the ability of the therapy to support sentient life over mere biologic
existence. Of course, it is always best if the patient is able to participate directly in
informed decision making, but baring this the concept of “substituted judgement” is
employed where family or surrogate decision makers speak for the patient, based on
their intimate knowledge of what the patient would have wanted.
In Barber V Superior Court of California, 1983, the court did not distinguish
between removing mechanical ventilation or removing fluids or nutrition because
all were interventions that could either benefit or burden [32]. But the issue of futil-
ity of care was entered into court proceedings. In a case in Boston at Massachusetts
General Hospital, the Suffolk Superior Court decided that physicians and the hospi-
tal could discontinue life-sustaining therapy despite the objections of a patient or
surrogate if further care was deemed futile [33]. This decision has not been tested in
the appellate courts. But among ethicists and intensivists a consensus is evolving for
physicians to have the medical responsibility and privilege to decide to limit care,
even against the wishes of the patient or the patient’s legal representative [34, 35].
An illness may well be incurable, but not necessarily terminal. Terminal is used
herein to mean a condition that will directly and inexorably result in death within
the foreseeable future. If the condition is also incurable, then death will result
regardless of whether medical treatment is undertaken or not [36]. And thus would
be considered futile.
Surveys from ICU’s in 1994–1995 involving 71,513 admissions indicate that
75% of the deaths involved patients in whom some form of limitation of treatment
took place [37]. Therapies commonly withheld or withdrawn were cardiopulmo-
nary resuscitation (CPR), mechanical ventilation, vasoactive drugs, antibiotics,
renal dialysis, blood and blood products. Decisions to recommend withholding or
withdrawal of therapies deemed futile depend often on the presence or absence of
the “persistent vegetative state,” as discussed by Waisel and Truog [37].
A presumptively terminally ill patient may request a therapy the clinician does
not believe will be successful. Some hospitals have incorporated policies that permit
physicians to unilaterally withhold treatments with a low likelihood of success [12].
Others recognize the inherent problems in determining qualitative and quantitative
thresholds for futility judgments. For example, how low does the probability of suc-
cess have to be for a therapy to be considered futile? How great a benefit must a
patient receive from a therapy for that therapy not to be considered futile? How
certain must physicians be of their predictions? [38]. How do the patient’s values
play into these determinations? [38]. Because these questions are difficult to answer,
a growing trend is to step away from defining a specific policy to limit futile care
and instead focus on individual benefits and burdens in the particular situations
[39].
Principle of Double Effect
With regards to palliation and comfort care, many clinicians are unaware of the cur-
rent ethical and legal consensus regarding palliative care at the end of life. As stated
earlier, this consensus is built around the Principle of the Double Effect. The thrust
of the principle is to focus on the intention of the caregiver in seeking to provide
comfort to terminally ill patients, even if the clinician realizes that a side effect of
the medications or treatments could be respiratory depression and earlier death.
492 J.M. Berger
Comatose patients on ventilatory support look the same to family members as

other patients, even though they may be in a persistent vegetative state or even brain
dead. These patients may even be theoretically capable of reproduction which
biologists sometimes cite as the sine qua non of life. Using a phrase such as
“withdrawing life support” is not only incorrect but is also misleading, and poten-
tially harmful to family members struggling with the diagnosis of brain death or
persistent vegetative state. Life support cannot be withdrawn from a patient who is
already dead, and such linguistic imprecision can confuse an already shaken family
as to the meaning of the diagnosis. At this point, the only purpose of “life” support
is to maintain homeostasis. (This section was taken out of context from Waisel and
Truog but it fits with the concept of futility of care) [37].
Although individual convictions and religious beliefs should be respected and
supported, maintenance of prolonged intensive care is expensive and State Laws
differ in the degree to which they require clinical diagnosis to defer to religious
conviction.
Palliative
As stated earlier, the goals of end-of-life care encompass symptom management for
comfort. Palliative interventions may be necessary for improved comfort. Palliative
care is defined as care that recognizes the inevitability of the patient’s death and
therefore whose goal is to lessen, ease, and make less severe the patient’s suffering,
without curing the disease. Symptom control of such things as pain, nausea/vomit-
ing, constipation, dyspnea, etc., should be the goal [38].
A multidisciplinary or interdisciplinary team approach to end-of-life care is the
most successful. Medical decision making such as withdrawal of treatments, total
parental nutrition, ventilator support, and DNR discussions should be part of the
duties of this palliative care team. In providing palliative care one must maintain a
respect for life, while at the same time be able to accept the ultimate inevitability of
death. The potential benefits of treatment must be balanced against the potential
burdens of such treatment. The physician must strive to preserve life but, when bio-
logically futile, provide comfort in dying. At the same time the physician must
recognize that individual needs must be balanced against those of society [39].
Luce and Rubenfeld considered the question of whether costs could be reduced
by limiting futile care [40]. The public must define futility if they are to accept
limits on such care! But it is unrealistic to expect the lay public to accept this respon-
sibility. Therefore, the healthcare profession must take the lead. Borrowing from
the nursing profession “Compassionate Stewardship” is also part of physician
behavior [41]. During 1993, an estimated 118 attempts at CPR were reported for
172 facilities with a total of 19,596 licensed beds, for a frequency of one CPR
attempt per 166 beds per year in one survey [42].
Reductio ad Absurdum, having a 108-year-old man make a decision about CPR
suggests the unreal and macabre. The level of competence to which patients should
be held varies with the expected harms or benefits of acting in accordance with the
patient’s choice. A minimal level of decision making competence should be applied
to a patient who consents to a lumbar-puncture for presumed meningitis. A maximum
standard should be applied for a patient who refuses surgery for a simple appendec-
tomy. CPR discussions held at the time of acute illness may lead patients and their
families to believe erroneously that any last hope is being withheld.
Decisions About Cardiopulmonary Resuscitation

and Do Not Resuscitate Orders
When patients were educated about CPR, 87% chose to forego CPR or allow the
physician to decide if it was appropriate. When surveyed, patients consistently over-
estimated their chances of surviving CPR and survival to discharge. The physician
must initiate discussion of CPR since no patients reported initiating the discussion
themselves although most desired to have this type of conversation [43]. The gen-
eral public has an inflated perception of CPR success. While most people believe
that CPR works 60–85% of the time, in fact the actual survival to hospital discharge
is more like 10–15% for all patients and less than 5% for the elderly and those with
serious illnesses [44].
DNR Discussion
Although the techniques of CPR were originally intended only for use after acute,
reversible cardiac arrests, the current practice is to use CPR in all situations unless
there is a direct order to the contrary [45]. Since cardiac arrest is the final event in all
terminal illness, everyone is eventually a candidate for this medical procedure [45].
DNR orders were developed to spare patients from aggressive attempts at revival
when imminent death is anticipated and inevitable [45]. Nevertheless, patients or
families sometimes request CPR even when care givers believe such attempts would
be futile [45]. Some have argued that in these circumstances a physician should be
able to enact a DNR order without consent of the patient or family [45, 46].
Many physicians feel “uncomfortable” about discussing DNR status with their
patients. Regardless of this when a physician initiates such a discussion, the manner
in which the discussion takes place could lead to a medical dilemma if not done
appropriately. A proper discussion consists of two questions.
Question 1
“Would you want to be resuscitated in the event of cardiopulmonary arrest?”

494 J.M. Berger
This question needs to be asked in lay terms that the patient can understand. This
question needs to be presented in the manner of informed consent with a presentation
of the true risks and realistic chances of successful outcome. If the patient chooses
to have full resuscitation, then a second question must be asked.
Question 2
“Let us assume you were resuscitated. If the critical care team, despite doing every-
thing they can to save your life, determine after 72 h that you have no chance to
regain a reasonable quality of life, would you agree to let them withdraw support
and allow natural death to occur with peace and dignity?” It is believed that most
patients who choose to be resuscitated will choose to not have their death prolonged
if there is no reasonable chance to recapture a meaningful life. The earlier these
questions are discussed in the course of a terminal illness, the more likely that a
prolonged course of suffering in dying can be avoided.
If one only asks a patient with a terminal disease “if your heart stops, would you
want us to start it again,” the implication is that the resuscitation will be successful
and all will be well. This of course is untrue. By simply changing a few words, “if
your heart stops beating, would you want us to try to start it again,” immediately
places doubt that the resuscitation will be successful and can then lead to further
inquire by the patient about “odds” “consequences,” etc. If the patient still wants an
attempt at resuscitation, the second question must be asked. There is of course the
possibility that a patient with capacity to make his/her own decisions about care will
still want everything done. Then an ethics consult should be obtained if the physi-
cian feels that the act of CPR would be futile and potentially lead to more harm and
suffering for the patient.
DNR Status and Palliative Surgical Procedure
A final issue that must be addressed is whether do-not-resuscitate (DNR) orders

should be routinely rescinded when terminally ill patients undergo palliative sur-
gery? If so, patients will be forced to balance the benefits of palliative surgery
against the risks of unwanted resuscitation. On the other hand, if physicians are
required to honor intraoperative DNR orders, they may feel unacceptably restrained
from correcting adverse effects for which they feel responsible [47]. Walker argued
for the permissibility of honoring intraoperative DNR orders [47]. Walker maintains
that the patient’s right to refuse treatment outweighs physicians’ concerns about
professional scrutiny over intraoperative deaths [47]. Physicians’ moral concerns
about hastening patient death are important but may be assuaged by (1) emphasiz-
ing patients’ acceptance of operative mortality risk; (2) viewing matters as analo-
gous to surgery on Jehovah’s Witnesses who refuse lifesaving transfusion; (3)
viewing the patient’s intraoperative death as a double effect, that is, an unintended
negative effect that is linked to the performance of a good act (palliation); and (4)
distinguishing this from assisted suicide [47].
In 1992, Franklin and Rothenberg reported on a survey of 156 accredited hospi-
tals in the USA as to their policies for suspending do not resuscitate (DNR) orders
when patients went to surgery even for palliative procedures [48]. One hundred
twelve hospitals responded. The majority (81%) noted that they suspended the DNR
order when patients went to surgery [48].
Today it is customary to engage in an informed discussion with all concerned
parties about the consequences of performing CPR, a chemical code only, or with-
holding resuscitative efforts should a code occur during palliative surgery and anes-
thesia. More recently it has been recommended by the American Society of
Anesthesiology, multiple Surgical Societies, as well as the AMA that the DNR order
could be maintained in force even during surgery [49].
Now it is obvious that the induction of general anesthesia including endotracheal
intubation incorporate life sustaining measures and it may not be possible to imme-
diately extubated patients at the end of surgery. These acts alone do not constitute
cardiopulmonary resuscitation. It therefore requires full discussion with the patient,
family, or surrogate decision makers and the surgeon about informed consent.
Next, resuscitative efforts can be expressly limited to chemical resuscitation
without chest compressions if full CPR would result in more harm to the patient than
good. Again this is a joint decision made by the patient and the entire care team.
Concluding Remarks
Neville Goodman stated that “Words are all we have to describe what we do, the
way we do it, and what we infer from clinical research [50]. We must use them care-
fully and properly” [50].
The late Primo Levi, an Italian journalist said “If we know that pain and suffer-
ing can be alleviated, and we do nothing about it, then we ourselves become the
tormentors” [51]. But “when men lack goals, they tend to engage in activity,”
(unknown author) [52]. It is our job as compassionate and professional physicians
to “Do the right thing, and do it first” as William Osler told us so many years ago
[1].
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498 J.M. Berger
Review Questions
1. The number of seriously ill patients who experience “substantial” pain ranges
from…
(a) 36–75%
(b) 5–10%
(c) 75–90%
(d) 25–30%
2. The Uniform Determination of Death Act (UDDA) defined death as a state of…
(a) Irreversible cessation of circulatory and respiratory functions
(b) Irreversible cessation of all the functions of the entire brain including the
brain stem
(c) Irreversible cessation of both cardio-respiratory function and brain functions
(d) Either irreversible cessation of circulatory and respiratory functions or irre-
versible cessation of all levels of brain function including the brain stem
(e) Any of the above
3. Symptoms that correlate with the terminal cancer syndrome are except…
(a) Anorexia/cachexia in association with increased heart rate
(b) Dysphasia
(c) Cognitive failure
(d) Weight loss
(e) The presence of pain
4. Which of the following acts is not protected by the rule of double effect?
(a) Do good if you can
(b) Do no harm
(c) Rationing of health care
(d) Physician-assisted suicide
5. Appropriate prescribing of opioids requires all of the following except…
(a) Complete medical history
(b) Diagnosis of pain generator
(c) Documentation of physical examination
(d) Documentation of benefit
(e) Treatment of side effects
(f) Increasing dosing of opioids for terminal sedation is not sanctioned by the
rule of double effect
6. Which of the following is not true with respect to do not resuscitate (DNR)
orders?
(a) DNR orders must be suspended when patients go to have palliative surgery
(b) DNR orders are written by physicians after obtaining consent from the
patient or assigned patient decision maker
(c) DNR orders obtained in the appropriate manner may not be over turned by
physicians or family members
(d) DNR does not mean “do not treat” or “do nothing”
7. Which of the following is a true statement about CPR?
(a) CPR is meant to be used in all circumstances of cardio-pulmonary arrest
(b) CPR is successful in more than 70% of cases
(c) Patients with end-stage disease who undergo CPR after cardiac arrest have
virtually no chance of leaving the hospital and returning home
(d) Most patients in long-term nursing care facilities do receive CPR when they
have a cardio-pulmonary arrest
8. Which statement is not true relative to the rule of double effect?
(a) Providing opioids for pain relief or terminal sedation is permissible as long
as the intent is not to hasten death
(b) Providing opioids and other sedatives for relief of suffering is permissible
even if there is a risk of hastening death as long as death is not the intent of
the treatment
(c) Providing treatments that can have a bad outcome are permissible as long as
the intent of the treatment is to provide the good effect and the patient or
authorized designee has consented to undergo the treatment and is aware of
the risks
(d) Physician-assisted suicide is protected by the rule of double effect
500 J.M. Berger
Answers
1. (a)
2. (e)
3. (e)
4. (d)
5. (f)
6. (a)
7. (d)
8. (d)
Chapter 28
Physician Coding, Billing, and Reimbursement
for Palliative Care
Rene R. Rigal
The advances of medical care as well as the social advances in our societies have
transformed the outcomes of many disease processes. Fatal conditions such as can-
cer, coronary artery disease, AIDS, and CNS diseases are now conditions with
which patients live for many years (living with disease) [1]. This has been com-
pounded by the increasingly graying of the population, particularly in the most eco-
nomically advanced countries. Thus, we find ourselves as physicians not “curing”
disease processes, but providing respite from symptoms such as shortness of breath,
nausea, fatigue, or chronic pain.
Palliative care has evolved as an interdisciplinary medical activity focused on pro-
viding quality of life instead of curing diseases. Palliative care physicians and their
care teams strive to decrease pain and other symptoms associated with serious ill-
nesses and enhance the remaining quality of life to the patients and their families [2].
Proper coding and billing for palliative care services provided is a core compe-
tency for palliative care physicians. Only then can we insure the continued services
that are provided to patients. Physicians practicing palliative medicine should obtain
fair reimbursement for their services and valuable skills. Intimate knowledge of bill-
ing and coding rules and resources is imperative.
Physicians and their practice staff report the provision of medical procedures and
services through the current procedural terminology (CPT), commonly referred as
the CPT codebook [3]. CPT is a listing of descriptive terms and identification codes
for reporting medical services and procedures performed by physicians and other
qualified health care professionals. The purpose of the terminology is to provide
uniform language that accurately describes medical, surgical, and diagnostic ser-
vices. It also provides an effective means for reliable nationwide communications
between physicians, Medicare, and third-party payers.
R.R. Rigal, M.D. (*)

Pain Management Center, Divine Providence Hospital,
Williamsport, PA, USA
e-mail: tainomd@hotmail.com

DOI 10.1007/978-1-4614-5164-8_28,
502 R.R. Rigal
Physician palliative care services are coded for billing using the same CPT that
other physicians use to bill Medicare or other insurance payers for any type of
patient care service they provide. There are, nevertheless, several “quirks” that are
innate to palliative medicine practice [4].
As in all areas of medicine, physicians must document the services provided to
patients and submit for billing (usually using form HC 1500) of that care to the
appropriate payer. Palliative medicine physician services, whether for hospice or
non-hospice care patients, whether provided in the home, in the office, or in the
hospital setting, are reimbursed using the same billing and coding guidelines that
apply throughout the healthcare system.
Two sets of codes are used to describe physician services to payers [4]:
• Current Procedural Terminology (CPT) Codes, which describe the type and
extent of services provided, the location of the service, and the relationship of the
physician to the patient [5].
• The International Classification of Diseases, 9th Revision (soon 10th), and
Clinical Modification codes define the medical diagnosis for which the physi-
cian service was required [6].
For physicians involved in the provision of palliative care services, the most
frequently used codes are for Evaluation and Management (E/M). The Center for
Medicare and Medicaid Services (CMS), has as of January 2010, eliminated
Medicare payment for consultations [7], thus most of the CPT coding will involve
E/M codes 99201-99349. These groups include evaluation and management codes
in the usual settings such as ambulatory outpatient, acute impatient hospital,
extended care institutions, or in patients’ homes.
Since palliative care physicians provide care in which there are extensive amounts
of information and counseling given to the patient, family, nursing staff, and request-
ing physicians, the time component in the physician–patient visit becomes an
important aspect in coding. “When more than 50 % of a patient/physician interac-
tion is comprised of counseling and/or information giving, then the TIME becomes
the factor that determines which E/M code to use” [3].
Time is defined differently depending on the setting [4, 8]:
• In the hospital: the time used to determine which E/M code to use is defined as
the total time that the physician is present in the hospital unit.
• In the nonhospital setting: total time is the time that the physician spends in
actual face to face with the patient.
When time is taken into account, we have the choice of either using an E/M
codes that incorporates the time spent providing the service, or independently bill
for the time (using codes 99354-99357) [8]. Local issues must be taken into account
when making this decision.
An ICD-9 (soon to be ICD-10) code must also be selected and must reflect the
reason for the services provided [4, 6]. A decision must be made between coding for
a symptom vs. a diagnosis. For example, it is probably safer to bill for a symptom
(back pain 724.2) instead of spinal stenosis, and thus avoid concurrent care issues
with the patient’s primary care physician or other consultants [9].
28 Physician Coding, Billing, and Reimbursement for Palliative Care 503
In addition, if the palliative care physician provides other than E/M (procedural)
services, then these procedures can be billed using the appropriate procedural codes
for the specific procedures performed, such as pain management blocks, paracentesis,
thoracentesis, etc. The time required to perform the procedure is not counted, as it is
included in the “global payment” for the particular procedure code submitted [8].
All the Federal and State agencies (CMS, HCFA) require extensive documenta-
tion prior to payment (and must be present to survive an audit). The documentation
should include the domains of quality palliative care [10] and should include the
following:
• Structure and process of care
• Physical aspect of care
• Psychological and psychiatric aspects of care
• Social aspects of care
• Spiritual, religious, and existential aspects of care
• Cultural aspects of care
• Care of the imminently dying patient
• Ethical and legal aspects of care
• Clarify the patient’s definition of quality of life and advance directives
• Detailed physical exam
• Development of an assessment and plan of care
• Communication of all of the above to primary care physician
The billing and coding guidelines previously described are common in many billing
situations by all physicians. However, there are some issues that are unique to palliative
care physicians, particularly those employed by Hospice Agencies [4, 8, 9]:
• Attending Physician—Hospice Employee: Care plan oversight, supervisory
activities, establishment of eligibility and of governing policies for the Hospice
is covered as part of the administrative duties and is included in the per diem
reimbursement that the Hospice receives. Patient care services for direct patient
care are not included in the per diem payment provided to the hospice agency
and these services should be submitted for payment to the hospice.
• Attending Physician not employed with the Hospice: can submit bills for
direct patient services using the CPT and ICD-9 codes as previously described
and submits these claims directly to Medicare Part B.
Most commercial insurance companies follow the CMS billing guidelines and
thus require physicians to code for direct patient services using the CPT and ICD-9
codes. Nevertheless, it is always prudent to verify with the commercial insurance
company and follow their proprietary processes.
Reimbursement for palliative care services provided to patients follows the usual
guidelines used for reimbursement in the USA. When these are followed, and the
care is properly documented, then the usual and customary payment (as established
by CMS or commercial insurance companies) can be expected. The most important
thing to do is to document what you do and how long it takes to do it.
504 R.R. Rigal
References
1. Cassell EJ. The nature of suffering and the goals of medicine. N Engl J Med. 1982;306:639–45.
2. Morrison RS, Meier DE. The national palliative care research center and the center to advance
palliative care: a partnership to improve care for persons with serious illness and their families.
J Pediatr Hematol Oncol. 2011;33:S126–31.
3. American Medical Association. Current procedural terminology. Chicago, IL: American
Medical Association; 1999.
4. Von Gunten CF, Ferris FD, Kirschner C, Emanuel LL. Coding and reimbursement mechanisms
for physician services in hospice and palliative care. J Palliat Med. 2000;3(2):157–64.
5. Standardizing CPT codes, guidelines and conventions; Administrative simplification White
Paper, May 19, 2009.
6. American Medical Association. International classification of diseases. 9th revision, clinical
modification. Chicago, IL: American Medical Association; 1997.
7. American Medical Association. Consultation services and transfer of care. 2010.
8. American Academy of Hospice and Palliative Medicine. AAHPM Coding & Billing task
force: Quick reference guide for physicians coding, billing and reimbursement for hospice and
palliative medicine services. 2006.
9. Ely JC, Twaddle ML. Essentials of coding and billing in palliative care. Paper presented in
annual assembly of AAHPN and HPNA. 2006.
10. National Consensus Project for Quality Palliative Care. Clinical practice guidelines for quality
palliative care. 2nd ed. 2006. http://www.nationalconsensusproject.org.
Index
A Angioplasty
Accumulation of respiratory tract secretions balloon catheter, 255
(ARTS), 62 complications, 256–257
Acetaminophen, 110 interventional options, 255
Activities of daily living (ADLs), 182 stent insertion, 256
Adjustment disorders, 30–32, 47 Anorexia, 218. See Cachexia syndrome
Adjuvants, 108, 114 Anticonvulsants, 115
Advanced certified hospice and palliative Antidepressants, 115
social worker (ACHP-SW), 4 Anti-nerve growth factor agents, 457–458
Advanced heart failure (HF) patients Anxiety disorder
communication, 379–380 benzodiazepines, 36–37
dyspnea clinical interview based on DSM criteria, 47
benzodiazepines, 377 patient-physician relationship, 35
nonpharmacological approach, 378 relaxation training and deep breathing
opioids, 377, 383, 384 exercises, 37
hospice care reimbursement, 380 screening, 36
implantable cardioverter defibrillator, Arrhythmias
378–379 bradyarrhythmias, 389
incidence, 375 tachyarrhythmias, 387–389
left ventricular assist device, 379 Artiticial nutrition (AN)
pacemakers, 378 clinical indications, 148
palliative care and hospice, 376 complications of, 148–149
pharmacological treatment, 377 enteral nutrition, 146
prognosis, 375, 376, 383, 384 immunonutrition, 148
symptoms, management of, 378 parenteral nutrition, 146–148
Aloysi, A.S., 111 Asenjo, J., 471
American Board of Medical Specialties, 2 Atrial fibrillation
AMPA ionotropic glutamate receptor case study, 391–393
antagonists, 461 embolic stroke risk, 388
Analgesics, 108 palliative care goals, 388
Angiography rhythm control strategies, 387
catheter insertion, 255, 256 symptoms, 387
contraindications, 254 treatment, 387
guide wire passage, 255, 256 Aura, 316, 346, 347
indications, 254 Axillary brachial plexus block, 473
vessel puncture, 255, 256 Axillary lymph node resection (ALND), 183

DOI 10.1007/978-1-4614-5164-8,
506 Index
B Cannabinoids, 459–460
Bilevel inspiratory positive pressure Cardiac electrophysiology
ventilation (BIPAP), 418 cardiac pacing, 386
Biliary catheter insertion, 270–271 catheter ablation, 387
Blalock, A., 370 implantable cardioverter-defibrillators,
Blalock–Taussig shunt, 370 386–387, 391, 393
Blind loop syndromes, 140 Cardiac pacing, 386
Boyle, G., 202 Cardiac surgical procedures, 370–371
Bradyarrhythmias, 389 Cardiopulmonary resuscitation (CPR), 493,
Brain aneurysms 499, 500
coils for, 260 Cardiothoracic surgery, 369–371
contraindications, 260 Casssel, E.J., 485
indications, 259–260 Catheter ablation, 387
Seldinger percutaneous catheter insertion, Celiac plexus neurolysis, 303–304
260 Cement, 307, 308, 311, 312, 314
triple-H therapy, 260 Central venous catheters (CVCs), 266–267
Breaking bad news Cerebral angiography, 259–260
assess patient readiness, 77 Certified Hospice and Palliative Care
availabilities and resources, 79 Administrator (CHPCA), 4
body language, 80 Certified Hospice and Palliative Licensed
briefly assess patient, 77 Nurse (CHPLN), 3
cultural and spiritual issues, 80–81 Certified Hospice and Palliative Nursing
delivery news, 77–78 Assistant (CHPNA), 4
delivery requirements, 75 Chest pain, 398
determining presence, 76–77 Christakis, N.A., 489
elements for meeting, 76 Christopher, K., 1, 50
over-optimism, 79 Chronic migraine, 328–329
patient remembering, 80 Chronic obstructive pulmonary disease
planning, 78 (COPD), 405–406
recommendation, 74–75 Cluster headaches
respond to emotion, 78 abortive treatment, 335, 338
team members limits, 79 criteria, 332–333
touching patients, 80 definition, 332
Breast cancer, 183 diagnosis, 334–335
Breathlessness. See Dyspnea etiology, 333–334
Bryson E.O., 111 features, 333
Bupivacaine, 467 hallmark of, 332
medications for, 335–337
pathophysiology, 333, 334
C prevalence, 332
Cachexia syndrome, 218 preventive treatment
agent, 122 antiepileptic drugs, 340
causes of, 120–121 civamide, 341
definition, 120 lithium carbonate, 340
melatonin, 122 melatonin, 340–341
nutritional care, 159 polypharmacy, 339
anorexia and decreased food intake, verapamil, 340
138–139 prognosis, 342
counseling, 143–144 surgical treatment, 341–342
definitions, 138 transitional treatment, 339
energy expenditure, 159 Coeliac plexus blocks
inflammatory and humoral activities, 141 anterior and posterior approaches, 269
metabolic perturbations, 139–140 biliary interventions, 270
oral nutritive supplements, 144–146 complications for, 269
systemic inflammatory response, 120 contraindications, 269
Index 507
indication, 268 Critical care units

procedural method, 270 diabetic ketoacidosis, 437, 439
Colostomy, 220–221 aggressive fluid management, 423
Communication among physicians, 84 complications, 421
Communication skills initial investigations, 421, 422
breaking bad news, 86 metabolic parameters, 422
assess patient readiness, 77 mortality rates, 421
availabilities and resources, 79 occurence, 421
body language, 80 potassium chloride, 421
briefly assess patient, 77 treatment, 422, 423
cultural and spiritual issues, 80–81 hypercalcaemia, 430–432
deliver news, 77–78 hyperkalaemia
delivery requirements, 75 aldosterone, 423, 424
determining presence, 76–77 beta-2 agonists, 425, 426
elements for meeting, 76 causes of, 423, 424, 438, 439
over-optimism, 79 drug therapy, 424
patient remembering, 80 electrocardiogram, 425, 437, 439
planning, 78 insulin, 425, 426
recommendation, 74–75 myocardium stabilisation, 425
respond to emotion, 78 renal replacement therapy, 426
team members limits, 79 hypocalcaemia, 433–434, 438, 439
touching patients, 80 hypokalaemia, 426–427, 437, 439
coordinated team work, 74 hyponatremia
distressed families, 81–83 causes and management options,
formal training, 86 428
health professionals, 83–84 classification, 427
physician interrupting patient, 86 management, 429–430
recognising diagnosis, 86 SIADH, 428, 429
training models, 74 NIPPV
Community palliative care programs, 10 acute respiratory failure, 418
Comprehensive health enhancement support adverse side effects, 420
system, lung cancer module comfort measures, 419, 420
(CHESS-LC), 98 contraindications, 420
Confusion assessment method (CAM), 38 nasal mask, 418, 419
Connor, S.R., 376 oronasal mask, 418, 419
Constipation, 134 Cruzan, N., 153
bowel regimen, 119, 120 Current procedural terminology (CPT) codes,
management of 501, 502
laxatives, 150–151
opioid antagonists, 151
rectally administered medications, 151 D
Continuous catheter techniques, 469, 470, Decision conflict, 94, 95
480, 481 Decision making process
Continuous positive pressure ventilation guidance with end-of-life decisions
(CPAP), 418 clinical decisions, 99
Cooley, D., 370 decision for specific situations,
Coordination of care, 16–17, 20 100–101
Cortical spreading depression (CSD), 317–318 initiating process, 99–100
Corticosteroids, 116–117, 145 patient’s needs/values and goal, 100
Cough, 124–125, 399–400, 414 providing information to patient and
Covered self-expanding metal stents family, 100
(CSEMS), 352, 357–358, 365, 367 specific areas, 99, 104
Cowley, L.T., 484 time-limited trial, 101
Cox, J.J., 458 models, 90–91
Cozzaglio, L., 489, 490 support, 94–99
508 Index
Decision support amitriptyline, 236–237

aids benzodiazepines, 240
definition, 95–96 candida albicans, 241
online resource guidance, 97 carbamazepine, 237
standards, 96 clonazepam, 241
clinical encounter, 96 CYP2D6 function, 236
coaching, 104 dexamethasone, 239–240
CHESS-LC, 98 gabapentin, 237
definition, 95 glycopyrrolate, 238–239
health professionals, 97–98 haloperidol, 238
randomized controlled trials, 98–99 lactulose, 239
definition, 94–95 megestrol acetate, 239
interventions, 95, 104 metaclopramide, 238
Dehydration management, 149 midazolam, 240
Delirium, 47, 134 nystatin, 241
agents, 126–127 senna, 239
causes of, 125–126 diclofenac
confusion assessment method, 38 COX enzyme inhibition, 235
environmental and psychosocial tapentadol, 236
interventions, 40 topical preparations, 235–236
MDAS, 38 tramadol, 236
medication, 39 dosing, PRN, 245
perceptual disturbances, 37 levorphanol
pharmacologic treatment, 126 buprenorphine, 243
subtypes, 125 modafinil, 243–244
tripartite approach, 38 octreotide, 244
den Daas, N., 485 mirtazepine, 242
DepoFoam, 467 pain
Depression disorder acetaminophen, 231
antidepressants, 34–35 fentanyl, 233
cognitive-behavioral therapy, 35 methadone, 233–235
HADS, 33 morphine, 231–233
hastened death, 32 routes, 245–246
medical conditions and medication use, 34 symptoms, 229, 230
prevalence rates, 32 Dugani, S., 471
suicidal ideas, 32–33 Duragesic™, 463
Diabetic ketoacidosis (DKA), 437, 439 Dyspnea
aggressive fluid management, 423 benzodiazepines, 377
complications, 421 BORG score, 396
initial investigations, 421, 422 definition, 122–123, 396
metabolic parameters, 422 medical management, 397
mortality rates, 421 non-invasive ventilation, 397
occurence, 421 nonpharmacological approach, 378
potassium chloride, 421 opioids, 123–124, 377
treatment, 422, 423 pschological components, 124
Do-not-resuscitate (DNR) orders, 493–495, reversible causes, treatment of, 123
499, 500 treatment, 396, 412, 414
Drug delivery
extended release enteral formulations,
463, 480, 481 E
parenteral formulations, 463–465 Elwyn, G., 96
Drug formulary Embolisation
codeine chemoembolisation, 259
administration, 236 contraindications, 257–258
Index 509
indications, 257 esophageal dilation, 350, 351

radioembolisation, 259 laser photoablation, 349, 350
End-of-life care photodynamic therapy, 349, 350
cardiopulmonary resuscitation, self-expanding metal stents,
493, 499, 500 351–353
death, definition of, 484–485 nutrition, 360–361
do-not-resuscitate orders, 493–495 pain management, 360
ethics pancreas and biliary tract, 356–360
decision making, 489 small and large intestines
and opioids use, 487–489 biliary stent, 353
principles of, 485–486 complications, 354–356
futility of care, definition of, 490–491 enteral/duodenal stent insertion,
length of survival, 484–485 353, 354
and palliative care, 492–493 gastrojejunostomy, 353, 354
principle of double effect, 491–492 self-expanding metal stents, 354–355
rule of double effect, 486–487, 498, 500 stent occlusion, 356, 357
substantial pain, 484, 498, 500 Gastrointestinal symptoms
supportive measures, withdrawal of, cachexia syndrome and fatigue,
489–490 120–122
Enteral nutrition (EN), 146, 160 constipation, 119–120
Enteral tube feeding, dementia patients, cough, 124–125
153, 159 delirium, 125–127
Epilepsy dyspnea, 122–124
drug-resistant epilepsy, 285 insomnia, 127–128
palliative treatment nausea and vomiting, 117–119
hemispherectomy, 285–286 xerostoma, 117
ketogenic diet, 286 Gastrostomy
multiple subpial transection, 286 complications, 272
sudden unexpected death, 285 contraindications, 271
Euvolemic hyponatremia, 428, 430 procedural method, 272
Exercise, 179 Gastrostomy tube, 220
Exparel™, 467 Glenn shunt, 370, 373, 374
Extended release enteral formulations, drug Glenn, W., 370
delivery, 463, 480, 481 Goodman, N., 495
Groshong, 266
F
Fainsinger, R., 289 H
Fatty-acid amide hydrolase (FAAH) inhibitors, Headaches
460–461 cluster
Femoral nerve block, 474 abortive treatment, 335, 338
Figley, C.R., 201 criteria, 332–333
Franklin, C.M., 495 definition, 332
Fyfe, A., 485 diagnosis, 334–335
etiology, 333–334
features, 333
G hallmark of, 332
Gastroduodenal obstruction, 353, 365, 367 medications for, 335–337
Gastrointestinal malignancies, endoscopic pathophysiology, 333, 334
therapies prevalence, 332
endoscopic retrograde preventive treatment, 339–341
cholangiopancreatography, 356, 359 prognosis, 342
esophagus surgical treatment, 341–342
argon plasma coagulation, 349, 350 transitional treatment, 339
510 Index
Headaches (cont.) hospital bed, oxygen, and commode

migraine for home use, 67
chronic, 328–329 impending death, 68
definition, 316 length of stay, 68
diagnosis, 318–320 nurse, role of, 166
etiology and pathophysiology, 317–318 open access hospice, 58
gender difference, 316 oral intake reduction, 59, 67–68
International Headache Classification, physiology of death, 63
316–317 primary caregiver, 67–68
pediatric populations, 331 routes of medication administration, 68
phases, 316 pharmacotherapy, 59
pregnancy and lactation, 330–331 rectal route, 61
prevalence, 316 subcutaneous route, 61
prognosis, 331–332 transdermal route, 60, 68
refractory, 329–330 transmucosal route, 61
status migrainosus, 316 routine home care, 52
treatment options, 302–328 statements, 67
Head and neck cancer, 183 symptom management, 67
Healthcare system death rattle, 62
access terminal agitated delirium, 62–63
doctors appointment, 213 terminal phase of illness, 58, 69
hospice experience, 213 time of symptoms, 63
information, 211–212 treatment, 67–68
insurance, 212–213 type of sedation, 68
resources, 212–213 Hospice and Palliative Medicine (HPM), 1
communication, 209–211 Hospice medicare benefit, 51–52
Hemispherectomy, 285–286 Hospital anxiety and depression scale
Hemoptysis (HADS), 33
blood screening, 403, 412, 414 Human chorionic gonadotropin (hCG),
bronchial artery embolisation, 403 461–462
causes for, 403 Hypercalcaemia
chest X-ray, 403, 412, 414 causes and clinical features, 430, 431,
computer tomography, 403, 412, 414 438, 439
description, 402 diuretic effect, 431
massive, 404, 412, 415 familial benign, 432
Hickman, S., 266 parathyroid hormone related peptide, 431
High dose topical capsaicin, 458–459, 480, 481 primary hyperparathyroidism, 432
Himelstein, B.P., 444 vitamin D, 431
Home palliative care, 57 Hyperkalaemia
Hopkins, J., 370 aldosterone, 423, 424
Hospice beta-2 agonists, 425, 426
average length of stay, 68 causes of, 423, 424, 438, 439
benefits and coverage, 51–52 drug therapy, 424
complication of immobility, 68 electrocardiogram, 425, 437, 439
continuous care, 52 insulin, 425, 426
definition, 50–51 myocardium stabilisation, 425
discharge patient and re-enroll, 67 renal replacement therapy, 426
functional decline, 58–59 Hypervolemic hyponatremia, 428, 430
funding and eligibility Hypocalcaemia, 433–434, 438, 439
life-prolonging therapy, 57 Hypokalaemia, 426–427, 437, 439
medicare guidelines, 53–57 Hyponatremia, 437–439
reasonable likelihood, 52 causes and management options, 428
general inpatient care, 52 classification, 427
history, 50 management, 429–430
home palliative care, 57 SIADH, 428, 429
Index 511
Hypothalamic stimulation, cluster headaches, indications, 262–264

342 procedural method, 263
Hypovolemic hyponatremia, 428, 430 Intrathecal neurolysis, 303
Intrathecal opioid pumps, 308–309
Ionsys, 463–464
I Ischaemic stroke
Ileostomy, 220–221 monitoring and reimaging, 262
Implantable cardioverter defibrillators (ICDs) tissue plasminogen activator
advanced HF patients, 378–379 contraindications, 261–262
implantation, 386 dosage, 262
non-invasive strategy, 387 indications, 261
reprogramming, 386
Inferior vena cava (IVC) filters, 265–266
Informed choice model, 90–91, 103 J
Infraclavicular brachial plexus block, 472 Joint commission on Accreditation of
Insomnia Healthcare Organizations, 4
causes, 127
definition, 127
melatonin, 128 K
sedating antidepressants, 128 Kainate ionotropic glutamate receptor
Institutional palliative care programs, 11 antagonists, 461
Interactive health communication systems Kaye, A.D., 471
(IHCS), 98 Klinner, W., 370
Intercostal neurolysis, 307
Interdisciplinary team communication, 84
International Association of Hospice and L
Palliative Care (IAHPC), 229, 230 Leao, A., 317
International Classification of Diseases Left ventricular assist device (LVAD),
(ICD-9) codes, 502 379, 383, 384
International Patient Decision Aids Standards Lema, M., 5
(IPDAS), 96, 104 Length of survival (LOS),
Interscalene brachial plexus block, 471–472 484–485
Interventional pain blocks, 313, 314 Levobupivacaine, 467
Interventional techniques Lidocaine, 466–467
neurolysis Local anesthetics (LAs)
alcohol, 300, 311, 314 dexamethasone, 468
celiac plexus, 303–304 epinephrine addition, 467
complications, 302 ester and amide, 466–467
cryoablation, 301–302 methemoglobinemia, 469
equipments, 302 Na channel blockade, 466
glycerol, 301, 311, 314 opioids, 468
informed consent, 302 sodium bicarbonate addition,
intercostal, 307 467–468
intrathecal, 303 structure of, 466
peripheral nerve, 303 toxicity, 468–469
phenol, 300–301, 311, 314 vasoconstrictors, 467
radiofrequency thermocoagulation, 301 Luce, J., 490, 492
sympathetic, 304–306 Lumbar sympathetic neurolysis, 304–305
noncancer palliative care, 309–310 Lung cancer, 413, 415
skeletal metastases (see Skeletal incidence, 408
metastases) mortality rates, 408
trigeminal ganglion, 306–307, superior vena caval obstruction, 409
313, 314 ventilatory failure risk, 408, 409
Intra-arterial thrombolysis (IAT) Lung infections, 404–405, 412, 415
contraindications, 263 Lymphedema, 183–184
512 Index
M mortality, 406
Mandela technique, 446 rapid eye movement, 407, 413, 415
McCarthy, M., 380 treatment options, 407–408
Memorial delirium assessment scale Neurological disease
(MDAS), 38 advance care planning, 287
Migraine communication, 287
chronic, 328–329 drug administration routes, 288
definition, 316 symptom management
diagnosis, 318–320 death rattle, 288
etiology and pathophysiology, 317–318 delirium, 289
gender difference, 316 depression, 291–292
International Headache Classification, drowsiness, 289–290
316–317 dyspnea, 288
nonpharmocologic treatment, 321 epileptic seizures, 290
pediatric populations, 331 myoclonus, 290
phases, 316 nausea and vomiting, 291
pregnancy and lactation, 330–331 pain, 290–291
prevalence, 316 terminal restlessness, 288–289
prognosis, 331–332 at terminal stage, 286–287
prophylaxis Neurolysis
abortive medications, 325–328 alcohol, 300
goals, 321 celiac plexus, 303–304
indications for, 321 complications, 302
nonprescription prophylactic cryoablation, 301–302
medications, 322–325 equipments, 302
refractory, 329–330 glycerol, 301
status migrainosus, 316 informed consent, 302
Miner, P.M., 317 intercostal, 307
Mirtazepine, 242 intrathecal, 303
Multidisciplinary team (MDT) peripheral nerve, 303, 313, 314
advantages and effectiveness, 14 phenol, 300–301
barriers, 14–15 radiofrequency thermocoagulation, 301
benefits, 20 sympathetic, 304–306
continuity of care, 20 NIPPV. See Non-invasive positive pressure
coordination of care, 16–17, 20 ventilation (NIPPV)
interdisciplinary team, 9–10 N-methyl-d-aspartate (NMDA) antagonists,
models, 10–11 116
overlapping dimensions, 9 Non-cardiac thoracic surgery, 371
roles of, 11–13 Non-invasive positive pressure ventilation
Multiple subpial transection, 286 (NIPPV)
acute respiratory failure, 418
adverse side effects, 420
N comfort measures, 419, 420
National Board for Certification of Hospice contraindications, 420
and Palliative Nurses (NBCHPN), nasal mask, 418, 419
3–4 oronasal mask, 418, 419
Nausea and vomiting, 117–119 Nonopioids, 109–110
Nav 1.7 blocking agents, 458 Nonsteroidal anti-inflmatory drugs (NSAIDs),
Navigante, A.H., 377 109–110, 235, 326, 464
Neonatal Intensive Care Unit (NICU), Norwood, W.I., 370
pediatric palliative care, 448–449 Numeric Pain Intensity Instrument/Scale, 170
Neurological cases, respiratory disease Nursing perspective and considerations
bulbar weakness, 406 coaching, 164
diaphragmatic weakness, 407 cultural and spiritual considerations, 172
Index 513
hospice care, 166 systematic titration, 111–112

interdisciplinary care team toxicities, 110
design and composition, 165 Orexigens, 145
meetings, 165–166 Osler, W., 483, 484, 495
nurse’s role, 164 Osmotic-controlled release oral delivery
nursing pain management system, 463
education, 170, 171 Ostomy, 221
family caregivers, 167 Outpatient Palliative Care Programs, 10
nursing assessment, 166–167 Overall, Y., 144
terminology, 168–169
pain assessment ways, 165
patient controlled analgesia (PCA) P
intravenous and subcutaneous routes, 172 Pacemakers
pain team, 172 advance HF patients, 378
parameters, 171 bradyarrhythmias, 389, 391, 393
patient and family education, 171–172 Pain
symptoms, 172 antineuropathic benefit, 134
Nutritional care distress, 107
appetite and rehabilitation clinic teams, 143 emergencies and emergency departments, 113
artiticial pharmacologic tools, 108
clinical indications, 148 WHO analgesic ladder, 108–109
complications of, 148–149 Pain Assessment Tool/Scale, 170
enteral nutrition, 146 Pain management
immunonutrition, 148 AMPA and kainate ionotropic glutamate
parenteral nutrition, 146–148 receptor antagonists, 461
assessment, 141–142, 159 anti-nerve growth factor agents, 457–458
cachexia cannabinoids, 459–460
anorexia and decreased food intake, drug delivery
138–139 extended release enteral formulations,
counseling, 143–144 463
definitions, 138 parenteral formulations, 463–465
inflammatory and humoral activities, 141 fatty-acid amide hydrolase inhibitors,
metabolic perturbations, 139–140 460–461
oral nutritive supplements, 144–146 high dose topical capsaicin, 458–459
ethical decision making, 153–155, 160 human chorionic gonadotropin, 461–462
maintain weight, 159 Nav 1.7 blocking agents, 458
with noncancer chronic illnesses, 152–153 regional anesthesia (see Regional anesthesia)
prevalence of malnutrition, 160 somatotropin, 462
score, 142 voltage-gated calcium channel blocking
support on tumor, 141 agents, 459
weight change, 142 Palliative care
decision making (see Decision making
process)
O definition of, 453, 455
Occipital nerve stimulation, cluster headaches, by NCP, 8–9
342 by NQF, 9
Olanzepine, 242 by WHO, 8, 19
Olsen, J., 317 and education
Olson, D.P., 80 HPM, 1
Opioids, 134 nursing, 3–4
atute monitoring, 112 physicians, 2
conversion table, 111 program certification, 4–5
dyspnoea, 397 social work, 4
nalbuphine, 110 symptoms, 1–2
514 Index
Palliative care (cont.) principles of, 444

facilities, 151–152 spiritual care, 447
goals of, 93 WHO definition, 441–442
guidance with complex treatment choices, Percutaneous endoscopic gastrostomy (PEG),
93–94, 103 220, 360, 361
hospice based, 20 Percutaneous transhepatic cholangiography
level of, 19 (PTC)
MDT (see Multidisciplinary team (MDT)) contraindications, 270–271
medical specialty risk, 86 procedural method, 271
number of domains, 19 Percutaneous vertebroplasty and kyphoplasty,
nutrition (see Nutritional care) 267–268
patient-and family centered, 19 Peripheral nerve blocks, regional anesthesia
preference-sensitive decisions, 92–93, 103 contraindications, 471
professionals, 19 of lower extremity
requirements, 19 femoral nerve block, 474
Palliative care physician services popliteal sciatic nerve block, 474
coding and billing, 501, 502 saphenous nerve block, 474–475
documentation, 502, 503 sciatic nerve block, 473–474
employed by Hospice Agencies, 503 single shot, 470
global payment, 503 of upper extremity
to payers axillary brachial plexus block, 473
clinical modification codes, 502 infraclavicular brachial plexus block,
current procedural terminology codes, 472
501, 502 interscalene brachial plexus block,
evaluation and management, 502 471–472
ICD-9 codes, 502 supraclavicular brachial plexus block,
reimbursement, 503 472
time component, physician–patient visit, 502 Peripheral nerve neurolysis, 303, 313, 314
Papadatou, D., 449 Photodynamic therapy (PDT), 365, 367
Parenteral nutrition, 146–148, 160 cholestasis, 359
Paternalistic model, 90–91, 103 esophageal cancer, 349, 350
Patient controlled analgesia (PCA) photosensitizing agent usage, 350
intravenous and subcutaneous routes, 172 Physical and occupational therapy
pain team, 172 anorexia, 178
parameters, 171 cachexia, 178
patient and family education, 171–172 muscle wasting, 178
symptoms, 172 primary fatigue, 178
Pediatric palliative care, 453–455 rehabilitation strategies
causes of death, 442, 443 breast cancer, 183
chronic complex conditions, 443 exercise, 179
deaths in head and neck cancer, 183
adolescents, 448 hospice and palliative care patient,
infant, 447 180–181
preschool children, 447–448 lymphedema, 183–184
school age children, 448 occupational therapy, 182
toddler, 447 physical modalities, 182
health care practitioners, stress and pulmonary rehabilitation, 182
burnout, 449–450 rehab team and setting, 179
implementation barriers, 444–445 Pleurx catheters, 221
initiation and team formation, 445 Popliteal sciatic nerve block, 474
integrated palliative care model, 443 Postdrome, 316, 317
NICU, 448–449 Potts shunt, 370
pain assessment scales, 445, 446 Preference-sensitive decisions, 92–93, 103
physical and emotional suffering, 445–446 Prodrome, 316
Index 515
Protein metabolism abnormalities, 141 depression disorder

Psychiatric disorders antidepressants, 34–35
adjustment, 30–32, 47 cognitive-behavioral therapy, 35
anxiety HADS, 33
benzodiazepines, 36–37 hastened death, 32
clinical interview based on DSM medical conditions and medication use,
criteria, 47 34
patient-physician relationship, 35 prevalence rates, 32
relaxation training and deep breathing suicidal ideas, 32–33
exercises, 37 end of life, psychosocial demands, 23–24
screening, 36 grief, 24
assessment types, 28 life meaning, 24–25
delirium, 47 patient-provider communication
confusion assessment method, 38 factors, 26–27
environmental and psychosocial guidelines, 27
interventions, 40 ineffective coping strategies and
MDAS, 38 beliefs, 25
medication, 39 primary medical caregiver, 26
perceptual disturbances, 37 resources, 25
tripartite approach, 38 phases of illness, 27
depression prognostic factors, 30
antidepressants, 34–35 psychopharmacologic agents, 28, 30
cognitive-behavioral therapy, 35 psychotherapeutic interventions, 28–29
hastened death, 32 repertoire of skills, 47
Hospital Anxiety and Depression Scale, spiritual distress, 25
33 symptoms, 28, 47
medical conditions and medication use, types of assessments, 28
34 Psychopharmacology, 28, 30
prevalence rates, 32 Psychotherapy, 28–32, 35, 37
suicidal ideas, 32–33 Pulmonary artery banding, 370–371
phases of illness, 27 Pulmonary rehabilitation, 182
prognostic factors, 30 Pyenson, B., 376
psychopharmacologic agents, 28, 30
psychotherapeutic interventions, 28–29
symptoms, 28, 47 Q
Psychological distress and psychiatric Quinlan, 154
comorbidities
adjustment disorder, 30–32, 47
anxiety disorder R
benzodiazepines, 36–37 Radiofrequency thermocoagulation, 311, 314
clinical interview based on DSM cluster headaches, 341
criteria, 47 lumbar sympathetic neurolysis, 305
patient-physician relationship, 35 thoracic sympathetic neurolysis, 306
relaxation training and deep breathing trigeminal ganglion, 307
exercises, 37 Radiology
screening, 36 angiography
delirium, 47 catheter insertion, 255, 256
confusion assessment method, 38 contraindications, 254
environmental and psychosocial guide wire passage, 255, 256
interventions, 40 indications, 254
MDAS, 38 vessel puncture, 255, 256
medication, 39 angioplasty
perceptual disturbances, 37 balloon catheter, 255
tripartite approach, 38 complications, 256–257
516 Index
Radiology (cont.) ester and amide, 466–467

interventional options, 255 methemoglobinemia, 469
stent insertion, 256 Na channel blockade, 466
brain aneurysms opioids, 468
coils for, 260 sodium bicarbonate addition, 467–468
contraindications, 260 structure of, 466
indications, 259–260 toxicity, 468–469
Seldinger percutaneous catheter vasoconstrictors, 467
insertion, 260 peripheral nerve blocks, 470–475
triple-H therapy, 260 regional nerve blocks, 469–470
central venous catheters (CVCs), 266–267 utility and safety, 465
cerebral angiography, 259–260 Regional nerve blocks, 469–470
coeliac plexus blocks Respiratory disease
anterior and posterior approaches, 269 American Thoracic Society, 395
biliary interventions, 270 symptoms, management of
complications for, 269 chest pain, 398
contraindications, 269 chronic obstructive pulmonary disease,
indication, 268 405–406
procedural method, 270 cough, 399–400
embolisation dyspnoea, 396–397
chemoembolisation, 259 hemoptysis, 402–404
contraindications, 257–258 lung cancer, 408–409
indications, 257 lung infections, 404–405
radioembolisation, 259 neurological cases, 406–408
gastrostomy stridor, 400–401
complications, 272 wheeze, 400
contraindications, 271 Robinson, M.R., 447
procedural method, 272 Ropivacaine, 467
intra-arterial thrombolysis Rotherberg, D.M., 495
contraindications, 263 Rubenfeld, G., 492
indications, 262–264 Rule of double effect, 486–487, 498–500
procedural method, 263
ischaemic stroke, 261–262
percutaneous transhepatic S
cholangiography, 270–271 Sano shunt, 370
percutaneous vertebroplasty and Saphenous nerve block, 474–475
kyphoplasty, 267–268 Saunders, C., 1, 50
transjugular intrahepatic portosystemic Schiavo, T., 153
shunt Sciatic nerve block, 473–474
complications, 273 Self-expanding metal stents (SEMS)
contraindications, 272 cost of, 358
procedural method, 273 esophageal, 352–353
venous thromboembolism malignant biliary obstruction, endoscopic
indications, 265 relief of, 356
inferior vena cava filters, 265–266 nitinol composition, 351
Raffin, T., 484 outcomes, 359
Ravasco, P., 143 proximal colon cancers, 354
Refeeding syndrome, 148–149 types, 352
Refractory migraine, 329–330 Seven “Cs” planning model, 193–194
Refractory status epilepticus (RSE), 290 Shang, E., 146
Regional anesthesia, 480, 481 Shared decision model, 91, 95, 103
benefits, 465 Shoulder-hand syndrome, 282
local anesthetics Single shot peripheral nerve blocks, 470
dexamethasone, 468 Skeletal metastases
epinephrine addition, 467 cement, 307, 308, 311, 312, 314
Index 517
complications, 308 reduce disability and impairment

intrathecal opioid pumps, 308–309 depression, 284
kyphoplasty, 307, 308 language and perceptual impairment, 283
morbidity, 307 rehabilitation practice, 282
neurosurgical ablative approaches, 308 sensorimotor training, 283
vertebroplasty, 307, 308 spasticity, 284
Social work Stroud, P., 485
care planning Stuppy D.J., 170
communication and, 196–197 Sufentanil NanoTab® patient controlled
family members, 197–198 analgesia system, 464
model, 195 Superior hypogastric plexus, 268–270
and patient–family meeting, 193–194 Supraclavicular brachial plexus block, 472
core therapeutic interventions, 199 Supraventricular tachycardia (SVT),
Dr. L’s view, 200–201 388, 392, 393
Marcia R’s view, 200 Sykes, N., 487
patient and family, 199 Sympathetic neurolysis
cultural awareness, 195–196 lumbar, 304–305
emotional support, 203 thoracic, 305–306
family meeting Symptom management
bedside care, 198 adjuvants, 114
Mary G’s view, 198 anticonvulsants, 115
Ramona F’s view, 198–199 antidepressants, 115
stories sharing, 197 breakthrough pain, 112–113
limitations of, 202 corticosteroids, 116–117
National Association of Social Workers, gastrointestinal system
190 cachexia syndrome and fatigue,
palliative care social worker 120–122
compassion fatigue, 201–202 constipation, 119–120, 134
consult, 192–193 cough, 124–125
psychosocial and spiritual aspects, delirium, 125–127, 134
202–203 dyspnea, 122–124, 134
role of, 190–191 insomnia, 127–128
social work assessment, 192–193 nausea and vomiting, 117–119
team configurations, 191 xerostoma, 117
team evolution, 191–192 hospice, 67
supervision, 203 death rattle, 62
Somatotropin, 462 terminal agitated delirium, 62–63
Spiegel, D., 485 NMDA antagonists, 116
Spinal cord nonopioids, 109–110
modulation, 312–314 opioids, 134
stimulation, 308, 309, 312, 314 atute monitoring, 112
Status migrainosus, 316 conversion table, 111
Stent occlusion, 356, 357 nalbuphine, 110
Stridor, 412, 414 systematic titration, 111–112
description, 400 toxicities, 110
emergency management, 400–401 pain
long-term management, 401 antineuropathic benefit, 134
Stroke distress, 107
incidence, 280 emergencies and emergency
medical care, 280 departments, 113
nutritional needs and pharmacologic tools, 108
access, 280–281 WHO analgesic ladder, 108–109
pressure sores, 281–282 side effects, 113–114
shoulder-hand syndrome, 282 Systemic-to-pulmonary arterial shunt, 370,
venous thrombosis, 281 373, 374
518 Index
T anorexia and cachexia syndrome,

Tachyarrhythmias 218
supraventricular, 387–388 autonomy assessment, 223
supraventricular tachycardia, 388 delirium, 218
ventricular tachycardia, 388–389 end-of-life assistance, 223–224
Taussig, H.B., 370 gastrointestinal or urinary tract
Terminal phase of illness, 58, 69 obstructions, 220–221
Thomas, V., 370 heart failure patients, 222
Thoracic sympathetic neurolysis, 305–306 hospice movement, 217
Thorns, A., 487 interstitial lung disease,
Time-limited trial (TLT), 101 218–219
Total parenteral nutrition (TPN), 146–148, 160 nutritional evaluation,
Tracheotomy, 218–219 219–220
Tramadol, 236 opioids, 218, 219
Tran De, Q.H., 471 pain evaluation, 218
Transformed migraine. See Chronic migraine patient’s comfort, 217
Transjugular intrahepatic portosystemic shunt pleural effusion, 221
(TIPS) psychological problems, 218
complications, 273 tracheotomy, 218–219
contraindications, 272 Veldink, J.H., 287
procedural method, 273 Venous thromboembolism
Trigeminal-autonomic cephalgias (TAC), 332 indications, 265
Trigeminal ganglion, 306–307, 313, 314 inferior vena cava filters,
Triple-H therapy, 260 265–266
Truog, R.D., 491, 492 Ventricular tachycardia, 388–389
Tuckman, B.W., 191 Voltage-gated calcium channel
Tunnelled central venous access, 266–267 (VGCC) blocking agents,
Type I cyclo-oxygenase (COX-I), 109–110 459, 480, 481
Type II cyclo-oxygenase (COX-II), 109–110
W
U Waisel, D.B., 491, 492
Uncovered self-expanding metal stents, 352, Walker, R., 494
354, 356, 358 Waterston shunt, 370
Uniform Determination of Death Act Weiss, S.C., 484
(UDDA), 484, 498, 500 Wheeze, 400
Urinary diversion, 221 Wolffe, H., 317
Urman, R., 471
X
V Xerostoma, 117
Vadivelu, N., 471
Vascular access
adjuvant or supplementary analgesic Y
agents, 218 Young, E., 484

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Essentials of Palliative Care

Essentials of Palliative Care

ISBN 978-1-4614-5163-1 ISBN 978-1-4614-5164-8 (eBook)

Library of Congress Control Number: 2012951667

© Springer Science+Business Media New York 2013

Printed on acid-free paper

Springer is part of Springer Science+Business Media (www.springer.com)

I want to thank my wife, Dr. Kim Kaye, for

Rochester, NY, USA Timothy E. Quill Rochester

• Dyspnea, respiratory failure, respiratory tract infections, pleural effusions, lymp-

The American Board of Medical Specialties is a self-policing organization that sets

New Haven, CT, USA Nalini Vadivelu

1 Introduction and Education .................................................................. 1

13 Vascular Access: Ostomies and Drains Care

Index ................................................................................................................ 505

Rita Agarwala, B.M., B.Sc. Department of Anesthetics, Epsom and St Helier

M. Khurram Ghori, M.D. Department of Anesthesiology, Yale University School

Matthew Peña, M.D. Department of Anesthesiology, Naval Medical Center San

Angèle Ryan and Jack M. Berger

A. Ryan, M.D. (*) • J.M. Berger, M.S., M.D., Ph.D.

N. Vadivelu et al. (eds.), Essentials of Palliative Care, 1

The American Board of Medical Specialties is a self-policing organization that sets

Sukanya Mitra and Nalini Vadivelu

Introduction and Basic Concepts

On September 1, 2011, The Joint Commission (formerly the Joint Commission on

S. Mitra, M.D. (*)

N. Vadivelu et al. (eds.), Essentials of Palliative Care, 7

It goes on further to clarify that palliative care:

• Provides relief from pain and other distressing symptoms.

Multidisciplinary Approach in Palliative Care

be skilled in care of the patient population to be served. Palliative-care teams may be

As an aside, it is to be noted that although the terms multidisciplinary and

Models of Palliative Care and Multidisciplinary Approach

(c) Institutional Palliative Care Programs—these are institutional-based programs in

Role Played by the Multidisciplinary Team in Palliative Care

• Specialist-level palliative care is delivered by an interdisciplinary team.

and family. Of particular importance is hiring physicians, nurses, and social

• The interdisciplinary team includes professionals with patient-population-specific

Advantages and Effectiveness and of MDT Approach

Barriers and Challenges

Many of these barriers and challenges may be overcome by an effective and

Care coordination is a comprehensive approach to achieving continuity of care

The Victorian Government Department of Human Services, Melbourne, Victoria,

healthcare providers, and between different categories of the providers themselves),

1. jointcommission.org. Washington, DC: The Joint Commission. Advanced certification for

1. According to the World Health Organization definition of palliative care, the

7. The following statement is true regarding research-evidenced benefits of a

Raphael J. Leo and Maria Theresa Mariano

Psychosocial Demands at the End of Life

R.J. Leo, M.A., M.D. (*) • M.T. Mariano, M.D.

N. Vadivelu et al. (eds.), Essentials of Palliative Care, 23

Grief, Life Meaning, and Spiritual Distress

and psychological reactions including fear, shock, anger, vulnerability, uncertainty,

Patient–Provider Communication: When Is Distress

It is common for terminal patients to experience transient feelings of sadness,

Table 3.1 Patient–clinician factors impeding communication about psychological distress

Psychiatric Disorders Encountered in the Palliative Care Setting

There is an extensive epidemiological literature that supports the high prevalence of

most common psychiatric conditions encountered in palliative care settings [30–34].

Table 3.2 Psychotherapeutic interventions that may be useful in addressing psychological