17 Shaw - Pediatric Pall Pain and Symptom MX
17 Shaw - Pediatric Pall Pain and Symptom MX
17 Shaw - Pediatric Pall Pain and Symptom MX
M
any children with life-limiting
conditions have distressing
symptoms not just at the end
of life, but throughout the course of their
illnesses, which may run years after the
initial diagnosis.1 Because pediatricians
treat these children throughout their dis-
ease trajectory, it is important to have the
basic skills to assess and treat pain and
other distressing symptoms. This article
reviews pain and symptom assessment
and management.
Several studies have shown a high
degree of symptom burden in pediat-
ric populations with terminal illness in
the last few weeks of life. Some com-
monly reported symptoms include pain,
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dyspnea, fatigue, poor appetite, nausea,
vomiting, constipation, and change in
sleep patterns.2-5 While much of the focus
in the medical literature has been on end
of life symptoms, many children living result of these symptoms may be differ- PAIN ASSESSMENT AND CONTROL
with life-limiting conditions experience ent for each child and family. However, Assessment
distressing symptoms throughout their the need for pain and symptom manage- Treatment of pain starts with its mul-
illness. The perception of suffering as a ment is clear. Good pain and symptom tifaceted assessment. For young or non-
control, especially in the last days and verbal children, we often rely on the
Tressia M. Shaw, MD, is Pediatric Palliative Care weeks of life, can have a lasting posi- caregiver’s report. Pain may manifest as
Program Director, Phoenix Children’s Hospital; tive impact on families; failure to achieve changes in behavior, irritability, or fa-
Pediatric Medical Director, Hospice of the Val- good symptom control, on the other hand, tigue. A complete pain history includes
ley; and Clinical Assistant Professor of Pediatrics, is associated with complicated grief and namely: location of the pain; and then for
University of Arizona College of Medicine. bereavement.6,7 For most children, symp- each site the quality, exacerbating/reliev-
Address correspondence to: Tressia M. Shaw, tom control can be achieved using stan- ing factors, onset, associated symptoms,
MD, Phoenix Children’s Hospital, 1919 E. Thomas, dard dosing protocols with well-known temporal pattern, impact on daily life/
Phoenix, AZ 85016; fax: 602-933-0222; email: medications such as opioids and benzo- activities, and response to treatments.
tshaw@phoenixchildrens.com. diazepines.2 Klick and Hauer identify An initial pain assessment should also
Disclosure: Dr. Shaw has no relevant financial
several guiding principles for symptom include a discussion of the child or fam-
relationships to disclose.
management, which are outlined in Side- ily’s history with pain, pain medications,
doi: 10.3928/00904481-20120727-13
bar 1 (see page 330). and what they perceive as barriers to
SIDEBAR 1. SIDEBAR 2.
Oxycodone
Oxycodone is another commonly used Fentanyl chronic, or neuropathic pain.1 Metha-
opioid. There is no intravenous prepara- Fentanyl is available in intravenous, done should be prescribed carefully and
tion of oxycodone in the United States, transdermal, intranasal, and transbuccal by an experienced practitioner. Frequent
but long acting oral forms are available. routes and is useful in patients with renal communication with the patient must be,
Compared to morphine, it has a slightly insufficiency or failure.18 The transder- especially in the first weeks of treatment,
longer half-life; for some patients every mal patch cannot be titrated quickly nor until a stable regimen is reached. Consul-
6-hour dosing may be possible. In ad- does it give quick pain relief at time of tation with a pain or palliative care spe-
dition, it is more expensive and in some initiation due to its long half-life and slow cialist is recommended for those unfamil-
settings may be less available than mor- absorption, respectively. Other analgesic iar with methadone and its side effects.
phine. The conversion ratio from mor- medications, such as morphine or oxyco-
phine to oxycodone is approximately done should first be titrated to relief prior Correct Dosage
1-2:1, which means the equivalent daily to conversion to a transdermal patch for Starting doses for commonly used opi-
dose of oxycodone would be 50% to chronic, stable pain control. Transbuccal oids are outlined in the Table (see page
100% of the daily morphine dose. 18 or intranasal routes can be used for acute 332), along with dosing tips in Sidebar
Clearance of oxycodone is also affected or breakthrough pain. These medication 4. Changing from one opioid to anoth-
by severe renal insufficiency or failure.19 delivery systems can be expensive and er to reduce the build-up of metabolites
are not widely available; therefore, use (“opioid rotation”) can be accomplished
Hydromorphone of a complementary medication, such as using equianalgesic dosing charts. Dos-
Hydromorphone is 5 to 7.5 times more morphine, for breakthrough pain, is often age calculations for opioid rotation can
potent than morphine,17,18 meaning much a reasonable option. Appropriate doses be confusing because they account for
lower does are needed to obtain the same must be calculated. incomplete cross-tolerance, meaning that
analgesic efficacy. Hydromorphone may the reduced efficacy of a medication over
be administered by all routes other than Methadone time that is related to tolerance does not
rectally. There is no long-acting form of Methadone is a long-acting, inexpen- translate completely to the new alternate
hydromorphone available for pediatric sive opioid. It is available as an oral and medication, rendering it more potent than
use in the US. Hydromorphone is a good parenteral medication and it acts on nu- predicted when using the standard con-
alternative if morphine or oxycodone is merous classes of pain receptors; it can version table. If a practitioner is inexpe-
not well tolerated. therefore be very useful in refractory, rienced with this paradigm, consulting
TABLE.
on patient response to treatment. Patient
monitoring should include assessment
Recommended Starting Doses for Opioids of vital signs and level of consciousness,
Drug Dosing Interval Starting Adult Doses as well as pain relief. Breathing may be
Morphine slowed when adequate pain control is
IV, SC 0.1 mg/kg/dose Every 2-4 h 2-6 mg achieved and should not be mistaken for
Oral 0.15-0.3 mg/kg/dose Every 4 h as scheduled 5-15 mg a medication’s side effect.1 Respiratory
Every 1 h as needed
depression caused by opioids will also
Oxycodone include an unexpected decreased level
Oral 0.1-0.2 mg/kg Every 4-6 h 5-10 mg
of consciousness. The use of naloxone
Hydromorphone to treat respiratory depression should be
IV, SC 0.02 mg/kg Every 2-4 h 0.5-1 mg
avoided as it may lead to an increase in
Oral 0.04-0.08 mg/kg Every 2-4 h 2-4 mg
pain and possibly even opioid withdraw-
Fentanyl
al. Usually holding or decreasing the opi-
IV 0.5-1 mcg/kg Every 1-2 h 25-50 mcg
Transdermal Convert from IV dose oid dose with close monitoring is effec-
tive in reversing respiratory depression in
IV = intravenous; SC = subcutaneous.
Data from Klick JC and Hauer J,1 Wolfe J,12 and Zernikow et al17 this setting.
with a pain or palliative care specialist opioids due to their histamine releasing Myoclonus
may be beneficial. properties; the itching usually resolves Myoclonus can be seen with higher
Combination medications, such as ac- within a few days of treatment initiation and longer term doses of opioids, due
etaminophen with codeine or oxycodone or increased dosage.1 Treatment with di- to the build-up of neuroexcitatory meta-
and acetaminophen with hydrocodone phenhydramine or hydroxyzine can be bolic byproducts which can also lead to
should be used with caution, if at all, in helpful until resolution. If pruritis is se- seizures and personality changes. The
children. It is easy to exceed maximal vere or refractory to treatment consider appearance of such side effects should
recommended doses of the acetamino- rotating to another opioid. prompt consideration of opioid rotation,
phen and ibuprofen when using these. as described above.
Optimally, the nonopioid analgesic will Nausea and vomiting
be prescribed concurrently but separately Nausea and vomiting usually are tem- Adjuvant Medications
from the opioid to ensure safe dosing of porary symptoms occurring at the time of A pain assessment may reveal differ-
each medication. In addition, use of hy- initiation or escalation of opioid medica- ent types of pain such as nociceptive as
drocodone in the pediatric population car- tion doses and can be treated with anti- well as neuropathic pain; the latter is dis-
ries concerns similar to codeine regarding emetics until resolution. Sedatives such tinguished by its associated sensations of
safety, metabolism, and efficacy.20 as promethazine should be avoided if shooting pain, burning, or allodynia (non-
possible. painful stimuli, such as light touch result-
Side Effects of Opioids ing in pain perception). Adjuvant medi-
Constipation Urinary retention cations, in conjunction with opioids, can
The most common side effect of opi- An uncommon side effect of opioid be useful for the treatment of neuropathic
oid treatment, constipation, should be treatment, urinary retention can be man- pain. Some common adjuvant medica-
managed proactively. A bowel regimen aged with nonpharmacologic techniques tion classes include: anti-inflammatories;
including a stool softener and an osmotic such as running water, manual pressure antidepressants (particularly tricyclics);
or motility agent should be started at the on the bladder (Crede’s maneuver) or, if anticonvulsants (commonly gabapentin);
initiation of opioid treatment unless the needed, intermittent catheterization may steroids; and muscle relaxants.
patient is experiencing diarrhea. As opi- be used until resolution.
oid doses escalate, so must the intensity Nonpharmacologic Treatments
of the bowel regimen. Respiratory depression Pain management should include an
Though commonly feared, respira- integrated strategy of medications as
Pruritis tory depression is a rare complication of well as nonpharmacologic therapies or
Often mistaken for an allergic reac- opioid treatment, particularly with ap- techniques. These strategies may include
tion, pruritis is an expected side effect of propriate titration of medications based biofeedback, guided imagery, hypnosis,
massage, acupuncture, herbals, or art safety and efficacy for the use of these Antiemetics are targeted at specific re-
therapy. Fifty-nine percent of parents medications.12 Benzodiazepines can also ceptors and mechanisms; they should be
whose children have cancer reported be considered in the treatment of dyspnea chosen based on the underlying reason for
using complementary therapies.21 The and can be helpful if there is associated the nausea. For example, ondansetron, a
evidence for these therapies is still be- anxiety or agitation.18 Oxygen can be serotonin receptor antagonist, works well
ing explored, but appears to have benefit considered for patients with hypoxia. A for nausea caused by chemotherapeutic
for some patients. Most clinicians en- fan blowing on the face is also effective and anesthetic agents. For opioid-induced
courage the use of complementary tech- for managing the sensation of breathless- nausea, dopaminergic (eg, haldoperidol),
niques unless there is evidence of harm ness, based on its stimulation of the V1 anticholinergic (eg, scopolamine), or pro-
to the patient, to the family’s budget, or branch of the facial nerve. Anticipatory kinetic (eg, metoclopramide) agents may
in the literature. Their use often enables education of families about end-of-life be more effective. Benzodiazepines (eg,
the parents to feel they are meaningfully lorazepam) are helpful when anxiety is
contributing to the child’s well-being. contributing to nausea.23 If the antiemetic
Therefore, care plans should be devel- It is important to consider medication chosen is ineffective in reliev-
oped based on individual response and in ing symptoms, a second antiemetic with a
partnership with the family.
that psychosocial distress or different mechanism of action should be
In addition, it is important to consider other environmental factors either added or substituted to the current
that psychosocial distress or other envi- regimen.1
ronmental factors may play a role in pain may play a role in pain Constipation is another common
generation. Recognition and discussion generation. symptom.1,23 Medications used to treat
of these factors can result in significant constipation fall into three categories:
benefit with few side effects. Interdis- stool softeners, osmotic agents, and stim-
ciplinary care team members such as changes in respiratory patterns (apnea, ir- ulants. Stool softeners, such as docusate,
psychologists, psychiatrists, counselors, regular breathing rates, and noisy breath- are usually ineffective when used alone
spiritual leaders, or social workers may ing) can help alleviate their distress. for this population; a stool softener plus
be helpful in this regard. either an osmotic agent or stimulant is
Secretion Control indicated. Osmotic agents include poly-
OTHER SYMPTOMS Secretions are another common re- ethylene glycol 3350, lactulose, and mag-
Respiratory Symptoms spiratory problem, often presenting well nesium sulfate. Stimulant medications in-
Dyspnea is one of the most common before end of life in children with se- clude senna or bisacodyl.
respiratory symptoms among children vere neurologic impairment. Excessive
with life-limiting conditions, especially or poorly controlled salivary secretions Appetite Changes
at the end of life. The treatment of dys- can be managed chronically with medi- Redirecting the parent to focus on pro-
pnea often requires an interdisciplinary cations such as anticholinergic agents, viding companionship and love, rather
approach and the use of relaxation tech- glycopyrrolate, or the use of a suction than food, and offering anticipatory guid-
niques and deep breathing, distraction, or machine.1 Management can include edu- ance as appetite, physical activity, and
hypnosis. First line medication treatment cating the family, a reduction of artificial metabolic activity typically decrease can
of nonspecific dyspnea from an irrevers- fluid intake, and in long term settings, be helpful. Earlier in the course of ill-
ible condition includes scheduled opioid possibly the use of botulinum toxin in ness, high calorie supplements or phar-
medications, with one-quarter to one-half the gland itself.22 macologic therapy may be of benefit. In
oral starting doses for pain.1,12 Patients the case of early satiety, small frequent
with dyspnea who are already receiving Gastrointestinal Symptoms meals may be appropriate and if the taste
opioids for pain control will, of course, Nausea, vomiting, anorexia, constipa- of food is altered by the illness or its treat-
need higher doses and should not be re- tion, and diarrhea are all common symp- ment, soliciting the child’s preferences
verted to starting doses. Administering toms that may be disease-related or a side can lead to improved nutritional intake. It
opioids for breathing distress often fright- effect of treatments.23 Management of is important to exclude remediable causes
ens both families and health care provid- these symptoms is directly related to the of decreased appetite, such as pain, nau-
ers due to the association of opioids with presumed cause, with an effective treat- sea, and depression.23 Many children
respiratory depression. ment plan based on a good history, exam, with profoundly debilitating neurologic
Recent evidence has shown both and review of current medications. conditions are dependent on medically
administered enteral feedings through- ditions, starting from time of diagnosis In: Wolfe J, Hinds P, Sourkes B. Textbook of In-
out their lives. At the end of life, it is the and extending all the way to the end of terdisciplinary Pediatric Palliative Care. Phila-
normal course of most conditions to have life. With just a few basic tools, the pe- delphia: Elsevier Press; 2011:284-310;368-384.
13. Gregoire MC, Frager G. Ensuring pain relief
loss of appetite and intolerance of feed- diatrician can help prevent and manage for children at the end of life. Pain Res Clin
ing.24 Continuing artificial hydration and many symptoms that may be experienced 2006;11(3):163-171.
nutrition at this point may worsen symp- by these children and families. For symp- 14. Friedrichsdorf SJ. Pain management in children
with advanced cancer and during end-of-life
toms.12,25 How this is addressed may de- toms that are difficult to control, consider care. Pediatr Hematol Oncol. 2010;27(4):257-
pend on the family’s beliefs and goals. consulting a physician who specializes in 261.
pain or palliative care. 15. Tschundy M, Arcara K. John Hopkins Hospital
The Harriet Lane Handbook, 19th ed. Philadel-
Mood Lability
phia, PA. Elsevier; 2012.
Anxiety, depression, insomnia, and ag- REFERENCES 16. World Health Organization. Pharmacological
itation are symptoms typically associated 1. Klick JC, Hauer J. Pediatric palliative care. Treatment Strategies. In: Persisting pain in chil-
with psychosocial or spiritual distress, in Curr Probl Pediatr Adolesc Health Care. dren package: WHO guidelines on the pharma-
2010;40(6):120-151. cological treatment of persisting pain in children
addition to underlying physical causes. with medical illnesses. WHO 2012.
2. Drake R, Frost J, Collins JJ. The symptoms
Their management often benefits from an of dying children. J Pain Symptom Manag. 17. Zernikow B, Michel E, Craig F, Anderson
interdisciplinary approach and nonphar- 2003;26(1):594-603. BJ. Pediatric palliative care: use of opioids
3. Pritchard M, Burghen E, Srivastava DK, et. for the management of pain. Paediatr Drugs.
macologic treatments. Reversible medical 2009;11(2):129-151.
al. Cancer-related symptoms most concerning
causes, such as pain, and medication side to parents during the last week and last day of 18. Watson M, Lucas C. Hoy A, Back I. Oxford
effects should be investigated as well.26 their child’s life. Pediatrics. 2008;121(5):e1301- Handbook of Palliative Care. New York: Ox-
1309. ford Press; 2005:191-195;520-533.
Selective serotonin reuptake inhibitors
4. Wolfe J, Grier HE, Klar N, et. al. Symptoms and 19. Hain RD, Miser A, Devins M, Wallace WH.
(SSRIs) can be helpful for depression and Strong opioids in pediatric palliative medicine.
suffering at the end of life in children with can-
anxiety, but must be taken for 4 to 6 weeks cer. N Engl J Med. 2000;342(5):326-333. Paediatr Drugs. 2005;7(1):1-9.
before they reach their full effectiveness. 5. Theunissen JM, Hoogerbrugge PM, van Achter- 20. Madadi P, Hildebrandt P, Gong I, et al. Fatal
berg T, Prins JB, Vernooij-Dassen MJ, van den hydrocodone overdose in a child: pharma-
For children at end of life with only days cogenetics and drug interactions. Pediatrics.
Ende CH, Symptoms in the palliative phase of
or weeks remaining, more immediate children with cancer. Pediatr Blood Cancer. 2010;126:e986.
acting medications should be considered 2007;49(2):160-165. 21. Post-White J, Fitzgerald M, Hageness S, Sencer
6. Contro N, Kreicbergs U, Reichard RW, Sourkes, SF. Complementary and alternative medicine
such as benzodiazepines and haloperidol use in children with cancer and general and
B. Anticipatory Grief and Bereavement. In:
for anxiety and agitation;26 psychostimu- Wolfe J, Hinds P, Sourkes B, eds. Textbook of In- specialty pediatrics. J Pediatr Oncol Nurs.
lants have been used in adult patients for terdisciplinary Pediatric Palliative Care. Phila- 2009;26(1):7-15.
delphia: Elesvier Press; 2011:41-54. 22. Little SA, Kubba H, Hussain SS. An evidenced-
rapid resolution of depression and asthe-
7. McCarthy M, Clarke N, Ting C. Conroy R, based approach to the child who drools saliva.
nia in the palliative setting and may be Clin Otolaryngol. 2009;34(3):236-239.
Anderson V, Heath J. Prevalence and predic-
beneficial in children as well.27 tors of parental grief and depression after the 23. Santucci G, Mack JW. Common gastrointesti-
death of a child from cancer. J Palliat Med. nal symptoms in pediatric palliative care: nau-
2010;13(11):1321-1326. sea, vomiting, constipation, anorexia, cachexia.
Fatigue Management Pediatr Clin N Am. 2007;54(5):673-689.
8. McSherry M, Kehoe K, Carroll JM, Kang TI,
Fatigue can be related to disease pro- Rourke MT. Psychosocial and spiritual needs of 24. Siden H, Tucker T, Derman S, et al. Pediatric
cess, treatments, medications, nutrition, children living with a life-limiting illness. Pedi- enteral feeding intolerance: a new prognostica-
anemia, pain, depression, anxiety, or atr Clin N Am. 2007;54(5):609-629, ix-x. tor for children with life limiting illness. J Palliat
9. Franck L, Greenberg C, Stevens B. Pain assess- Care 2009;25(3):213-217.
other causes. Other than with reversible ment in infants and children. Pediar Clin N Am. 25. Wagner B, Ersek M, Riddell S. HPNA position
causes such as anemia, fatigue is very 2000;47(3):487-512. statement: artificial hydration and nutrition in
difficult to treat. Structuring activities to 10. Weissman, D. Is it pain or addiction?, 2nd ed. end of life care. Available at: www.hpna.org.
Fast Facts and Concepts #68. EPERC website. Accessed July 6, 2012.
include rest time may be helpful. 26. Wusthoff CJ, Shellhaas RA, Licht DJ. Manage-
Available at: www.eperc.mcw.edu. Accessed
July 3, 2012. ment of common neurologic symptoms in pedi-
CONCLUSION 11. Weissman, David. Pseudoaddiction, 2nd ed. atric palliative care: seizures, agitation, and spas-
Fast Facts and Concepts #69. EPERC website. ticity. Pediatr Clin N Am. 2007:54(5):709-733.
The pediatrician is at the front line of
Available at: www.eperc.mcw.edu. Accessed 27. Homsi J, Walsh D, Nelson KA. Psychostimu-
symptom assessment and management July 3, 2012. lants in supportive care. Support Care Cancer.
for children living with life-limiting con- 12. Wolfe J. Easing Distress When Death is Near. 2000:8(5):385-397.