Cancer Pain , Malang UB

12 December 2019

Willy Halim,MD, PhD, FIPP

Anesthesiologist-Pain Practitioner
Quality of life and suffering?
Multidimensionality !

Somatic

Spiritual Functional

Suffering

Existential Psychic

Social
 Cancer related pain
• Survey in 11 European countries and Israel 1

• Survey screened for patients with at least weekly pain

– 56% suffered moderate-to-severe pain
– 77% received prescription analgesics
– 41% received strong opioids

• Patients receiving prescription analgesics

– 63% breakthrough pain
– 69% pain-related difficulties with every day activities
– 50% believed quality of life is not considered priority by health care
professionals
Breivik et al Ann Oncol 2009
 P M: multidisciplinary approach
• Type of pain: nociceptive, neuropathic, visceral

• Integration of symptomatic (analgesic) and causal treatment (e.g.

hormonal, cytostatic, surgical, radiation therapy)

• “Global patient care”: attention for biopsychosocial problems

– Psychological counceling
– Maintenance of quality of life (allertness)
– Prevention and management of treatment side effects

• Pain management
– Analgesic medication
– Co-analgesics
– Interventional pain management techniques

4
CBO guideline: Management of Cancer pain The Netherlands 2008
WHO Pain Ladder

WHO Switzerland 1986

5
 WHO Pain Ladder

Optimize dose
Foresee breakthrough medication
Manage side effects

refractory Assess possibility of adjuvant

treatment alone
• Identify cause of pain
• Consult with oncologist the value of anti-cancer/tumor
treatment
• Evaluate the psychological impact of the cancer and 6

the pain
 Possible causes of cancer pain
• Tumor pressure on nerve, organ or bone

• Surgery – acute – wound healing

• chronic- nerve lesion

• Radiation therapy: burns

• Chemotherapy: neurotoxicity

• Bone metastases
 Palliative cancer treatment for PM

• Surgery, radiation and/chemotherapy to reduce

tumor size and pressure on organs, nerve or
bone.

• The treatment selection is done in consultation

with oncologist
 Biphosphonates

• Bone metastases – extremely painful can lead

to vertebral compression fractures.

• Medication – biphosphonates – preventive role

– Evidence for
• Pain due to metastases of Kahler
• Pain due to metastases of prostate cancer (zoledronine
acid)
• Biphosphonates of little added value for bone metastases
of other types of cancer
CBO guideline: Management of Cancer pain The
Netherlands 2008
 Step 1
Paracetamol and NSAID’s
• Paracetamol is useful as step 1 in patients
with cancer
– No evidence at long-term in this patient group

– The use of NSAID’s can be considered for

short term treatment alone or in association
with opioids
– The potential benefit should be weighted
against the risk for side effects (GI bleeding)
 Step 2: Weak opioids
• Patients treated immediately with strong opioids ,
compared to those treated accoding to WHO ladder :
– better pain control,
– better quality of life
– Less side effects
– Less need for treatment adaptation

• Two reasons for use of weak opioids

– Strong opioid prescription severely restricted
– Regulations on driving and strong opioid use
Marinangeli 2004
Maltoni 2005
 Step 3: Strong opioids
• Aim for stable plasma level during the day
– Use long-acting preparations

– Dose titration can be done with the long-acting preparation

• Foresee breakthrough medication

– Rapidly acting

• Inform the patient on how and when to use breakthrough

medication

CBO guideline: Management of Cancer pain

The Netherlands 2008
 Step 3: Strong opioids
• No difference in efficacy and safety between IR and SR
preparations

• No comparative trials between different strong opioids

– Morphine, Oxycodone, Hydromorphone, Fentanyl,
Buprenorphine and Methadone

– All have comparable efficacy and side effects

– Methadon has risk for accumulation

CBO guideline: Management of Cancer pain
The Netherlands 2008
 Step 3: Strong opioids

• Combination of strong opioids

• Desirable effects outweighted by disadvantages
• Only weak recommendations

• Alternative administration routes

• Comparable efficacy and side effects sc, iv, rectal and
transdermal
• Local side effects possible with rectal and transdermal

Fallon and Laird Pal Med. 2011

Radbruch et al. Pal Med 2011
 Step 3: Strong opioids
• Spinal opioids:
• Few RCTs of low quality
• Weak recommendation

• Opioids and renal impairment

• Few information of low quality
• Recommendations based on pharmacokinetic data
• Risk stratified according to activity of metabolites and potential
accumulation

Kurita et al Pal Med. 2011

King et al Pal Med 2011
 Step 3: Strong opioids
• Opioid rotation
• One opioid stopped and replaced by another
– Preserve analgesic effect; reduce side effect
– Incomplete cross tolerance between opioids

• Equianalgesic tables to be used as a guide

– Starting dose – 1/3 to 2/3 lower than calculated
dose
– Continuous monitoring of effects and side effects

Vissers et al. Pain Pract. 2010

 Step 3: Strong opioids
• Breakthrough medication
• Most evidence for oromucosal fentanyl
– Can be used in combination with all maintenance opioid
treatments
– Rapid onset of action
– Start dose 400 µg

• Experience – same opioid IR as long acting opioid

– Slower onset of action, longer duration of action
– Dose 1/6 of the total daily dose

CBO guideline: Management of Cancer pain

The Netherlands 2008
 Treatment of neuropathic pain
• Opioids to be considered when mixed pain:
neuropathic/nociceptive
• Gabapentine and pregabalin preferred (better safety profile)
• Tricyclic antidepressants 1st line if tolerated

• Capsaicine local
• Lidocaine local to be considered for well defined pain area’s

• Other antineuropathic treatment only in consultation with pain

specialist

CBO guideline: Management of Cancer pain

The Netherlands 2008
 Pain in patient with cancer
Tumor induced Metastases induced Treatment induced

Chemotherapy/ Bone metastases of

Nociceptive pain
radiotherapy Multiple myeloma or
responsive prostate cancer
Analgesics -
strong opioids

Discuss palliative Consider

cancer treatment Neuropathic pain
biphosponates
with medical
oncologist
Anti-neuropathic
drugs

Associations possible (not opioids)

Interventional pain management where appropriate
 Invasive Pain Therapy in the Palliative Care

• Epidural and intrathecal medication administration

• Celiac blockade
• Splanchnic blockade
• Hypogastric blockade

• Fenolisation sacraal
• Perifere zenuwblokkades, sometimes.
• Cervical cordotomy
At ' high-input ' pain: interrupts the pain conduction
with a lesion of a nerve or nerve course.

Goal: long-term pain relief and/or a reduction in

medication use in patients with cancer.

To whom?
When?  Not as the last step!
 Chroniche pijn
• Chronicle pain: an important cause of suffering and
the reduced quality of life

• Chroniche pain is seen after eg:

Cancer,
Traumatic injuries,
Excessive training / exercise
Nerve damage
Inadequate / inefficient treatment of acute pain. 
• The chronical pain: "the invisible disease".

• Pain is not only a medical problem but also a social

problem!
Pijn according to Descartes

Rene
Descartes
1596-1650
 Pain
Incentive

Nociceptic pain

Impulse

Neuropathic pain

Sensation
 The pain threshold
• Insomnia • Good night
• Fear • Understanding
• Poor communication • Party
• Depression • Diversion
• Stacking of problems • Activity
• Lost time • Own contribution
• Lack of goals and hope • Clear goals
• Boredom / loneliness • Good insight
• Creativity
• Fight against fear
 Typen pijn

• Nociceptieve
• actuele pijn: botmetastase, fractuur,
osteoporose, artrose
• viscerale pijn: van organen in borst/buik holte,
vb. koliekpijn

• Neuropathische
• fantoompijn, dystrofie, diabetische neuropathie,
postherpetische neuralgie
• Idiopathische
• chronische lage rugpijn; fibromyalgie
 Neuropathische pijn
IASP definitie

• Pijn veroorzaakt door een laesie of dysfunctie

van het zenuwstelsel

Merksey en Bogduk, 1994

 Neuropathische pijn

Voorbeelden van verschillende etiologie

• CTS
• Radiculopathie
• Diabetische polyneuropathie
• CRPS
• Trigeminusneuralgie
• Post CVA pijn
Morfine Oxycodon Fentany Hydromorf Transtec
mg per 24 mg per 24 1 µg/uur on mg per (buprenorphine)
uur uur 24 uur
p.o sc/iv p.o sc/iv pleister p.o mcgr per uur
30-60mgr

Nociceptieve pijn
30 10 15 7,5 12 4 oraal
35 microg/uur
60 20 30 15 25 8
90 mgr oraal
120 40 60 30 50 16 52,5
microg/uur
180 60 90 45 75 24
120 mgr
240 80 120 60 100 32 oraal
70 microg/uur
360 120 180 90 150 48
240mgr oraal
480 160 240 120 200 64 2x70
microg/uur

• oorzaak is nociceptieve stimulus

• meestal goed gelokaliseerd
• voor de patiënt herkenbaar (heeft eerder
dergelijke pijn ervaren)
• viscerale pijn kan “referred” zijn (pijn in het
dermatoom met dezelfde innervatie als het
orgaan waarin de pijn ontstaat)
 Tabel Konversi
Morfine Oxycodon Fentany Hydromorf Transtec
mg per 24 mg per 24 1 µg/uur on mg per (buprenorphine)
uur uur 24 uur
p.o sc/iv p.o sc/iv pleister p.o mcgr per uur
30-60mgr
30 10 15 7,5 12 4 oraal
35 microg/uur
60 20 30 15 25 8
90 mgr oraal
120 40 60 30 50 16 52,5
microg/uur
180 60 90 45 75 24
120 mgr
240 80 120 60 100 32 oraal
70 microg/uur
360 120 180 90 150 48
240mgr oraal
480 160 240 120 200 64 2x70
microg/uur
Resepsie PAIN CLINIC
in the St-Anna Hospital
Consultation Room
 CELIAC blockade & Neurolysis

1914: Kappis: percutane posterior benadering

1914: Wendling: door de lever

Labat, Farr & others: gemodifeerde Kappis methode

1957: Jones: Alcohol neurolysis of the splanchnicus

nerves and celiac plexus for prolonged
relief of abdominal pain
 CELIAC blockade & Neurolysis
Indikasi: pain di perut bagian atas akibat penyakit
ganas, biasanya pankreas, lambung, hati.

Werking: serat aferen dari organ dimatikan.

Bijwerkingen:
• hypotensie,
• ‘diarree’
• kerusakan organ2,
• dwarslaesie (zzz).

Werkingsduur: 1/2 - 1 jaar, kan herhaald worden.

Plexus Celiac
 Anatomy

Three pairs of ganglia exist within the plexus:

1. The plexus coeliacus
2. The superior contemporary ganglia
3. the aortic renal ganglia

• Postganglionic nerves of this ganglia invade all abdominal

organs except: part of the transversal colon, the left colon,
the rectum and the pelvic organs (this comes from Th10-L1
spinal levels also the uterus and cervic)
 Indications

• Any pain from visceral structures that have been ingested

by plexus coeliacus.

• These structures include pancreas, liver, gallbladder,

omentum, including the pancreas, liver, gallbladder,
omentum, mesentry, and alimentary tract from the
stomach to the transverse portion of the colon.
 Contraindications
• On anticoagulant therapy

• Congenital abnormal coagulopathy

• Antiblastic cancer therapies

• Liver abnormality associated with alcohol abuse

• Local or intra-abdominal infection

• Sepsis

• Bowel obstruction (greater intestinal motility!)

 Neurolytic Blockade

• 6% to 10% phenol in iohexol (Omnipaque)

• Absolute alcohol: 97% alcohol

• 50% alcohol in salt

• RF thermocoagulation (RFTC) machine

 PROCEDURE
• Once contact with the L1 vertebral body, redirected slightly lateral ( about
60 degree from the midline ) so as to ”walk off” the lateral surface of L1
body, after no more contact with the body:
• The left-sided needle is gradually advanced 1,5 to 2 cm or until the
pulsations emanating from the aorta and transmitted to the advancing
needle are felt.
• The right-sided needle is then advanced slightly further, 3 to 4 cm past
contact with the vertebral body.
• Ultimately, the tips of the needles should be just posterior to the aorta on
the left and to the anterolateral aspect of the aorta on the right.
• Essential anteroposterior and lateral control / images for the correct position.
• Ideally on AP view, contrast material is confined to the midline and
concentrated near the Th12-L1 vertebral body.
Approach to the L1 anterior
Lateral View
Lateral View with contrast
AP view with contrast
Lateral view with contrast
Lateral view with contrast
After Alcohol injection
 COMPLICATIES
• Back pain, usually due to pain

• Hypotension; Paraesthesia of lumbar somatic nerves; intra

vascular injection (venous or arterial); loss of lumbar
somatic nerves, subarachnoidal or epidural injection;
diarrhea; renal injury; paraplegia; pneumothorax;
chylothorax; vascular thrombosis or embolism; vascular
trauma; perforation of cyst of the tumor; injection of the
psoas; intradiscal injection; absces; peritonitis;
retroperitoneal hematoma; urinary tract abnormalities;
ejaculation failure.
 Splanchnic Blockade

Kappies 1914 als eerste ; 1918 publikaties van 200

cases

Als aanvullende na coeliacus blokkade

Anterolateraal van Th11 en Th12 vertebraal

 Neurolytic Blockade

Benefits Phenol: no pain with injection

possible combination with contrast

Benefits Alcohol: works longer

less affinity for blood vessels
 RF Lesion

• A narrow compartment: possibly RF

• On the mid-third part of the lateral side of

the T11 or / and T12 vertebral corpus.
 Effectiveness

Immediate success: 70% to 80%

Sustained effect: 60% to 75%

 Anatomy
• The splanchnic nerves transmit most of the nociceptive information
from the viscera.

• These nerves are contained in a narrow compartment made up by:

medially: the vertebral body
laterally: the pleura
ventrally: the posterior mediastinum
dorsally: the pleura attachment to the vertebra
caudally: the crura of the diaphragm

• Abram and Boas have determined that the volume of this

compartment is approximately 10 ml on each side.
Location
 Indication
• As a diagnostic tool in chronic benign abdominal pain
syndromes such as chronic pancreatitis

• Lower chance of success with this procedure in chronic non-

malignant abdominal pain than in neoplastic origin

• Contraindications:
• Absolute: local infection; coagulopathy
• Relative: Tumor distorting anatomy
• Abdominal aortic aneurysm
• Respiratory insufficiency
 Technique
• With the oblique fluoroscopic view still in place, a 14-gauge,
5-cm extracath is inserted, such that the catheter toward the
target as a pinhead.
• When two thirds of the extracath is inserted, the stylet is
removed and the RF needle is inserted.
• With short thrusts of 0,5 cm at a time, the tip of the needle is
advanced anteriorly, keeping in mind that the needle stays
• hugging the lateral aspect of the Th11 or Th12 vertebral
body, close to the costovertebral angle.
• After advancing 1 to 1,5 cm anteriorly the lateral view is taken.
In the lateral view, the needle is advanced until it reaches the
junction of anterior one third and posterior two third of the
vertebral body.
• Eights millimeters of iohexol is injected to note that the
solutions in antero-posterior and lateral views hug the
spine.
Entry Point
Needle at the entry point
Lateral view
Needle at Th.12 Right
Th. 11 and Th.12 both sides
 Hypogastric Plexus Block & Neurolysis
Anatomy
•The superior hypogastrc plexus is the extension of the aortic
plexus in the retroperitoneal space, below the aortic bifurcation.
•It receives fibers from the lumbar sympathetic nerve of L5.
•It is situated on the anterior aspect of L5-S1 & on the disc
between L5 & S1.
•It lies close to sympathetic chain at this level, the common and
internal iliac arteries and veins on each side.
•The ureter is located just lateral to these structures in close
proximity to the anterolateral aspect of the L5 vertebral body.
•It contains almost exclusively sympathetic fibers.
•As it cources distally, the superior hypogastric plexus converges
and forms a bilateral plexus called the hypogastric nerve.
 Indications
• The first group:

• Patients with gynaecologic disorders: most common causes of pain in

these patients are endometriosis, adhesions, and chronic inflammation.

• The second group:

• Nongynaecologic patients: interstitial cystitis, irritable bowel syndrome, or
chronic pain after a surgical procedure such as supra-pubic prostatectomy.

• The third group:

• Neoplasm of the pelvic viscera.

• Contraindications: Local infection &

Coagulopathy
 Needle Entry of Hypogastric Plexus
5 to 7 cm lateral from the midline of the L4-5 spinous processes
Lateral Approach
Entry Point
Lateral
Lateral Vieuw
Contrast AP
 Ganglion IMPAR

Trans sakro-coccygeal via Lateral view. Ganglion

antara Coccyc1-2 via
Ligamentumsakrococcygeum coccygeal disc Impar dengan kontras
Ganglion IMPAR
 Complications

• A potential for intravascular injection in all approaches

• A potential risk of discitis with the intradiscal approach

• Helpful Hints:
1. Measure the length of the needle required by placing the
needle against the skin and taking a posteroanterior image
2. Bowel preparation prior to block is helpful to evacuate bowel
content and gases
 Complications

• A potential for intravascular injection in all approaches

• A potential risk of discitis with the intradiscal approach

Helpful Hints:
1. Measure the length of the needle required by placing the
needle against the skin and taking a posteroanterior image
2. Bowel preparation prior to block is helpful to evacuate bowel
content and gases
 Conclusions
• The superior hypogastric plexus, an extension of the preaortic plexus, is
easily accescible to blockade by local anesthetics and neurolytic agents.

• Long lasting pain relief has been achieved in patients with pelvic cancer
pain.

• However, there is a discrepancy between the diagnostic and therapeutic

blockade in patients with nonmalignant pain.

• Since diagnostic blockade can give significant pain relief in a large variety
of patients, it is worthwhile to investigate new methods that provide lasting
neural blockade of the superior hypogastric plexus and long lasting relief of
this devastating condition.
 Cordotomy
1. Sampson Lipton brought the percutaneous lateral chordotomy in
the late sixties.
2. Sam put the specialty of anaesthesiology on the map in the invasive
treatment of pain.
3. This technique is now on its way out.
4. A number of reasons for that:
a.Decreasing of the number of patients since the
advent of intraspinal medication.
b.very little opportunity left to teach the procedure .
5. So, the generation of good cordotomists is a dying species.
 Indications :

• A percutaneous cordotomy is a RF heat lesion in the lateral

spinothalamic tract at the C1-C2 level.

• Since the spinothalamic fibres cross over, the procedure is

performed on the side opposite to the side of the pain.

• It is indicated for strictly unilateral pain of malignant origin.

 Contra Indications:
• Bilateral pain
• Pain extending to levels cranial to C5. This because the
afferent fibres ascend for 3-4 segments before they cross over
to join the tract
• Pain of non malignant origin
• A life expectancy of longer than one year
• A poor lung function, causing the patient to be dyspnoeic
when lying down. A cordotomy generally does not affect lung
function but there may be a transient decrease in some patients
• Vertebral and epidural metastases. This is because the
procedure involves puncture of the dural sac and this in itself
may lead to a disturbance of a delicate equilibrium, causing
paraplegia
 Complications:
• Usually transient Motor loss if the lesion has been made too close to the pyramidal
tract.

• Paraplegia in patient with a compromised CSF circulation.

• Ondine’s syndrome, in fact a myth from one author to another. Voluntarily breathing
but respiration stops when the patient faals asleep.

• Transient urinary retention for the first 48 hours following the procedure.

• Dysesthesia, a most unpleasant complication where the patient reports a difficult to

define, unpleasant sensation in the originally painful side of the body.This usually
does not develop until 1 year following the procedure. That’s why no cordotomy for
patients with a long life expectancy
Ligamentum Dentate
 Technique

• The lateral spinothalamic tract lies immediate

anterior to the dentate ligament.

• Requirement for accurate placement of the electrode

is injection of soluble contrast (an emulsion of fat)
into the dural sac anterior to the dentate ligament.

• The following steps: positioning and instrumentation;

puncture of the dura and injecting contrast; entering the
electrode; stimulation and lesioning
 Puncture of the dura and injecting
contrast
• Don’t try to do both the injection of the contrast and the RF procedure
through the same needle.

• The dura at this level is thick, firm, and immobile structure, By changing
of the direction, the puncturing site of the dura serves as the fulcrum.

• Since the dura obviously is very close to the target point, a large angular
variation is needed to effectuate a very small change in the position of the
tip.

• Two-needle technique must be used.

• A spinal needle is entered through an entry point at the level of the

posterior aspect of the dome.
 Penetration of the dura
• The level of penetration of the needle is the usually 6 to 8 cm.
• Puncturing the dura causes a characteristic “plop-feeling”.
• Ensure a free flow of CSF, and it is then replaced.
• Contrast mixture must be prepared only in an eccentric 20 ml syringe.
• The syringe is filled with a mixture of 3 ml of fat-soluble contrast medium, 7
ml of normal saline and 10 ml of air.
• The syringe must now be violently shaken in order to get an emulsion.
• Always shake the syringe in a horizontal plane, because the contrast
particles in the emulsion gravitate downwards.
• Inject 1 ml of the shaken mixture through the spinal needle and always with
the hub of the needle down.
 Interpretation
Three lines should be clearly visible now.

• An anterior (upper) line showing the anterior border of the spinal cord.

• A second line just posterior and usually parallel to it. This is the
dentate ligament.

• A third, posterior line indicating the posterior border of the dural sac
 Entering the electrode
• The entering must be fast and very precise.
• The target point for the electrodeis:
1. Just anterior to the dentate ligament for pain in the leg
2. 1 mm anterior to the dentate ligament for pain in the arm
• In both instances the target point should be in the caudal aspect
of the dome
• It is of utmost importance that this target point is approached in a
perpendicular direction!
• If upwards: is very easy to pass the spinal cord.
• If downwards: one gets dangerously close to the motor tract in the
posterior segment of the cord.
 Perpendicularly entering to the target point

• After puncturing the dura the stylet is removed.

• A free flow of CSF should now be observed.
• The electrode is then inserted into needle and the impedance is measured.
The impedance should be low, varying from 200-500 Ohms
• Advance the electrode into the cord at the selected target point.
• Not gradually but with a sharp, short distance stab.
• As soon as entry into the cord occurs the impedance rises sharply.For the
Levin system 1300 Ohms is a normal reading.
• Entering into the cord will produce a sharp stab of pain to the patient in the
neck region.
• If no entry occurs, the needle is probably located too far anteriorly.
 Stimulation and lesioning
• 50 Hz stimulation may provoke 2 types of responses:
• 1. a regional feeling of paresthesiae.
• 2. a temperature response, like a feeling of heat or of a cold wind
and usually entire contralateral.
The non-temperature response is not satisfactory.
If a temperature response is found, the location of that
response is of secondary importance.

• If there is difficulty in finding the temperature response, the electrode is

usually slightly too far anterior.

• The stimulation threshold must be in the range of 0,05 to 0,2 Volts.

 Stimulation and lesioning

• If the position is satisfactory, motor stimulation now carried out at 2 Hz.

• Contractions at the homolateral tract may occur but should not occur
below a level of 1 Volt. But negotiable in case of an extremely low sensory
threshold, where in all probability a low- temperature lesion will suffice.
• Lesions are then made, starting at 75ºC, for one minute.
• During the lesion the grip strength of the homolateral hand is checked
continuously and from time to time the patient is asked to raise the
homolateral leg.
• At any sign of decreasing strength the lesion is stopped immediately.
• Following the lesion the contralateral sensitivity to pinprick is checked.
• There should be a very marked difference with the homolateral side.
• If this is not so,more lesions are made with temperature increments of
5ºC.
 Postoperative care
• The bladder function should be checked and in case of urinary retention
catherisation is required for some days.

• The patient should be mobilised the next day under supervision. Slight
homelateral weakness, which is ascribed to the formation of oedema, is a
normal occurence.

• Care should be taken to reduce the intake of oral opioids.

• A high peak of body temperature during the first 24 hours is not

unusual. It is a reaction to the injection of contrast material into the dural
space.
 Final remarks
• No easy procedure!

• Time is a factor.

• Uncomfortable and painful repeated insertions.

• As time passes, the patient is getting more desperate and the doctor feels
more and more pressed to deliver fast.

• A smooth cordotomy takes less than 20 minutes and fair time as an outer
limit is 40 minutes.

• A cordotomy with PRF gave an effect but less complete and short of
duration.
Entry point at the level of the posterior aspect
of the dome
Anteriorly direction.aiming for the anterior aspect of the
dome, just a few mm posterior to the tip
Anterior line, Ligamentum Dentatum, Posterior line van
Spinal Cord
The needle tip is between