Management of cancer liver pain

Management of Cancer Liver Pain -
Dr. Samir A ElKafrawy
Management
of
cancer liver pain
By
Dr. Samir A El-Kafrawy
MD, Anaesthesia & Pain Relief
Elsahel Teaching hospital,
Cairo, Egypt

Introduction
• In spite of the widespread dissemination of
guidelines and the recognition that pain
management is a priority in cancer liver ,
this knowledge is not really making much
practical impact on professional attitudes.

Pain Measurements
• Many of the tools available for pain
measurements are valid for use.
• The intensity scales and the numerical
scales are equivalent when submitted to
factor analysis.
• Numerical rating scales have a common
meaning among cultures and keep some
desirable psychometric properties.

• Questionnaires are used when we need to
know how much a given pain level bothers
the patient ?, what pain level can be
considered tolerable ?, what corresponds to
satisfactory pain relief ?.
• Multiple pain complains should be
classified according to their degree of
importance.
• If pain is due to therapy, try to predict the
time and course of pathology.

Pharmacological management
• Drug therapy has become the mainstay treatment
• Drug therapy can control the pain in 70-90% of
cancer patients.
• The WHO “ analgesic ladder” is the preferred
approach for drug selection.
1. NSAIDs for mild to moderate pain.
2. Weak opioids for moderate pain not responding to
NSAIDs.
3. Strong opioids may and should be added to any step.

Objectives of pharmacotherapy
• Increase hours of sleep .
• Relief of pain when resting .
• Relief of pain during activity .

General rules
• “Round The Clock “ administration , persistent
pain requires prevention therapy.
• Route of administration : oral route is the first
choice.
• Control of side effects and associated symptoms.
• Reassessment is a continuous necessity .
• Learn how to use few drugs well I.e. adequate
knowledge of pharmacology of drugs used.

• Start treatment while the nature and the cause of the
pain are being assessed .
• When drug stops to be effective , prescribe more
potent drugs.
• Use pure drugs , not compounds.
• Check interactions with other drugs patient is
receiving.
• Administration up to the time of death.
• When seriously worsening the quality of life or not
controlling pain , consider invasive techniques.

Drugs Used

Analgesics
Classification:
1. Simple analgesics.
2. Weak opioids.
3. Strong opioids.
Aim:
• Allow patients to function at the level they
choose.
• To die relatively pain free.
• Drugs are selected in a step-wise fashion based on
the overall severity of the pain.

Simple Analgesics
• They constitute a heterogenous group of
compounds that differ in chemical structure but
share many pharmacological actions.
• They interfere with the enzyme Cyclooxygenase ,
a fundamental step in the biotransformation of
arachidonic acid to prostaglandins and
thromboxane both in the peripheral and central
nervous system( evidence appearance of
neurological side effects such as tremors , ataxia,
and myoclonus.)

• The thalamus hypothalamus and periaquiductal
grey could be the main sites of central analgesia.
• They are simple only because they produce neither
tolerance nor physical dependence.
• They have a ceiling effect for analgesia.
• They provide additive analgesia when combined
with opioids in more sever pain.
• They are effective in relieving the pain caused by
mechanical distortion or distension of ,liver
capsule and stretching and mechanical
compression of the peritoneum.

• They may be combined with Tricyclic
antidepressants or anxiolytics to increase
sleep , thus adding to the analgesic effect.
• Choice depends on availability, individual
toxicity , response and serum half-life.
• Patients unable to take aspirin may well
tolerate one of the alternative NSAIDs ,
specially that some of these drugs may be
taken once or twice a day.
• Several days administration is necessary to
achieve maximum relief.

• Hypo-albuminaemic patients :
( the case in advanced cancer liver) are
more susceptible to toxic manifestations, “
the concentration of the free drug varies
inversely with plasma albumin
concentration”.

Doses:
• Aspirin : 250-1000 mg every 6 hours.
• Paracetamol : 500-1000 mg / 4-6 hrs ( liver
toxicity limits its use in patients with liver
damage.
the drug is well tolerated by patients with
peptic ulcer and does not affect plasma uric
acid concentration, moreover side effects
are minimal.

Side effects:
• Gastrointestinal disturbances ( gastro-
duodenopathy) diminished if the drug is given
with milk, on a full stomach or with antacids .
• Bleeding diathesis
• Nephropathy : acute tubular necrosis, papillary
necrosis,and interstitial nephritis .
• Vasomotor rhinitis, angioneuritic edema,
hypotension, shock, loss of consciousness ,
complete vasomotor collapse.
• Tinitus is a common warning symptom of toxic
effects.

opioids
Classifications :
A- According to their receptor interactions:
1. Agonists:
2. Partial agonists.
3. Mixed agonist antagonists: have a limited or no
role in liver cancer pain due to :
- Ceiling effect of analgesia.
- Potential precipitation of an abstinence
syndrome in patients under pure agonist
drugs.

B- according to their potency;
1. Weak opioids:
• Not truly weak.
• No ceiling effect .
• Toxic metabolites e.g. propoxyphene and
meperidine.
• Available as compounds with acetaminophen ,
limiting the dose.
N.B : codeine is available and dose can be increased.
2. Strong opioids.

Strategy of opioid therapy
• Establishment of initial dose .
• Prescription of fixed – round the clock
therapy .
• Titration of the dose against the effect as
well as side effects .
• Treatment of side effects .

Factors to be considered
• Marked affection of the liver needs
modification of the dose .
• Renal impairment leads to accumulation of
metabolites myoclonus and seizures .
• Low albumin level in plasma protein
binding sensitivity to the drug .

Opioid administration
• There is a wide individual variability in the
response to different opioids.
• The therapeutic window ( balance between
therapeutic benefit and the pattern of adverse
effects ) varies from drug to drug and may be
more favorable with an opioid other than
morphine .
• The process of switching opioid drugs require
knowledge of equianalgesic opioid dosing.

• The dose should be adjusted and should generally
be reduced by 25-50% to account for incomplete
cross tolerance between different opioids.
• Four to five half lives are needed to approach a
pharmacological steady state after drug is started
or changed.
• Opioids with short half lives are preferred for
rapid dose titration.
• The agonist antagonist have a limited role due to
ceiling effect for analgesia and the possibility of
precipitating abstinence syndrome .

Weak opioids
Include codeine , hydrocodeine , propoxyphene ,
meperidine and tramadol .
Codeine :
• Readily absorbed from GIT .
• 30 mg codeine are equivalent to 650 mg aspirin .
• When drugs are combined , the analgesic effect
exceeds 60 mg codeine .
• Available as sustained release tablets .
• Dose 30-130 mg / 4-6 hours .

Tramadol
• A drug with opioid Mu receptor agonist
activity and also has monoamine reuptake
blocking properties .
• Presents a lower incidence of opioid side
effects at the same level of analgesia .
• Low potential for development of tolerance
and absence of addictive potential .
• Absence of interaction with other drugs .
• Oral dose equivalency of tramadol with
morphine 4 : 1 ( 50-100 mg ) .

Strong opioids
Include :
1. Morphine .
2. Hydromorphone .
3. Oxycodone .
4. Oxymorphone .
5. Buprenorphine .
6. Levorphanol .
7. Fentanyl .

• The physician should have at least three
opioids available for use in the management
of severe cancer liver pain to optimize the
chances of maximum opioid analgesia .
• Switching of opioid drugs requires
knowledge of equianalgesic opioid dosing .
• The dose should be adjusted and should be
reduced by 25-50 5 to account for incomplete
cross tolerance between different opioids .
• 4 –5 half lives are needed to approach
pharmacological steady state after dosing is
started or changed .

Morphine sulphate or hydrochloride
• Dose : 5-100 mg up to 200 mg / 4 hours.
• Initial dose depends mainly on patient’s
previous medications .
• The first and last dose are timed to the
patient’s waking and bed time .what about
midnight dose ? .
• Reduction and increase is by 50 % .

Sustained release Morphine
• Available as 10 , 30 ,60 ,100 mg tablets .
• Dose is obtained by dividing the oral daily
dose by 2 .
• maximum plasma concentration occurs after
2-4 hours , and remains for 12 hours .

Pethidine
• Potency is 1/8 of that of morphine .
• High doses may cause tremors , twitches ,
agitation and convulsions 9 more in
impaired renal function 0 .
• Dose : 50-100 mg every 3-4 hours, given by
injection.

Methadone
• Not preferred in :
1. The elderly ( more sensitive to the
clinical effects of opioids .
2. Patients with severe metabolic
dysfunction
• When changing from methadone to an
opioid a reduction of the equivalent dose
by at least 75% is recommended .
• More potent than morphine , repeated
doses several times more potent .

Methadone “ cont.”
• Dose : 5-10 mg every 4-6 hours for 3 days
then every 8-12 hours .
• Cumulative effect specially in elderly
patients .
• Contraindications :
confusion ,significant respiratory , hepatic
and renal dysfunction .

Buprenorphine
• 60 - 80 times more potent and less
dependant than morphine .
• Dose : sublingual 0.2 – 0.4 mg .
• Onset of action 30 minutes .
• Peak effect : 3 hours .
• Duration of action : 6 - 9 hours .

Fentanyl Patches
• Transdermal fentanyl may be used in
patients with stable pain states who are
either non compliant with oral medication
or unable to swallow or absorb medications
or the patient prefers this rout of
administration .
• If pain is dynamic resort to subcutaneous or
intravenous administration .

Fentanyl Patches “ cont.”
• Deliver 25 ,50 ,75 and 100 µg of
fentanyl / hour
• It is feasible to combine different patches
to achieve the desired dose.
• Large individual variation so dose titration
is essential .
• Peak plasma concentration is reached after
24 hours , so efficacy and toxicity should
generally become apparent during the first
day .

• After removal of the patch , the clinical
effects will not diminish for many hours
due to absorption of the drug from
subcutaneous depot( elimination half life is
24 hours ).
• Should not be used in patient with increased
intracranial pressure , brain tumors ,patients
with bradyarrhythmias , impaired
consciousness or coma .
• Several days should elapse before a new
patch is applied to the same area.

• Dose may be increased after 3 days .
• Dose conversion chart for patients to chose
the correct patch size .
• Patient should receive the opioid he was
taking for the next 6-12 hours .
• Short acting morphine should be available
for breakthrough pain .

Side effects of opioids
An obstacle to effective therapy if not
properly assessed and treated , so treatment
of opioid side effects is an integral part of
therapy

Constipation
• Treatment given prophylactically in the
form of stool softeners and ataractics .
• Osmotic agents : lactulose or enema .
• In refractory cases : oral naloxone , initial
dose 0.8 mg once or twice daily up to 3-12
mg daily without precipitating withdrawal
symptoms or reversing analgesia .

Nausea and Vomiting
Give prophylactic anti-emetic drugs .
• Metochlopromide : 30-60 mg/24 hours .
• Chlorpromazine : 50-150 mg/24 hours .
• Prochlorperazine : 15-50 mg/24 hours .
• Haloperidol : 1.5-5 mg/24 hours .
• In refractory cases : switch to another
opioid or rout of administration .

Itching
Treatment :
• Diphenhydramine.
• Naloxone in refractory cases .

Sedation
• Common with initiation of therapy and
escalation of opioid dosing , tolerance to
the effect often develop rapidly .
• Depressant effects on the cognitive
functions of patients with cancer liver is
debated .
• Treatment: methylphenidate , changing the
administration from systemic to spinal rout .

Delirium
• A dose related phenomenon .
• Some patients experience hallucinations ( or
other symptoms of delirium ) at low doses .
• Occurs more frequently with meperidine
and pentazocine .
• Treatment with Haloperidol .
• Alternative : change the opioid or switch to
spinal opioid .

Myoclonus and seizures
• More frequent with higher doses .
• May be associated with delirium .
• Responds to clonazepam .
• If sever , try another opioid or other
analgesic approach .

Urinary retention
• Due to increased bladder sphincter tone .
• Described more with spinal opioids .
• Tolerance often develops .

Respiratory depression
• Strong opioids are respiratory depressant .
• The pain is a powerful respiratory stimulant
and partially antagonize the depressant
effect of opioids .
• More frequent with intrathecal opioids .

Other side effects
• Postural hypotension .
• Shivering .
• Oligurea .
• Headache .
• Dysphoria .
• Agitation .
• Abdominal pain .

Corticosteroids
• Indicated in dull pain caused by stretching
and distortion of liver capsule .
• These are benificial in improving appetite ,
nausea and mood .

Management of cancer liver pain

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Management of cancer liver pain

Similar to Management of cancer liver pain (20)

More from Samir Elkafrawy

More from Samir Elkafrawy (6)

Recently uploaded

Recently uploaded (20)

Management of cancer liver pain