Transcript Cancer Pain - International Pain School

International Pain School
Cancer Pain
Low technology treatment methods
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Aims and topics
• General aspects concerning cancer pain
• Recommendations and guidelines for the use of drugs
in the management of cancer pain
• Issue of opioid availability
• Essential analgesic drug list
• Pearls of wisdom
• Case report
• Reference list
Cancer Pain
• Up to 70% of cancer patients suffer from pain.
• Most patients can obtain sufficient pain relief with oral
analgesics.
• Use alternative methods for drugs administration (e.g.
intravenous or subcutaneous) only when oral
administration is not possible.
• Use the Pain Relief Ladder of the World Health
Organization (WHO) as a guideline for the use of drugs
in the management of pain.
Cancer Pain
• Cancer pain may include different qualities, locations
and intensities depending on the type and stage of the
cancer.
• The dosage of drugs might require frequent changes
during treatment due to progression of the tumour or
to side effects.
• In the case of new symptoms and pain you should
always think of a reasonable alternative and
symptomatic treatment.
Cancer Pain
• Pain intensity is influenced not only by somatic findings
but also by psychological factors such as fear,
depression, sleeplessness
• In this case you often can reduce analgesics by
“treating” the psychosocial factors.
– Talk about the problems with your patient and his
family.
Case report
James Window is a 59 year old policeman, suffering from
prostate cancer since 2009. Following surgery, he went
into remission for 2 years and continued with his work.
However, he then experienced back pain and after
undergoing tests, metastases were detected in his spine.
He underwent radiotherapy and received ibuprofen 2 x
600mg/day, resulting in reduction of pain for about 3
months.
Case report (cont.)
The local pain increased despite taking more ibuprofen?.
As a result, James‘s physician prescribed, tramadol, a lowefficacy opioid. He was started on the lowest dosage of
2 x 50mg/day, with an extended-release formulation. After
a short time, the dose was increased to 2 x 100mg and
then to 2 x 150mg. At this point, the pain decreased to a
tolerable level without side effects.
Case report (cont.)
At this stage, his physician decided to change the
treatment to morphine. He started with a dose of 2 x
30mg morphine using an extended-release formula and
10mg morphine with an immediate-release (IR) formula in
the event of „break-through pain“. After 3 days of
treatment using this regimen, the physician counted the
number of IR tablets that James used (6-7 a day) and
converted the dose to the extended-release formula. The
dosage of morphine prescribed to Richard was then 2 x
100mg / day. w/o leaving the option for IR MO?
WHO Pain Relief Ladder
By the clock
Step I
Step II
Step III
By the mouth
By the ladder
By the individual
Low potent
opioids
Nonopioids
Nonopioids
High
potent
opioids
Nonopioids
Combination of drugs
• Often we need to combine several drugs to improve the
total analgesic effect
– a non-opioid with an opioid.
– ibuprofen or diclofenac with paracetamol
(acetaminophen) or metamizol (dipyrone) (i.e. an
NSAID with a simple analgesic).
– There is no improvement in the analgesia by
combining metamizol with paracetamol (i.e. two
simple analgesics).
Non-opioids
• COX inhibitors inhibit peripheral and central (dorsal
horn of the spinal cord) hyperalgesia by ínhibiting
production of prostaglandins
• Analgesic: paracetamol, metamizol
• Analgesic and anti-inflammatory: ibuprofen, diclofenac
• Selective COX inhibitors: celecoxib, etoricoxib
Possible side-effects
• Overdose of acetaminophen can lead to liver failure.
• Ibuprofen and diclofenac can produce gastrointestinal
problems such as ulcers and kidney failure
• Metamizol rarely provokes leukopenia and
agranulozytosis (about 1:1 Mio, higher risk in
Scandinavia because of genetic reasons)
Dosage
• Paracetamol: 4 x 1000mg (daily dose < 4.0g because of
possible liver toxicity)
• Metamizol: 4 x 500 – 1000mg (daily dose < 6.0g)
• Ibuprofen: 3 x 400-800mg (maximum daily dose 2400mg)
• Diclofenac 3 x 50mg or 2 x 75mg extended release
formula (maximum daily dose 150mg)
• Celecoxib 2 x 100mg-2 x 200mg, Etoricoxib 1 x 60-90mg
• Duration of treatment ?
Treatment with opioids
• Opioids are the most potent of the analgesic drugs and
you should use them early in cancer pain treatment
– They bind to opioid receptors in the cell membranes
in the central and peripheral nervous system: µ-, ĸ-,
δ-receptors
• Typical side effects of opioids are dose related and
mostly appear at the beginning of treatment
• Titrate opioids slowly to the most effective analgesic
dose to reduce side effects
Opioid side effects
• constipation, reduction of the gastrointestinal motility
• nausea, vomiting,
• sedation, dizziness
• cognitive impairment
• respiratory depression, antitussive effects
• pruritus
• muscle rigidity, urinary retention
Treatment with opioids
• Don‘t be afraid of opioid dependency when treating
cancer pain
– addiction is exceedingly rare during long-term
opioid treatment of cancer pain.
– Under-treatment of pain may lead to drug-seeking
behavior by the patient (=pseudo-addiction).
Treatment with opioids
• Don‘t be afraid of respiratory depression – patients
receiving long-term opioid therapy generally
develop tolerance to the respiratory-depressant
effects of opioids.
• Side effects – except for constipation – decrease during
prolonged and regular administraiton of opioids.
• Opioid-induced-constipation requires that you combine
a laxative in nearly all patients treated with an opioid.
Treatment with opioids
• How to use opioids in cancer pain?
• Prefer the extended-release/prolonged-release
formulations of oral opioids: onset within 30 - 60 minutes,
duration 8 - 12 hours
• Treat breakthrough pain with immediate-release
formulations: onset within 30 minutes, duration 4 - 6
hours (prescribe 1/5 of the daily opioid dose)
• The combination of opioids and non-opioids helps to
reduce the dosage and the side effects of the single drug
Weak opioid
• Tramadol belongs to step II of the WHO ladder, it binds
not only to opioid receptors but also to norepinephrone
and serotonin reuptake inhibitors
• It has 0.2 times the analgesic potency of morphine
• It exists as an oral and parenteral formulation
• Decrease the dosage in case of renal or hepatic
impairment because of the risk of accumulation and
respiratory depression
Strong opioids
• Morphine is a strong µ-opioid agonist and belongs to
step III of the WHO ladder
• Commonly used as reference for all other opioids
• It can be applied by all routes of administration
• The active metabolites accumulate in case of renal
impairment and can increase side effects
• There are extended- (10, 20, 30, 60, 100, 200mg) and
immediate-release (10mg, 20mg) formulations.
Strong opioids
• Hydromorphone is also a strong µ-opioid agonist
• It has about a 4 - 5 times the analgesic potency of
morphine, with a 12h duration of effect
• It has an oral and parenteral formulation for s.c., i.m. or
i.v. application, an extended- (4mg, 8mg, 12mg 16mg
24mg capsules) and immediate-release formulations
(1.3mg, 2.6mg capsules)
• Has a low plasma protein binding and therefore, a
possibly lower risk of interaction with other drugs
Strong opioids
• Oxycodone: with 2 times the analgetic potency of
morphine and a 8 - 12h duration
• High oral bioavailability of 60-80%
• It is available as an oral extended- (10mg, 20mg, 40mg,
80mg) and immediate-release formula (Oxycodone
5mg, 10mg, 20mg capsules buccal or sublingual) or
Oxycodone iv 10mg, 20mg
• There is a fixed formula with naloxone to reduce the
risk for drug induced constipation (Targin)
Strong opioids
• Fentanyl: has 80-100 times the analgetic potency of
morphine, it is metabolized in the liver, has a rapid
onset and a short duration
• It mainly exists as a parenteral formula but a
transdermal application (Fentanyl patches with 12, 25,
50, 75, 100µg/h, change of the patches every 72 hours)
is also widely used
• For breakthrough pain there are nasal buccal or
transmucosal formula (100, 200, 400, 600, 800, 1200,
1600µg)
Routes of opioid administration
• Oral, rectal
• Nasal, sublingual, buccal
• Transdermal as a patch
• Intramuscular via intermittent injection (NOT recommended
particularily when long term treatment is planned!)
• Subcutaneous - intermittent injections or
continuous infusion
• Intravenous - intermittent injections or continuous infusion
• Spinal epidural
• Spinal intrathecal
Case report
• Richard‘s disease progressed and with it the intensity of
his pain and onset of a new type of pain: burning pain
which did not respond to the morphine. Also he got a
sensitive deficit perineal because of an infiltration of
the Pudendal nerve??
• Richard‘s physician prescribed dexamethason 12 mg
and gabapentine 3 x 300mg (starting with x mg and
increaseing in 100mg steps). As a result, the pain
decreased again.
Neuropathic pain
• This pain results from a damage to afferent neurons
and altered pain transmission and processing in the
spinal cord and brain
• Pain characteristics and sensations are different
• Neuropathic pain can be difficult to treat, often you
need more than opioids: anticonvulsants,
antidepressants
• Examples for neuropathic pain in cancer pain:
neuropathy after chemotherapy or radiotherapy,
compression of nerves by the tumor or metastases
How to diagnose neuropathic pain?
• The patient‘s description of the pain quality: lancinating,
burning, pricking, tender, numb, throbbing, nagging, hot
• The pain projection and and pain radiation along a
course of nerves with segmental or peripheral
distribution, a glove-like distribution or attributed to a
dermatome
• Paresis or muscular weakness and pain in the
extremities in the case of a plexopathy
How to diagnose neuropathic pain?
• By careful neurological examination:
• Look for somatosensory abnormalities such as
dysaesthesias, hyperalgesia, hypaesthesia, dynamic or
thermal allodynia
• Look for paresis or muskular weakness and pain
• For examination use a stub-point needle, a warm or
cold spoon, a cottonwool tip
Drugs for neuropathic pain
• Most commonly used anticonvulsants are gabapentin,
pregabalin and carbamazepine
• Most commonly used antidepressant:
amitriptyline, doxepin
• They act as sodium and calcium channel blockers
of the neuronal cells
• Because of possible side-effects of the central nervous
system carefully raise the dosage: „start low, go slow“!
Drugs for neuropathic pain
• Carbamazepine: initial dose 2 x 100mg/day
up to 2 x 800mg/day
• Gabapentin: initial dose 3 x 100mg/day
up to 3 x 800mg/day
• Amitriptyline/Doxepin: initial dose 1 x 25mg in the
evening up to 1 x 75mg
• Possible side effects: constipation, dry mouth,
drowsiness, sedation, arrhythmias, induction and
elevation of liver enzymes, edema
Drugs for neuropathic pain
• Corticosteroids such as dexamethason can reduce pain
due to nerve structure compression or edema of
metastases
• Prescribe initially 1 x 16-24mg/day in the morning
or radiotherapy and taper off gradually after pain
reduction
• Sometimes a combination with opioids will improve
pain reduction
Case report
• James‘s pain was treated sufficiently but he experienced
new symptoms: constipation and nausea.
• The constipation was treated with lactulose 3 x
10mg/day and the nausea wtih metoclopramide 4 x
10mg/day
• James‘s situation was stable for the next 6 months.
Case report
• After this time pain increased again because of his
progressive disease. He got a new burning pain without
reduction of the pain intensity by taking more
morphine. Also he got a sensitive deficit perineal
because of an infiltration of the plexus pudendus.
Under the treatment with dexamethasone 12 mg and
gabapentin 3 x 300mg/day (going up in 100mg steps)
the pain decreased again.
was already in slide 24
Case report
• Due to his cancer (and possibly a side effect of the
medications??), James felt tired and lethargic. He had
lost a great deal of strength and energy. Though the
quality of his life was good on some days, on other days
he was depressed. On the days he was depressed, the
pain was more obtrusive than during the ‘good’ days.
His family and friends spent time with James and paid
him more attention. Consequently, until his death there
was no need to increase the doses of the medications
he was given.
Treatment of constipation
• Sometimes it is harder to treat the constipation
than pain.
• Opioids reduce the gastrointestinal motility, decrease
gastrointestinal mucus secretion, increase fluid
absorption mainly by binding to peripheral opioid
receptors in the mesenteric and submucous plexus and
to cerebral and spinal receptors
• There is no tolerance to constipation !
Treatment of constipation
• Co-administer laxatives such as:
lactulose 3 x 10mg to 3 x 40mg/day or
macrogol 1-3 sachets/day or
non-resorbable oils/paraffines
• Emphasize the need for a normal daily fluid intake
• As long as is possible, encourage the patient
to be mobile
Treatment of opioid induced emesis
• About 20% of the patients treated with opioids
suffer from emesis
• First choice: metoclopramide 4 x 10mg and haloperidol
3 x 0.3-0.5mg orally, subcutaneously or intravenously
• It is better to combine opioids and antiemetics at
the beginning of the treatment as a prophylaxis
• After 7 days of treatment, try to withhold the
medication; tolerance to opioid-induced emesis
typically developes after this period of time.
Issue of opioid availability
• Many patients all over the world do not receive
adequate relief of pain because of excessive
regulatory restrictions on the availability and
accessibility of opioids.
• There is a reluctance about using opioid analgesics
and fear of abuse
• Another problem is the lack of knowledge regarding
pain relief and opioids among professionals and
the public
• Ensure opioid availability!
Essential WHO analgesic drug list
• Tramadol
• Carbamazepine
• Morphine, Sevredol
• Gabapentin
• Hydromorphine
• Amitriptylin
• Oxycodone
• Dexamethasone
• Fentanyl
• Lactulose
• Paracetamol
• Macrogol
Acetaminophenon
• Metamizol, Dipyrone
• Ibuprofen, Diclofenac
• Haloperidol
• Metoclopramide
Pearls of wisdom
• Sufficient pain reduction can normally be obtained
using the principles of the WHO Pain Relief Ladder
• Prefer administration of analgesics using the oral route
• Change type and dosage of the drugs as necessary
• Be aware of psychosocial elements influencing
cancer pain
• Don‘t be afraid of opioid related respiratory depression
• Treat opioid induced side effects
Reference list
• Core Curriculum for Professional Education in Pain
J. Edmond Charlton
• Guide to Pain Management in Low-Resource-Settings IASP
• The Pain Management Core Curriculum for European
Medical Schools, Version October 2009 DGSS, EFIC
• Medikamentöse Schmerztherapie bei Tumorpatienten,
ein Leitfaden,10. überarbeitete Auflage E. Klaschnik
This talk was originally prepared by:
Barbara Kleinmann, MD
Freiburg, Germany
International Pain School
Talks in the International Pain School include the following:
Physiology and pathophysiology of pain
Nilesh Patel, PhD, Kenya
Assessment of pain & taking a pain history
Yohannes Woubished, M.D, Addis Ababa,
Ethiopia
Clinical pharmacology of analgesics
and non-pharmacological treatments
Ramani Vijayan, M.D. Kuala Lumpur, Malaysia
Postoperative – low technology treatment methods
Dominique Fletcher, M.D, Garches & Xavier
Lassalle, RN, MSF, Paris, France
Postoperative– high treatment technology methods
Narinder Rawal, M.D. PhD, FRCA(Hon),
Orebro, Sweden
Cancer pain– low technology treatment methods
Barbara Kleinmann, MD, Freiburg, Germany
Cancer pain– high technology treatment methods
Jamie Laubisch MD, Justin Baker MD, Doralina
Anghelescu MD, Memphis, USA
Palliative Care
Jamie Laubisch MD, Justin Baker MD,
Memphis, USA
Neuropathic pain - low technology treatment methods
Maija Haanpää, MD, Helsinki & Aki Hietaharju,
Tampere, Finland
Neuropathic pain – high technology treatment methods
Maija Haanpää, M.D., Helsinki & Aki Hietaharju,
M.D., Tampere, Finland
Psychological aspects of managing pain
Etleva Gjoni, Germany
Special Management Challenges
Debra Gordon, RN, DNP, FAAN, Seattle, USA
International Pain School
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