Pain Management in Terminally Illness

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Pain Management in Terminally Illness

• Associate Professor Cynthia Goh
• Head, Department of Palliative Medicine
• National Cancer Centre Singapore
• Centre Director, Lien Centre for Palliative Care
• Duke-National University of Singapore Graduate
  Medical School

Intensive Course in Basic Palliative Care for
Medical Teachers 7 Nov 2009 Bangkok
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What are the Special Characteristics of Cancer
Pain?
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What are the Special Characteristics of Cancer
Pain?

• Cancer is a multi-system disease

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What are the Special Characteristics of Cancer
Pain?

• Cancer is a multi-system disease
• 80 of patients with cancer pain have pain at
  more than one site

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What are the Special Characteristics of Cancer
Pain?

• Cancer is a multi-system disease
• 80 of patients with cancer pain have pain at
  more than one site
• 30 of patients with cancer pain have pain at 4
  or more sites

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What are the Special Characteristics of Cancer
Pain?

• Cancer is a multi-system disease
• 80 of patients with cancer pain have pain at
  more than one site
• 30 of patients with cancer pain have pain at 4
  or more sites
• Different pains may have different causes
  mechanisms

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A
Fracture from bone metastasis
D
B
Inflammation from IV site
Pressure sore
C
Constipation colic
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Physical Causes of Pain

• Cancer-related
• Bone
• Nerve compression/infiltration
• Soft tissue infiltration
• Visceral
• Muscle spasm
• Lymphoedema
• Raised intracranial pressure
• Treatment related
• surgery postoperative scars /adhesions
• Radiotherapy burns/ fibrosis
• Chemotherapy neuropathy

• Associated with cancer/ debility
• Constipation
• Pressure sores
• Bladder spasms
• Stiff joints
• Post-herpetic neuralgia
• Unrelated to cancer
• Arthritis
• Angina
• trauma

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Physical Causes of Pain

• Cancer-related
• Bone
• Nerve compression/ infiltration
• Soft tissue infiltration
• Visceral
• Muscle spasm
• Lymphoedema
• Raised intracranial pressure
• Treatment related
• Surgery postoperative scars /adhesions
• Radiotherapy burns/ fibrosis
• Chemotherapy neuropathy

• Associated with cancer/ debility
• Constipation
• Pressure sores
• Bladder spasms
• Stiff joints
• Post-herpetic neuralgia
• Unrelated to cancer
• Arthritis
• Angina
• trauma

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Physical Causes of Pain

• Cancer-related
• Bone
• Nerve compression/ infiltration
• Noft tissue infiltration
• Visceral
• Muscle spasm
• Lymphoedema
• Raised intracranial pressure
• Treatment related
• Surgery postoperative scars /adhesions
• Radiotherapy burns/ fibrosis
• Chemotherapy neuropathy

• Associated with cancer/ debility
• Constipation
• Pressure sores
• Bladder spasms
• Stiff joints
• Post-herpetic neuralgia
• Unrelated to cancer
• Arthritis
• Angina
• trauma

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Physical causes of pain

• Cancer-related
• Bone
• Nerve compression/ infiltration
• Soft tissue infiltration
• Visceral
• Muscle spasm
• Lymphoedema
• Raised intracranial pressure
• Treatment related
• Surgery postoperative scars /adhesions
• Radiotherapy burns/ fibrosis
• Chemotherapy neuropathy

• Associated with cancer/ debility
• Constipation
• Pressure sores
• Bladder spasms
• Stiff joints
• Post-herpetic neuralgia
• Unrelated to cancer
• Arthritis
• Angina
• trauma

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What are the Mechanisms of the Pain?

• Is the pain nociceptive?
• neuropathic?
• or mixed?

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What are the Special Characteristics of Cancer
Pain?

• Cancer is a multi-system disease
• 80 of patients with cancer pain have pain at
  more than one site
• 30 of patients with cancer pain have pain at 4
  or more sites
• Different pains may have different causes
  mechanisms
• The meaning of the pain has a great bearing on
  pain perception

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International Association for the Study of Pain

• Definition of Pain
• Pain is an unpleasant sensory emotional
  experience associated with actual or potential
  tissue damage or described in terms of such
  damage

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Multidimensional Nature of Pain
Suffering
loss of beauty
loss of independence
loss of health
Total Pain
financial worries
loss of role
impending loss of family possessions
fear of suffering
fears of the unknown
Cicely Saunders, 1967
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The Perception of Pain is affected by

• MOOD
• MORALE
• MEANING of the pain

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The Classic WHO 3-step Ladder
Step 3

World Health Organization 1990
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Pain Ruler Combined Non-verbal, Numeric
Categoric Scales
Worst pain you can imagine
No pain
Mild
None
Moderate
Severe
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Drugs available
Step 3

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Step 2 of the WHO Ladder

• Weak opioid codeine
• codeine/paracetamol
• codeine/aspirin
• tramadol
• sustained-released
  tramadol
• tramadol/paracetamol
• Low dose strong opioid, e.g., MST 10 mg

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Step 3 of the WHO Ladder

• Strong opioids
• morphine
• fentanyl
• oxycodone
• methadone
• pethidine (NOT recommended)

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Adjuvants / Co-analgesics

• Aspirin
• Ibuprofen
• Mefenamic acid
• Naproxen Na
• Ketoprofen

• Non-selective COX inhibitors

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Adjuvants / Co-analgesics

• Celecoxib
• Etoricoxib

• Selective COX-2 inhibitors

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Adjuvants / Co-analgesics

• Selective COX-2 inhibitors

• Reduced risk of GIT bleeding
• Renal effects unchanged
• Cardioprotection lost

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Co-analgesics in Cancer Pain

• bone pain
• raised intracranial
• pressure
• nerve compression pain

• NSAID/radiotherapy
• dexamethasone
• diuretic (?)
• corticosteroids

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Co-analgesics in Cancer Pain

• chlorpromazine nerve blocks
• diazepam/baclofen
• metronidazole clindamycin

• rectal tenesmoid pain
• muscle spasm
• infected malignant ulcer

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Co-analgesics in Cancer Pain

• Neuropathic pain
• Gastric distension

• amitripyline
• valproate
• carbamazepine
• gabapentin
• pregabalin
• metoclopramide

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Monitor effect of treatment at appropriate
time intervals
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REVIEWREVIEW

• And REVIEW AGAIN!!!

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Use of the WHO Ladder

• Step up when patient is taking drug in full
  dosage and pain is still unacceptable
• Full dosage of paracetamol 1g 4 hourly
• of paracetamol/codeine 2 tabs 4 hourly
• Full dosage of codeine 60mg 4 hourly
• Full dosage of tramadol 100mg qds

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Use of Opioids in Cancer Pain
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Considerations in choice of opioid

• Efficacy
• Side effect profile
• Cost
• Convenience
• Clinician familiarity
• Availability

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Consider the most suitable route of
administration
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The preferred route of opioid administration is
oral Consider alternative routes only when the
patient is

• Unable to swallow
• Unable to retain - vomiting
• Unable to absorb
• Unconscious

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Routes of opioid administration

• Possible routes
• buccal / sublingual
• transdermal
• rectal
• inhalational
• parenteral - IV, IM, SC
• intraspinal -
• epidural / intrathecal

• Recommended routes
• oral
• transdermal
• parenteral IV, SC

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Parenteral Systemic Opioid Therapy

• Intravenous
• Subcutaneous
• Intramuscular (not recommended)
• bolus
• continuous infusion
• patient-controlled analgesia (PCA)

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Common misconceptions aboutparenteral routes
(IV,IM,SC)

• These are NOT more efficacious than the
• oral route provided the ingested drug is
• retained
• absorbed
• hepatic first-pass metabolism is accounted for

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Treating a Pain Emergency

• Use IV route
• Teach the patient the numeric pain score
• Sit by the bedside titrate 1 mg at a time the
  pain score down to 2/10
• Dose needed for titration can be taken as the 4
  hourly dose
• Convert to 4 hourly oral morphine
• When stabilised, convert to MST

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Morphine the Gold Standard

• A Practical Guide to its Usage

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Oral morphine is

• safe
• effective
• cost-effective
• enhances mobility
• personal autonomy sense of normality

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Preparations of morphine

• Liquid mixture 1mg per ml
• 2mg per ml
• Immediate-release tablets
• Sustained-release tablets
• Suppositories
• Injection

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Morphine should be given

• by the mouth
• by the clock
• by the ladder

World Health Organization 1986
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Dosing Intervals of morphine

• Liquid mixture 4 hourly
• Immediate-release tablets 4 hourly
• Sustained-release tablets 12 hourly
• Suppositories 4 hourly
• IV,IM,SC injections 4 hourly
• N.B. There is no place for repeated
  IMmorphine

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Conversion Factorsaccording to route of
administration
Oral to parenteral 3 to
1Parenteral to epidural 10 to 1Epidural
to intrathecal 10 to 1
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Starting dose of oral morphine

• Following the WHO ladder
• if patient still has significant pain on
• codeine 60mg 4 hourly or
• tramadol 100mg qds
• start with
• immediate-release morphine
• 10 mg 4 hourly

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Starting dose of oral morphine

• If 2nd step of WHO ladder is omitted
• patient is on paracetamol 1g qds
• Starting dose should be
• immediate-release morphine
• 2.5 to 5 mg 4 hourly
• or
• sustained-release morphine (MST tablets)
• 10mg at night or 12 hourly

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Morphine Titration

• Titrate using an immediate-release
• preparation
• Switch to a sustained-release preparation
• for convenience of dosing increased compliance
• Bear in mind the cost

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When titrating morphine

• Review after 1st dose or within 24 hours
• There is no place for a 2-week or
• 6-week review when titrating morphine

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A long-acting preparation may be preferred for

• convenience of dosing
• to improve patient compliance
• when large volumes are needed

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Warn the patient he may get nausea on first
starting morphine

• This effect will wear off after a few days
• Prescribe an antiemetic if necessary

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Rescue or breakthrough dosing

• Peri-operative pain
• Patient-controlled analgesia (PCA)
• Chronic pain prescribe rescue or breakthrough
  doses
• Use 4 hourly dose
• Repeat up to 1 hourly

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Starting oral morphine 1

• Use an immediate-release preparation for
• dose titration
• If pain score is 5 above
• on maximum doses of weak opioid
• step up to 10 mg morphine mixture 4 hourly
• If patient is opioid-naïve
• start with 2.5mg 4 hourly for moderate pain
• 5mg 4 hourly for severe pain

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Starting oral morphine 2

• Review 1 hour after 1st dose of
• oral morphine
• Things to note
• Respiratory rate / somnolence
• Pain score whether pain is fully or only
  partially controlled on this dose
• Whether dose is retained nausea/vomiting

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Stepping up if dose is inadequate

• Step up by 30 - 50 of previous dose
• e.g. from 10 to 15mg 4 hourly
• 30 to 40 mg 4 hourly
• 90 to 120 mg 4 hourly

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The correct dose of morphine

• is that which gives
• complete pain relief
• without sedation

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To convert from immediate-release to
sustained-release morphine

• take the total 24-hour dose
• split into 12 hourly doses

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Remember that sustained-release morphine
tablets should not be crushed or chewedThat
converts them to immediate-release morphine
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Breakthrough or Rescue doses

• Do not use MST for breakthrough
• Onset of action of immediate-release morphine is
  20 - 40 minutes
• Onset of action of MST is 4 hours

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Unwanted effects of morphineNausea Vomiting

• Affects 2/3 of patients when
• starting morphine
• usually improves within 1 week
• Home care patients may require
• a prophylactic anti-emetic

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Unwanted effects of morphine Drowsiness

• may be troublesome on first starting
• improves after 3-7 days
• may be exacerbated by other drugs or metabolic
  upset

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Unwanted effects of morphine Constipation

• affects nearly all patients
• requires prophylactic treatment
• such as
• stool softener (e.g. lactulose)
• bowel stimulant (e.g. senna)

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Other Unwanted Effects of Morphine

• sweating
• dry mouth
• cutaneous itch
• myoclonic jerks

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Tolerance Addiction

• Tolerance to effects side-effects of morphine
  occurs but is
• not clinically important
• Addiction, defined as psychological dependence on
  a drug giving rise to
• drug-seeking behaviour, has NOT been observed in
  morphine use for pain,
• despite extensive studies

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Addiction to morphine does NOT occur if it is
used purely for pain relief
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Fears about morphine Respiratory
Depression

• Does NOT occur
• when the correct dose of morphine is matched
  against the pain

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Pain is the physiological antagonist to the
respiratory depressant effects of opioid
analgesics
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Other Opioids
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What is Fentanyl?

• Fentanyl citrate is
• a synthetic opioid
• widely used in IV anaesthesia
• pure m receptor agonist
• 75-100 x more potent than morphine
• Highly lipid soluble short-acting
• metabolised in liver to inactive norfentanyl
  excreted in urine
• use with caution in hepatic or renal dysfunction

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Transdermal Fentanyl

• Slow onset of action 12.7 to 16.6 hours
• Time to steady state 17 to 48 hours
• Long washout period 13 to 25 hours after patch
  removal
• Not suitable for pain titration
• Good for chronic stable pain

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Transdermal Fentanyl

• Cautions
• Not suitable for acute post-operative pain
• Elimination half-life prolonged in elderly (43.1
  vs 20 hours p lt0.05)
• Absorption increased by 1/3 with rise of body
  temperature to 40ºC

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Durogesic D-TRANS Easier to Apply Due to S-cut
Slit
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Technology Advantages of D-TRANS
Drug-in-Adhesive Matrix Technology

• D-TRANS
• Layers
• Backing layer
• Solid drug-in-adhesive matrix
• Contains and releases fentanyl (in dissolved
  state)
• Simultaneously functions as adhesive

• Reservoir System
• Layers
• Backing layer
• Reservoir with permeation membrane
• Fentanyl embedded in a gel
• Contains ethanol to enhance permeation
• Adhesive layer

Reservoir
....................
.....................
.....
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Product close-up (group shot)
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Product close-up (25mcg/h)
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Difficult Pain Problems

Unacceptable side effects somnolence itch naus
ea/vomiting giddiness Opioid switch may be a
solution
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Difficult Pain Problems

Pain of different intensities e.g. neuropathic
pain incident pain
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Pain with different intensities
Drug level above which side effects occur

Morphine Dose
Drug level needed to cover background pain
Time
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Difficult Pain Problems

• Strategies
• Use rescue medications
• Optimize adjuvant drugs
• Use psychostimulants
• Immobilize fractures
• Disease-modifying therapy
• Intraspinal routes for opioids
• Nerve blocks

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Episodic or Breakthrough Pain
Terminology Breakthrough
Pain Transitory exacerbations of pain that
occur in addition to otherwise stable persistent
pain Portenoy Hagen,
1990 Episodic or transient pain
Mercadante, Fulfaro
Casuccio, 2002

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Episodic or Breakthrough Pain
Incidence of Uncontrolled Episodic Pain 51 to
93 of cancer patients Portenoy Hagen,
1990 Portenoy et al, 1999 Swanwick et al,
2001 A Heterogeneous group End-of-dose pain
2 - 29Neuropathic pain 23 - 62Incident
pain 49 - 64

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Management of Episodic Pain

End-of-dose pain 2 29 Increase
the dose to last until the next dose kicks
in Add the previous days rescue doses
incorporate amount into the regular daily dose

Portenoy, 1997
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Management of Episodic Pain

Neuropathic pain 23 62 Assess
frequency, duration and intensity Adjust
adjuvants for neuropathic pain to reduce
frequency, intensity duration of episodes
Remember NNTs of anticonvulsants are still
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Wiffen et al, 1990
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Management of Episodic Pain

Incident pain 49 64 Avoid the
incident if possible e.g.
suppress cough


immobilize fracture
change life-style Use pre-emptive
analgesia e.g. before
bathing before
wound dressing
before going out

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Management of Episodic Pain

• Rescue Medications or Breakthrough doses
• Extra doses of analgesic taken in addition to the
  regular doses
• Used for pain exacerbations or episodic pain
• NB!! If the episode is very brief, rescue
  medications will not be feasible

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Management of Episodic Pain

Rescue Medications Can be used
pre-emptively e.g. before change of wound
dressing If activity or incident finishes before
effect of rescue medication wears off, expect a
period of somnolence
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Choice of Rescue Medication

Ideally they should have rapid
onset of action short duration of
action For patients on sustained-release morphine
or fentanyl patch, use immediate-release morphine
mixture or tablets equivalent to the 4 hourly
dose (1/6 daily dose)
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Pain with different intensities
Drug level above which side effects occur

Morphine Dose
Drug level needed to cover background pain
Time
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Difficult Pain Problems

• Strategies
• Use rescue medications
• Optimize adjuvant drugs
• Use psychostimulants
• Immobilize fractures
• Disease-modifying therapy
• Intraspinal routes for opioids
• Nerve blocks

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Thank you