Palliative Pain Management

1. Palliative Pain Management

2. Content
•Pain – definition, assessment
•Nociceptive and Neuropathic Pain
•Types of pain in cancer
•Opioids – principles and WHO ladder
•Opioids – titration, relative potency,
prescribing, formulations, side-effects
•Opioid Induced Neurotoxicity (OIN)
•Adjuvants for types of cancer pain

3. Principles used in symptom control
•What causes the symptom ?
–Physical
–Psycho-social
–Spiritual

•How do we manage it ?

•Treat the treatable

•Symptom control

•Review your
management –
things change!

4. Total
Suffering
Pain
Social &
Financial
Spiritual
Cultural Psychological
Physical
Symptoms
Total Pain/Suffering
Woodruff

5. Pain and advanced cancer
•.. are not synonymous

•¼ of patients do not have pain
•¾ of patients experience pain at some stage of
their illness
–1/3 of patients have 1 pain
–1/3 of patients have 2 pains
–1/3 of patients have >3 pains

6. Causes of pain in cancer patients
Cancer related …
•Visceral
•Bone
•Soft tissue infiltration
•Nerve compression/infiltration
•Muscle spasm
•Raised intracranial pressure
•Metabolic/ Endocrine

7. Causes of pain in cancer patients
Treatment related …
•Surgery
–Surgical wound – acute / chronic
–Adhesions
•Radiotherapy
–Acute / chronic e.g. mucositis / fibrosis
•Chemotherapy
–Acute / chronic e.g. mucositis / neuropathy

8. Causes of pain in cancer patients
Associated factors …
•Constipation
•Pressure sores
•Bladder spasm
•Joint stiffness
•Post herpetic neuralgia

9. Causes of pain in cancer patients
Concurrent illnesses …
•Low back Pain
•Angina
•Arthritis
•IBS
•Trauma
•Other

10. Specific assessment tools
•Visual analogue scales
•Numeric analogue scales


•Categorical scales


•Body charts
0 10
Severe 3
Moderate 2
Mild 1
None 0
Visual analogue scale
Categorical scale

11. What is “Total Pain”?
Total
Pain
Physical
Other symptoms
Adverse Rx effects
Insomnia/Chronic fatigue
Psychological
Anger
Disfigurement
Fear of pain/death
Helplessness
Social
Family/Finance worries
Loss of job/income
Loss of role
Abandonment/Isolation
Spiritual
Why me?
Anger at God
What is the point?
Guilt

13. Other cancer problems
•Social circumstances
•Family communication
•Patient coping - denial
•Family coping
•Treatment side-effects
•Disease symptoms - recurrent disease
•Genetics

14. SYMPTOMS IN ADVANCED CANCER 0 10 20 30 40 50 60 70 80 90
Asthenia
Anorexia
Pain
Nausea
Constipation
Sedation/Confusion
Dyspnea
% Patients (n=275)
Ref: Bruera 1992 “Why Do We Care?” Conference; Memorial Sloan-Kettering

15. Pain
•Defined as an unpleasant sensory and emotional
experience associated with actual or potential
tissue damage

•Acute pain is generally sudden in onset,
temporary, and subsides of its own accord or after
successful treatment of the cause

•Chronic pain persists or recurs for prolonged and
often indefinite periods of time

16. Pain Assessment
•Measure pain levels with the patient at regular
intervals.
•Cause of pain should be identified and treated
promptly.
•Patients can describe:
–location of pain
–aggravating or relieving factors
–intensity or severity
–goals for pain control
–duration, and when it occurs

17. Pain Scale
Visual Analog Scale (VAS) 100mm long
Simple Descriptive Pain Intensity Scale
Numeric Rating Scale (NRS)
No
Pain
No Pain
No Pain
Mild
Pain
Moderate
Pain
Severe
Pain
Worst Possible Pain
0 1 2 3 4 5 6 7 8 9 10
Worst Possible Pain

18. Assessing pain
Investigations may be useful

19. Assessing pain
Investigations may be useful

20. Classification of Pain
•Nociceptive pain - tissue damage (two types)
•Somatic
–e.g. metastatic bone pain
•Visceral
–e.g. liver capsule pain
–e.g. colic from malignant bowel obstruction

•Neuropathic - arises from nerve damage
•Central [brain, spinal cord, autonomic]

•Peripheral nerves
–Dysesthetic (burning)
–Lancinating/shooting
–Sensory changes – hyperaesthesia, allodynia, numbness

21. •Somatic Pain
•Arises from bone, muscle, cutaneous and
connective tissue
•Localised
•Typically clinically described as throbbing,
aching or stabbing
•Visceral Pain
•Arises from internal organs
•Generalised / diffuse
•Clinically, typically described as cramping or
gnawing
Nociceptive Pains

22. •Arises from neural tissue
•Clinical descriptions variable
•Continuous ‘burning’
•Spontaneous ‘lancinating’ or ‘electric’
•Associations
•Allodynia
abnormal sensations
•Hyperalgesia
Neuropathic Pain

23. Types of pain in cancer
•Visceral pain
•Neuropathic pain
•Bony pain
•Referred pain
•Breakthrough pain

24. Visceral Pain
•Results from infiltration , compression,
distension or stretching of thoracic and
abdominal viscera
•Often poorly localised
•Often referred to cutaneous sites
•Can usually be well controlled and
responds well to analgesics

25. Neuropathic pain
•Pain caused by injury to,
or disease of, the PNS or
CNS

•Puzzling & frustrating:
–often seems to have no
cause
–may respond poorly to
treatment
–can last indefinitely
–can escalate over time
–often results in severe
disability

26. Neuropathic pain
•Most distinguishing feature:
anatomical pattern of distribution,
pain follows nerve distribution

•Two broad classifications:
–constant (often described as
burning, throbbing, or stinging)
–intermittent (often described as
sharp, jabbing, or shooting)
•Often worse at night

27. ‘Bony’ pain
•Can be very painful

•Cancer cells multiply
inside the bone and put
pressure on the nerves

•Also causes bones to
crumble – this exposes
the nerves, and leads to
more pain

•Responds well to
analgesics and
radiotherapy

28. Referred pain
•Pain from internal
organs felt at a site
distant from the tissue
damage

e.g. pancreatic cancer
pain is felt in the back

29. Breakthrough pain
•Transient increase in pain over ‘baseline’
•Rapid onset and severe
•Frequent breakthrough pain may indicate
inadequate control of ‘baseline’ pain

30. Dose for breakthrough cancer pain

The breakthrough dose should be equivalent to a
4 hourly dose
•i.e. - 1/6
th
of total daily opioid dose
•Generally use the same opioid as being used for
regular regimen

31. Around-the-Clock
(ATC) Medication
Pain Relief
Threshold
Persistent Pain
Treating Persistent Pain
Pain Intensity

Time
Theoretical Model

32. Breakthrough pain (BTP)
Around-the-clock
Medication
Time
Breakthrough
Pain
Theoretical Model
Pain Intensity

33. Increasing ATC Medication – May
Increase Side Effects
Around-the-
clock
Medication
Breakthrough
Pain
Theoretical Model
Pain Intensity

Time

35. Commonly used medication in
palliative care patients
•Analgesics
•Antiemetics
•Laxatives
•Antispasmodics
•Anticholinergics
•Anticonvulsants
•Antidepressants
•Corticosteroids
•Antibiotics
•Sedatives

36. Drug complications
•Allergy
•Predicted
pharmacological effects
•Increased drug levels
–Organ failure
–Increasing age
•BNF appendices
–Organ failure
•Liver impairment
•Renal impairment
–Drug interactions

37. Basic Principles of Opioid Analgesia
The right dose of opioid is the one that achieves the
best analgesia with the fewest side effects.

•By the cause of the pain(s)
•By the clock
•By the ladder
•By the mouth
•For breakthrough pain
•For the individual
•Adjuvant therapies as needed
•Prevent side effects

38. Opioid Side Effects
Advise patients

•Constipation
–Co-prescribe laxatives e.g. Senna/Lactulose
•Nausea & vomiting (30%)
–Prophylactic anti-emetics e.g.. Haloperidol/Cyclizine/
Domperidone/Metoclopramide
•Sedation
–Reassure and monitor
–Advise re driving
•Dry mouth

39. Polypharmacy
•Concurrent use of several different medications
•Drug interactions
•Increased cost
•Non compliance
•Adverse effects
•Study GP
–Use >5 medications – increased risk

40. •Polypharmacy & drug interactions
•Cytochrome P450 interactions with inhibition
or induction of drug biotransformation
(‘bullets’ & ‘blanks’)
•Terfenadine/ ketoconazole- cardiac
dysrhythmias by inhibition of terfenadine
metabolism
•Rifampicin / phenytoin increases
phenytoin clearance- reduced effect

41. World Health Organization Pain Ladder
Cancer Pain Management
Increasing Pain
Step 1
Step 2
Step 3
Non-opioid
+/- Adjuvant
Opioid for mild
to moderate pain
+/- Non-opioid
+/- Adjuvant
Opioid for moderate
to severe pain
+/- Non-opioid
+/- Adjuvant
Address psychosocial and spiritual issues; consider adjuvant therapies
Step 4 ?

42. Analgesics
P
A
I
N
Paracetamol

Codeine

Dihydrocodeine

Tramadol

Morphine

Diamorphine
MILD
SEVERE
Simple analgesics



Opioid agonists



Strong opioid agonists

43. Paracetamol
Active metabolite of phenacetin

Mode of action: Analgesic
Weak prostaglandin inhibitor

Indications: Mild to moderate pain without
inflammation

Adverse effects: Rare at normal dosage
Liver/renal toxicity in overdosage

44. Mode of Action

Produce analgesia through actions at regions in the brain that contain endogenous
opioid peptides
Receptor Subtype
Mu Delta Kappa
Opioid Peptides + +
AGONIST
Codeine
Morphine

PARTIAL AGONIST
Buprenorphine

(+)
+


±

(+)
(+)





(+)

45. Prescribing Opioids
•Weak opioids
–Dose often Codeine limited by presence of
paracetamol
–Tramadol
•Strong opioids
–Morphine, oxycodone, diamorphine, fentanyl,
hydromorphone, methadone, buprenorphine
•Do NOT use:
–Pethidine

46. Codeine/Morphine relative potency

47. Initiating Opioids: Starting Doses
•Morphine 2.5-5 mg q4hr PO
•Oxycodone 1-2 mg q4hr PO
•Diamorphine 2.5mg q4hr SC


•Fentanyl transdermal – ONLY for stable pain
–12 mcg/hr patch may be excessive in opioid naïve
patients

•Add breakthrough dose (4 hrly prn)

•Consider smaller doses in frail, renally impaired and
elderly patients

48. Pharmacokinetics of Opioids
•Onset of pain relief
–Oral opioids 15–30 min
–SC opioids 5–10 min
–IV opioids 1 min

•Duration of pain relief
–Short-acting oral opioids 3–5 hours
–Long-acting oral opioids 8–12 hours
–Fentanyl patches 72 hours
–IV or SC opioids 2–4 hours

49. Short-acting
Formulations
(4 hour duration)
•Opioid-naïve
patients
•Pain crises
•Breakthrough
cancer pain
Long-acting
Formulations
(12 hour duration)
•Reserve for stable
situations
Opioid Formulations

50. Routes of Opioid Administration
•Preferred route – oral
•When unable to swallow: SC, CSCI, IV, TD
•Seldom used (only in special situations):
–Sub Lingual (breakthrough pain, fentanyl)
–Intraspinal (epidural or intrathecal)
•Do NOT use IM

51. Titrating the Dose of Opioid
Increase the dose by 25-50% if the patient is not
achieving adequate pain control.

Take into account number of breakthrough doses
taken.

52. Opioid Myths
Many patients harbor fears about opioids.

•“It means the end is near”
•“Opioids cause addiction”
•“Opioids will lose their effectiveness over time,
leaving nothing to treat severe pain ‘at the end’”
•“Opioids will make me a zombie or take away my
mental capacity”
•“They will stop my breathing”
•“They will my shorten life”

53. Common Opioid Adverse Effects
Common side effects:
•Constipation (requires ongoing laxatives)
•Nausea
–Usually resolves after a few days
–Metoclopramide or cyclizine in the first few days
•Sleepiness (usually resolves after a few days)

Less common side effects:
•Opioid neurotoxicity
•Sweating, dry mouth, pruritis – very uncommon
(especially with appropriate dosing)
•Respiratory depression

55. Opioid Induced Neurotoxicity (OIN)
•Clinical Presentation
–Myoclonus, hallucinations, cognitive impairment,
delirium, severe somnolence, dysaesthesia, allodynia
•Mechanism unclear
–Opioid metabolites
–Opioids themselves
•Increased risk
–Renal impairment, high doses of opioids, infection
(sepsis)

56. Management of Opioid Neurotoxicity
(OIN)

Seek advice from the Specialist Palliative Care
Team

Exclude other causes for symptoms.

The main strategies for treatment of OIN are:
–Hydration
–Opioid dose reduction
–Opioid switching
–Change route of administration

57. Constipation – management

•Pre-empt constipation by putting everyone at risk (e.g.
patients on opioids) on regular aperients

•Treat reversible causes e.g. give analgesia if pain on
defecation, alter diet, ↑ fluid intake

•Treat with regular stool softener (e.g. lactulose) ± regular
bowel stimulant (e.g. senna) or a combination drug (e.g. co-
danthrusate). Titrate dose against response

58. -If that is ineffective consider adding rectal measures.
•if soft stools and lax rectum—try bisacodyl suppositories
(0 must come into direct contact with rectum);
•if hard stools—try glycerol suppositories—insert into the
faeces and allow to dissolve
•- If still not cleared refer to the district nurse for lubricant
± high phosphate (stimulant) enema (usually act in
~20min.)
•- Once cleared leave on a regular aperient with
instructions to ↑ aperients if constipation recurs.

Constipation – management

60. Types of pain in cancer
•Visceral pain
•Neuropathic pain
•Bony pain
•Referred pain
•Breakthrough pain

61. Adjuvants for Visceral Pain
•Liver metastases or malignant bowel
obstruction
–Corticosteroids (Dexamethasone 2-8 mg OD or BD)
–NSAIDs e.g. Diclofenac SR 75mg bd

•Colic
–Hyoscine Butylbromide SC (20mg)

62. Dysaesthetic pain
(burning)
Neuralgic pain
(lancinating)
Opioid and dose titration
(moderate to severe pain)
Gabapentin or Pregabalin or TCA
TCA and Gabapentin or Pregabalin +/- lidocaine patch
Corticosteroid (may be used first line in pain crisis)
NMDA antagonists (ketamine)
Drugs for Neuropathic Pain

63. Adjuvants for Bone Pain [1]
•NSAIDs
–Limited use in severe pain
–Renal and gastro-intestinal side effects
–Limitations of Cox-2 specific NSAIDs recently noted
•Steroids
–Useful in pain crises
•Radiotherapy
–75% to 85% response rate (decreased pain)
–Few side effects with palliative therapy
–Response within 1 to 2 weeks (maximum response up to 4
weeks later)
–Duration of analgesia is several months

64. Adjuvants for Bone Pain [2]
•Bisphosphonates
–Reduction of skeletal events (good evidence)
–Management of more acute pain with parenteral
infusion (some controversy)
•Surgery
–impending or pathological fracture

65. Key points

66. Pain Management
•Nociceptive Pain
–Somatic: arises from bone, muscle, cutaneous tissue and CT. localised, clinically
presents as throbbing/aching/stabbing pain.
–Visceral: internal organs, generalised diffuse achy pains like period pains
•Neuropathic Pain
–Arises from neural tissue: PNS or CNS
–Can be continuous or spontaneous, descriptions vary from burning to electric
–Associated with allodynia (slightest touch causes pain), hyperalgesia (exaggerated pain
response)
–May be disproportionate to injury (chronic) or indicate neural compression (cancer)
–May respond poorly to treatment
–Can last indefinitely and escalate over time – severe disability
–Distinguishing feature: anatomical pattern of distribution
–Constant or intermittent – burning, throbbing OR sharp stabbing, jabbing
–Often worse at night
–Rx: gabapentin, pregabalin, amytriptyline, paroxetine, opioids help a bit, ketamine
•Visceral Pain
–Arises from internal organs, is generalised or diffuse and poorly localised
–Crampy/colicky pain
–May respond better to anti-cholinergic/anti-spasmodics e.g. buscopan

67. Pain Management
•Referred Pain
–Pain from internal organs felt at a distant site from tissue damage
–E.g. back pain in pancreatic cancer, shoulder tip pain in diaphragm irritation
•“Bony” Pain
–Can be really painful
–Cancer cells multiply inside bones and put pressure on the nerves, they also cause
bone to crumble which exposes the nerves  pain
–Responds well to analgesics and radiotherapy
–Pathological fractures and prophylactic stinting
•Breakthrough Pain
–Transient increase in pain over “baseline”
–Rapid onset of severe pain
–May indicate inadequate control of baseline pain if frequently occurring
–Dose = 1/6 of daily opioid dose ( one 4hourly dose)
–Same opioid as baseline medication, faster acting if possible
–Careful of A/Es
–If too much breakthrough being used: review analgesia and change dose

68. Pain Management
•Prescribing Opioids
–Weak: codeine dose often limited by paracetamol. Tramadol used but nauseating and
causes delirium
–Strong: morphine, oxycodone (oxycontin-baseline and oxynorm-breakthrough),
diamorphine, hydromorphone, methadone (good for neuropathic pain but last line),
buprenorphine
–Do NOT use pethidine: useless, causes epileptic fits
–Codeine is metabolised to morphine – 10g codeine = 1g morphine
•E.g. 2 x 8/500 codeine = 16 codeine = 1.6 morphine

69. Pain Management
•Starting Doses
–Morphine: 2.5-5mg q4hr PO
–Oxycodone 1-2mg q4hr PO
–Diamorphine 2.5mg q4hr SC
–Fentanyl transdermal patch for stable pain 12mcg/hr (=45mg oral morphine)
–Add breakthrough dose: 1/6 daily dose
–Smaller doses in renal impairment, old, frail, hepatic failure
–Monitor A/Es for toxicity
–Onset: 15-30min PO, 5-10min SC, 1min IV
–Duration: short acting 3-5 hours (4hrly), long acting 8-12hrs, fentanyl patch 72hrs,
IV/SC 2-4hrs
–Long acting: stable pain
–Short acting: breakthrough, pain crises, opioid naïve pts
–CSCI: continuous sub cutaneous infusion
–Do NOT use IM
–Inadequate pain control: increase dose by 25-50%
–A/Es: constipation (laxatives), nausea, (anti-emetics), sleepiness. OD, sweating, dry
mouth, pruritis, resp depression

70. Pain Management
•Opioid Induced Neurotoxicity
–Presentation: myoclonus, hallucinations (flashes of light), cognitive impairment,
delirium, severe somnolence, dysaethesia, allodynia
–Mechanism: unsure if due to opioid metabolites or opioids themselves
–Increased risk: renal impairment, high dose opioids, infection (natural opioid released
by body)
–RR 8+: watch
–RR<8 – give naloxone slowly. Reverses A/Es as well as pain effects
–Management: hydration, opioid dose reduction, opioid switching, changed route
•Adjuvants for visceral Pain
–Liver mets or malignant bowel obstruction: steroids, NSAIDs
–Colic: hyoscine butylbromide – buscopan 20mg
•Adjuvants for bone pain
–NSAIDs – if not severe, careful with kidneys and liver
–Steroids: good for pain crises. Not long term
–Radiotherapy: 75-85% response rate within 1-2weeks, lasts several months
–Bisphosphonates: reduces skeletal events, helps with pain
–Surgery: stent impending or pathological fracture