Pain Management in Palliative Care

1
Pain Management in Palliative Care

• John Shuster, MD

2
Sources

• Adapted from AMAs EPEC Curriculum
• Education for Physicians on End-of-Life Care
• www.ama-assn.org

3
Pain Management in Palliative Care

• Pain Pathophysiology
• Goals of Care and Assessment
• Pharmacologic Management Principles
• Opiates in Palliative Pain Management
• Side Effects of Opiates
• Cases

4
Pain Pathophysiology

• Acute pain
• Identified event, resolves daysweeks
• Usually nociceptive
• Chronic pain
• Cause often not easily identified, multifactorial
• Indeterminate duration
• Nociceptive and / or neuropathic

5
Nociceptive Pain

• Direct stimulation of intact nociceptors
• Transmission along normal nerves
• Sharp, aching, throbbing
• Usually easy to describe, localize

6
Nociceptive Pain

• Tissue injury sometimes apparent
• Management
• Opioids
• Adjuvant / coanalgesics

7
Neuropathic Pain

• Disordered peripheral or central nerves
• Compression, transection, infiltration, ischemia,
  metabolic injury
• Everyone has experienced transient neuropathic
  pain
• Funny bone
• Leg asleep

8
Neuropathic Pain

• Pain may exceed observable injury
• Described as burning, tingling, shooting,
  stabbing, electrical
• Management
• Opioids
• Adjuvant / coanalgesics often required

9
Other Types of Pain

• Bone Pain
• Anti-inflammatory drugs
• Visceral Pain
• Relieve obstruction, reduce peristalsis
• THM Multiple types of pain, multiple treatment
  approaches (that dont always include opiates)

10
Goals of Pain Management

• Symptom Reduction (Nociception, Hurt)
• Minimizing Suffering/Optimizing Quality of Life
• Minimizing Functional Impairment
• Physical
• Psychological
• Social/Interpersonal

11
Symptom Reduction

• Easiest Goal to Measure
• No Such Thing as a Nociometer
• Still a subjective phenomenon
• Usually Measured with Numerical Scales
• 0-5 (simpler)
• 0-10 (better validated)
• The Patients Assessment is the One That Counts

12
Patient Self-Reports of Pain

• Validation of 1-10 Pain Rating Scale
• 1-4 Mild Pain
• 5-6 Moderate Pain
• 7-10 Severe Pain -Serlin, Mendoza, et
  al (1995)

13
Minimizing Functional Impairment

• Measuring impact of pain (or relief) on
• Mobility, Activity
• Self-Care
• Sleep
• Energy
• Mood
• Other physical symptoms
• Relationships

14
Pain Assessment Key Elements

• Location
• - Look for 1 site, kind of pain.
• Intensity (e.g., 0-10 scale)
• - Worst, Best, Usual, Now, Tolerable
• Quality
• - Somatic, Neuropathic, Bone, Visceral
• Onset and Duration

15
Pain Assessment Key Elements

• Methods of Relief
• Sources of Exacerbation
• Consequences of Pain (on Function, Quality of
  Life)
• - Symptoms (e.g., Nausea), Sleep, Appetite,
  Physical Activity, Interpersonal, Emotional,
  Concentration

16
Pain Management

• Dont delay for investigations or disease
  treatment
• Unmanaged pain ? nervous system changes
• Permanent damage, amplified pain
• Treat underlying cause (e.g., radiation for a
  neoplasm)

17
Placebos

• There is no role for placebos to assess or treat
  pain
• The placebo effect is real

18
Opiates Palliative Indications

• Pain
• Dyspnea
• Cough

19
WHO 3-stepLadder
3 severe
Morphine Hydromorphone Methadone Levorphanol Fenta
nyl Oxycodone Adjuvants
2 moderate
A/Codeine A/Hydrocodone A/Oxycodone A/Dihydrocodei
ne Tramadol Adjuvants
1 mild
ASA Acetaminophen NSAIDs Adjuvants
20
Case 1

• 70 YO man with advanced prostate cancer.
• Severe lower back pain (8/10 with movement, 4/10
  at rest).
• No neurologic impairment.
• APAP/Codeine reduces pain at rest to 2/10 does
  not affect pain with movement.
• What next?

21
Case 1 (cont.)

• Refer to WHO Ladder.
• Bone pain - NSAID.
• Severe pain - Stronger opiate (e.g., morphine).

22
Clinical Opioid Pharmacology

• Conjugated in liver
• Excreted via kidney (9095)
• Duration of effect of immediate-release
  formulations (except methadone)
• 35 hours po / pr
• Shorter after dosing by parenteral bolus
• Steady state after 45 half-lives

23
Clinical Opioid Pharmacology

• Cmax after
• PO ? 1 h
• SC, IM ? 30 min
• IV ? 6 min
• Half-life at steady state
• PO / PR / SC / IM / IV ? 3-4 h

24
Routine Oral DosingImmediate-release preparations

• Codeine, Hydrocodone, Morphine, Hydromorphone,
  Oxycodone (plain)
• Dose q4H - Dose Finding
• Adjust dose daily
• Mild / moderate pain ? 2550
• Severe / uncontrolled pain ? 50100
• Adjust more quickly for severe uncontrolled pain

25
Routine Oral DosingExtended-release preparations

• Improve compliance, adherence
• Eliminates need to watch the clock
• Avoids bolus effect
• Dose q 8, 12, or 24 h (product specific)
• Dont crush or chew tablets
• Adjust dose q 24 days (once steady state reached)

26
Routine Oral DosingLong-half-life opioids

• Dose interval for methadone is variable (q 6 h or
  q 8 h usually adequate)
• Adjust methadone dose q 47 days

27
Breakthrough Dosing

• Use immediate-release opioids
• 10 of 24-h dose
• Offer after Cmax reached
• PO / PR ? q 1 h
• SC, IM ? q 30 min
• IV ? q 1015 min
• Do NOT use extended-release opioids for
  breakthrough pain!

28
Clearance Concerns

• Conjugated by liver
• 9095 excreted in urine
• Dehydration, renal failure, severe hepatic
  failure
• ? dosing interval, ? dosage size
• If oliguria or anuria
• STOP routine dosing of morphine
• use ONLY prn

29
Case 2

• 47 YO woman with metastatic colorectal carcinoma
  stable analgesia on morphine 12mg/Hr by SC
  infusion pump.
• Develops confusion, myoclonus, moaning (pain?)
  over 48 hours.
• Hospice nurse reports diminished urine output
  over last few days.
• What do you recommend?

30
Case 2 (Cont.)

• Probable accumulation of morphine metabolites due
  to renal insufficiency.
• Check renal function.
• Gentle rehydration? (hypodermoclisis)
• Opiate rotation?

31
Not Recommended

• Meperidine
• Poor oral absorption
• Normeperidine is a toxic metabolite
• longer half-life (6 hours), no analgesia
• psychotomimetic adverse effects, myoclonus,
  seizures
• if dosing q 3 h for analgesia, normeperidine
  builds up
• accumulates with renal failure

32
Not Recommended

• Propoxyphene
• No better than placebo
• low efficacy at commercially available doses
• Toxic metabolite at high doses

33
Not Recommended

• Mixed agonist-antagonists
• Pentazocine, Butorphanol, Nalbuphine, Dezocine
• Compete with agonists ? withdrawal
• Analgesic ceiling effect
• High risk of psychotomimetic adverse effects with
  pentazocine, butorphanol

34
Ongoing Assessment

• Increase analgesics until pain relieved or
  adverse effects unacceptable
• Be prepared for sudden changes in pain

35
Alternative Routesof Administration

• Enteral feeding tubes
• Transmucosal
• Rectal
• Transdermal
• Parenteral
• Intraspinal

36
Transdermal Patch

• Fentanyl
• Peak effect after application ? 24 hours
• Patch lasts 4872 hours
• Ensure adherence to skin
• Poorly absorbed in very thin/cachectic patients?

37
Parenteral

• SC, IV, IM
• Bolus dosing q 34 h
• Continuous infusion
• Easier to administer
• More even pain control

38
Intraspinal

• Epidural
• Intrathecal
• Morphine, Hydromorphone, Fentanyl
• Consultation

39
Changing Routesof Administration

• Equianalgesic table
• Guide to initial dose selection
• Significant first-pass metabolism of PO / PR
  doses
• Codeine, Hydromorphone, Morphine
• PO / PR to SC, IV, IM
• 23 1

40
Equianalgesic Dosesof Opioid Analgesics

• PO / PR(mg) Analgesic SC / IV / IM (mg)
• 100 Codeine 60
• 15 Hydrocodone -
• 4 Hydromorphone 1.5
• 15 Morphine 5
• 10 Oxycodone -

41
Changing Opioids

• Also consult an equianalgesic table
• Careful with cross-tolerance
• Start with 5075 of published equianalgesic
  dose
• More if pain is high
• Less if patient is frail or has adverse effects
• Monitor and adjust dose after conversion

42
Changing Opioids

• Transdermal fentanyl
• 25-mg patch 45135 (likely 5060) mg morphine /
  24 h
• Methadone
• start with 1025 of published equianalgesic dose

43
Case 3

• Mrs D, 45 years old
• Breast cancer, metastases to bone
• Comfortable on morphine at6 mg / h SC
• Convert to oral medications before discharge

44
Case 3 (Cont.)

• Convert to SR with breakthrough
• 6mg/Hr 144 mg/24Hr SC
• 144mg SC 432mg/24Hr PO
• Round down to 400mg
• Dose SR morphine 200mg PO q12Hr
• Breakthrough dose 40 mg (round down to 30mg)
• Dont forget a laxative!

45
Opioid Adverse Effects

• Common Uncommon
• Constipation Bad dreams / hallucinations
• Dry mouth Dysphoria / delirium
• Nausea / vomiting Myoclonus / seizures
• Sedation Pruritus / urticaria
• Sweats Respiratory depression
• Urinary retention

46
Opioid Allergy

• Nausea / vomiting, constipation, drowsiness,
  confusion
• Adverse effects, not allergic reactions
• Anaphylactic reactions are the only true
  allergies
• e.g., bronchospasm

47
Constipation

• Common to all opioids
• Opioid effects on CNS, spinal cord, myenteric
  plexus of gut
• Easier to prevent than treat

48
Constipation

• Diet usually insufficient
• Bulk forming agents not recommended
• Stimulant laxative
• senna, bisacodyl, glycerine, casanthranol, etc
• Combine with a stool softener
• senna docusate sodium

49
Constipation

• Prokinetic agent
• Metoclopramide
• Osmotic laxative
• MOM, lactulose, sorbitol
• Other measures

50
Respiratory Suppression

• Opioid effects differ for patients treated for
  pain
• Pain is a potent stimulus to breathe
• Loss of consciousness precedes respiratory
  depression
• Development of pharmacologic tolerance is rapid

51
Respiratory Suppression

• Management
• Identify, treat contributing causes
• Reduce opioid dose
• Observe
• If signs emerge (sedation with RR unstable vital signs)
• Naloxone, 0.04-0.1 mg IV q 1-2 min

52
Nausea / vomiting

• Onset with start of opioids
• Tolerance develops within days
• Prevent or treat with dopamine-blocking
  antiemetics
• Prochlorperazine, 10 mg q 6 h
• Haloperidol, 1 mg q 6 h
• Metoclopramide, 10 mg q 6 h

53
Nausea / vomiting

• Other antiemetics may also be effective
• Alternative opioid if refractory

54
Sedation

• Onset with start of opioids
• Distinguish from exhaustion due to pain
• Tolerance develops within days
• Complex in advanced disease

55
Sedation

• If persistent, alternative opioid or route of
  administration
• Psychostimulants may be useful
• Methylphenidate, 5 mg q am and q noon, titrate

56
Pain Management in Palliative Care

• John Shuster, MD