1. Palliative Care Toolkit: Pain management
By Roshni Guerry, MD
Supportive and Palliative Care Inpatient Medical Director

2. Objectives
Describe four classifications of opioids and their preferred indications
List which opioids are preferred for renal and liver patients
Describe the timeline for opioid withdrawal and how to manage symptoms
Develop a plan for tapering opioids when appropriate

3. “There is no pain that can not be made worse with inappropriate therapy.”

4. Analgesics Classifications
Opioids are classified by their interaction with the opioid receptors.
pure agonist: morphine, hydromorphone (Dilaudid ®) oxycodone, codeine, meperidine, fentanyl, methadone
mixed agonist-antagonist: butorphanol (Stadol ®), pentazocine (Talwin ®), nalbuphine (Nubain ®), Buprenophine/naloxone(Suboxone ®)
partial agonist: buprenorphine
pure antagonist: naloxone, naltrexone

5. Agonist-Antagonists Mixed Agonist-Antagonists
Claim to be less addicting—not substantiated
Will potentiate withdrawal in patients being treated with pure agonists—need to dose higher for first 72 hours then lower
Have an analgesic ceiling
Are psychotomimetic—can cause psychosis
Suboxone—need special DEA

6. Oral Opioids—Duration of Action
Ultra short
Short
Long

7. A. Ultra short acting opioid
Fentanyl
Very potent (given IV, it has times the potency of morphine)
Transmucosal (buccal) delivery systems are available for breakthrough pain:
Actiq ® (Lozenge), Fentora TM (Buccal tablet)
Onset of analgesia within ~10 minutes; peak effect ~20-40 mins; duration of analgesia 2-3 h
NOTE: Should only be used in opioid tolerant patients by clinicians familiar with the pharmacology of transmucosal systems.

8. B. Oral Short Acting Opioids
Oral only
oxycodone (Percocet ® , Tylox ® 0)
hydrocodone (Vicodin ® Lortab ®, Lorcet ®)
Parenteral or Oral
morphine
hydromorphone (Dilaudid ®)
oxymorphone
(Opana ®)
meperidine (Demerol ®)
codeine
fentanyl

9. Oral Short Acting Opioids
Oral dosing:
onset in min
peak effect in minutes
duration of effect 2-4 hours (6-8 hours for oxymorphone)
Can be dose escalated or re-administered every 2-4 hours for poorly controlled pain

10. Combination Products

11. Opioid combination products
The following opioids are available as combination products with acetaminophen, aspirin, or ibuprofen
Codeine; hydrocodone; oxycodone; tramadol
Typically used for
Moderate, episodic (PRN) pain
Breakthrough pain in addition to a long-acting opioid (for moderate, and for some patients severe, pain).
Never prescribe more than one combination drug at any one time.
Keep acetaminophen dosing:
< 4 grams/day for combination products

12. Which combination product?
Analgesic potency of combination meds
Aspirin < Codeine < Hydrocodone = Oxycodone
Toxicity:
All the combination products can cause opioid toxicities: nausea, sedation, constipation, etc.
There is little published data that supports the use of one product over another in terms of routine toxicity;
however …
Codeine is probably the most emetogenic opioid.

13. Tramadol (Ultram ®) Lowers seizure threshold
A synthetic analog of codeine
Analgesic effect roughly equivalent to Tylenol #3 ®
Efficacy variable; has an analgesic ceiling and maximum 24 hour dose of 400 mg
No anti-inflammatory effects
Side effects similar to opioids at high dose--nausea, confusion, dizziness, constipation
Does have abuse potential
Lowers seizure threshold

14. C. Long Acting Opioids Oral Transdermal Extended-release morphine:
MS Contin®
Kadian®
Oramorph SR
ER oxycodone
Oxycontin®
Oxycodone SR
ER oxymorphone
Opana SR
Methadone (pain expert involvement recommended)
** CAN DOSE EXTENDED RELEASE Q12 H or Q8 H
Transdermal
Fentanyl Patch (Duragesic®)

15. KETAMINE Ketamine is a dissociative amnestic Benefits
NMDA receptor antagonist
Benefits
Pain Relief
Minimal effect on ventilatory drive or blood pressure
Bronchodilation
Extremely Potent Anti-Depressant

16. Ketamine for who? For who not?
GOOD candidates:
with acute pain
Opioid Tolerant, Chronic Pain
Refractory Major Depression
Severe Lung Disease
POOR candidates
Intracranial trauma
previous psychotic illness
severe uncontrolled heart failure or severe hypertension

17. Downside of Ketamine Adverse Reactions Treating Side Effects
Dose dependent psychomimetic effects
Visual Hallucinations, vivid dreams, psychosis, dysphoria, frank psychosis
Increased Intracranial Pressure
Salivation
Treating Side Effects
Usually occur in the first 30 min
Sedation – Usually secondary to opioids
Dysphoria / Hallucinations – 10-20% use benzos, antipsychotics, or discontinue infusion

18. Dosing Ketamine Adults: Recommended duration 24-72 hrs
Ordering based on IDEAL Body Weight
mg/kg bolus and mg/kg/hr infusion

19. Opioids in Renal Failure
Not Recommended
Use with Caution
Safest in Renal Failure
Meperidine
Hydromorphone
Fentanyl
Codeine
Oxycodone
Methadone
Morphine
Oxymorphone

20. Opioids in Liver Failure

21. Assessing Sedation—PASERO SCALE

22. Treating Extreme Sedation with Naloxone (Narcan®)
In palliative care, naloxone is indicated when:
The goals of care are such that reversing CNS depression is appropriate to patient’s goals
Patients have decreased respirations and decreased level of consciousness (arousal)
Adult dosing:
Administer naloxone—1 amp (0.4 mg) diluted in 9 cc saline—push 1cc per minute until level of consciousness improves.
Naloxone’s effects last only ~20mins, so continued monitoring will be necessary after initially reviving the patient

23. Opioid Induced Hyperanalgesia
Proposed mechanisms:
Toxic effect of opioid metabolites?
Central sensitization due to activation of NMDA receptors?
Features
Increasing sensitive to painful stimuli
Worsening pain despite increasing opioids
PE exam
Allodynia, myoclonus, delirium, seizures
Therapies
Reduce of discontinue opioid, opioid rotation, use ketamine infusion

24. Withdrawal Withdrawal is very uncomfortable but NOT life threatening
Early symptoms
Agitation, anxiety, muscle aches, increased tearing, insomnia, runny nose, sweating, yawning
Late symptoms
Abdominal cramping, diarrhea, dilated pupils, goose bumps, nausea, vomiting
Withdrawal is very uncomfortable but NOT life threatening
----- Meeting Notes (4/24/14 21:21) -----
erase duration

26. Withdrawal Onset: Varies 6-12 hours for short acting drug
72-96 hours following methadone
Duration
5-10 days and more intense for short acting
Less severe but longer for methadone

27. How to Taper
Education on what it will look like– discomfort, anxiety, restlessness, nausea, sweating etc.
Speed depends on clinical circumstances–
slow taper (reduce dose by 10% every 2 weeks or even longer)
Rapid taper– can be done but will need additional med management for withdrawal
Clonidine- alpha 2 agonist can be used to help withdrawal

28. Learning Points
Write down 3 new things you learned from this presentation

30. References
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Jensen, MK et al. 10-year follow-up of chronic non-malignant pain patients: opioid use, health related quality of life and health care utilization. Eur J Pain. 2006; 10(5):
Jost, L, Roila, F. Management of cancer pain: ESMO clinical recommendations. Ann Oncol. 2009; 20 (suppl 4): iv170-iv173.
Management of Cancer Pain, Structured Abstract. January Agency for Healthcare Research and Quality, Rockville, MD.
Mercadante, S. Arcuri E. Pharmacological management of cancer pain in the elderly. Drugs Aging. 2007: 24(9):
Smith, HS. Opioid Metabolism. Mayo Clin Proc. 2009; 84(7):
Stevens, RA, Ghazi, SM. Routes of opioid analgesic therapy in the management of cancer pain. Cancer Control. 2000; 7(2):