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

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

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

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

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

Oral Opioids—Duration of Action Ultra short Short Long

A. Ultra short acting opioid Fentanyl Very potent (given IV, it has 50-100 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.

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

Oral Short Acting Opioids Oral dosing: onset in 20-30 min peak effect in 60-90 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

Combination Products

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

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.

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

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®)

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

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

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

Dosing Ketamine Adults: Recommended duration 24-72 hrs Ordering based on IDEAL Body Weight 0.1-0.2 mg/kg bolus and 0.1-0.2 mg/kg/hr infusion

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

Opioids in Liver Failure

Assessing Sedation—PASERO SCALE

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

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

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

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

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

Learning Points Write down 3 new things you learned from this presentation. 1. 2. 3.

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