Fast Fact and Concept #57: Neuroexcitatory Effects of Opioids: Patient Assessment

Authors: Robin K. Wilson, PhD and David E. Weissman, MD

2nd Edition

Everyone recognizes the common opioid side effects: constipation, nausea, pruritis, and urinary retention. Less well appreciated are the neuroexcitatory effects, commonly seen among patients on chronic opioids. Among these, myoclonus is typically the herald symptom. Myoclonus may occur in patients on chronic therapy with most opioids including morphine, hydromorphone, fentanyl, meperidine, and sufentanil. Higher doses more frequently result in myoclonus, but the dose relationship is variable. Myoclonus can occur with all routes of administration. Current research implicates the 3-glucuronide opioid metabolites as the most likely cause of neuroexcitatory side effects. Co-morbid factors including renal failure, electrolyte disturbances, and dehydration, can also contribute to myoclonus development.

Myoclonus, the uncontrollable twitching and jerking of muscles or muscle groups, usually occurs in the extremities, starting with only an occasional random jerking movement; a patient's spouse may be the first to recognize this symptom. With continued administration, the jerking may increase in frequency; at the extreme, there is constant jerking of random muscle groups in all extremities. As myoclonus worsens, patients may develop other neuroexcitatory signs: hyperalgesia (increased sensitivity to noxious stimuli), delirium with hallucinations, and eventually, grand mal seizures. Well meaning clinicians may misinterpret the hyperalgesia as increasing pain, leading to a vicious cycle of increasing dose, increasing hyperalgesia, increasing dose, worsening delirium, and finally seizures. After identifying a patient with possible opioid toxicity, the clinician should complete the following assessment.

Physical Examination

a) Assess frequency of myoclonic jerks. Stand at the bedside and observe a patient for 30-60 seconds. Watch for and count the number of uncontrolled jerking movements.

b) Determine if there is evidence of a new or worsening delirium. Complete a bedside mini-mental assessment.

c) Assess hydration status.

d) Estimate prognosis: hours, days, weeks, months or years? A longer prognosis demands a more definitive change in treatment.

Chart review

a) Review the recent opioid analgesic history: What is the current drug and dose? How has the dose changed over the past few days and weeks?

b) Review the medication list for potentially exacerbating drugs. (e.g. haloperidol, phenothiazines)

c) Review recent laboratory studies if available. Check renal and liver function, check for low magnesium, glucose or sodium.

See Fast Fact #58 for treatment options.

References:

1. Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, Mercadante S, Pasternak G, and Ventafidda V. Strategies to manage the adverse effects of oral morphine: an evidence based report. Journal of Clinical Oncology 2001 19: 2542-2554.
2. Mercadante S. Pathophysiology and treatment of opioid-related myoclonus in cancer patients. Pain 1998; 74: 5-9.
3. Smith M. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. Clinical and Experimental Pharmacology and Physiology 2000; 27: 524-528.
4. Wright A, Mather L, Smith M. Hydromorphone-3-glucuronide, a more potent neuro-excitant than its structural analogue morphine-3-glucuronide. Life Sciences 2001; 69: 409-420.
5. Fast Facts are edited by David E. Weissman, MD; Palliative Care Center, Medical College of Wisconsin. For comments/questions write to: dweissma@mcw.edu. The complete set of Fast Facts are available at EPERC: www.eperc.mcw.edu

Fast Facts were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information: Users are free to d ownload and distribute Fast Facts for educational purposes only. Citation for referencing: Wilson RK and Weissman DE. Fast Facts and Concepts #57 Neuroexcitatory effect of opioids Part 1, 2 nd Edition. July 2006. End-of-Life / Palliative Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Purpose: Instructional Aid, Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain>opioids, Pain>evaluation