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

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

Author(s): Robin Wilson; David E. Weissman

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.

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 an increased need for opioid, 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 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 and appropriate to the clinical situation. Check renal and liver function; Check for low magnesium, glucose or sodium.

Once the assessment process is complete, a rational treatment decision can be made (see Fast Fact #58: Neuroexcitatory Effects of Opioids: Treatment).

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.

Mercadante S. Pathophysiology and treatment of opioid-related myoclonus in cancer patients. Pain 1998; 74: 5-9. Smith M. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. Clinical and Experimental Pharmacology and Physiology 2000; 27: 524-528.

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.

Copyright and Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing. Fast Facts and Concepts #57 Wilson RK and Weissman DE. Neuroexcitatory effects of opioids: Patient Assessment. December, 2001. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Fast Facts and Concepts was originally developed as an end-of-life teaching tool by Eric Warm, MD, U. Cincinnati, Department of Medicine. See: Warm, E. Improving EOL care--internal medicine curriculum project. J Pall Med 1999; 2: 339-340.

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.

Creation Date: 12/2001

Format: Handouts

Purpose: Instructional Aid, Self-Study Guide, Teaching

Training: Fellows, 1st/2nd Year Medical Students, 3rd/4th Year Medical Students, PGY1 (Interns), PGY2-6, Physicians in Practice
Specialty: Anesthesiology, Emergency Medicine, Family Medicine, General Internal Medicine, Geriatrics, Hematology/Oncology, Neurology, OB/GYN, Ophthalmology, Pulmonary/Critical Care, Pediatrics, Psychiatry, Surgery
Non-Physician: Nurses

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Addiction, Chronic non-malignant pain, Controlled substance regulations, Pain, Pain assessment, Pain treatment

The Fast Facts series is distributed for educational use only and does not constitute medical advice. For the most current version of Fast Facts visit the EPERC web site at www.eperc.mcw.edu. This mirror version is provided subject to copyright restrictions for educational use within the Inter-Instutional Collaborating Network on End-of-Life Care (IICN).