Opioid withdrawal in the emergency setting
- Andrew Stolbach, MD, MPH, FAACT, FACMT, FACEP
Andrew Stolbach, MD, MPH, FAACT, FACMT, FACEP
- Associate Professor of Emergency Medicine
- Johns Hopkins University
- Robert S Hoffman, MD
Robert S Hoffman, MD
- Professor of Emergency Medicine
- Director, Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine
- New York University School of Medicine
- Section Editor
- Stephen J Traub, MD
Stephen J Traub, MD
- Section Editor — Toxicology
- Associate Professor of Emergency Medicine
- Mayo Medical School
- Deputy Editor
- Jonathan Grayzel, MD, FAAEM
Jonathan Grayzel, MD, FAAEM
- Senior Deputy Editor — UpToDate
- Deputy Editor — Emergency Medicine (Adult and Pediatric)
- Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Assistant Professor of Emergency Medicine
- University of Massachusetts Medical School
Opiates, extracted from the poppy plant (Papaver somniferum), have been used recreationally and medicinally for millennia. Opiates belong to the larger class of drugs, the opioids, which include synthetic and semi-synthetic drugs, as well.
The Drug Abuse Warning Network in the United States estimates there were 162,137 heroin-related emergency department visits and 37,007 unspecified opiate-related emergency department visits in 2004 . In addition to opioid overdose, a significant number of these visits related to opioid withdrawal.
This topic review will discuss the clinical features and management of opioid withdrawal in the emergency setting. A summary table to facilitate emergency management is provided (table 1). Discussions of opioid withdrawal during detoxification treatment, opioid intoxication, opioid withdrawal in neonates, and general management of the poisoned patient are found elsewhere. (See "Medically supervised opioid withdrawal during treatment for addiction" and "Acute opioid intoxication in adults" and "Neonatal abstinence syndrome" and "General approach to drug poisoning in adults".)
PHARMACOLOGY AND CELLULAR TOXICOLOGY
Repeated, regular use of opioids produces tolerance that predisposes an individual toward withdrawal. Chronic opioid exposure causes adaptations that increase excitability in neurons in the locus ceruleus, the major noradrenergic center in the brain. The presence of opioids brings these neurons toward their normal firing rates .
The vast number of opioids precludes presenting pharmacokinetic data for each one here. A few clinically important generalizations can be made. The majority of opioids have volumes of distribution of 1 to 10 L/kg, which makes removal of a significant quantity of drug by hemodialysis impossible. They have variable protein binding (from 89 percent for methadone to 7.1 percent for hydrocodone) and are renally eliminated. Many opioids are metabolized to active metabolites. Examples include hydrocodone (metabolized to hydromorphone by Cytochrome [CY] P2D6) and morphine (metabolized to morphine-6-glucuronide). Cytochrome P polymorphisms cause variations in clinical effect.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- United States Substance Abuse and Mental Health Services Administration. Emergency Department Data. http://www.samhsa.gov/data/emergency-department-data-dawn/reports. (Accessed on October 10, 2016).
- Nestler EJ. Under siege: The brain on opiates. Neuron 1996; 16:897.
- Wesson DR, Ling W. The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs 2003; 35:253.
- Tompkins DA, Bigelow GE, Harrison JA, et al. Concurrent validation of the Clinical Opiate Withdrawal Scale (COWS) and single-item indices against the Clinical Institute Narcotic Assessment (CINA) opioid withdrawal instrument. Drug Alcohol Depend 2009; 105:154.
- Dahan A, Yassen A, Romberg R, et al. Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth 2006; 96:627.
- Boas RA, Villiger JW. Clinical actions of fentanyl and buprenorphine. The significance of receptor binding. Br J Anaesth 1985; 57:192.
- Aghajanian GK, Wang YY. Common alpha 2- and opiate effector mechanisms in the locus coeruleus: intracellular studies in brain slices. Neuropharmacology 1987; 26:793.
- Gold MS, Redmond DE Jr, Kleber HD. Clonidine blocks acute opiate-withdrawal symptoms. Lancet 1978; 2:599.
- Ling W, Amass L, Shoptaw S, et al. A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network. Addiction 2005; 100:1090.
- Ahmadi-Abhari SA, Akhondzadeh S, Assadi SM, et al. Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial. J Clin Pharm Ther 2001; 26:67.
- Elman I, D'Ambra MN, Krause S, et al. Ultrarapid opioid detoxification: effects on cardiopulmonary physiology, stress hormones and clinical outcomes. Drug Alcohol Depend 2001; 61:163.
- Suzuki T, Tsuda M, Narita M, et al. Diazepam pretreatment suppresses morphine withdrawal signs in the mouse. Life Sci 1996; 58:349.
- Streel E, Verbanck P. Ultra-rapid opiate detoxification: from clinical applications to basic science. Addict Biol 2003; 8:141.
- Dervan LA, Yaghmai B, Watson RS, Wolf FM. The use of methadone to facilitate opioid weaning in pediatric critical care patients: a systematic review of the literature and meta-analysis. Paediatr Anaesth 2017; 27:228.
- Sanchez-Pinto LN, Nelson LP, Lieu P, et al. Implementation of a risk-stratified opioid weaning protocol in a pediatric intensive care unit. J Crit Care 2017; 43:214.
- PHARMACOLOGY AND CELLULAR TOXICOLOGY
- CLINICAL FEATURES OF OPIOID WITHDRAWAL
- Physical examination
- DIFFERENTIAL DIAGNOSIS
- LABORATORY EVALUATION
- Withdrawal from interruption in opioid use
- - Opioid agonist therapy
- - Buprenorphine
- Withdrawal due to opioid antagonist and other circumstances not amenable to treatment with opioid agonist
- - Non-opioid adjunctive medications
- Treatment of symptoms
- Ultrarapid opioid detoxification
- ADDITIONAL RESOURCES
- NEONATAL AND PEDIATRIC CONSIDERATIONS
- Neonatal withdrawal
- Children receiving intensive care
- SUMMARY AND RECOMMENDATIONS