Case Report

Physician-Patient Miscommunication Results in Medication Error

Howard Greller, MD
Fellow, Medical Toxicology
New York City Poison Control Center
455 First Avenue - Room 123
New York, NY 10016

Lewis S. Nelson, MD
Assistant Professor of Clinical Surgery / Emergency Med

Int J Med Toxicol 2003; 6(1): 3



This case report is supported by an unrestricted educational grant from Orphan Medical, Inc.
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A Toxicologic Mystery

A 53-year-old man presents to the emergency department after taking the first dose of a medication prescribed to him by his private physician "for opioid withdrawal." He states that he last used heroin this morning, along with some methadone. He denies the use of alcohol, cocaine or other drugs of abuse. In the ED, he is agitated and diaphoretic. His heart rate is 112/min, RR 22/minute, and he is normotensive and afebrile. His finger stick blood glucose is 100 mg/dL, and the pulse oximeter reads 100% saturation on room air. His pupils are mildly dilated at 5 mm and they are reactive. His mucous membranes are moist; he has prominent, active bowel sounds and while in the ED he has an episode of diarrhea. His ECG shows sinus tachycardia at a rate of 112/minute, without axis or ischemic changes.

The bottle of medication is pictured here:

What was he prescribed?

Discussion

It was clear from the patient's initial presentation that he was suffering from acute opioid withdrawal. The classic constellation of symptoms includes nausea, vomiting, diaphoresis, yawning, rhinorrhea, piloerection, myalgias, arthralgias, and anxiety. While not a threat to life or limb, it is an emotionally and physically disturbing process. Therefore patients routinely seek, and physicians prescribe, medication "for opioid withdrawal." Some of the more common agents are listed below along with a brief synopsis of their clinical utility.

Methadone is a long acting synthetic opioid agonist, which is generally considered the treatment of choice for both the management and prevention of acute withdrawal. Because of its long half-life, it is dosed daily. However, the prescription of methadone for the treatment of opioid dependence is limited to federally mandated clinics and is not permitted by individual practioners. In contrast, in most states physicians may prescribe methadone for chronic pain. See www.methadone.org, or www.asam.org for more information. Recently, it appears that the company that produces parenteral methadone will no longer do so, raising interesting concerns for the emergency department management of opioid withdrawal.

Levo-α-acetylmethadol (LAAM) is an agent used similar to methadone in opioid substitution programs. Like methadone, it is a long-acting synthetic opioid agonist, with two active metabolites, and duration of effect of almost 4 days. It is scheduled for three times a week dosing. LAAM blocks the delayed rectifier current of cardiac repolarization (IKr), leading to prolongation of the QT interval and ventricular dysrhythmias at normal doses (there are also data linking high dose methadone to QT prolongation) [1, 2].

Clonidine, an α2-receptor antagonist, is used to reduce the autonomic consequences of opioid withdrawal. There may be functional overlap between the α2-receptor and the μ receptor in the locus ceruleus, possibly explaining why clonidine overdose resembles opioid intoxication, and can sometimes be reversed with naloxone. Clonidine is an effective adjunct to the standard therapies for opioid withdrawal, often used in conjunction with methadone. However, it does not blunt opioid craving, the primary reason that patients seek medical attention when withdrawing.

Benzodiazepines (GABAA agonists) and anti-emetics such as metoclopramide (ReglanŽ) are other agents commonly used in the treatment of opioid withdrawal. Benzodiazepines blunt the sympathetic outflow that results from the withdrawal from opioids, and are primarily a symptomatic treatment.

Buprenorphine is an interesting new agent. It is the first agent approved by the FDA for the office-based management of opioid addiction. It is a long acting partial agonist, with an elimination half-life of approximately 37 hours (see www.buprenorphine.samhsa.gov/about.html) that is typically prescribed on a three times a week dosing schedule. It is a schedule III medication, and physicians who prescribe it must undergo a special training program offered by a proprietary agency, the American Society of Addiction Medicine (www.asam.org), as well as the federal government. It is marketed in two forms, Subutex and Suboxone. Subutex is buprenorphine alone; Suboxone is buprenorphine and naloxone. Subutex is intended for use in the treatment of withdrawal, while Suboxone is intended for use in the maintenance treatment of opioid addiction. See also www.drugabuse.gov/NIDA_Notes/NNVol10N1/Bupren.html.

There are other agents that are associated with opioids and management of addiction. These concern themselves more with "detoxifying" the patient, rather than preventing or ameliorating withdrawal. Rapid Opioid Detoxification (ROD), Rapid Opioid Detoxification under Anesthesia (RODA) and Ultra Rapid Opioid Detoxification (UROD) are three of the different modalities used, with the promise of same day, outpatient treatment for opioid addiction. In these settings, patients are taken through a "controlled" opioid withdrawal, with various degrees of control ranging from mild sedation to general anesthesia. Once they have completed the withdrawal, they are given a cocktail of agents designed to mitigate the lingering effects of the withdrawal, which can last for up to one week. They are also given agents that are long acting opioid receptor antagonists, such as naltrexone, that prevent them from experiencing the euphoria of opioids. This therapy often results in high recidivism rates, and there have been a number of reports of serious adverse events. Recently, two physicians have had their licenses suspended, and heavy fines levied after the deaths of seven patients. See www.nytimes.com/2003/03/06/nyregion/06DOCS.html. [3].

Click here to see the agent this patient was prescribed.

Conclusion

The patient was unaware that the intent of this drug was to "induce opioid withdrawal" rather than to treat his withdrawal syndrome when it developed spontaneously. Thus, this case may also be viewed as a preventable medication error. The patient was attempting to do as the label indicated...he was trying to prevent the progression of opioid withdrawal as prescribed. This illustrates the importance of providers, pharmacists and patients communicating about the use and indication of prescribed medications.

References
  1. Katchman AN, McGroary KA, Kilborn MJ et al. Influence of Opioid Agonists on Cardiac Human Ether-a-go-go-related Gene K+ Currents. JPET 2002: 303; 688-694.
  2. Krantz, MJ, Lewkowiez L, Hays H et al. Torsade de Pointes Associated with Very-High-Dose Methadone. Ann Intern Med 2002: 137; 501-504.
  3. Hamilton RJ, Olmedo RE, Shah S et al. Complications of ultrarapid opioid detoxification with subcutaneous naltrexone pellets. Acad Emerg Med 2002: 9(1); 63-8.

 



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