Effect of Innappropriate Naltrexone Use in a Heroin Misuser S H Boyce,Pararmstrong, J Stevenson

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CASE REPORTS Effect of innappropriate naltrexone use in a heroin misuser S H Boyce,PARArmstrong, J Stevenson ......

Emerg Med J 2003;20:381–382

Naltrexone is a long acting opioid receptor antagonist Box 1 Side effects of naltrexone use used in controlled opioid withdrawal drug programmes. When taken by an opioid dependent patient an acute • Nausea withdrawal reaction will be precipitated. The case is • Vomiting presented where a known opioid drug misuser inadvert- • Anxiety ently ingested naltrexone in conjunction with heroin result- • Headache ing in severe agitation, requiring heavy sedation followed • Sleep disturbance by general anaesthesia to enable investigation and • Lacrimation management of his clinical condition. • Diarrhoea • Sweating • Muscle/joint pains

altrexone is a long acting opioid receptor antagonist used in drug rehabilitation programmes to maintain occurred overnight requiring additional sedation with intra- Nopioid abstinence. However, when consumed in venous midazolam. The following morning he took his own conjunction with an opioid substance, prolonged opioid with- discharge. Retrospectively urine toxicology screen confirmed drawal will be precipitated resulting in unpredictable and life the presence of cannabinoids, benzodiazepines, and opioids. threatening medical consequences. We present a case where a known drug misuser consumed naltrexone in conjunction DISCUSSION with heroin. Naltrexone is a comparatively new medication used in drug rehabilitation programmes to maintain abstinence from CASE REPORT heroin and methadone and prevent relapse in former addicts. A 39 year old man presented to the accident and emergency Naltrexone is a competitive opioid receptor antagonist acting department having taken up to three, 50 mg tablets of at the µ and κ opioid receptors by blocking the euphoric effects naltrexone and having smoked an unknown quantity of of exogenous administered opioids. Naltrexone use is re- heroin. He was known to be an injecting drug user and to suf- stricted to specialist clinics and is initially given orally in doses fer from epilepsy. No other recreational drugs, alcohol, or pre- of 25 mg daily, increasing to 50 mg, with courses of treatment scribed medications were known to have been consumed. On lasting many months. The total weekly dose may be divided arrival he was extremely agitated being restrained by four and given on three days of the week only to improve patient police officers. He was confused, sweating, with episodes of compliance. Oral absorption of naltrexone is rapid with peak profuse projectile diarrhoea and vomiting. Glasgow Coma plasma concentrations occurring after three hours and Scale was 12 (spontaneous eye opening, localising to pain, and remains metabolically active for 24–72 hours, however, the using inappropriate speech). Pupils were dilated but reactive precise pharmacodynamics are not completely understood to light. Heart rate was regular at 180 beats/minute and respi- and large differences in serum concentrations of the drug are ratory rate 40 breaths/minute. Blood pressure, oxygen satura- thought to reflect variable first pass mechanism.1 Side effects tion, blood glucose, and temperature were normal. There was of naltrexone use are outlined in box 1. no evidence of head injury and no history of seizure. Urea, Before being given naltrexone, patients are required to be electrolytes, full blood count, and arterial blood gas measure- opioid free for a period of 7–10 days and undergo a supervised ments were normal. Initial attempts at sedation using a com- naloxone challenge before being accepted into a controlled bination of titrated intravenous midazolam and droperidol detoxification programme. Although the effects of the were unsuccessful. After receiving a total of 20 mg midazolam receptor block are surmountable, addicts are cautioned that and 15 mg droperidol he continued to be confused, agitated, attempts would require large amounts of opioids, which may and increasingly violent. An urgent CT head scan was lead to a fatal overdose.2 Naltrexone has also been adminis- arranged to exclude any intracranial pathology. To expedite tered to addicts, either alone or in combination with clonidine, this he was anaesthetised and ventilated. Rapid sequence under heavy sedation or general anaesthesia, a process known induction of anaesthesia was carried out using 200 mg propo- as ultra rapid opioid detoxification, in an attempt to reduce the fol, and 100 mg suxamethonium. Anaesthesia was maintained immediate symptoms of acute opioid withdrawal and begin a with a propofol infusion and incremental paralysis with atra- maintenance oral naltrexone programme earlier.3 Recent curium. studies have highlighted limited success using naltrexone in CT of his brain was normal. A lumbar puncture was the treatment of longstanding alcoholism by reducing the performed while the patient was still anaesthetised. This alcohol craving in this group.45 showed no abnormality. The patient was extubated four hours Accidental or intentional ingestion of naltrexone in opioid after induction and transferred to the medical high depend- dependent people will result in an acute block of opioid recep- ency unit for observation. Further episodes of agitation tors and precipitate a severe opioid withdrawal reaction.

www.emjonline.com 382 Boyce, Armstrong, Stevenson

required, however, antiemetics and oral diazepam for agitation Box 2 Management of naltrexone precipitated acute were given. After observation for 24 hours the patient was opioid withdrawal discharged with no adverse effects. • Sedation (benzodiazepines) Conclusion • Antiemetics (metclopropamide) The nature, severity, and duration of naltrexone induced acute • Intravenous fluids opioid withdrawal varies greatly between people and the • Non-opioid analgesia (non-steroidal preparations) clinical course of events is unpredictable. With the trend for • May require antispasmodic agents (hyoscine) more addicts to be treated with naltrexone in the community, • May require general anaesthesia and the possibility that current addicts may see naltrexone as a misguided means to break the cycle of drug dependence, the potential exists for increasing numbers of similar presenta- Symptoms of withdrawal can appear after only five minutes tions. Physicians involved in the emergency care of these following ingestion and may last up to 48 hours. Symptoms patients must be aware of the dramatic clinical course of the include confusion, agitation, hallucinations, sweating, tachy- ingestion of naltrexone in opioid misusers and be prepared to cardia, abdominal pain, and episodes of profuse vomiting manage the complications. and/or diarrhoea, which may result in significant fluid losses. Management is supportive with sedation (benzodiazepines), Contributors antiemetics (metclopropamide), intravenous fluids, and non- Stephen Boyce was involved in the research, overall coordination and opioid analgesia (non-steroidal preparations). Antispasmodic writing of the paper. Peter Armstrong identified the case and contrib- uted to the case report and literature search. James Stevenson was agents (hyoscine) may be required for intestinal cramps. involved in the research and writing of the paper. Both Stephen Boyce Opioid administration has no effect and is potentially danger- and James Stevenson will act as guarantors for the paper. ous. Greater doses of opioids would be required to reverse the receptor block and the resulting respiratory depression may be ...... deeper and more prolonged. Patients may become extremely Authors’ affiliations agitated and possibly violent requiring restraint, the adminis- SHBoyce,PARArmstrong, J Stevenson, Accident and Emergency tration of heavy sedation, and possibly general anaesthesia Department, Crosshouse Hospital, Kilmarnock, UK (see box 2). Correspondence to: Dr S Boyce, 176 Troon Avenue, Greenhills, East The problem of acute opioid withdrawal precipitated by Kilbride G75 8TJ, UK; [email protected] naltrexone appears to be an increasing problem for physicians. Two case reports have been published in the literature from Accepted for publication 1 March 2002 6 Italy in 1999, where an injecting heroin user and an ex-heroin REFERENCES 7 addict receiving methadone treatment both consumed 1 Ferrari A, Bertolotti M, Dell’Utri A, et al. Serum course of naltrexone and naltrexone. In each case, despite repeated attempts at 6 beta-naltrexone levels during long-term treatment in drug addicts. Drug sedation, both patients exhibited increasing agitation and Alcohol Depend 1998;52:211–20. 2 O’Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification delirium requiring to be anaesthetised with propofol, intu- techniques. JAMA 1998;279:229–34. bated, and ventilated. In each case the patients recovered with 3 Rabinowitz J, Cohen H, Tarrasch R, et al. Compliance to naltrexone no adverse effects. More recently concern regarding this pres- treatment after ultra-rapid opiate detoxification: an open label naturalistic 8 study. 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