DISCUSSION

Naltrexone (half-life 4 hours) is liver-metabolized to 6B-naltrexol (half-life 13 hours),^{Reference Anton1} and excreted in the urine. Both are competitive reversible opioid receptor antagonists, strongest at the mu receptor (where they outcompete other opioids, including methadone), less strong at the kappa receptor, and weakest at the delta receptor. The combined effect is to lower mesolimbic dopamine concentration,^{Reference Anton1} reducing euphoria from opioid and alcohol use and decreasing cravings. It is first-line pharmacologic therapy for alcohol use disorder^{Reference Anton1} and possible alternative therapy for select patients with opioid use disorder. While a once-monthly depot version is approved in the United States,^{Reference Anton1} the only Canadian formulations are daily 25- and 50-mg tablets.

Naltrexone use may become more common for alcohol use disorder, and emergency physicians need to be aware of the consequences of its inappropriate ingestion. Because this is a competitive antagonist whose effects will persist at least 24 hours, patients generally require 7 days or more without opioids before its initiation^1–3; otherwise, administration can result in profound opioid withdrawal (COWS >36; in the first case, the score was 41) for 24–48 hours, and this can be life-threatening.^{Reference Armstrong, Little and Murray2–Reference Wrightman, Nelson, Lee, Fox and Smith4}

The diagnosis is exclusionary, as ominous metabolic, structural, traumatic, and additional toxicological entities also require consideration.^{Reference Armstrong, Little and Murray2–Reference Wrightman, Nelson, Lee, Fox and Smith4} Confirmatory serum (quantitative) and urine (qualitative) tests may not be available in all settings and results typically take days to return, outside the time frame for management.

In 132 patients at a single Iranian ED, nearly all (96.2%) had agitation, while approximately one-quarter each had nausea, vomiting, abdominal pain, and one-sixth had diarrhea. Ominously, the authors attributed a 32% “partial recovery” to a high incidence of aspiration pneumonia; one patient had a fatal myocardial infarction during the recovery phase.^{Reference Hassanian-Moghaddam, Afzali and Pooya3} An Australian ED described 18 patients considered to have primary gastrointestinal symptoms, treated chiefly with crystalloid fluid and antiemetics over a mean 11-hour length of stay. Fourteen patients had primarily severe agitation, treated with a mean dose of 211 mg of diazepam or midazolam over a mean length of stay of 23 hours; two patients required intubation for airway compromise.^{Reference Armstrong, Little and Murray2}

Lack of evidence-based guidelines adds to management challenges. Agitation can be managed with benzodiazepines. Nausea and vomiting are treated with antiemetics and airway protection is paramount.^{Reference Armstrong, Little and Murray2,Reference Hassanian-Moghaddam, Afzali and Pooya3} Fluid losses should be estimated and replaced with crystalloid to maintain blood pressure and urine output. Musculoskeletal pain should be managed with nonopioid analgesia, and withdrawal can be treated with clonidine 0.1–0.2 mg every 6 hours.^{Reference Armstrong, Little and Murray2} In consultation with addiction specialist or toxicologist, opioids with strong affinity for the mu receptor such as hydromorphone^{Reference Volpe, Tobin and Mellon5} can be considered for withdrawal management. While mean hospitalization time has been reported as 18 hours,^{Reference Armstrong, Little and Murray2} far longer stays occur if substantial sedation or intubation is required.^{Reference Armstrong, Little and Murray2–Reference Wrightman, Nelson, Lee, Fox and Smith4}