Physostigmine for gamma-hydroxybutyrate coma: inefficacy, adverse events, and review

Physostigmine has been proposed as an antidote for gamma hydroxybutyrate (GHB) intoxication, based on associated awakenings in 1) patients anesthetized with GHB and 2) five of six patients administered physostigmine for GHB intoxication. However, there are neither well-supported mechanisms for physostigmine reversal of GHB effects, supportive animal studies, nor randomized, placebo-controlled trials demonstrating safety, efficacy, or improved outcomes. We sought to determine the outcomes of patients with GHB-induced coma after a physostigmine treatment protocol was instituted in an urban Emergency Department and ambulance service. Our search of medical records located five cases of GHB toxicity, all with co-intoxicants, who received physostigmine. None demonstrated response and, further, there were associated adverse events, including atrial fibrillation (2), pulmonary infiltrates (1) and significant bradycardia (1), and hypotension (1). We also reviewed 18 published GHB toxicity case series for incidence of adverse effects, stimulant co-intoxicants (which may heighten risk of physostigmine), complications, and outcomes of supportive care for GHB toxicity. We conclude that physostigmine is not indicated for reversal of GHB-induced alteration of consciousness; it is not efficacious, it may be unsafe, particularly in the setting of recreational polydrug use; and supportive care results in universally good outcomes.