From benzodiazepine to etomidate: A risky novel psychoactive substance

Etomidate is a hypnotic agent predominantly administered as anesthesia and is popular for its ultra-short-acting, rapid-distributing properties. Its primary mechanism of action is on gamma-aminobutyric acid type A receptors,[1] similar to propofol and benzodiazepines. After administration, liver esterases metabolized etomidate, which is hydrolyzed into an inactive metabolite, etomidate acid, of which 75% is excreted by the kidneys.[1,2]

Propofol has been regulated since the 2010s due to controversies surrounding adverse reactions and fatal incidents, causing etomidate to become an alternative for inducing sleep.[3] In recent years, studies reported problematic use, adverse reactions, and even fatalities related to etomidate,[4,5] including hypokalemia, hypocortisolism,[4] nausea, vomiting, and myoclonus.[3] Currently, research on the patterns of etomidate administration as a novel psychoactive substance is limited.

We report the case of a 21-year-old female patient diagnosed with attention-deficit/hyperactivity disorder during childhood but was not consistently followed up. She was diagnosed with other specified bipolar disorder and borderline personality disorder in adulthood. She and her cohabiting boyfriend earned by selling drug-laced coffee sachets, primarily containing synthetic cathinone mixtures. She began to excessively use benzodiazepines at approximately 18 years of age, and she developed tolerance to midazolam, flunitrazepam, and clonazepam at the age of 20 years. She began using etomidate via e-cigarette cartridges earlier this year to help herself sleep, purchasing them through social media after being introduced by a friend. The seller also provided home delivery services, with each cartridge costing approximately $55–60.

The patient initially used one cartridge every 3 days within a few months, but this escalated to 3–5 cartridges per day within 2 months. She experienced poisoning symptoms after use, including dissociation, myoclonus, and dystonia. Her family and friends attempted to prevent her from continuing etomidate cartridge usage due to her excessive use and difficulty reducing consumption. However, the patient demonstrated withdrawal symptoms, including anxiety, irritability, visual hallucinations, severe mood swings, suicidal ideation, and a strong craving for etomidate. Subsequently, she was admitted to a psychiatric ward and underwent a 3-day detoxification treatment. Her withdrawal, hallucinations, and affective symptoms were treated with oxazepam (90 mg/day), which is primarily metabolized by the kidneys, and aripiprazole (20 mg/day), which exhibits lower hepatotoxicity. Laboratory tests indicated no significant abnormalities in her electrolyte levels or endocrine system, and etomidate acid, a metabolite of etomidate, was found in her urine. After her discharge, she completely discontinued using etomidate for 2 weeks under family supervision. Her mood is currently stable, and she reports no other discomfort.

This case emphasized the clinical risks associated with etomidate as a sleep-inducing substance among emerging substance users. Further study is warranted to investigate the characteristics of high-risk populations for etomidate addiction and the presence of cross-tolerance with benzodiazepines.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initial will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.