The Effect of Flumazenil (Ro 15–1788) in the Management of Self‐induced Benzodiazepine Poisoning

Abstract

Abstract. A double‐blind randomized study was performed to evaluate the efficacy and safety of flumazenil, a benzodiazepine antagonist. The study comprised 52 patients admitted to an intensive care unit because of suspected pure or mixed benzodiazepine poisoning. The degree of consciousness was assessed according to a modified Glasgow Coma Scale (MGCS), graded from 4 to 20, immediately before and at consecutive intervals after an i.v. injection of flumazenil or placebo. If there were no clear signs of arousal within 5 min after the blind injection, an injection of flumazenil was given in open design. Five minutes after the blind administration of active drug the MGCS score was increased by an average of 7.4 (p<0.001) in the flumazenil group. In the placebo group the average MGCS score of 7.8 on admission was not significantly increased by placebo, but 5 min after flumazenil injection it had increased by 7.3 to 15.1 (p<0.001). Patients who had ingested both alcohol and benzodiazepines were aroused as promptly and clearly (MGCS +8.8; p<0.001) as those who had taken benzodiazepines alone (MGCS +8.4; p<0.001). The patients poisoned with a combination of benzodiazepines and other hypnotic drugs responded less, but still highly significantly (MGCS +5.8; p<0.001). Flumazenil was well tolerated and the safety of the antidote seems acceptable. It is concluded that flumazenil can facilitate differential diagnosis and that it is an effective tool in the treatment of drug overdosage when benzodiazepines are involved.

Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication – A Systematic Review with Meta‐Analyses of Randomised Trials

“…The present meta‐analyses included 13 trials with a total of 994 randomised (990 treated and evaluable) patients . All trials were randomised, double‐blind, placebo‐controlled, prospective trials.…”

“…Three trials had exclusion criteria related to the use of benzodiazepines: known or suspected benzodiazepine overdose , known therapeutic use of benzodiazepines and known hypersensitivity to benzodiazepines . One trial excluded patients with the evidence of alcohol or tricyclic antidepressants (TCAs) ingestion , and four trials excluded patients with (severe) organic injury and/or liver or renal impairment . Another four trials excluded patients with known or suspected brain trauma, new neurological findings or epilepsy .…”

“…In all included trials, a total of 720 patients (72.4%) were intoxicated with benzodiazepines. Ten studies provided information about single‐ versus multi‐drug intoxication with benzodiazepine on total 596 patients, and of these, 205 patients suffered from a single‐drug intoxication with benzodiazepines and 391 patients suffered from a multi‐drug intoxication with the most common other drugs being: ethanol, anxiolytics (including barbiturates), opioids and TCAs . Three studies did not provide information about co‐ingested drugs .…”

“…All included trials administered flumazenil intravenously and initial dose of flumazenil varied from 0.1 mg to 2.5 mg. Total flumazenil dose varied from 1.0 to 10.0 mg (table ). Nine studies informed about average used flumazenil dose, which varied from 0.77 to 7.13 mg (table ) .…”

How Are Patients Who Are Admitted to the Intensive Care Unit after Common Poisonings Diagnosed and Managed?

“…15 Gastrointestinal decontamination strategies used to decrease absorption include gastric emptying (GE) with ipecac or gastric lavage, single-dose activated charcoal (AC), or whole bowel irrigation (WBI). Comatose patients require assessment for hypoglycemia and treatment with oxygen, naloxone, and thiamine.…”