Remimazolam and serious adverse events: A scoping review

Remimazolam is anticipated to be an interesting anaesthetic and sedative. It combines the pharmacodynamic properties of midazolam with pharmacokinetic properties similar to remifentanil. However, worrisome case reports of anaphylaxis, delayed emergence and re-sedation have emerged recently and necessitate further investigation.PubMed (including MEDLINE) and EMBASE were searched for all studies reporting serious adverse events where remimazolam was administered for sedation or anaesthesia.Thirty-six case reports and 73 trials were identified, involving a total of 6740 patients who received remimazolam. Hypotension was reported in 911 cases, delayed emergence in 68 cases, anaphylaxis in 10 cases and re-sedation in 8 cases. The incidence of hypotension seems to be lower compared with other anaesthetics, even in high-risk patients.Delayed emergence might be related to the metabolism of remimazolam through carboxylesterase 1 (CES1), a tissue esterase predominant in the liver. There is significant interindividual variation, and it is inhibited by flavonoids, fatty acids and alcohol. Individual benzodiazepine sensitivity has also been reported. A higher BMI, older age and low plasma albumin concentration are risk factors for delayed emergence. Anaphylaxis might be related to a non-IgE-mediated effect of the excipient dextran-40 or a partially IgE-mediated reaction to remimazolam itself. Resedation has been reported after flumazenil reversal and is explained by the specific pharmacokinetic properties of flumazenil and remimazolam. Reversal by flumazenil should be reserved for and used carefully in patients with delayed emergence.

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