Remimazolam: An Updated Review of a New Sedative and Anaesthetic

Abstract

Remimazolam (CNS7056) is a novel benzodiazepine for intravenous sedation; it has an ultra-short duration of action and was recently approved for use in procedural sedation and general anaesthesia. It acts on γ-aminobutyric acid type A receptors and is rapidly converted into an inactive metabolite by tissue esterase enzymes. Remimazolam has been successfully used in endoscopic inspection or surgery and general anaesthesia induction and maintenance with fast and predictable onset and recovery times, high procedure success rates, and minor respiratory and hemodynamic fluctuations and without serious drug-related adverse reactions. If needed, the effects of remimazolam can be reversed by flumazenil, which allows prompt termination of sedation. Although remimazolam has great potential for sedation in patients admitted to intensive care units, future studies are needed to evaluate its efficacy and safety in patients requiring sedation for a long period, and numerous studies are warranted to explore the optimal dose in different application scenarios. The review aimed to provide an introduction to the process of remimazolam synthesis and its current clinical uses and future clinical developments.

Anesthetic Concerns in Psychiatric Disease

“…It has smaller effects on the respiratory and circulatory systems than propofol and midazolam, and may be a potentially safer option for pediatric, geriatric, and obese populations and those with multiple comorbidities. However, additional work is needed to determine safety of long-term use and use in ICU sedation, and to determine optimal dosing for specific indications [44,45].…”

Remimazolam for sedation: A protocol for a systematic review with meta‐analysis, trial sequential analysis, and GRADE approach

“…The US Food and Drug Administration approved remimazolam for procedural sedation in July 2020, and the European Medicines Agency approved remimazolam for procedural sedation in August 2021. 12 The clinical use of remimazolam varies and the drug has been approved for general anaesthesia in Japan since January 2020 and in China since November 2021. During the COVID-19 pandemic, Belgian authorities approved remimazolam for compassionate use in COVID-19-positive patients if midazolam and propofol were unavailable.…”

Remimazolam and serious adverse events

“…Similarly with other benzodiazepines, flumazenil is a competitive antagonist and can be used to reverse the sedation caused by remimazolam. 4 However, unlike earlier reviews reporting a favourable safety profile, worrisome case reports concerning anaphylaxis, delayed emergence, and resedation have emerged recently and necessitate further investigation. Two recent editorials have highlighted the potential of anaphylaxis related to remimazolam.…”

“…Its negative effects on the cardiovascular and respiratory system during sedation and general anaesthesia are generally weaker than propofol and better tolerated. Similarly with other benzodiazepines, flumazenil is a competitive antagonist and can be used to reverse the sedation caused by remimazolam 4 …”

“…3 When compared with midazolam, the pharmacokinetic properties of remimazolam were found to be a three times larger systemic clearance (70 l h À1 ), a similar volume of distribution (35 l), a significantly shorter terminal half-life (0.75 h), and most importantly, a very short contextsensitive half-time that forms a plateau at 7 to 8 min after an infusion of 2 h. Between 65 and 90 kg, clearance seemed to be independent of body weight. 4 Like midazolam, remimazolam has a highly selective affinity for the GABA A -receptor benzodiazepine site.…”