New horizons for sedation: The ultrashort acting benzodiazepine remimazolam

Procedural sedation is used in 98% of endoscopies performed in the United States. The predominant agents used are benzodiazepines, opioids, and propofol. The optimal sedation depends on the procedure being performed and its duration. An ideal sedative would allow for flexible, rapid onset and offset of sedation with predictable short duration of action with minimal cardiopulmonary risk factors. Remimazolam is a novel “soft drug” with the characteristics of a benzodiazepine and organ-independent metabolism. Remimazolam binds selectively and with high affinity to the gamma-aminobutyric acid receptor, with no off-target activities. In animal studies, remimazolam has a short, initial phase half-life and high volume of distribution, indicating extensive tissue distribution, minimal tissue accumulation, and rapid elimination. Remimazolam is hydroxylated to an inactive metabolite, and its effects can be reversed with flumazenil. In clinical studies for procedural sedation, remimazolam was well tolerated with no serious adverse events. Times to onset or offset of sedation were shorter with remimazolam versus active control. All remimazolam-related adverse reactions are well known to clinicians and can be managed by trained staff. This article summarizes the preclinical and clinical data on the efficacy and safety or remimazolam for endoscopic sedation. Remimazolam is in clinical development for procedural sedation, general anesthesia, and sedation in the intensive care unit. Remimazolam is a promising new sedative or anesthetic agent with scientific support for continued clinical development. Phase III studies with remimazolam for procedural sedation are underway.