Remimazolam: Pharmacologic Considerations and Clinical Role in Anesthesiology

Abstract

Midazolam, fentanyl, and propofol are commonly used for sedation in modern anesthesia practice. These agents possess characteristics that have afforded various anesthetics to be delivered and produce relatively safe and effective outcomes. However, each agent has certain drawbacks in clinical practice. Remimazolam, a novel benzodiazepine created out of so-called soft drug development, is an ultrashort-acting intravenous sedative-hypnotic currently being investigated in clinical trials. In this review, we evaluate the recent literature on the use of remimazolam in clinical practice as compared with current sedative agents, and we describe its potential roles for use in sedation. A literature search of the Medline database (2012-May 2016) was performed. Additional references were identified from a review of literature citations, manufacturer reports, and professional meeting abstracts. All premarket studies involving remimazolam as the primary study drug were evaluated. Literature describing the pharmacokinetics and pharmacodynamics of remimazolam, propofol, and midazolam was also included. Phase I and II studies in the United States have shown remimazolam to be a safe and effective option for procedural sedation. Unlike midazolam and propofol, remimazolam undergoes organ-independent metabolism to an inactive metabolite. Because remimazolam follows first-order pharmacokinetics, prolonged infusions or higher doses are unlikely to result in accumulation and extended effect, making it favorable for use as an intravenous anesthetic and for sedation in the intensive care unit. It is expected that phase III trials will further describe the niche that remimazolam may be able to occupy in clinical practice. Postmarket cost-benefit analyses will need to be performed.

Psychomotor Recovery Following Remimazolam-induced Sedation and the Effectiveness of Flumazenil as an Antidote

“…22,23 With such structural modifications, remimazolam is extensively metabolized by plasma and tissue esterases, thereby resulting in an ultraeshort-acting sedative effect profile. 2 These properties make remimazolam a potential candidate to replace propofol and midazolam in procedural anesthesia.…”

Midazolam plasma concentration after anesthesia premedication in clinical routine - an observational study

“…If only intended for providing preoperative anxiolysis and not added as medication for maintaining the anesthetic, a reliably performing, shorter acting anxiolytic could be a more suiting companion for this purpose. If preferring a benzodiazepine, remimazolam may in the future be an interesting option [9]. …”

The effect of preoperative administration of morphine in alleviating intraoperative pain of percutaneous transforaminal endoscopic discectomy under local anesthesia

“…[ 4 , 20 ] Propofol, the most widely used sedative drug for its rapid onset and offset, can induce sedation by acting on γ-aminobutyric acid subtype A (GABA A ) receptors in the central nervous system and other tissues. [ 21 ] However, due to its adverse effects such as cardiorespiratory depression, a professional anesthetist is required to monitor the patient's vital signs during the operation. In the studies reported by Hoogland et al, [ 11 , 20 ] intravenous analgesia with opioid medication and midazolam sedation were used to enhance the effect of local anesthesia.…”

“…[ 22 ] But it shows significant disadvantages regarding to time of onset and offset. [ 21 ] Interestingly, a Cochrane review found that there was low-quality evidence that intravenous midazolam administered before a procedure reduced anxiety when compared with placebo. [ 23 ] Therefore, further studies are needed to evaluate the effect of intraoperative administration of sedative drugs in PTED surgery.…”