title: 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.
authors: Department of Pharmacy, Lemuel Shattuck Hospital, Boston, Massachusetts.
authors: Alexandra M
authors: AM
authors: Wesolowski
authors: Harvard Medical School, Boston, Massachusetts.|Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Michael P
authors: MP
authors: Zaccagnino
authors: Harvard Medical School, Boston, Massachusetts.|Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors: Raymond J
authors: RJ
authors: Malapero
authors: Department of Anesthesiology, Louisiana State University Health Science Center, New Orleans, Louisiana.|Department of Pharmacology, Louisiana State University Health Science Center, New Orleans, Louisiana.
authors: Alan D
authors: AD
authors: Kaye
authors: Harvard Medical School, Boston, Massachusetts. rurman@partners.org.|Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts. rurman@partners.org.
authors: Richard D
authors: RD
authors: Urman
mesh_terms: D000776:Anesthesiology; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008874:Midazolam / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology
chemical_list: D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; C522201:remimazolam; D008874:Midazolam; D015742:Propofol
keywords: anesthesia; benzodiazepine; hypnotic; midazolam; remimazolam; sedative