Re-sleeping after reversal of remimazolam by flumazenil

Yamamoto, Tohei; Kurabe, Miyuki; Kamiya, Yoshinori

doi:10.1007/s00540-021-02915-x

Cited by 49 publications

(40 citation statements)

References 5 publications

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“…Accordingly, after administration of flumazenil, patients should be monitored for re-sedation, respiratory depression, and other persistent or recurrent hypnotic effects for a sufficient time period. In practice, routine administration of flumazenil to reverse remimazolam-induced sedation is not recommended because of the likelihood of rebound sedation [ 49 , 50 ].…”

Section: Clinical Applications Of Remimazolammentioning

confidence: 99%

Remimazolam: pharmacological characteristics and clinical applications in anesthesiology

Kim

2022

Anesth Pain Med

118

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A novel ultra-short-acting benzodiazepine (BDZ), remimazolam (CNS 7056), has been designed by ‘soft drug’ development to achieve a better sedative profile than that of the current drugs. Notably, the esterase linkage in remimazolam permits rapid hydrolysis to inactivate metabolites by non-specific tissue esterase and induces a unique and favorable pharmacological profile, including rapid onset and offset of sedation and a predictable duration of action. Similar to other BDZs, its sedative effects can be reversed using flumazenil, a BDZ antagonist. The pharmacokinetics and pharmacodynamics of remimazolam are characterized by relatively high clearance, small steady-state volume of distribution, short elimination half-life, short context-sensitive half-life, and fast onset and recovery, indicating rapid elimination, minimal tissue accumulation, and good control. In addition, remimazolam possesses a superior safety profile, including low liability for cardiorespiratory depression and injection pain, making it a preferred hypnotic agent in various clinical settings. Early clinical investigations suggest that remimazolam is well tolerated and effective for procedural sedation and for induction and maintenance of general anesthesia. To date, however, the clinical use of remimazolam has been confined to a few volunteer studies and a limited number of clinical investigations. Therefore, further studies regarding its recovery issues or postoperative complications, characteristics of electroencephalogram changes, and cost-benefit analyses are required to facilitate its widespread use.

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Section: Clinical Applications Of Remimazolammentioning

confidence: 99%

Remimazolam: pharmacological characteristics and clinical applications in anesthesiology

Kim

2022

Anesth Pain Med

118

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“…Individuals carrying these variants may be at risk of extended effects of remimazolam and other drugs metabolized by this enzyme. Extended effects of remimazolam have occasionally been observed ( Zhou et al, 2020a ; Yamamoto et al, 2021b ), and further evaluation of the correlation of genetic variations in CES1 and the pharmacokinetics of remimazolam are warranted as well as interaction studies with other drugs known to be metabolized by this enzyme. Alcohol is a known inhibitor of CES1 ( Parker et al, 2015 ) and is reported to increase the exposure (C max ) to remimazolam by 1.2–2.1 fold in a dose-dependent manner ( Pesic et al, 2020b ).…”

Section: Remimazolammentioning

confidence: 99%

Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent

Kilpatrick¹

2021

Front. Pharmacol.

127

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A program to identify novel intravenous sedatives with a short and predictable duration of action was initiated in the late 1990’s by Glaxo Wellcome. The program focussed on the identification of ester-based benzodiazepine derivatives that are rapidly broken down by esterases. Remimazolam was identified as one of the lead compounds. The project at Glaxo was shelved for strategic reasons at the late lead optimization stage. Via the GSK ventures initiative, the program was acquired by the small biotechnology company, TheraSci, and, through successive acquisitions, developed as the besylate salt at CeNeS and PAION. The development of remimazolam besylate has been slow by industry standards, primarily because of the resource limitations of these small companies. It has, however, recently been approved for anesthesia in Japan and South Korea, procedural sedation in the United States, China, and Europe, and for compassionate use in intensive care unit sedation in Belgium. A second development program of remimazolam was later initiated in China, using a slightly different salt form, remimazolam tosylate. This salt form of the compound has also recently been approved for procedural sedation in China. Remimazolam has the pharmacological profile of a classical benzodiazepine, such as midazolam, but is differentiated from other intravenous benzodiazepines by its rapid conversion to an inactive metabolite resulting in a short onset/offset profile. It is differentiated from other intravenous hypnotic agents, such as propofol, by its low liability for cardiovascular depression, respiratory depression, and injection pain. The benzodiazepine antagonist flumazenil can reverse the effects of remimazolam in case of adverse events and further shorten recovery times. The aim of this review is to provide an analysis of, and perspective on, published non-clinical and clinical information on 1) the pharmacology, metabolism, pharmacokinetics, and pharmacodynamic profile of remimazolam, 2) the profile of remimazolam compared with established agents, 3) gaps in the current understanding of remimazolam, 4) the compound’s discovery and development process and 5) likely future developments in the clinical use of remimazolam.

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“…However, a re-sedation case in a patient who was aroused following flumazenil administration was reported. 15 Re-sedation is likely to occur following the administration of a large volume of remimazolam during general anesthesia. However, even brief sedation can result in re-sedation.…”

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confidence: 99%

Efficacy and Safety Profile of Remimazolam for Sedation in Adults Undergoing Short Surgical Procedures

Morimoto¹

2022

TCRM

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Sedation for short-term procedures is increasingly being used in clinical practice. Selection of appropriate drugs is important for effective and safe sedation; however, an ideal sedative remains unavailable. Remimazolam is a novel, ultrafast-acting benzodiazepine with a shorter duration of action than other agents in this class. It is currently expected to become a popular agent for short-term procedural sedation. Remimazolam shows higher clearance, a smaller volume of distribution, and a shorter half-life than midazolam. It showed dose-dependent sedative action, with onset of sedation within 60s of administration. The results of clinical trials indicate that remimazolam is more useful than midazolam for short procedural sedation such as in patients who undergo colonoscopy and that its safety profile is comparable with that of midazolam. Anesthesia-induced vascular pain is lesser and reduction in blood pressure is lesser with remimazolam than with propofol. Moreover, the availability of flumazenil (a benzodiazepine antagonist) is a specific advantage of remimazolam. These characteristics and the results of clinical trials suggest that remimazolam will be a safer alternative to previous sedative drugs for sedation during the short surgical procedures. Although short-acting agents are useful, they might lead to immediate hyper-sedation. Remimazolam is a promising agent for short-term procedural sedation; however, clinicians should be mindful of the risks of this agent.

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Re-sleeping after reversal of remimazolam by flumazenil

Cited by 49 publications

References 5 publications

Remimazolam: pharmacological characteristics and clinical applications in anesthesiology

Remimazolam: pharmacological characteristics and clinical applications in anesthesiology

Remimazolam: Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent

Efficacy and Safety Profile of Remimazolam for Sedation in Adults Undergoing Short Surgical Procedures

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