A mechanism of re-sedation caused by remimazolam

Yamamoto, Tohei; Kurabe, Miyuki; Kamiya, Yoshinori

doi:10.1007/s00540-021-02930-y

Cited by 16 publications

(20 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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“…There has been an observation of re-sedation after flumazenil reversal ( Yamamoto et al, 2021b ; Yamamoto et al, 2021a ). This may have been due to residual remimazolam, the metabolite CNS 7054 building up to levels that can activate the GABA A receptor or a combination of both, potentially as a result of compromised organ function.…”

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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“…Compared with patients in the RT group, the EP group's onset time was significantly higher in (41 s vs 32 [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] s, p < 0.05; Table 3). However, there were no significant differences in the procedure time (p = 0.846) or cecal intubation time (p = 0.320) between the two groups (Table 3).…”

Section: Secondary Outcomesmentioning

confidence: 99%

“…39 A recent study highlighted the clinical benefits of using electroencephalogram measures, which significantly correlate with sedation scale scores and do not require patient stimulation. 39,40 We did not apply routine flumazenil reversal at the end of the colonoscopies because of the possibility of resedation and economic reasons. 41 Dehydration after bowel preparation combined with the vasodilatory effects of fentanyl is considered the main causes of perioperative hypotension.…”

mentioning

confidence: 99%

The Efficacy and Safety of Remimazolam Tosilate versus Etomidate-Propofol in Elderly Outpatients Undergoing Colonoscopy: A Prospective, Randomized, Single-Blind, Non-Inferiority Trial

Liu

Ding

Shi

et al. 2021

DDDT

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A mechanism of re-sedation caused by remimazolam

Cited by 16 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

The Efficacy and Safety of Remimazolam Tosilate versus Etomidate-Propofol in Elderly Outpatients Undergoing Colonoscopy: A Prospective, Randomized, Single-Blind, Non-Inferiority Trial

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