• Br J Anaesth · Jul 2022

    Randomized Controlled Trial

    Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study.

    • Dongwoo Chae, Hyun-Chang Kim, Young Song, Young Seo Choi, and Dong Woo Han.
    • Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea.
    • Br J Anaesth. 2022 Jul 1; 129 (1): 49-57.

    BackgroundRemimazolam is a new rapid offset benzodiazepine used for procedural sedation and general anaesthesia. This study evaluated the efficacy and safety of i.v. bolus remimazolam during induction of anaesthesia.MethodsA total of 120 patients undergoing general anaesthesia were randomly allocated into six dose groups (n=20) of i.v. bolus remimazolam (0.02-0.27 mg kg-1). Loss of consciousness, respiratory depression, patient state index (PSI), and haemodynamic variables were evaluated during anaesthetic induction. Parametric time-to-event models were used to identify the 50% effective dose (ED50)/95% effective dose (ED95) associated with loss of consciousness and respiratory depression. Non-linear mixed-effect models analysed the PSI and haemodynamic changes after i.v. bolus remimazolam.ResultsLoss of consciousness and respiratory depression onset showed steep dose-responses with ED50/ED95 of 0.11/0.19 and 0.14/0.27 mg kg-1 and Hill coefficients of 5.3 and 4.6, respectively. Older age was significantly associated with lower ED50/ED95 for both endpoints. ED50/ED95 and the Hill coefficient of PSI decline were 0.12/0.68 mg kg-1 and 1.7, respectively. We propose optimal doses of 0.25-0.33, 0.19-0.25, and 0.14-0.19 mg kg-1 in patients aged <40, 60-80, and >80 yr, respectively, based on the ED95 estimates for the corresponding age groups. The maximum percentage reduction of MAP was 27.8% and the ED50/ED95 were 0.14/2.60 mg kg-1. The effect of remimazolam on heart rate was insignificant.ConclusionsThe ED50/ED95s of i.v. bolus remimazolam were successfully estimated from the time to loss of consciousness and respiratory depression. No serious adverse events occurred within the range of tested doses.Clinical Trial RegistrationNCT04901871.Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…