Top

Published in:

16-09-2022 | Flumazenil | Editorial

Caution!! Reappearance of remimazolam effect after a flumazenil bolus: a larger bolus of flumazenil and a lower total remimazolam clearance are higher risks

Author: Kenichi Masui

Published in: Journal of Anesthesia | Issue 1/2023

Excerpt

Remimazolam is a novel benzodiazepine anesthetic [1]. A previous study has suggested that large individual variability exists in appropriate remimazolam concentration for anesthesia maintenance [2]. As there are limited clinical experiences and limited studies, it may be difficult to determine the dosage of remimazolam during anesthesia maintenance. To avoid intraoperative awareness, remimazolam may be overdosed. The too high concentration may cause delayed recovery from remimazolam anesthesia. In such cases, one may consider the use of flumazenil, which is an antagonist of benzodiazepine, for immediate emergence from remimazolam anesthesia. …

Masui K. Remimazolam besilate, a benzodiazepine, has been approved for general anesthesia!! J Anesth. 2020;34:479–82.CrossRef

Schuttler J, Eisenried A, Lerch M, Fechner J, Jeleazcov C, Ihmsen H. Pharmacokinetics and pharmacodynamics of remimazolam (CNS 7056) after continuous infusion in healthy male volunteers: part I. Pharmacokinet Clin Pharmacodynam Anesthesiol. 2020;132:636–51.

Kheterpal S, Vaughn MT, Dubovoy TZ, Shah NJ, Bash LD, Colquhoun DA, Shanks AM, Mathis MR, Soto RG, Bardia A, Bartels K, McCormick PJ, Schonberger RB, Saager L. Sugammadex versus neostigmine for reversal of neuromuscular blockade and postoperative pulmonary complications (STRONGER): a multicenter matched cohort analysis. Anesthesiology. 2020;132:1371–81.CrossRef

Amrein R, Hetzel W, Hartmann D, Lorscheid T. Clinical pharmacology of flumazenil. Eur J Anaesthesiol Suppl. 1988;2:65–80.

Zwiers A, van den Heuve M, Smeets J, Rutherford S. Assessment of the potential for displacement interactions with sugammadex. Clin Drug Investig. 2011;31:101–11.CrossRef

Sparr Harald J, Vermeyen Karel M, Beaufort Anton M, Rietbergen H, Proost Johannes H, Saldien V, Velik-Salchner C, Wierda JMKH. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics. Anesthesiology. 2007;106:935–43.CrossRef

Le Corre F, Nejmeddine S, Fatahine C, Tayar C, Marty J, Plaud B. Recurarization after sugammadex reversal in an obese patient. Can J Anesth J Can D’anesth. 2011;58:944.CrossRef

Masui K, Stöhr T, Pesic M, Tonai T. A population pharmacokinetic model of remimazolam for general anesthesia and consideration of remimazolam dose in clinical practice. J Anesth. 2022;36:493–505.CrossRef

Fiset P, Lemmens HL, Egan TE, Shafer SL, Stanski DR. Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam. Clin Pharmacol Ther. 1995;58:567–82.CrossRef

10.

Freyer N, Knospel F, Damm G, Greuel S, Schneider C, Seehofer D, Stohr T, Petersen KU, Zeilinger K. Metabolism of remimazolam in primary human hepatocytes during continuous long-term infusion in a 3-D bioreactor system. Drug Des Devel Ther. 2019;13:1033–47.CrossRef

11.

Short TG, Young KK, Tan P, Tam YH, Gin T, Oh TE. Midazolam and flumazenil pharmacokinetics and pharmacodynamics following simultaneous administration to human volunteers. Acta Anaesthesiol Scand. 1994;38:350–6.CrossRef

12.

Masui K, Hagihira S. Equilibration rate constant, ke0, to determine effect-site concentration for the Masui remimazolam population pharmacokinetic model in general anesthesia patients. J Anesth. 2022. https://doi.org/10.1007/s00540-022-03099-8.CrossRef

13.

Kilpatrick GJ, McIntyre MS, Cox RF, Stafford JA, Pacofsky GJ, Lovell GG, Wiard RP, Feldman PL, Collins H, Waszczak BL, Tilbrook GS. CNS 7056: a novel Ultra–short-acting Benzodiazepine. Anesthesiolo J Am Soc Anesthesiol. 2007;107:60–6.

14.

Price JC, Mayberg HS, Dannals RF, Wilson AA, Ravert HT, Sadzot B, Rattner Z, Kimball A, Feldman MA, Frost JJ. Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C] flumazenil. J Cereb Blood Flow Metab. 1993;13:656–67.CrossRef

15.

Yamamoto T, Kurabe M, Kamiya Y. Re-sleeping after reversal of remimazolam by flumazenil. J Anesth. 2021;35:322.CrossRef

16.

Stöhr T, Colin PJ, Ossig J, Pesic M, Borkett K, Winkle P, Struys MMRF, Schippers F. Pharmacokinetic properties of remimazolam in subjects with hepatic or renal impairment. Br J Anaesth. 2021;127:415–23.CrossRef

Title: Caution!! Reappearance of remimazolam effect after a flumazenil bolus: a larger bolus of flumazenil and a lower total remimazolam clearance are higher risks
Author: Kenichi Masui
Publication date: 16-09-2022
Publisher: Springer Nature Singapore
Keywords: Flumazenil
Benzodiazepine
Rocuronium
Published in: Journal of Anesthesia / Issue 1/2023
Print ISSN: 0913-8668
Electronic ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-022-03107-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Caution!! Reappearance of remimazolam effect after a flumazenil bolus: a larger bolus of flumazenil and a lower total remimazolam clearance are higher risks

Excerpt

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Excerpt

Please log in to get access to this content

Other articles of this Issue 1/2023

Correction to: The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series

Does pericapsular nerve group block have limited analgesia at the initial post-operative period? Systematic review and meta-analysis

Response to a letter to the editor by Jia and Teng: remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery

Reply to “Re-sedation after a large dose of flumazenil”

Predictive factors for favorable short-term response to interlaminar epidural block for cervical radiculopathy

Tolerance to remimazolam at a high effect-site concentration