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. 2022 May 18;17(5):e0268568.
doi: 10.1371/journal.pone.0268568. eCollection 2022.

Factors affecting prolonged time to extubation in patients given remimazolam

Yoko Shimamoto  1 , Michiyoshi Sanuki  1 , Shigeaki Kurita  1 , Masaya Ueki  1 , Yoshie Kuwahara  1 , Ayumu Matsumoto  1
Affiliations

Factors affecting prolonged time to extubation in patients given remimazolam

Yoko Shimamoto et al. PLoS One. .

Abstract

Purpose: To analyze the cause of prolonged recovery from general anesthesia with remimazolam.

Methods: We studied 65 patients under general anesthesia with remimazolam. According to time to extubation, patients were divided into short period (SP) (n = 34, < 15 min) and long period (LP) (n = 31, ≥ 15 min) groups. Variables affecting time to extubation such as age, sex, height, body weight, body mass index (BMI), plasma albumin concentration, ASA class, duration of surgery, and total duration of general anesthesia, and total dose of remimazolam were compared between SP and LP groups. At the end of remimazolam infusion and upon extubation, predictive remimazolam concentrations were calculated using pharmacokinetic/pharmacodynamic three compartment modeling.

Results: LP group showed significantly higher BMI, older age, and lower plasma albumin concentration compared with those of SP group. Logistic regression analysis showed that the probability of time to extubation of ≥ 15 min was higher in patients with BMI greater than 22.0 kg/m2 (AUC 0.668, 95% CI 0.533‒0.803), ages older than 79.0 years (AUC 0.662, 95% CI 0.526‒0.798), and plasma albumin concentrations lower than 3.60 g/dl (AUC 0.720, 95% CI 0.593‒0.847). LP group showed significantly lower predicted remimazolam concentration than SP group upon extubation despite no difference in concentration between both groups at the end of infusion. Pharmacological analysis estimates that LP group is more sensitive to remimazolam than SP group through amplified responses.

Conclusions: Lower remimazolam doses should be considered for the overweight patients, elderly, and those with lower plasma albumin concentration.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Receiver‒operating characteristic curve.
(a) Time to extubation ≥ 15 min for body mass index (BMI) over 22.0 kg/m2. (b) Time to extubation ≥ 15 min for age over 79.0 years. (c) Time to extubation ≥ 15 min for plasma albumin concentration below 3.60 g/dl.
Fig 2
Fig 2. Predicted remimazolam concentration.
(a) at the end of infusion. (b) at the extubation. SP, short period group; LPF(-), long period group without flumazenil; LPF(+), long period group with flumazenil.
Fig 3
Fig 3. Schematic representation of the dose-response curve; log predicted remimazolam concentration on X-axis, and linear central nervous system effect on Y-axis.
The dose-response curve in the SP group was shifted to the left in the LPF(-) group. a: Central nervous system effect at the end of infusion in the LPF(-) group. b: Central nervous system effect at the end of infusion in the SP group. c: Central nervous system effect at the extubation in the SP and LPF(-) groups. Open circle and open triangle: SP group. Filled circle and filled triangle: LPF(-) group. X1 and X2 refer to the difference between the log predicted concentration at the end of infusion and that at the extubation in the SP and LPF(-) groups, respectively. X2 is significantly greater than X1. Y1 and Y2 refer to the change in response between the SP and LPF(-) groups, respectively. Since the triangleΔ○□ and the triangle ●▲■ are similar figures. The ratio of Y2 to Y1 is determined by a following formula, Y2/Y1 = X2 /X1. Because X2 is significantly greater than X1, Y2 is estimated to be larger than Y1. SP, short period group; LPF(-), long period group without flumazenil.
See this image and copyright information in PMC

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