Anesth Pain Med.  2022 Jul;17(3):262-270. 10.17085/apm.21121.

Effect-site concentration of remimazolam at loss and recovery of responsiveness during general anesthesia: a simulation study

• Kim KM
• Bang JY
• Lee JM
• Yang HS
• Choi BM
• Noh GJ

• KMID: 2535318
• DOI: http://doi.org/10.17085/apm.21121

Abstract

Background
The objective of this study was to investigate the effect-site concentration (Ce) of remimazolam at loss of response (LOR) and recovery of response (ROR) in patients underwent general anesthesia using simulation. In addition, the relationships between patient’s factors and simulated Ce at LOR and ROR were examined. Methods: The medical records of 81 patients who underwent elective surgery under general anesthesia using remimazolam with simulation of Ce between August 4, 2021 and October 12, 2021, were retrospectively reviewed. Remimazolam was administered as an induction dose of 6 or 12 mg/kg/h until the patient became unresponsive, followed by 0.3–2 mg/kg/ h to maintain BIS values below 60. Simultaneously, simulations of manual infusion mode were performed using Asan Pump software and the Ce of remimazolam was simulated using the Schüttler model. Whenever infusion rate of remimazolam was manually changed, the simulated Ce was confirmed almost simultaneously. LOR and ROR, defined as unresponsive and eye-opening to verbal commands, respectively, were recorded in the Asan Pump program. Results: The median (1Q, 3Q) simulated Ce at LOR and ROR were 0.7 (0.5, 0.9) and 0.3 (0.2, 0.4) μg/ml, respectively. LOR was achieved in 1.9 min after remimazolam infusion with cumulative doses of 0.3 mg/kg. There was a significant relationship between age and simulated Ce at ROR (Ce at ROR = –0.0043 × age + 0.57, r = 0.30, P = 0.014). Conclusions: For optimal dosage adjustment, simulating Ce while administering remimazolam with a weight-based dose during anesthesia is helpful. Elderly patients may recover from anesthesia at lower Ce of remimazolam.

Keyword

Anesthesia; Concentration; Hypnotic; Remimazolam; Simulation

Figure

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  Fig. 1. Simulated effect-site concentration (Ce) at the time of loss of responsiveness (LOR). Data are expressed as median (1Q, 3Q). Red horizontal lines indicate median values. *P < 0.001 vs. infusion rate 6 (Mann–Whitney Rank Sum Test).

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  Fig. 2. The relationship between age and simulated effect-site concentration (Ce) at the time of loss of responsiveness (LOR, A) and at the time of recovery of responsiveness (ROR, B). Red solid line represents linear regression of the Ce at ROR vs. Age (Ce at ROR = –0.0043 × age + 0.57, r = 0.30, P = 0.014).

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  Fig. 3. Simulated effect-site concentration (Ce) at the time of recovery of responsiveness (ROR). Data are expressed as median (1Q, 3Q). Red horizontal line indicates median value.

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  Fig. 4. The relationship between the probability of recovery of responsiveness (ROR) and effect-site concentration of remimazolam. The estimates of Ce50,ROR (effect-stie concentration of remimazolam, associated with 50% probability for recovery of responsiveness) and γ (steepness of the concetration-response curve) are 0.632 – 0.205 × (age/56) μg/ml and 32.3, respectively. Ce50,ROR and Ce95,ROR (effect-stie concentration of remimazolam, associated with 95% probability for recovery of responsiveness) are 0.34 μg/ml and 0.31 μg/ml for a hypothetical patient aged 80 year, 0.45 μg/ml and 0.41 μg/ml for a hypothetical patient aged 50 year, 0.52 μg/ml and 0.48 μg/ml for a hypothetical patient aged 30 year, respectively.

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