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

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      https://www.riss.kr/link?id=A108210025

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      다국어 초록 (Multilingual 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) g/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.
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      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 relations...

      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) g/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.

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      참고문헌 (Reference)

      1 한동우, "마취 영역에서 약동, 약력 모형화" 대한마취통증의학회 9 (9): 77-86, 2014

      2 Minto CF, "Using the time of maximum effect site concentration to combine pharmacokinetics and pharmacodynamics" 99 : 324-333, 2003

      3 Sanders RD, "Unresponsiveness ≠ unconsciousness" 116 : 946-959, 2012

      4 Louizos C, "Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships" 17 : 34-91, 2014

      5 Holford NH, "Understanding the dose-effect relationship : clinical application of pharmacokinetic-pharmacodynamic models" 6 : 429-453, 1981

      6 Lohmer LL, "Time-to-event modeling for remimazolam for the indication of induction and maintenance of general anesthesia" 60 : 505-514, 2020

      7 Absalom AR, "Target-controlled infusion : a mature technology" 122 : 70-78, 2016

      8 Obara S, "Simulation of residual sedation effect of remimazolam : pharmacokinetic-pharmacodynamic simulation can be an additional standard anesthesia monitoring method" 36 : 167-170, 2022

      9 Doi M, "Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial" 34 : 491-501, 2020

      10 Nakanishi T, "Remimazolam for induction of anesthesia in elderly patients with severe aortic stenosis: a prospective, observational pilot study" 21 : 306-, 2021

      1 한동우, "마취 영역에서 약동, 약력 모형화" 대한마취통증의학회 9 (9): 77-86, 2014

      2 Minto CF, "Using the time of maximum effect site concentration to combine pharmacokinetics and pharmacodynamics" 99 : 324-333, 2003

      3 Sanders RD, "Unresponsiveness ≠ unconsciousness" 116 : 946-959, 2012

      4 Louizos C, "Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships" 17 : 34-91, 2014

      5 Holford NH, "Understanding the dose-effect relationship : clinical application of pharmacokinetic-pharmacodynamic models" 6 : 429-453, 1981

      6 Lohmer LL, "Time-to-event modeling for remimazolam for the indication of induction and maintenance of general anesthesia" 60 : 505-514, 2020

      7 Absalom AR, "Target-controlled infusion : a mature technology" 122 : 70-78, 2016

      8 Obara S, "Simulation of residual sedation effect of remimazolam : pharmacokinetic-pharmacodynamic simulation can be an additional standard anesthesia monitoring method" 36 : 167-170, 2022

      9 Doi M, "Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial" 34 : 491-501, 2020

      10 Nakanishi T, "Remimazolam for induction of anesthesia in elderly patients with severe aortic stenosis: a prospective, observational pilot study" 21 : 306-, 2021

      11 Zhou J, "Population pharmacokinetic/pharmacodynamic modeling for remimazolam in the induction and maintenance of general anesthesia in healthy subjects and in surgical subjects" 66 : 109899-, 2020

      12 Park JH, "Population pharmacokinetic analysis of propofol in underweight patients under general anaesthesia" 121 : 559-566, 2018

      13 Platten HP, "Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction" 63 : 552-560, 1998

      14 Eisenried A, "Pharmacokinetics and pharmacodynamics of remimazolam (CNS 7056) after continuous infusion in healthy male volunteers: part II. Pharmacodynamics of electroencephalogram effects" 132 : 652-666, 2020

      15 Schüttler J, "Pharmacokinetics and clinical pharmacodynamics" 132 : 636-651, 2020

      16 Beal SL, "NONMEM users guide"

      17 Minto CF, "Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development" 86 : 10-23, 1997

      18 Iwakiri H, "Individual effect-site concentrations of propofol are similar at loss of consciousness and at awakening" 100 : 107-110, 2005

      19 Doi M, "Efficacy and safety of remimazolam versus propofol for general anesthesia : a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial" 34 : 543-553, 2020

      20 Sukumar V, "Effect site concentration of propofol at induction and recovery of anaesthesia-a correlative dose-response study" 62 : 263-268, 2018

      21 Liu T, "Effect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: a randomized, double-blind, controlled trial" 9 : e00851-, 2021

      22 Nakayama J, "Anesthetic management of super-elderly patients with remimazolam : a report of two cases" 7 : 71-, 2021

      23 Bertz RJ, "Alprazolam in young and elderly men : sensitivity and tolerance to psychomotor, sedative and memory effects" 281 : 1317-1329, 1997

      24 Antonik LJ, "A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): part I. Safety, efficacy, and basic pharmacokinetics" 115 : 274-283, 2012

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      2012-01-01 평가 등재후보학술지 유지 (기타) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 0.13 0.13 0.12
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      0.13 0.13 0.279 0.04
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