Simulation of residual sedation effect of remimazolam: pharmacokinetic–pharmacodynamic simulation can be an additional standard anesthesia monitoring method

Obara, Shinju

doi:10.1007/s00540-021-02963-3

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…Therefore, the dose was not lowered any further, and propofol was additionally administered. Also, the attending anesthesiologists had background knowledge of pharmacokinetic/pharmacodynamic simulation that the resultant RzCe of 0.25 µg/mL corresponds to remimazolam 0.3 mg/kg/h, indicating that the probability of the MOAA/S ⩽1 (i.e., equal or deeper than the level where a subject responds only after painful trapezius squeeze) is less than 5%, 29 which may have dictated clinical behavior. It is undeniable that remimazolam 0.3 mg/kg/h alone could have been maintained without the addition of propofol.…”

Section: Discussionmentioning

confidence: 99%

Total intravenous anesthesia management with simultaneous use of remimazolam and propofol: A case series of three patients

Watanabe,

Obara,

Inoue

2023

SAGE Open Medical Case Reports

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Remimazolam is an ultra-short-acting benzodiazepine anesthetic agent. Because of pharmacodynamic interactions in the sedation effect between benzodiazepines and propofol, the combination of remimazolam and propofol may allow for a dose reduction of each agent while providing effective sedation for general anesthesia. We experienced three cases in which general anesthesia was induced with remimazolam and maintained with relatively small doses of remimazolam and propofol target-controlled infusion. In all cases, electroencephalogram changes associated with sedation induced by remimazolam were carefully observed during anesthesia induction before administration of propofol. The time required for recovery from anesthesia was 8–13 min. This is the first report in which remimazolam and propofol were concomitantly used for general anesthesia based on the concept of pharmacodynamic interaction. This anesthetic combination may be beneficial in reducing doses of each anesthetic and avoiding delayed recovery from anesthesia, although further study is needed to confirm this.

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Section: Discussionmentioning

confidence: 99%

Total intravenous anesthesia management with simultaneous use of remimazolam and propofol: A case series of three patients

Watanabe,

Obara,

Inoue

2023

SAGE Open Medical Case Reports

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“…In terms of optimal dosage adjustment, therefore, it would be clinically advantageous if the individual remimazolam Ce could be simulated and applied in clinical practice rather than simply traditional observations of autonomic response along with monitoring of depth of anesthesia. The feasibility of predicting the potential remimazolam effects by estimating the Ce of anesthetics using pharmacokinetic/pharmacodynamic simulation has also been reported [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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 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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“…They documented that flumazenil cannot completely reverse remimazolam, similar to the relationship between rocuronium and sugammadex, and it shows merely competitive antagonism against benzodiazepines [20,35]. Unfortunately, there are no detailed data on the loss of the efficacy of flumazenil administered as an antagonist to remimazolam; moreover, there are no recommendations for flumazenil dose to date [36]. Therefore, routine administration of flumazenil for remimazolam reversal is not recommended due to the likelihood of re-sedation occurrence [2].…”

Section: Considerable Adverse Events Related To Remimazolammentioning

confidence: 99%

Clinical profile of a new anesthetic: remimazolam

Lee

Kim

2023

Med Biol Sci Eng

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Remimazolam is a novel ultrashort-acting benzodiazepine that acts on g-aminobutyric acid A receptor. It has been approved for use as a general anesthetic and sedative. This medication is recommended for inducing and maintaining anesthesia using continuous intravenous infusion; however, bolus dosing of remimazolam can also be adopted. Continuous intravenous infusion should be started at a rate of 6 or 12 mg/kg/h until loss of consciousness is achieved. Subsequently, this infusion rate should be decreased at a rate of 1 mg/kg/h as appropriate to maintain proper anesthetic depth (maximum allowable rate, 2 mg/kg/h). These recommended doses show more stable hemodynamics than those of propofol. The clinical profiles of anesthesia induction and maintenance are comparable between remimazolam and propofol. Although remimazolam has a slightly longer anesthetic induction time than propofol, the results are not inferior to each other. Recovery profiles show somewhat contradictory results, but the effects of remimazolam and propofol are comparable. Whether the bispectral index or other anesthetic depth indices are suitable for monitoring the sedative effect of remimazolam remains controversial. The appropriate ranges of electroencephalography (EEG) indices for remimazolam are unclear, but it has higher EEG indices than propofol. Thus, co-administration of opioids with a low dose of remimazolam is recommended to maintain the appropriate ranges for patients. Despite the favorable effects of remimazolam, the risk of re-sedation should always be considered after remimazolam reversal, especially when using flumazenil. Thus, remimazolam is considered comparable with propofol for inducing general anesthesia.

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Simulation of residual sedation effect of remimazolam: pharmacokinetic–pharmacodynamic simulation can be an additional standard anesthesia monitoring method

Cited by 7 publications

References 18 publications

Total intravenous anesthesia management with simultaneous use of remimazolam and propofol: A case series of three patients

Total intravenous anesthesia management with simultaneous use of remimazolam and propofol: A case series of three patients

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

Clinical profile of a new anesthetic: remimazolam

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