已发表罗库溴铵药代动力学/药效学模型的神经肌肉终点预测能力：一项观察性试验。

Neuromuscular end-point predictive capability of published rocuronium pharmacokinetic/pharmacodynamic models: An observational trial.

机构信息

Department of Anesthesia and Perioperative Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Belgium; Department of Anesthesiology and Reanimation, AZ Sint Jan Brugge-Oostende, Belgium.

Department of Anesthesia and Perioperative Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Belgium.

出版信息

J Clin Anesth. 2023 Nov;90:111225. doi: 10.1016/j.jclinane.2023.111225. Epub 2023 Aug 3.

DOI:10.1016/j.jclinane.2023.111225

PMID:37542918

Abstract

BACKGROUND

Objective neuromuscular monitoring remains the single most reliable method to ensure optimal perioperative neuromuscular management. Nevertheless, the prediction of clinical neuromuscular endpoints by means of Pharmacokinetic (PK) and Pharmacodynamic (PD) modelling has the potential to complement monitoring and improve perioperative neuromuscular management.s STUDY OBJECTIVE: The present study aims to assess the performance of published Rocuronium PK/PD models in predicting intraoperative Train-of-four (TOF) ratios when benchmarked against electromyographic TOF measurements.

DESIGN

Observational trial.

SETTING

Tertiary Belgian hospital, from August 2020 up to September 2021.

PATIENTS AND INTERVENTIONS

Seventy-four patients undergoing general anaesthesia for elective surgery requiring the administration of rocuronium and subject to continuous EMG neuromuscular monitoring were included. PK/PD-simulated TOF ratios were plotted and synchronised with their measured electromyographic counterparts and their differences analysed by means of Predictive Error derivatives (Varvel criteria).

MAIN RESULTS

Published rocuronium PK/PD models overestimated clinically registered TOF ratios. The models of Wierda, Szenohradszky, Cooper, Alvarez-Gomez and McCoy showed significant predictive consistency between themselves, displaying Median Absolute Performance Errors between 38% and 41%, and intra-individual differences (Wobble) between 14 and 15%. The Kleijn model outperformed the former with a lower Median Absolute Performance Error (16%, 95%CI [0.01; 57]) and Wobble (11%, 95%CI [0.01; 34]). All models displayed considerably wide 95% confidence intervals for all performance metrics, suggesting a significantly variable performance.

CONCLUSIONS

Simulated TOF ratios based on published PK/PD models do not accurately predict real intraoperative TOF ratio dynamics.

TRIAL REGISTRATION

NCT04518761 (clinicaltrials.gov), registered on 19 August 2020.

摘要

背景

客观的神经肌肉监测仍然是确保围手术期最佳神经肌肉管理的唯一最可靠方法。然而，通过药代动力学（PK）和药效动力学（PD）建模来预测临床神经肌肉终点具有补充监测和改善围手术期神经肌肉管理的潜力。

研究目的

本研究旨在评估已发表的罗库溴铵 PK/PD 模型在预测术中四成肌松监测（TOF）比时的性能，将其与肌电图 TOF 测量进行基准比较。

设计

观察性试验。

地点

比利时三级医院，时间为 2020 年 8 月至 2021 年 9 月。

患者和干预措施

纳入 74 例行全身麻醉的择期手术患者，这些患者需要给予罗库溴铵，并接受连续肌电图神经肌肉监测。绘制 PK/PD 模拟的 TOF 比，并与他们的肌电图测量值同步，并通过预测误差导数（Varvel 标准）分析它们之间的差异。

主要结果

已发表的罗库溴铵 PK/PD 模型高估了临床上记录的 TOF 比。Wierda、Szenohradszky、Cooper、Alvarez-Gomez 和 McCoy 的模型在彼此之间显示出显著的预测一致性，显示出中位数绝对性能误差在 38%至 41%之间，个体内差异（摆动）在 14%至 15%之间。Kleijn 模型表现优于前一种模型，中位数绝对性能误差较低（16%，95%CI [0.01；57]）和摆动（11%，95%CI [0.01；34]）。所有模型的所有性能指标的 95%置信区间都相当宽，表明性能变化显著。