Effect-Site Concentration of Remimazolam by Age Groups During Target-Controlled Infusion for Total Intravenous Anesthesia: A Retrospective Comparative Study.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-11-12 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S480734

Jaesik Park, Kwon Hui Seo, Jueun Kwak, Hyebin Baek

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引用次数: 0

Abstract

Purpose: Pharmacokinetic and pharmacodynamic (PKPD) models exist for remimazolam, but data for target-controlled infusion (TCI) are limited. The Schüttler PKPD model, a three-compartment model including body weight as a covariate, does not account for age as a variable. This study aimed to investigate remimazolam's effect-site concentration (Ce) in different age groups during sedation and general anesthesia with TCI using Schüttler PKPD model.

Patients and methods: Records of patients who underwent remimazolam TCI with the Schüttler model were reviewed. During anesthesia induction, the target Ce of remimazolam was gradually increased until loss of responsiveness, and it was titrated to maintain bispectral index of 40-70 during operation. Patients were categorized into young (20-40 years, n=24), middle-aged (41-60 years, n=27), and elderly (61-80 years, n=35) groups. Bispectral index and hemodynamic variables were also assessed.

Results: The elderly group had significantly lower remimazolam Ce compared to the young and middle-aged groups at all sedation levels, intubation, and surgery. Mean highest intraoperative Ce was 0.78±0.10, 0.71±0.07, and 0.61±0.10 µg/mL in young, middle-aged, and elderly groups, respectively (P<0.001). The recovery of responsiveness during emergence occurred at significantly lower Ce in the elderly group (0.28±0.06 µg/mL) than in the young (0.41±0.07 µg/mL) and middle-aged groups (0.35±0.07 µg/mL, P<0.001). Ce during sedation and general anesthesia was comparable between the young and middle-aged groups. The bispectral index was similar across groups but fluctuated more in the elderly group during general anesthesia. Elderly patients also showed the greatest systolic blood pressure suppression (18.4 ± 13.29% before intubation and 34.31 ± 14.91% during surgery).

Conclusion: Older patients may require lower target Ce during remimazolam TCI for sedation and anesthesia, with emergence occurring at lower Ce. Blood pressure suppression may be greater in elderly patients under deep sedation or general anesthesia.

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目标控制输注全静脉麻醉过程中各年龄组雷马唑仑的效应部位浓度：回顾性比较研究。

目的：雷米唑仑存在药代动力学和药效学（PKPD）模型，但用于靶控输注（TCI）的数据有限。Schüttler PKPD 模型是一个三室模型，其中体重是一个协变量，但该模型没有考虑年龄这一变量。本研究旨在使用 Schüttler PKPD 模型研究不同年龄组在使用 TCI 进行镇静和全身麻醉时瑞马唑仑的效应部位浓度（Ce）：回顾了使用 Schüttler 模型进行雷马唑仑 TCI 的患者记录。在麻醉诱导过程中，逐渐增加瑞马唑仑的目标浓度，直至失去反应性，并在手术过程中滴定以维持双光谱指数在 40-70 之间。患者分为青年组（20-40 岁，24 人）、中年组（41-60 岁，27 人）和老年组（61-80 岁，35 人）。同时还评估了双频谱指数和血液动力学变量：结果：与年轻组和中年组相比，老年组在所有镇静水平、插管和手术中的瑞马唑仑Ce都明显较低。年轻组、中年组和老年组术中平均最高 Ce 分别为 0.78±0.10、0.71±0.07 和 0.61±0.10 µg/mL（PPC 结论：老年患者可能需要更低的目标 Ce：老年患者在使用雷马唑仑TCI进行镇静和麻醉时可能需要较低的目标Ce，在较低的Ce下就会出现。深度镇静或全身麻醉时，老年患者的血压抑制可能会更严重。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.