An Experimental Study to Optimize Neuromuscular Blockade Protocols in Cynomolgus Macaques: Monitoring, Doses, and Antagonism

IF 0.8 4区农林科学 Q3 VETERINARY SCIENCES

Journal of Medical Primatology Pub Date : 2024-09-22 DOI:10.1111/jmp.12736

Hélène Letscher, Julien Lemaitre, Emma Burban, Roger Le Grand, Pierre Bruhns, Francis Relouzat, Aurélie Gouel-Chéron

{"title":"An Experimental Study to Optimize Neuromuscular Blockade Protocols in Cynomolgus Macaques: Monitoring, Doses, and Antagonism","authors":"Hélène Letscher, Julien Lemaitre, Emma Burban, Roger Le Grand, Pierre Bruhns, Francis Relouzat, Aurélie Gouel-Chéron","doi":"10.1111/jmp.12736","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Neuromuscular blocking agents (NMBAs) are a crucial component of anesthesia and intensive care through the relaxation of skeletal muscles. They can lead to adverse reactions such as postoperative residual neuromuscular block. Only one agent is capable of an instant block reversal in deep block situations, but is restricted to aminosteroid agents. Among animal models, non-human primates are an essential model for a great diversity of human disease models. The main objective of this study was to establish a model for NMBA monitoring with current available drugs before testing new reversal agents.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Seven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anesthesia was maintained with isoflurane. Either rocuronium bromine (with or without sugammadex reversal) or atracurium besylate was evaluated. Monitoring was performed with two devices, TOF-Watch and ToFscan, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann–Whitney statistical analyses were done when indicated.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>NMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrode placement, to be efficient and valid in cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro-muscular block at equivalent doses to clinical doses in humans. The rocuronium-induced profound neuromuscular block could be reversed using the cyclodextrin sugammadex as a reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>These results support the use of non-human primate models for neuromuscular block monitoring. This represented the first step before the forthcoming testing of new NMBA-reversal agents.</p>\n </section>\n </div>","PeriodicalId":16439,"journal":{"name":"Journal of Medical Primatology","volume":"53 5","pages":""},"PeriodicalIF":0.8000,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jmp.12736","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Primatology","FirstCategoryId":"97","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jmp.12736","RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Neuromuscular blocking agents (NMBAs) are a crucial component of anesthesia and intensive care through the relaxation of skeletal muscles. They can lead to adverse reactions such as postoperative residual neuromuscular block. Only one agent is capable of an instant block reversal in deep block situations, but is restricted to aminosteroid agents. Among animal models, non-human primates are an essential model for a great diversity of human disease models. The main objective of this study was to establish a model for NMBA monitoring with current available drugs before testing new reversal agents.

Methods

Seven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anesthesia was maintained with isoflurane. Either rocuronium bromine (with or without sugammadex reversal) or atracurium besylate was evaluated. Monitoring was performed with two devices, TOF-Watch and ToFscan, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann–Whitney statistical analyses were done when indicated.

Results

NMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrode placement, to be efficient and valid in cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro-muscular block at equivalent doses to clinical doses in humans. The rocuronium-induced profound neuromuscular block could be reversed using the cyclodextrin sugammadex as a reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count.

Conclusion

These results support the use of non-human primate models for neuromuscular block monitoring. This represented the first step before the forthcoming testing of new NMBA-reversal agents.

Abstract Image

查看原文本刊更多论文

优化猕猴神经肌肉阻断方案的实验研究：监测、剂量和拮抗

背景神经肌肉阻滞剂（NMBA）通过松弛骨骼肌而成为麻醉和重症监护的重要组成部分。它们可能导致不良反应，如术后残留神经肌肉阻滞。只有一种药物能够在深度阻滞情况下立即逆转阻滞，但仅限于类固醇药物。在动物模型中，非人灵长类动物是多种人类疾病模型的重要模型。本研究的主要目的是在测试新的逆转剂之前，用现有药物建立一个 NMBA 监测模型。方法七只健康雄性猕猴被随机分配到本研究中。使用猕猴进行的实验已获得当地伦理委员会的批准（CEtEA #44）。所有动物均按照机构指南使用氯胺酮和美托咪定进行麻醉，并进行静脉置管和气管插管。异氟醚维持麻醉。对溴化洛库铵（使用或不使用苏加麦克斯逆转）或苯磺酸阿曲库铵进行了评估。使用 TOF-Watch 和 ToFscan 两种设备进行监测，分别测量 T4/T1 和 T4/Tref 比率。必要时进行非参数 Mann-Whitney 统计分析。结果与人类相比，NMBA 监测需要调整刺激强度和电极位置，才能在猕猴中有效进行。给药时，两种 NMBA 都能诱导深度和持续的神经肌肉阻滞，其剂量与人类的临床剂量相当。环糊精苏麦得可作为逆转剂逆转罗库溴铵诱导的深度神经肌肉阻滞。通过临床观察、血液生化或全血计数，我们发现这些模型未出现不良反应。结论这些结果支持使用非人灵长类动物模型进行神经肌肉阻滞监测。这为即将进行的新型 NMBA 逆转剂测试迈出了第一步。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Medical Primatology 生物-动物学

CiteScore

1.40

自引率

42.90%

发文量

审稿时长

6 months

期刊介绍： The Journal of Medical Primatology publishes research on non-human primates as models to study, prevent, and/or treat human diseases; subjects include veterinary medicine; morphology, physiology, reproductive biology, central nervous system, and cardiovascular diseases; husbandry, handling, experimental methodology, and management of non-human primate colonies and laboratories; non-human primate wildlife management; and behaviour and sociology as related to medical conditions and captive non-human primate needs. Published material includes: Original Manuscripts - research results; Case Reports - scientific documentation of a single clinical study; Short Papers - case histories, methodologies, and techniques of particular interest; Letters to the Editor - opinions, controversies and sporadic scientific observations; Perspectives – opinion piece about existing research on a particular topic; Minireviews – a concise review of existing literature; Book Reviews by invitation; Special Issues containing selected papers from specialized meetings; and Editorials and memoriams authored by the Editor-in-Chief.