Hélène Letscher, Julien Lemaitre, Emma Burban, Roger Le Grand, Pierre Bruhns, Francis Relouzat, Aurélie Gouel-Chéron
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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":"{\"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. 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An Experimental Study to Optimize Neuromuscular Blockade Protocols in Cynomolgus Macaques: Monitoring, Doses, and Antagonism
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.
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.
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