• Shao-Ping Li, Xian-Long Zhou, and Yan Zhao.
• 169 Donghu Road, Emergency Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.
• Biomed. Pharmacother. 2020 Jan 1; 121: 109405.

BackgroundMechanical ventilation (MV) is identified as an independent contributor to diaphragmatic atrophy and contractile dysfunction. Appropriate sedation is also essential during MV, and anesthetics may have direct adverse effects on the diaphragm. However, there is a lack of research into the effects of different anesthetics on diaphragm function during MV.ObjectivesIn the present study, we aim to examine the effect of midazolam, dexmedetomidine, and propofol on diaphragm function during MV.DesignAnimal study.SettingUniversity research laboratory.SubjectsMale Wistar rats.InterventionsAnimals were experienced 12 h of MV or spontaneous breathing (SB) with continuous anesthetics infusion. Diaphragm contractile properties, cross-sectional areas, microcirculation, oxidative stress, and proteolysis were examined.Measurements And Main ResultsDiaphragmatic specific force was markedly reduced in the midazolam group compared with the dexmedetomidine (-60.4 ± 3.01%, p < 0.001) and propofol group (-58.3 ± 2.60%, p < 0.001) after MV. MV sedated with midazolam induced more atrophy of type II fibers compared with dexmedetomidine (-21.8 ± 2.11%, p = 0.0001) and propofol (-8.2 ± 1.53%, p = 0.003). No significant differences of these indices were found in the midazolam, dexmedetomidine, and propofol groups under SB condition (all p > 0.05, respectively). Twelve hours of MV resulted in a time dependent reduction in diaphragmatic functional capillary density (PB -25.1%, p = 0.0001; MZ -21.6%, p = 0.0003; DD -15.2%, p = 0.022; PP -24.8%, p = 0.0001, respectively), which did not occur in the gastrocnemius muscle. The diaphragmatic lipid peroxidation adducts 4-HNE and HIF-1α levels were significantly lower in dexmedetomidine group and propofol group compared to midazolam group (p < 0.05, respectively). Meanwhile, the catalase and SOD levels were also relatively lower (p < 0.05, respectively) in midazolam group compared to dexmedetomidine group and propofol group.ConclusionsTwelve hours of mechanical ventilation during midazolam sedation led to a more severe diaphragm dysfunction than dexmedetomidine and propofol, possibly caused by its relative weaker antioxidant capacity.Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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