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ANESTHETIC PHARMACOLOGY

Midazolam-Induced Muscle Dysfunction and Its Recovery in Fatigued Diaphragm in Dogs

Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan

Address correspondence and reprint requests to Yoshitaka Fujii, MD, Department of Anesthesiology, University of Tsukuba, Institute of Clinical Medicine, 2-1-1, Amakubo, Tsukuba City, Ibaraki 305-8576, Japan. Address e-mail to yfujii{at}md.tsukuba.ac.jp

Midazolam, widely used for sedation and anesthesia, decreases contractility in nonfatigued diaphragm; however, its effects on contractility in fatigued diaphragm that are implicated as a cause of respiratory failure have not been established. We therefore studied the effects of midazolam on diaphragm muscle function and recovery in fatigued diaphragm. Dogs were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. When fatigue was established, Group I received no study drug; Group II was infused with a sedative dose (0.1 mg · kg^-1 · h^-1) of midazolam; and Group III was infused with an anesthetic dose (0.5 mg · kg^-1 · h^-1) of midazolam. We assessed diaphragm muscle function (contractility and electrical activity) by transdiaphragmatic pressure (Pdi) and integrated electrical activity of the diaphragm (Edi). In the presence of fatigue, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), Pdi at high-frequency (100-Hz) stimulation did not change, and Edi to each stimulus did not change. With an infusion of midazolam, in Groups II and III, Pdi at both stimuli and Edi at 100-Hz stimulation decreased from fatigued values (P < 0.05). The decrease in Pdi and Edi was more in Group III than in Group II (P < 0.05). At 60 min after the cessation of midazolam administration, in Group II, Pdi and Edi recovered from midazolam-induced values (P < 0.05) and returned to fatigued values. In Group III, Pdi and Edi did not change from midazolam-induced values. We conclude that midazolam causes, in a dose-related manner, diaphragm muscle dysfunction in fatigued canine diaphragm and that at a sedative dose, but not at an anesthetic dose, midazolam does not delay its recovery.

IMPLICATIONS: Midazolam, widely used for sedation and anesthesia, inhibits diaphragm muscle function in fatigued diaphragm in dogs in a dose-dependent manner.

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