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Anesth Analg 2002;95:944-947
© 2002 International Anesthesia Research Society

ANESTHETIC PHARMACOLOGY

Flumazenil Recovers Diaphragm Muscle Dysfunction Caused by Midazolam in Dogs

Yoshitaka Fujii, MD, Aki Uemura, MD, and Hidenori Toyooka, MD

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

Address correspondence and reprint requests to Yoshitaka Fujii, 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}igaku.md.tsukuba.ac.jp

We studied the effects of flumazenil on diaphragm muscle dysfunction caused by midazolam in dogs. Animals were divided into three groups of eight each. In each group, anesthetic doses (0.1 mg/kg initial dose plus 0.5 mg · kg-1 · h-1 maintenance dose) of midazolam were administered for 60 min. Immediately after the end of midazolam administration, Group 1 received no study drug; Group 2 was infused small-dose (0.004 mg · kg-1 · h-1) flumazenil; Group 3 was infused with large-dose (0.02 mg · kg-1 · h-1) flumazenil. We assessed diaphragm muscle function (contractility and electrical activity) by transdiaphragmatic pressure (Pdi) and integrated electrical activity of the diaphragm (Edi). After midazolam was administered in each group, Pdi at low-frequency (20-Hz) and high-frequency (100-Hz) stimulation decreased from baseline values (P < 0.05), and values of Edi at 100-Hz stimulation were less than those obtained during baseline (P < 0.05). In Group 1, Pdi and Edi to each stimulus did not change from midazolam-induced values. In Groups 2 and 3, with an infusion of flumazenil, Pdi at both stimuli and Edi at 100-Hz stimulation increased from midazolam-induced values (P < 0.05). The increase in Pdi and Edi was more in Group 3 than in Group 2 (P < 0.05). We conclude that flumazenil recovers the diaphragm muscle dysfunction (reduced contractility and inhibited electrical activity) caused by anesthetic doses of midazolam in dogs.

IMPLICATIONS: In dogs, flumazenil recovers diaphragm muscle dysfunction (reduced contractility and inhibited electrical activity) caused by midazolam in a dose-related manner.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2002 by the International Anesthesia Research Society.