Flumazenil recovers diaphragm muscle dysfunction caused by midazolam in dogs.

UNLABELLED: 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.