Effects of diazepam on diaphragmatic functionand recovery in pentobarbital-anesthetized dogs: An open-label, dose-finding, pharmacologic study

Abstract

Background: Diazepam, a highly lipid-soluble benzodiazepine, is commonly used as a sedative agent during and after surgery. Based on a literature search, no published data are available concerning diaphragmatic function (as measured by contractility and electrical activity) during and after the administration of diazepam.

Objective: The purpose of this study was to assess the effects of diazepam use on diaphragmatic function and recovery in pentobarbital-anesthetized dogs.

Methods: This open-label, dose-finding, pharmacologic study was conductedat the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Healthy adult mongrel dogs weighing 10 to 15 kg were assigned to 1 of 3 study groups: low dose (0.2-mg/kg) diazepam, high-dose (0.5-mg/kg) diazepam, or control (no study drug). Each dog was anesthetized with pentobarbital 2 mg/kg · h IV Study drug was administered IV for 1 hour. Diaphragmatic function was assessed before (baseline) and at 0 (immediately after), 1, and 2 hours after the end of study drug administration, using measurement of transdiaphragmatic pressure (Pdi), defined as the difference between gastric and esophageal pressures, and by integrated electrical activity (20- and 100-Hz stimulation) of the crural (Edi-cru) and costal (Edi-cost) parts of the diaphragm. The percentage changes from baseline in Edi-cru (%Edi-cru) and Edi-cost (%Edi-cost) were calculated.

Results: Twenty-four mongrel dogs were used in the study; 8 dogs were assigned to each treatment group. During diazepam administration in the low-dose group, significant decreases from baseline in Pdi were found with 20-Hz stimulation (15.6 [1.7] vs 13.3 [1.9] cm H2O; P < 0.05) and 100-Hz stimulation (22.0 [2.1] vs 19.6 [1.8] cm H2O; P < 0.05). In the high-dose group, the decreases in Pdi were significant with 20-Hz stimulation (15.5 [1.8] vs 10.0 [2.0] cm H2O; P < 0.05) and 100-Hz stimulation (22.2 [1.9] vs 16.2 [ 2.0 ] cm H2O; P < 0.05). In the low-dose group at 100-Hz stimulation, mean (SD) %Edi-cru and %Edi-cost were significantly lower compared with baseline (88.8% [6.6%] and 88.5% [5.9%], respectively; both, P < 0.05). In the high-dose group at 100-Hz stimulation, mean (SD) %Edi-cru and %Edi-cost were significantly lower compared with baseline (77.5% [4.3%] and 78.0% [5.0%], respectively; both, P < 0.05). The decreases in Pdi, %Edi-cru, and %Edi-cost were significantly greater in the high-dose group compared with the low-dose group (all, P < 0.05).

Conclusion: The results of this experimental study of the effects of diazepamon diaphragmatic function and recovery in pentobarbital-anesthetized dogs suggest that diazepam inhibits diaphragmatic function in a dose-related manner and delays recovery.

Keywords: benzodiazepine; contractility; diaphragm; diazepam; muscle.