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


CONCLUSIONS
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.
Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
Yoshitaka
Y
Fujii
benzodiazepine; contractility; diaphragm; diazepam; muscle