IngentaConnect Comparison of effects of propofol and midazolam at sedative conce...

Abstract:

Background:

Propofol and midazolam are common sedatives for critically ill patients. Little is known about the effects of propofol and midazolam on central sympathetic activity when drug concentrations in extracellular milieu are under precise control. Previous work using an in vitro neonatal rat splanchnic nerve-spinal cord preparation has demonstrated that tonic sympathetic activity is generated spontaneously in the thoracic spinal cord. The aim of this study was to investigate the concentration effects of propofol and midazolam on spinally generated sympathetic activity. Methods:

Using an in vitro neonatal rat splanchnic nerve-spinal cord preparation that allows the precise control of drug concentrations, the central sympathetic effects elicited by the application of propofol (10-640 μm) and midazolam (10-640 μm) were compared. Results:

There was a prompt decrease in sympathetic activity on application of propofol or midazolam in a concentration-dependent manner. A significant decrease in sympathetic activity was observed on application of propofol at 80-640 μm; however, the application of propofol at 10-40 μmcaused only a slight alteration in activity. The sympathetic activity was not altered significantly by 10 μmof midazolam, but the application of midazolam at 20-640 μmcaused a significant decrease in activity. Thus, in these experimental conditions, the minimum concentration of propofol causing a significant decrease in sympathetic activity was 80 μmand that of midazolam was 20 μm. Conclusions:

The current findings suggest that the administration of 9-19 μmof propofol or 0.7-0.9 μmof midazolam, the clinically relevant concentrations for sedation, does not alter central sympathetic outflow at the spinal cord level. However, propofol at a concentration of 86 μm, which could be achieved by a single-bolus loading dose to induce sedation, depresses central sympathetic activity.

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Comparison of effects of propofol and midazolam at sedative concentrations on sympathetic tone generation in the isolated spinal cord of neonatal rats