Effects of midazolam on cerebral hemodynamics and cerebral vasomotor responsiveness to carbon dioxide

Although it is known that hypercarbia increases and benzodiazepines decrease cerebral blood flow (CBF), the effects of benzodiazepines on CBF responsiveness to CO2 are not well documented. The influence on CBF and CBF-CO2 sensitivity of placebo or midazolam, which is a new water-soluble benzodiazepine, was measured in eight healthy volunteers using the noninvasive 133Xe inhalation method for CBF determination. Under normocarbia, midazolam decreased CBF from 40.6 +/- 3.2 to 27.0 +/- 5.0 ml 100 g-1 min-1 (means +/- SD). At a later session under hypercarbia, CBF was 58.8 +/- 4.4 ml 100 g-1 min-1 after administration of placebo, and 49.1 +/- 10.2 ml 100 g-1 min-1 after midazolam. The mean of the slopes correlating PaCO2 and CBF was significantly steeper with midazolam (2.5 +/- 1.2 ml 100 g-1 min-1 mm Hg-1) than with placebo (1.5 +/- 0.4 ml 100 g-1 min-1 mm Hg-1). Our results suggest that midazolam may be a safe agent to use in patients with intracranial hypertension, since it decreases CBF and thus cerebral blood volume; however, it should be administered with caution in nonventilated patients with increased intracranial pressure, since its beneficial effects on cerebrovascular tone can be readily counteracted by the increase in arterial CO2 tension induced by this drug.