Effects of ketamine on cerebral blood flow velocity in humans. Influence of pretreatment with midazolam or esmolol

Abstract

During normoventilation and 'light', haemodynamically stable, steady-state anaesthesia with isoflurane 0.3%, the effect of ketamine intravenously was investigated in 24 patients randomly assigned to one of the following groups: group 1 (control group) no ketamine, group 2 (ketamine group) ketamine 2 mg.kg-1, group 3 (ketamine/midazolam group) ketamine 2 mg.kg-1 after pretreatment with midazolam and group 4 (ketamine/esmolol group) ketamine 2 mg.kg-1 while maintaining mean arterial blood pressure at a preketamine level with esmolol. Ketamine-induced cerebrovascular changes were measured by means of transcranial Doppler ultrasonography. Control readings in patients without ketamine challenge demonstrated stable cardiovascular and cerebrovascular baseline conditions. Cerebral blood flow velocity and mean arterial blood pressure, however, significantly increased after administration of ketamine without pretreatment. The increase in cerebral blood flow velocity could not be blocked by maintaining mean arterial blood pressure at baseline value with esmolol. In contrast, the effects of ketamine on cerebral blood flow velocity and mean arterial blood pressure were prevented by prior administration of midazolam. The results suggest that ketamine may significantly influence intracerebral haemodynamics via a direct drug effect rather than via a secondary effect due to changes in arterial carbon dioxide and/or mean arterial blood pressure.