Effects of ephedrine, dobutamine and dopexamine on cerebral haemodynamics: transcranial Doppler studies in healthy volunteers

Abstract

Sympathomimetic drugs are assumed to have no direct effects on cerebral haemodynamics on the basis of animal experiments; there is little evidence of their direct effects in humans. This study aimed to address this issue. The effects of ephedrine, dobutamine, and dopexamine on cerebral autoregulation, cerebral vascular reactivity to carbon dioxide, estimated cerebral perfusion pressure, and zero flow pressure (ZPF) were studied in 10 healthy volunteers using transcranial Doppler ultrasound. The strength of autoregulation was measured using the transient hyperaemic response test. The reactivity to carbon dioxide was measured as the change in middle cerebral artery flow velocity with a step change in end-tidal carbon dioxide. For the estimated cerebral perfusion pressure and the ZFP, established formulae were used which utilized instantaneous values of arterial pressure and middle cerebral artery flow velocity. Measurements were made at baseline and after i.v. infusion of the study drug to an endpoint of 25% increase in mean arterial pressure (MAP) (ephedrine, dobutamine) or cardiac index (dopexamine). There was no significant change in the strength of autoregulation (from (mean (SD)) 1.07 (0.16) to 1.07 (0.18); from 1.07 (0.16) to 1.03 (0.19); from 1.04 (0.12) to 1.04 (0.25)), reactivity to carbon dioxide (from 40% (8) to 36 (10); from 37 (12) to 37 (11); from 45 (12) to 43 (11)) with ephedrine, dobutamine, or dopexamine, respectively. Despite a clinically significant increase in MAP with ephedrine and dobutamine and a clinically significant increase in cardiac index with dopexamine, the estimated cerebral perfusion pressure did not change significantly (from 81 (38) to 60 (16) mm Hg with ephedrine; from 67 (22) to 63 (11) mm Hg with dobutamine; from 87 (27) to 79 (17) mm Hg with dopexamine). The ZFP increased significantly with ephedrine (from 29 (10) to 44 (11) mm Hg) and dobutamine (from 35 (14) to 43 (10) mm Hg) but not dopexamine (from 3 (23) to 11 (22) mm Hg). Sympathomimetic agents do not significantly change cerebrovascular homeostasis as assessed by the transient hyperaemic response test, reactivity to carbon dioxide and estimated cerebral perfusion pressure.