The different effects of midazolam and propofol sedation on dynamic cerebral autoregulation

Although midazolam and propofol reduce cerebral blood flow (CBF) similarly, they generate different effects on the autonomic nervous system and endothelium-induced relaxation. Midazolam induces sympathetic dominance, whereas propofol induces parasympathetic dominance. Midazolam has no effect on endothelium-dependent relaxation, whereas propofol suppresses endothelium-dependent relaxation. Moreover, midazolam apparently constricts cerebral arterioles. We therefore hypothesized that midazolam and propofol have different effects on dynamic cerebral autoregulation.

Ten healthy male subjects received midazolam, propofol, and placebo administrations in a randomized, single-blind, crossover study. The modified Observer's Assessment of Alertness/Sedation scale was used to assess sedation depth. After reaching a target depth of sedation (Observer's Assessment of Alertness/Sedation scale score 3, responds only after name is called loudly and/or repeatedly) or after 15 minutes of normal saline administration as placebo, dynamic cerebral autoregulation was evaluated by spectral and transfer function analyses between mean arterial blood pressure variability in the radial artery measured by tonometry, and CBF velocity variability in the middle cerebral artery measured by transcranial Doppler ultrasonography.

Steady-state CBF velocity decreased significantly with midazolam and propofol administration (significant interaction effects, P = 0.024). However, transfer function gain in the low-frequency range decreased significantly only with midazolam administration (significant interaction effects, P = 0.015), suggesting a reduced magnitude of transfer from mean arterial blood pressure oscillations to CBF fluctuations during midazolam sedation.

Our results suggest that midazolam and propofol sedation have different effects on dynamic cerebral autoregulation despite causing equivalent decreases in steady-state CBF velocity. Only midazolam sedation is likely to improve dynamic cerebral autoregulation.