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Sedation for the mechanically-ventilated, brain-injured patient remains challenging. The purpose of this pilot study was to compare the cerebral physiologic effects of sedation with propofol versus dexmedetomidine in mechanically-ventilated, brain-injured patients. Using a randomised, crossover, unblinded clinical trial, we enrolled patients with severe brain injury (Glasgow Coma Score ≤8) from traumatic injury, subarachnoid haemorrhage or intracerebral haemorrhage undergoing multimodal monitoring (intracranial pressure, brain temperature, oximetry and microdialysis). Patients received an infusion of either propofol or dexmedetomidine for six hours and then a crossover for the subsequent six hours after sufficient washout/in. Clinical and physiological measurements were recorded hourly. In eight patients, (four traumatic injury, three subarachnoid haemorrhage and one intracerebral haemorrhage), the mean dose of propofol used was 25.5 µg/kg/minute while the mean dose of dexmedetomidine was 0.54 µg/kg/hour. All subjects were effectively sedated to a goal of Richmond Agitation Sedation Scale -2 and Bispectral Index of 50-70 throughout the study period. We did not observe any statistically significant differences between the groups in systemic or cerebral physiologic metrics. Though differences were noted in cerebral metabolic substrates (lactate/pyruvate ratio), none were statistically significant. In our pilot cohort, dexmedetomidine and propofol appear equally effective in sedating severely brain-injured patients and neither is associated with adverse physiological effects as measured by multimodal monitoring. Larger long-term studies are required to determine whether clinically favourable benefits demonstrated in the medical critical care setting also apply to this patient population. [ABSTRACT FROM AUTHOR]