Effect of midazolam versus propofol sedation on markers of neurological injury and outcome after isolated severe head injury: a pilot study.

ABSTRACT

BACKGROUND: Midazolam and propofol are sedative agents commonly administered to patients with brain injury. We compared plasma concentrations of glial cell S100beta protein and nitric oxide (NO) between patients who received midazolam and those who received propofol sedation after severe brain injury, and investigated the association between S100beta and NO concentrations and neurological outcome. DESIGN: 28 patients with severe head injury (Glasgow Coma Score <9) who required sedation and ventilation were randomly assigned to receive midazolam (n =15) or propofol (n = 13) based sedation. Blood samples were drawn daily for 5 days for estimation of S100beta and NO concentrations. Neurological outcome was assessed 3 months later as good (Glasgow Outcome Score [GOS], 4-5) or poor (GOS, 1-3). RESULTS: A good neurological outcome was observed in 8/15 patients (53%) in the midazolam group and 7/13 patients (54%) in the propofol group. Patients with a poor outcome had higher serum S100beta concentrations on ICU admission and on Days 1-4 in the ICU than those with a good outcome (mean [SD] on Day 1, 0.99 [0.81] v 0.41 [0.4] microg/L; Day 2, 0.80 [0.81] v 0.41 [0.24] microg/L; Day 3, 0.52 [0.55] v 0.24 [0.25] microg/L; and Day 4, 0.54 [0.43] v 0.24 [0.35] microg/L; P<0.05). There was no significant difference on Day 5. Plasma NO concentrations were not associated with outcome. In subgroup analysis, there was no difference in S100beta and NO concentrations between patients with a good outcome versus those with a poor outcome in either the midazolam or propofol group. CONCLUSIONS: Plasma concentrations of markers of neurological injury in patients with severe head injury were similar in those who received midazolam sedation and those who received propofol. Patients who had a poor neurological outcome at 3 months had consistently higher serum S100beta concentrations during the initial 4 days after injury than patients who had a good outcome.