Midazolam versus propofol for long-term sedation in the ICU: A randomized prospective comparison

Objective: To compare the efficacy, safety, and cost of midazolam and propofol in prolonged sedation of critically ill patients. Design: Randomized, prospective study. Setting: General intensive care unit (ICU) in a 1100-bed teaching hospital. Patients: 67 critically ill, mechanically ventilated patients. Interventions: Patients were invasively monitored and mechanically ventilated. A loading dose [midazolam 0.11 ± 0.02 (SEM) mg.kg^-1, propofol 1.3 ± 0.2 mg.kg^-1] was administered, followed by continuous infusion, titrated to achieve a predetermined sedation score. Sedation was continued as long as clinically indicated. Measurements and results: Mean duration of sedation was 141 and 99 h (NS) for midazolam and propofol, respectively, at mean hourly doses of 0.070 ± 0.003 mg.kg^-1 midazolam and 1.80 ± 0.08 mg.kg^-1 propofol. Overall, 68% of propofol patients versus 31% of midazolam (p < 0.001) patients had a > 20% decrease in systolic blood pressure alter the loading dose, and 26 versus 45% (p < 0.01) showed a 25% decrease in spontaneous minute volume. Propofol required more daily dose adjustments (2.1 ± 10.1 vs 1.4 ± 0.1, p < 0.001). Nurse-rated quality of sedation with midazolam was higher (8.2 ± 0.1 vs 7.3 ± 0.1 on a 10-cm visual analog scale, p < 0.001). Resumption of spontaneous respiration was equally rapid. Recovery was faster after propofol (p < 0.02), albeit with a higher degree of agitation. Amnesia was evident in all midazolam patients but in only a third of propofol patients. The cost of propofol was 4-5 times higher. Conclusions: Both drugs afforded reliable, safe, and controllable long-term sedation in ICU patients and rapid weaning from mechanical ventilation. Midazolam depressed respiration, allowed better maintenance of sedation, and yielded complete amnesia at a lower cost, while propofol caused more cardiovascular depression during induction.