Propofol vs midazolam for ICU sedation: A Canadian multicenter randomized trial

Study objectives: To determine whether sedation with propofol would lead to shorter times to tracheal extubation and ICU length of stay than sedation with midazolam. Design: Multicenter, randomized, open label. Setting: Four academic tertiary-care ICUs in Canada. Patients: Critically ill patients requiring continuous sedation while receiving mechanical ventilation. Interventions: Random allocation by predicted requirement for mechanical ventilation (short sedation stratum, < 24 h; medium sedation stratum, ≥ 24 and < 72 h; and long sedation stratum, ≥ 72 h) to sedation regimens utilizing propofol or midazolam. Measurements and results: Using an intention-to-treat analysis, patients randomized to receive propofol in the short sedation stratum (propofol, 21 patients; midazolam, 26 patients) and the long sedation stratum (propofol, 4 patients; midazolam, 10 patients) were extubated earlier (short sedation stratum: propofol, 5.6 h; midazolam, 11.9 h; long sedation stratum: propofol, 8.4 h; midazolam, 46.8 h; p < 0.05). Pooled results showed that patients treated with propofol (n = 5 46) were extubated earlier than those treated with midazolam (n = 53) (6.7 vs 24.7 h, respectively; p < 0.05) following discontinuation of the sedation but were not discharged from ICU earlier (94.0 vs 63.7 h, respectively; p = 0.26). Propofol-treated patients spent a larger percentage of time at the target Ramsay sedation level than midazolam-treated patients (60.2% vs 44.0%, respectively; p < 0.05). Using a treatment-received analysis, propofol sedation either did not differ from midazolam sedation in time to tracheal extubation or ICU discharge (sedation duration, < 24 h) or was associated with earlier tracheal extubation but longer time to ICU discharge (sedation duration, ≥ 24 h, < 72 h, or ≥ 72 h). Conclusions: The use of propofol sedation allowed for more rapid tracheal extubation than when midazolam sedation was employed. This did not result in earlier ICU discharge.