Comparative study of propofol versus midazolam in the sedation of critically ill patients: results of a prospective, randomized, multicenter trial.

OBJECTIVES: To compare the effectiveness, characteristics, duration of action, hemodynamic and biochemical effects, and side effects of propofol and midazolam used for continuous intravenous sedation of ventilated critically ill patients.

DESIGN: Multicenter, prospective, randomized, nonblinded study.

SETTING: Nine Spanish general intensive care units (ICUs).

PATIENTS: Ninety-eight patients admitted to the ICU who were mechanically ventilated and required sedation for a minimum of 48 hrs.

INTERVENTIONS: Propofol or midazolam was used for induction and maintenance of continuous intravenous sedation for a maximum of 5 days. The effectiveness of those two regimens was assessed according to their effects on ventilatory management and the presence of agitation.

MEASUREMENTS AND MAIN RESULTS: In 93% of the patients studied, there was a medical cause necessitating mechanical ventilation. The mean (+/-SD) duration of sedation was 81 +/- 25 hrs and 88 +/- 27 hrs for the propofol and midazolam groups, respectively. The induction dose was 2.24 +/- 0.43 mg/kg over 318 +/- 363 secs for propofol, and 0.22 +/-0.07 mg/kg over 33 +/-29 secs for midazolam. The maintenance dose was 2.8 +/-1.1 mg/kg/hr for propofol and 0.14 +/- 0.10 mg/kg/hr for midazolam. There was no difference regarding the opiate and muscle relaxant requirements between the two groups. Sedation with propofol was more effective in achieving patient-ventilator synchrony than that with midazolam after the first hour of treatment (p < .01). Patients sedated with propofol awoke more rapidly and with less variability that those patients sedated with midazolam (23 +/- 16 mins vs. 137 +/- 185 mins, respectively, p < .05), particularly in those patients requiring deep sedation (27 +/- 16 mins vs. 237 +/- 222 mins, respectively, p < .01). No hemodynamic or biochemical changes were detected in any of the treatment groups. During induction, five patients in the propofol group and two patients in the midazolam group had hypotension.

CONCLUSIONS: In this population of critically ill patients, propofol is an effective and safe alternative for sedation, with some advantages, such as short duration of action and high effectiveness over the conventional regimen with benzodiazepines and opiates.