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CRITICAL CARE AND TRAUMA

A Lack of Evidence of Superiority of Propofol Versus Midazolam for Sedation in Mechanically Ventilated Critically Ill Patients: A Qualitative and Quantitative Systematic Review

Bernhard Walder, MD^*, Nadia Elia, MD, Iris Henzi, MD, Jacques R. Romand, MD^*, and Martin R. Tramèr, MD, DPhil

Divisions of *Surgical Intensive Care, Anaesthesiological Investigations, and Anaesthesiology, Department APSIC, University Hospitals of Geneva, Geneva, Switzerland

Address correspondence and reprint requests to B. Walder, MD, Division of Surgical Intensive Care, University of Geneva Hospitals, Rue Micheli-du-Crest 24, CH-1211 Genève 14, Switzerland. Address e-mail to Bernard.Walder{at}hcuge.ch

Propofol and midazolam are often used for sedation in the intensive care unit. The aim of this systematic review was to estimate the efficacy and harm of propofol versus midazolam in mechanically ventilated patients. A systematic search (Medline, Cochrane Library, Embase, bibliographies), any language, up to June 1999 was performed for reports of randomized comparisons of propofol with midazolam. Data from 27 trials (1624 adults) were analyzed. The average duration of sedation varied between 4 and 339 h. In 10 trials, the duration of adequate sedation was longer with propofol (weighted mean difference 2.9 h; 95% confidence interval [CI], 0.2–5.6 h). In 13 trials (mostly postoperative), sedation lasted 4 to 35 h; in 9 of those, average weaning time from mechanical ventilation with propofol was 0.8–4.3 h; with midazolam it was 1.5–7.2 h (weighted mean difference 2.2 h [95% CI, 0.8 to 3.7 h]). In 8 trials, sedation lasted 54 to 339 h; there was a lack of evidence for difference in weaning times. Arterial hypotension (relative risk 2.5 [95% CI, 1.3 to 4.5]; number-needed-to-treat, 12), and hypertriglyceridemia (relative risk 12.1 [95%CI, 2.9 to 49.7]; number-needed-to-treat, 6) occurred more often with propofol. The duration of adequate sedation time is longer with propofol compared with midazolam. In postoperative patients with sedation <36 h, weaning is faster with propofol.

Implications: The duration of adequate sedation time is longer with propofol compared with midazolam. In postoperative patients with sedation <36 h, weaning is faster with propofol. The clinical relevance of these differences remains unclear. Specific adverse effects are more common with propofol. For rational decision making, reliable data are needed on cost, mortality, intensive care unit populations other than postoperative, and long-term sedation.

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