Safety and Efficacy of Volatile Anesthetic Agents Compared With Standard Intravenous Midazolam/Propofol Sedation in Ventilated Critical Care Patients: A Meta-analysis and Systematic Review of Prospective Trials

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Inhalation agents are being used in place of intravenous agents to provide sedation in some intensive care units. We performed a systematic review and meta-analysis of prospective randomized controlled trials, which compared the use of volatile agents versus intravenous midazolam or propofol in critical care units.


A search was conducted using MEDLINE (1946–2015), EMBASE (1947–2015), Web of Science index (1900–2015), and Cochrane Central Register of Controlled Trials. Eligible studies included randomized controlled trials comparing inhaled volatile (desflurane, sevoflurane, and isoflurane) sedation to intravenous midazolam or propofol. Primary outcome assessed the effect of volatile-based sedation on extubation times (time between discontinuing sedation and tracheal extubation). Secondary outcomes included time to obey verbal commands, proportion of time spent in target sedation, nausea and vomiting, mortality, length of intensive care unit, and length of hospital stay. Heterogeneity was assessed using the I2 statistic. Outcomes were assessed using a random or fixed-effects model depending on heterogeneity.


Eight trials with 523 patients comparing all volatile agents with intravenous midazolam or propofol showed a reduction in extubation times using volatile agents (difference in means, −52.7 minutes; 95% confidence interval [CI], −75.1 to −30.3; P < .00001). Reductions in extubation time were greater when comparing volatiles with midazolam (difference in means, −292.2 minutes; 95% CI, −384.4 to −200.1; P < .00001) than propofol (difference in means, −29.1 minutes; 95% CI, −46.7 to −11.4; P = .001). There was no significant difference in time to obey verbal commands, proportion of time spent in target sedation, adverse events, death, or length of hospital stay.


Volatile-based sedation demonstrates a reduction in time to extubation, with no increase in short-term adverse outcomes. Marked study heterogeneity was present, and the results show marked positive publication bias. However, a reduction in extubation time was still evident after statistical correction of publication bias. Larger clinical trials are needed to further evaluate the role of these agents as sedatives for critically ill patients.

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