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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

Jerath, Angela FRCPC, FANZCA, MBBS, BSc; Panckhurst, Jonathan MBChB; Parotto, Matteo PhD, MD; Lightfoot, Nicholas FANZCA, MBChB; Wasowicz, Marcin PhD, MD; Ferguson, Niall D. FRCPC, MSc; Steel, Andrew FRCPC, FFICM, FRCA, MBBS, BSc; Beattie, W. Scott PhD, FRCPC

doi: 10.1213/ANE.0000000000001634
Critical Care and Resuscitation: Meta-Analysis
Continuing Medical Education

BACKGROUND: 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.

METHODS: 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 I 2 statistic. Outcomes were assessed using a random or fixed-effects model depending on heterogeneity.

RESULTS: 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.

CONCLUSIONS: 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.

Supplemental Digital Content is available in the text.Published ahead of print November 8, 2016.

From the *Department of Anesthesia and Pain Medicine, Toronto General Hospital, Toronto, Ontario, Canada; Department of Anesthesia and Pain Medicine, Middlemore Hospital, Auckland, New Zealand; and Interdepartmental Division of Critical Care, University of Toronto, Ontario, Canada.

Published ahead of print November 8, 2016.

Accepted for publication August 24, 2016.

Funding: Alternative Funding Plan (AFP), Mount Sinai Hospital-University Health Network Academic Medical Organization.

Conflicts of Interest: See Disclosures at the end of the article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Address correspondence to Angela Jerath, FRCPC, FANZCA, MBBS, BSc, Department of Anesthesia and Pain Medicine, Toronto General Hospital, 3-EN 200 Elizabeth St, Toronto, ON, M5G 2C4 Canada. Address e-mail to

© 2017 International Anesthesia Research Society
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