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Practice Patterns and Outcomes Associated With Early Sedation Depth in Mechanically Ventilated Patients

A Systematic Review and Meta-Analysis*

Stephens, Robert J., BS1; Dettmer, Matthew R., MD2; Roberts, Brian W., MD3; Ablordeppey, Enyo, MD, MPH4,5; Fowler, Susan A., MLIS6; Kollef, Marin H., MD7; Fuller, Brian M., MD, MSCI4,5

doi: 10.1097/CCM.0000000000002885
Review Article

Objectives: Emerging data suggest that early deep sedation may negatively impact clinical outcomes. This systematic review and meta-analysis defines and quantifies the impact of deep sedation within 48 hours of initiation of mechanical ventilation, as described in the world’s literature. The primary outcome was mortality. Secondary outcomes included hospital and ICU lengths of stay, mechanical ventilation duration, and delirium and tracheostomy frequency.

Data Sources: The following data sources were searched: MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, Cochrane Database of Systematic Reviews databases,, conference proceedings, and reference lists.

Study Selection: Randomized controlled trials and nonrandomized studies were included.

Data Extraction: Two reviewers independently screened abstracts of identified studies for eligibility.

Data Synthesis: Nine studies (n = 4,521 patients) published between 2012 and 2017 were included. A random effects meta-analytic model revealed that early light sedation was associated with lower mortality (9.2%) versus deep sedation (27.6%) (odds ratio, 0.34 [0.21–0.54]). Light sedation was associated with fewer mechanical ventilation (mean difference, –2.1; 95% CI, –3.6 to –0.5) and ICU days (mean difference, –3.0 (95% CI, –5.4 to –0.6). Delirium frequency was 28.7% in the light sedation group and 48.5% in the deep sedation group, odds ratio, 0.50 (0.22–1.16).

Conclusions: Deep sedation in mechanically ventilated patients, as evaluated in a small number of qualifying heterogeneous randomized controlled trials and observational studies, was associated with increased mortality and lengths of stay. Interventions targeting early sedation depth assessment, starting in the emergency department and subsequent ICU admission, deserve further investigation and could improve outcome.

1Washington University School of Medicine in St. Louis, St. Louis, MO.

2Emergency Services Institute, Respiratory Institute, Cleveland Clinic Foundation, Cleveland, OH.

3Department of Emergency Medicine, Cooper University Hospital, Camden, NJ.

4Department of Emergency Medicine, Division of Critical Care, Washington University School of Medicine in St. Louis, St. Louis, MO.

5Department of Anesthesiology, Division of Critical Care, Washington University School of Medicine in St. Louis, St. Louis, MO.

6Bernard Becker Medical Library, Washington University in St. Louis, St. Louis, MO.

7Department of Medicine, Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO.

*See also p. 490.

This systematic review has been registered with the PROSPERO international prospective register of systematic reviews (#CRD42017057264).

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Mr. Stephens received funding from Washington University Institute of Clinical; and supported by a Translational Sciences grant UL1TR000448, sub-award TL1TR000449, from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). Dr. Roberts was supported by a grant from the NIH/National Heart, Lung, and Blood Institute (K23HL126979). Dr. Ablordeppey was supported by the Washington University School of Medicine Faculty Scholars grant and the Foundation for Barnes-Jewish Hospital; and her institution received funding from Washington University School of Medicine and the BJH Foundation. Dr. Kollef is supported by the Foundation for Barnes-Jewish Hospital. Dr. Fuller was funded by the KL2 Career Development Award, and this research was supported by the Washington University Institute of Clinical and Translational Sciences (grants UL1 TR000448 and KL2 TR000450) from the NCATS. He was also funded by the Foundation for Barnes-Jewish Hospital Clinical and Translational Sciences Research Program (grant # 8041–88). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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