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Original research
Inconsistent relationship between depth of sedation and intensive care outcome: systematic review and meta-analysis
  1. Leanne M Aitken1,
  2. Kalliopi Kydonaki2,
  3. Bronagh Blackwood3,
  4. Laurence G Trahair4,
  5. Edward Purssell1,
  6. Mandeep Sekhon5,
  7. Timothy S Walsh6
  1. 1 School of Health Sciences, City, University of London, London, UK
  2. 2 School of Health and Social Care, Edinburgh Napier University, Edinburgh, UK
  3. 3 Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast Faculty of Medicine Health and Life Sciences, Belfast, UK
  4. 4 Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
  5. 5 School of Population Health & Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK
  6. 6 Department of Anaesthesia, Critical Care & Pain Medicine and Usher Institute, The University of Edinburgh, Edinburgh, UK
  1. Correspondence to Dr Leanne M Aitken, School of Health Sciences, City University of London, London EC1V 0HB, UK; leanne.aitken.1{at}


Purpose To determine the effect of depth of sedation on intensive care mortality, duration of mechanical ventilation, and other clinically important outcomes.

Methods We searched MEDLINE, Embase, Cochrane Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PsycINFO from 2000 to 2020. Randomised controlled trials (RCTs) and cohort studies that examined the effect of sedation depth were included. Two reviewers independently screened, selected articles, extracted data and appraised quality. Data on study design, population, setting, patient characteristics, study interventions, depth of sedation and relevant outcomes were extracted. Quality was assessed using Critical Appraisal Skills Programme tools.

Results We included data from 26 studies (n=7865 patients): 8 RCTs and 18 cohort studies. Heterogeneity of studies was substantial. There was no significant effect of lighter sedation on intensive care mortality. Lighter sedation did not affect duration of mechanical ventilation in RCTs (mean difference (MD): −1.44 days (95% CI −3.79 to 0.91)) but did in cohort studies (MD: −1.52 days (95% CI −2.71 to −0.34)). No statistically significant benefit of lighter sedation was identified in RCTs. In cohort studies, lighter sedation improved time to extubation, intensive care and hospital length of stay and ventilator-associated pneumonia. We found no significant effects for hospital mortality, delirium or adverse events.

Conclusion Evidence of benefit from lighter sedation is limited, with inconsistency between observational and randomised studies. Positive effects were mainly limited to low quality evidence from observational studies, which could be attributable to bias and confounding factors.

  • critical care

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  • Twitter @Leanne_Aitken, @Claire Kydonaki@CKydonaki, @Mandy_sekhon

  • Contributors Review concept and design: LMA, KK, BB and TSW. Study identification, critical appraisal and data extraction: LMA, KK, BB, LGT and MS. Statistical analysis: EP. Interpretation of analysis: all authors. Drafting of manuscript: LMA. Critical revision of the manuscript for important intellectual content: all authors.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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