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Intensive care
Research
Pharmacological interventions for prevention and management of delirium in intensive care patients: a systematic overview of reviews and meta-analyses
  1. Marija Barbateskovic1,2,
  2. Sara Russo Krauss1,
  3. Marie Oxenboell Collet2,3,
  4. Laura Krone Larsen4,
  5. Janus Christian Jakobsen1,2,5,
  6. Anders Perner2,3,
  7. Jørn Wetterslev1,2
  1. 1 Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  2. 2 Centre for Research in Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  3. 3 Department of Intensive Care, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  4. 4 Department of of Neuroanaesthesiology, Rigshospitalet, Copenhagen University hospital, Copenhagen, Denmark
  5. 5 Department of Cardiology, Holbaek Hospital, Holbaek, Denmark
  1. Correspondence to Marija Barbateskovic; marija.barbateskovic{at}ctu.dk

Abstract

Objectives We assessed the evidence from reviews and meta-analyses of randomised clinical trials on the effects of pharmacological prevention and management of delirium in intensive care unit (ICU) patients.

Methods We searched for reviews in July 2017 in: Cochrane Library, MEDLINE, Embase, Science Citation Index, BIOSIS Previews, CINAHL and LILACS. We assessed whether reviews were systematic according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and assessed the methodological quality using ROBIS.

Outcome measures Primary outcomes: all-cause mortality, serious adverse events, prevention of delirium and management of delirium. Secondary outcomes: quality of life; non-serious adverse events and cognitive function.

Results We included 378 reviews: 369 narrative reviews, eight semisystematic reviews which failed on a maximum of two arbitrary PRISMA criteria and one systematic review fulfilling all 27 PRISMA criteria. For the prevention of delirium, we identified the one systematic review and eight semisystematic reviews all assessing the effects of alpha-2-agonists. None found evidence of a reduction of mortality (systematic review RR 0.99, 95% CI 0.79 to 1.24). The systematic review and three semisystematic reviews found no evidence of an effect for the prevention of delirium (systematic review RR 0.85, 0.63 to 1.14). Conversely, four semisystematic reviews found a beneficial effect. Serious adverse events, quality of life, non-serious adverse events and cognitive function were not assessed. We did not identify any systematic or semisystematic reviews addressing other pharmacological interventions for the prevention of delirium. For the management of manifest delirium, we did not identify any systematic or semisystematic review assessing any pharmacological agents.

Conclusion Based on systematic reviews, the evidence for the use of pharmacological interventions for prevention or management of delirium is poor or sparse. A systematic review with low risk of bias assessing the effects of pharmacological prevention of delirium and management of manifest delirium in ICU patients is urgently needed.

PROSPERO registration number CRD42016046628.

  • clinical pharmacology
  • quality in health care

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2018-024562

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    Footnotes

    • Patient consent for publication Not required.

    • Contributors Coordinating the review: MB. Conception and design of the review: MB, JCJ, AP, JW. Performing search strategies and literature searches: MB. Performing the literature screening: MB, SRK, LKL, MOC. Performing the data extraction: MB, SRK, LKL, MOC. Writing the review: MB, JW, JCJ, AP, MOC, LKL, SRK. All authors critically reviewed and revised the manuscript and approved the final version for publication. MB is the guarantor of the review.

    • Funding MB, MOC, JCJ, AP and JW were supported by the public Innovation Fund Denmark (4108-00011B), which did not have any role in study design, data collection, data analysis, data interpretation or writing of the report. No other sources of financial support were obtained for this review.

    • Competing interests MB, MOC, JCJ, AP and JW had financial support from the public Innovation Fund Denmark; AP is head of research at the Dept. of Intensive Care unit at Rigshospitalet. The department receives support for research from CSL Behring, Fresenius Kabi and Ferring Pharmaceuticals. AP and JW are members of the AID-ICU steering group (NCT03392376); no other relationships or activities that could appear to have influenced the submitted work.

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

    • Data sharing statement No additional data are available.