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Dexmedetomidine vs other sedatives in critically ill mechanically ventilated adults: a systematic review and meta-analysis of randomized trials

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Abstract

Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD − 1.8 h, 95% CI  – 2.89 to  – 0.71; low certainty), and ICU length of stay (MD  – 0.32 days, 95% CI  – 0.42 to  – 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.

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Author notes

  1. Fayez Alshamsi, Laiya Carayannopoulos, Anders Granholm, and Joshua Piticaru all contributed equally and are all co-second authors.

Authors and Affiliations

  1. Division of Critical Care, Intensive Care Unit, Department of Medicine, McMaster University, St Joseph’s Healthcare Hamilton, 50 Charlton Ave E, Hamilton, ON, L8N 4A, Canada

    Kimberley Lewis, Kallirroi Laiya Carayannopoulos, Joshua Piticaru, Dipayan Chaudhuri, Laura Spatafora, John Centofanti, Jessica Spence, Bram Rochwerg, Dan Perri, Tim Karachi, Mark Soth & Waleed Alhazzani

  2. Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada

    Kimberley Lewis, Dipayan Chaudhuri, Jessica Spence, Bram Rochwerg, Anne Holbrook & Waleed Alhazzani

  3. Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Alain, United Arab Emirates

    Fayez Alshamsi

  4. Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Anders Granholm & Morten Hylander Møller

  5. Department of Critical Care Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

    Zainab Al Duhailib

  6. Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Canada

    Yuhong Yuan

  7. Department of Anesthesia, McMaster University, Hamilton, Canada

    John Centofanti & Jessica Spence

  8. Population Health Research Institute, McMaster University, Hamilton, Canada

    Jessica Spence

  9. Division of Clinical Pharmacology and Toxicology, McMaster University, Hamilton, Canada

    Dan Perri & Anne Holbrook

  10. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, Baltimore, USA

    Dale M. Needham

  11. Armstrong Institute for Patient Safety and Quality, John Hopkins University, Baltimore, USA

    Dale M. Needham

  12. Outcomes After Critical Illness and Surgery (OACIS) Group, Johns Hopkins University, Baltimore, USA

    Dale M. Needham

  13. Department of Physical Medicine and Rehabilitation, School of Medicine, Johns Hopkins University, Baltimore, USA

    Dale M. Needham

  14. School of Pharmacy, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Northeastern University, Boston, MA, USA

    John W. Devlin

  15. Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Aichi, Japan

    Osamu Nishida

  16. Division of Critical Care Medicine, Department of Medicine, Western University, London, Canada

    Kimia Honarmand

  17. Department of Pulmonary and Critical Care, Dokuz Eylul University School of Medicine, Izmir, Turkey

    Begüm Ergan

  18. Department of Medical Imaging, Memorial University of Newfoundland, St. John’s, Canada

    Eugenia Khorochkov

  19. Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, USA

    Pratik Pandharipande

  20. Department of Emergency and Critical Care, College of Medicine, Imam Abdulrahman Ben Faisal University, Al Khobar, Kingdom of Saudi Arabia

    Mohammed Alshahrani

  21. Department of Intensive Care, Monash Health School of Clinical Sciences, The School of Clinical Medicine, University of New South Wales, Clayton, VIC 3168, Randwick, 2031, Australia

    Yahya Shehabi

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  1. Kimberley Lewis
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  2. Fayez Alshamsi
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  26. Morten Hylander Møller
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  27. Waleed Alhazzani
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Consortia

the GUIDE group

Contributions

KL, WA, JP, FA, LC, MHM, AG, JD, DN, YS, AH, BR, DP contributed to the study conception and design. Data collection was done by KL, JP, FA, KL, ZA, DC, LS, YY, ON, KH, BE, EK. Material preparation and analysis was performed by KL, JP, LC, FA, AG, JC, LS. The first draft of the manuscript was written by KL, WA, MHM. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. We would like to thank Karin Dearness for her continuous support and wisdom in all things related to search strategies.

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Correspondence to Kimberley Lewis.

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The order in the authorship list was determined by alphabetical order.

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Lewis, K., Alshamsi, F., Carayannopoulos, K.L. et al. Dexmedetomidine vs other sedatives in critically ill mechanically ventilated adults: a systematic review and meta-analysis of randomized trials. Intensive Care Med 48, 811–840 (2022). https://doi.org/10.1007/s00134-022-06712-2

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