Level of sedation in critically ill adult patients: a protocol for a systematic review with meta-analysis and trial sequential analysis

Ameldina Ceric, Johan Holgersson, Teresa May, Markus B. Skrifvars, Johanna Hästbacka, Manoj Saxena, Anders Aneman, Anthony Delaney, Michael C. Reade, Candice Delcourt, Janus Jakobsen, Niklas Nielsen

Research output: Contribution to journalReview articlepeer-review


Introduction It is standard of care to provide sedation to critically ill patients to reduce anxiety, discomfort and promote tolerance of mechanical ventilation. Given that sedatives can have differing effects based on a variety of patient and pharmacological characteristics, treatment approaches are largely based on targeting the level of sedation. The benefits of differing levels of sedation must be balanced against potential adverse effects including haemodynamic instability, causing delirium, delaying awakening and prolonging the time of mechanical ventilation and intensive care stay. This systematic review with meta-analysis aims to investigate the current evidence and compare the effects of differing sedation levels in adult critically ill patients. Methods and analyses We will conduct a systematic review based on searches of preidentified major medical databases (eg, MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify trials meeting inclusion criteria. We will include randomised clinical trials comparing any degree of sedation with no sedation and lighter sedation with deeper sedation for critically ill patients admitted to the intensive care unit. We will include aggregate data meta-analyses and trial sequential analyses. Risk of bias will be assessed with domains based on the Cochrane risk of bias tool. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed using Grades of Recommendations, Assessment, Development and Evaluation. Ethics and dissemination No formal approval or review of ethics is required as individual patient data will not be included. This systematic review has the potential to highlight (1) whether one should believe sedation to be beneficial, harmful or neither in critically ill adults; (2) the existing knowledge gaps and (3) whether the recommendations from guidelines and daily clinical practice are supported by current evidence. These results will be disseminated through publication in a peer-reviewed journal.

Original languageEnglish
Article numbere061806
JournalBMJ Open
Issue number9
Publication statusPublished - 2022 Sept 8

Bibliographical note

Funding Information:
All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: MR declare that his institution received grant support from National Health and Medical Research Council, Australia, Medical Research Future Fund, and Royal Brisbane and Women’s Hospital Research Foundation the past 36 months. MR also received payment for expert testimony from government of the Northern Territory High Court of New Zealand, payment (<NZ$3000) for being a member of DSMB for clod stored platelet trial, and his wife has stock investment in ETF that includes biomedical shares. JHä declares that a consultation fee contract with Paion will be signed in near future, payments for consulting from Paion fees will be made to the institution, and support for attending board meetings at Paion. JHä also has a role in Edcational Committee of Scandinavian Society of Anaesthesiology and Intensive Care and minor stocks in Orion Pharma. MSk received research grant from Academy of Finland research grant and received payment for lecture honoraria for BARD Medical (Ireland). All other authors declare no conflict of interest.

Publisher Copyright:
© 2022 BMJ Publishing Group. All rights reserved.

Subject classification (UKÄ)

  • Anesthesiology and Intensive Care

Free keywords

  • Adult anaesthesia
  • Adult intensive & critical care
  • Anaesthesia in cardiology
  • Anaesthesia in neurology


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