Ketamine for critically ill patients with severe acute brain injury: Protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

PLoS One. 2021 Nov 15;16(11):e0259899. doi: 10.1371/journal.pone.0259899. eCollection 2021.

Abstract

Introduction: Intensive care for patients with severe acute brain injury aims both to treat the immediate consequences of the injury and to prevent and treat secondary brain injury to ensure a good functional outcome. Sedation may be used to facilitate mechanical ventilation, for treating agitation, and for controlling intracranial pressure. Ketamine is an N-methyl-D-aspartate receptor antagonist with sedative, analgesic, and potentially neuroprotective properties. We describe a protocol for a systematic review of randomised clinical trials assessing the beneficial and harmful effects of ketamine for patients with severe acute brain injury.

Methods and analysis: We will systematically search international databases for randomised clinical trials, including CENTRAL, MEDLINE, Embase, and trial registries. Two authors will independently review and select trials for inclusion, and extract data. We will compare ketamine by any regimen versus placebo, no intervention, or other sedatives or analgesics for patients with severe acute brain injury. The primary outcomes will be functional outcome at maximal follow up, quality of life, and serious adverse events. We will also assess secondary and exploratory outcomes. The extracted data will be analysed using Review Manager and Trials Sequential Analysis. Evidence certainty will be graded using GRADE.

Ethics and dissemination: The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.

Prospero no: CRD42021210447.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Injuries* / drug therapy
  • Critical Care
  • Critical Illness
  • Humans
  • Ketamine* / administration & dosage
  • Ketamine* / adverse effects
  • Meta-Analysis as Topic
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Systematic Reviews as Topic
  • Treatment Outcome

Substances

  • Ketamine

Grants and funding

The authors received financial support from the Department of Neurosurgery Research Pool (Neurokirurgisk forskningspulje) at Rigshospitalet, Master Carpenter Sophus Jacobsen and wife Astrid Jacobsen’s Foundation (Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen’s Fond), Rigshospitalet’s 3-year PhD scholarship, and the Danish Victims Foundation (20-610-00103) in the form of salary for author TA. Funding was also received from: The A.P. Møller Foundation (20-L-0041), Knud and Edith Eriksen’s Memorial Fund (Knud og Edith Eriksens Mindefond, 62786-2021), and The Novo Nordisk Foundation (NNF20OC0065750). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.