Abstract
Background: Patients with severe acute brain injury have a high risk of a poor clinical outcome due to primary and secondary brain injury. Ketamine reportedly inhibits cortical spreading depolarization, an electrophysiological phenomenon that has been associated with secondary brain injury, making ketamine potentially attractive for patients with severe acute brain injury. The aim of this systematic review is to explore the current literature regarding ketamine for patients with severe acute brain injury. Methods: We systematically searched international databases for randomized clinical trials comparing ketamine by any regimen versus placebo, no intervention, or any control drug for patients with severe acute brain injury. Two authors independently reviewed and selected trials for inclusion, extracted data, assessed risk of bias, and performed analysis using Review Manager and Trial Sequential Analysis. Evidence certainty was assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcomes were the proportion of participants with an unfavorable functional outcome, the proportion of participants with one or more serious adverse events, and quality of life. Results: We identified five randomized trials comparing ketamine versus sufentanil, fentanyl, other sedatives, or saline (total N = 149 participants). All outcomes were at overall high risk of bias. The proportions of participants with one or more serious adverse events did not differ between ketamine and sufentanil or fentanyl (relative risk 1.45, 95% confidence interval 0.81–2.58; very low certainty). Trial sequential analysis showed that further trials are needed. Conclusions: The level of evidence regarding the effects of ketamine on functional outcome and serious adverse events in patients with severe acute brain injury is very low. Ketamine may markedly, modestly, or not at all affect these outcomes. Large randomized clinical trials at low risk of bias are needed.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Neurocritical Care |
| ISSN | 1541-6933 |
| DOI | |
| Status | E-pub ahead of print - 2024 |
Bibliografisk note
Funding Information:This research received grants for funding of this systematic review plus a randomized clinical trial on the same topic from the following: Research Fund at Department of Neurosurgery Rigshospitalet (Neurokirurgisk forskningspulje), Master carpenter Sophus Jacobsen and wife Astrid Jacobsen\u2019s Foundation (Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond), The A.P. M\u00F8ller Foundation (Fonden til L\u00E6gevidenskabens Fremme, 20-L-0041), Knud and Edith Eriksen\u2019s Memorial Foundation (Knud and Edith Eriksens Mindefond, 62786-2021), a 3-year PhD grant from the Research Board at Rigshospitalet, Dagmar Marshall Foundation, Danish Society for Anaesthesiology and Intensive Care Medicine (DASAIM) Research Initiative 2021, Merchant Jakob Ehrenreich and wife Grete Ehrenreich\u2019s Foundation (Grosserer Jakob Ehrenreich og Hustru Grete Ehrenreichs Fond), the Danish Victims\u2019 Foundation (20-610-00103), and the Novo Nordisk Foundation (NNF20OC0065750).
Publisher Copyright:
© Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society 2024.