Ketamine for Critically Ill Patients with Severe Acute Brain Injury: A Systematic Review with Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials.
Trine Hjorslev Andreasen, Frederik Andreas Madsen, Marija Barbateskovic, Jane Lindschou, Christian Gluud, Kirsten Møller
Neurocritical care April 1, 2025 DOI: 10.1007/s12028-024-02075-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Sample size | 149 |
| Population | Patients with severe acute brain injury |
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | Brain injuries Cortical spreading depression Intensive care units Critical care medicine Neuroprotection Pain management |
| Citations | 8 |
| Key findings | The evidence for ketamine's effects on functional outcome and serious adverse events in patients with severe acute brain injury is very low certainty, and large trials are needed. |
Abstract
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. 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. 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. 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.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 4
- Ketamine's Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review. Pharmaceuticals August 29, 2025
- Ketamine in Neurocritical Care: New Potentials and Perspectives. Cureus June 1, 2025
- S-ketamine versus placebo for cortical spreading depolarisation in severe acute brain injury (KETA-BID): protocol for a pilot, randomised, blinded clinical trial. BMJ Open July 28, 2025
- A review of the therapeutic and neuroprotective properties of ketamine Medical Science of Ukraine June 30, 2026