Ketamine and Esketamine for the Prevention of Delirium in Surgical Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Nestor Cordeiro Dos Santos Neto, R. Rolim Neto, Esther Frota Gomes, Marina Carvalho Lima Mendonça, Diego Bastos Porto, Manoel Amora Albano Amora Neto, Lucilaide Oliveira Santos, Hildegard Loren Rebouças Santos
Journal of Intensive Care Medicine January 7, 2026 DOI: 10.1177/08850666251410471 via OpenAlex
Summary
AI-generated from the abstractA systematic review and meta-analysis of eight randomized controlled trials with 1,645 patients found that ketamine or esketamine reduced the incidence of delirium by about half (odds ratio 0.50) compared to placebo. The benefit was significant in older adults (mean age over 60) but not in younger patients. However, neuropsychiatric adverse events such as hallucinations and nightmares were more common with ketamine (odds ratio 1.60). No consistent effects were seen on pain scores, opioid use, or length of hospital or ICU stay. The authors conclude that ketamine may help prevent delirium in older surgical patients, but the risk of neuropsychiatric side effects must be considered.
Study at a glance
| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 1,645 |
| Population | Adult surgical patients, some requiring postoperative ICU care |
| Interventions | Ketamine Esketamine |
| Topics | Ketamine |
| Keywords | Randomized controlled trial Incidence geometry Placebo Adverse effect |
| Citations | 1 |
| Key finding | Ketamine or esketamine significantly reduced delirium incidence compared to placebo, especially in older adults, but increased neuropsychiatric adverse events. |
Abstract
BackgroundDelirium is a common and serious complication in critically ill and surgical patients, associated with increased morbidity, prolonged hospitalization, and long-term cognitive impairment. Ketamine and esketamine have been proposed as potential protective agents due to their anti-inflammatory, analgesic, and NMDA receptor-blocking properties.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the use of ketamine or esketamine for the prevention of delirium in adult surgical patients, some of whom required postoperative Intensive Care Unit (ICU) level care. The primary outcome was the incidence of delirium. Secondary outcomes included pain assessment, opioid consumption, ICU and hospital length of stay, mortality, and neuropsychiatric adverse events. Risk of bias was assessed using the Cochrane RoB 2.0 tool. This review was registered in PROSPERO (CRD420251061137) and conducted according to PRISMA 2020 guidelines.ResultsEight RCTs involving a total of 1645 patients were included. Ketamine or esketamine significantly reduced the incidence of delirium compared to placebo (odds ratio [OR] = 0.50; 95% CI: 0.28-0.91; p = .02). Subgroup analysis revealed a significant benefit in older adults (mean age > 60 years), but not in younger populations. Neuropsychiatric adverse events-such as hallucinations and nightmares-were more frequent in the ketamine group (OR = 1.60; 95% CI: 1.15-2.21; p = .005). No consistent effects were observed on pain scores, opioid consumption, or length of stay.ConclusionKetamine and esketamine may reduce the incidence of delirium in surgical patients, particularly in older adults, although this benefit must be weighed against a higher incidence of neuropsychiatric symptoms.