Interventions to prevent postoperative neurocognitive complications: an umbrella review of meta-analyses of randomised controlled trials

Citation:

D'Amico F, Turi S, Manazza M, Lo Bianco G, Monti G, Zangrillo A, et al. Interventions to prevent postoperative neurocognitive complications: an umbrella review of meta-analyses of randomised controlled trials. Anaesthesia. 2025;doi:10.1111/anae.70061.

Study at a glance

- Design and scope: PROSPERO-registered umbrella review of meta-analyses of RCTs in adults undergoing cardiac and non-cardiac surgery; 114 meta-analyses (257,077 patients) searched to 23 August 2025.

- Interventions: 12 intervention categories (pharmacological and non-pharmacological), including dexmedetomidine, cerebral monitoring, acupuncture, sleep interventions, steroids, antipsychotics, peripheral nerve blocks, esketamine, remimazolam, neuraxial and inhalational techniques, and remote ischaemic preconditioning.

- Primary outcome: Any postoperative neurocognitive complication (delirium and/or postoperative cognitive dysfunction). Overall pooled effect for “any intervention vs control” OR 0.57 (95% CI 0.53–0.61; I2=94%), suggesting reduced odds but with extreme heterogeneity and very-low-certainty evidence.

- Selected interventions with apparent benefit: Dexmedetomidine (OR 0.48), cerebral monitoring (0.52), acupuncture (0.39), sleep interventions (0.54), antipsychotics (0.48), peripheral nerve blocks (0.55), esketamine (0.42) and remimazolam (0.71) were each associated with lower odds of neurocognitive complications; certainty mostly low or very low.

- Interventions without clear benefit or possible harm: Neuraxial anaesthesia, low-dose anaesthesia, remote ischaemic preconditioning and acetylcholinesterase inhibitors showed no convincing reduction in complications. In non-cardiac surgery, inhalational anaesthesia was associated with higher odds of complications vs comparator techniques (OR about 1.6); low-certainty evidence.

- Risk of bias and certainty: Many contributing meta-analyses were low or critically low quality. ROBIS rated the umbrella review overall at high risk of bias (likely favouring interventions). GRADE for the overall pooled effect was downgraded to very low (risk of bias, marked inconsistency, indirectness, and suspected publication bias).

- Clinical takeaway: A broad range of perioperative strategies look potentially protective against postoperative delirium and cognitive dysfunction, but the body of evidence is very uncertain; results are mainly hypothesis-generating and insufficient for strong practice-changing recommendations.