Perioperative non-invasive brain stimulation for the prevention of postoperative delirium: a systematic review and meta-analysis of randomised controlled trials

Background: Postoperative delirium is a common perioperative complication. Early randomised trials suggested that non-invasive brain stimulation may reduce postoperative delirium, whereas the recent MODEST trial found no preventive benefit. We synthesised the randomised evidence for perioperative non-invasive brain stimulation. Methods: We searched eight bibliographic databases and ClinicalTrials.gov from inception to 30 September 2026 for randomised controlled trials of perioperative non-invasive brain stimulation in adults undergoing surgery. The primary outcome was postoperative delirium. Random-effects meta-analyses estimated risk ratios (RRs), mean differences, or standardised mean differences. Risk of bias was assessed using RoB 2 and certainty of evidence using GRADE. Results: Nine trials contributed data from 1451 participants. Postoperative delirium occurred in 72 of 750 participants receiving active stimulation and 166 of 701 controls (RR 0.41, 95% confidence interval [CI] 0.31-0.56; I2=24.7%; moderate-certainty evidence). Estimates also favoured stimulation for hypoactive and hyperactive delirium, but not clearly for mixed delirium. Pain, anxiety, and sleep outcomes favoured stimulation but were highly heterogeneous and supported by very-low-certainty evidence. Length of hospital stay was not reduced. Adverse events could not be pooled because reporting was incomplete and inconsistent. Conclusions: Perioperative non-invasive brain stimulation may reduce postoperative delirium, but the evidence does not establish a class effect or support routine clinical use. Geographical concentration, methodological concerns, heterogeneous stimulation protocols, and discordance with the MODEST trial warrant independent multicentre sham-controlled trials. PROSPERO registration: CRD420261522168 Keywords: meta-analysis; non-invasive brain stimulation; perioperative neurocognitive disorders; postoperative delirium; transcranial direct current stimulation; transcranial magnetic stimulation