Neuroinflammation is postulated as a potential mechanism underlying postoperative delirium. This study aimed to investigate the impact of non-steroidal anti-inflammatory drug (NSAID) use on postoperative delirium. We conducted a literature search in electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, to identify eligible randomized controlled studies. The primary outcome was the incidence of postoperative delirium, and the secondary outcomes included pain scores and the amounts of opioid used at 24 h postoperatively. We estimated the effect size through calculating the odds ratios (ORs) or mean differences (MDs) with 95% CIs, as appropriate. In the analysis of eight studies involving 1,238 participants, the incidence of postoperative delirium was 11% and 19% in the NSAID and control groups, respectively, with a significant reduction in the NSAID group (OR: 0.54, 95% CI [0.38, 0.7], P = 0.0001, I2 = 0%). NSAID use had a significant effect on postoperative pain reduction (MD: -0.75, 95% CI [-1.37, -0.13], P = 0.0172, I2 = 88%). Significant lower postoperative opioid consumption was observed in the NSAID group (MD: -2.88, 95% CI [-3.54, -2.22], P = 0.0000; I2 = 0%). NSAID administration reduced the incidence of postoperative delirium, severity of pain, and opioid dose used.
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