Effect of parecoxib on postoperative delirium in patients with hyperlipidemia: a randomized, double-blind, single-center, superiority trial

Background: Hyperlipidemia has been implicated in the higher risk of developing postoperative delirium. Prostaglandin endoperoxide synthase-2 mediates neuroinflammatory processes in postoperative delirium. This study aims to investigate whether preoperative administration of parecoxib is more efficient than a placebo in averting postoperative delirium in patients with hyperlipidemia. Materials and methods: In this randomized, double-blind, superiority trial, participants with hyperlipidemia were randomized in a 1:1 ratio to receive parecoxib (40 mg parecoxib administered intravenously before anesthesia induction) or placebo (normal saline). The primary outcome was postoperative delirium incidence within three days, with a 5.4% difference set as the superiority threshold. Secondary outcomes were cumulative incidences of emergence delirium and prostaglandin endoperoxide synthase-2 levels, inflammatory cell counts, and pain score on postoperative day 1 and postoperative adverse events. Results: This trial conducted between August 2023 and August 2024 at a tertiary hospital in China included 452 adults with hyperlipidemia, with 226 in the parecoxib group and 226 in the placebo group. The incidence of postoperative delirium in the parecoxib group was 13.72%, a reduction of 12.39% compared to the placebo group (hazard ratio, 0.491; 95% confidence interval: 0.318 to 0.759; P < 0.001). The parecoxib group also had a lower incidence of emergence delirium, prostaglandin endoperoxide synthase-2 levels, white blood cell counts and neutrophil, and pain scores on postoperative day 1. The occurrence of adverse events was comparable between the two groups. Prostaglandin endoperoxide synthase-2 expression levels, white blood cell counts, and pain scores mediated the reduction of postoperative delirium incidence by parecoxib. Conclusion: Parecoxib may help in reducing the hyperlipidemia-related postoperative delirium incidence. The effective anti-inflammatory activity of prostaglandin endoperoxide synthase-2 inhibition by parecoxib and postoperative pain control may be important mechanisms for preventing postoperative delirium.