The Effect of Preoperative Methylprednisolone on Postoperative Delirium in Older Patients Undergoing Gastrointestinal Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Preoperative administration of methylprednisolone reduced circulating markers of endothelial activation. This randomized, double-blind, placebo-controlled trial was to evaluate whether a single preoperative dose of methylprednisolone reduced the rate of postoperative delirium (POD) in older patients undergoing gastrointestinal surgery and its association with the shedding of endothelial glycocalyx markers. Methods: About 168 patients, aged 65-80 years and scheduled for laparoscopic gastrointestinal surgery, were randomized to 2 mg/kg methylprednisolone (Group M, n = 84) or equivalent dose of placebo (Group C, n = 84). The primary outcome was the incidence of delirium during the first 5 days after surgery, assessed by the Confusion Assessment Method (CAM). POD severity was rated daily using CAM-Severity (CAM-S). Levels of syndecan-1, heparan sulfate, tumor necrosis factor-alpha (TNF-alpha), and brain-derived neurotrophic factor (BDNF) were measured at baseline, 1 day, and 3 days after surgery. Results: Compared with placebo, methylprednisolone greatly reduced the incidence of delirium at 72 hours following surgery (9 [10.7%] vs 20 [23.8%], p=.03, OR = 2.22 [95% CI 1.05-4.59]). No between-group difference was found in the cumulative CAM-S score (p=.14). The levels of heparan sulfate, syndecan-1, and TNF-alpha in Group M were lower than that in Group C (p<.05 and p<.01), while the level of BDNF in Group M was higher than that in Group C (p<.01). Conclusions: Preoperative administration of methylprednisolone does not reduce the severity of POD, but may reduce the incidence of delirium after gastrointestinal surgery in older patients, which may be related to a reduction in circulating markers of endothelial degradation, followed by the increase of BDNF level.