Association Between Intraoperative Dexamethasone and Postoperative Mortality in Patients Undergoing Oncologic Surgery: A Multicentric Cohort Study

Objective: We examined the effects of dexamethasone on postoperative mortality, recurrence-free survival, and side effects in patients undergoing oncologic operations. Background: Dexamethasone prevents nausea and vomiting after anesthesia and may affect cancer proliferation. Methods: A total of 30,561 adult patients undergoing solid cancer resection between 2005 and 2020 were included. Multivariable logistic regression was applied to investigate the effect of dexamethasone on 1-year mortality and recurrence-free survival. Effect modification by the cancer's potential for immunogenicity, defined as a recommendation for checkpoint inhibitor therapy based on the National Comprehensive Cancer Network guidelines, was investigated through interaction term analysis. Key safety endpoints were dexamethasone-associated risk of hyperglycemia >180 mg/dL within 24 hours and surgical site infections within 30 days after surgery. Results: Dexamethasone was administered to 38.2% (11,666/30,561) of patients (6.5±2.3 mg). Overall, 3.2% (n=980/30,561) died and 15.4% (n=4718/30,561) experienced cancer recurrence within 1 year of the operation. Dexamethasone was associated with a -0.6% (95% confidence interval: -1.1, -0.2, P=0.007) 1-year mortality risk reduction [adjusted odds ratio (ORadj): 0.79 (0.67, 0.94), P=0.009; hazard ratio=0.82 (0.69, 0.96), P=0.016] and higher odds of recurrence-free survival [ORadj: 1.28 (1.18, 1.39), P<0.001]. This effect was only present in patients with solid cancers who were defined as not to respond to checkpoint inhibitor therapy [ORadj: 0.70 (0.57, 0.87), P=0.001 vs ORadj: 1.13 (0.85, 1.50), P=0.40]. A high (>0.09 mg/kg) dose of dexamethasone increased the risk of postoperative hyperglycemia [ORadj: 1.55 (1.32, 1.82), P<0.001], but not for surgical site infections [ORadj: 0.84 (0.42, 1.71), P=0.63]. Conclusions: Dexamethasone is associated with decreased 1-year mortality and cancer recurrence in patients undergoing surgical resection of cancers that are not candidates for immune modulators. Dexamethasone increased the risk of postoperative hyperglycemia, however, no increase in surgical site infections was identified.