Effect of intraoperative dexmedetomidine on long-term survival in older patients after major noncardiac surgery: 3-year follow-up of a randomized trial

Abstract

Study objective: To assess the impact of intraoperative dexmedetomidine on long-term outcomes of older patients following major noncardiac surgery mainly for cancer.

Design: A long-term follow-up of patients enrolled in a randomized trial.

Setting: The initial trial was performed in a tertiary care hospital in Beijing, China.

Participants: Patients aged 60 years or older who were scheduled for major noncardiac surgery.

Intervention: Participants were randomized to receive either dexmedetomidine (a loading dose of 0.6 μg/kg over 10 min, followed by a continuous infusion of 0.5 μg/kg/h until 1 h before end of surgery) or placebo during anesthesia.

Measurements: The primary endpoint was overall survival. Secondary endpoints included recurrence-free survival and event-free survival. Cox proportional hazard models were used to adjust for predefined confounding factors. Propensity score matching was employed for sensitive analysis.

Results: Among 620 patients who were randomized in the initial trial, 619 were included in the long-term analysis (mean age 69 years, 40% female, 77% oncological surgery). The median follow-up duration was 42 months (interquartile range 41 to 45). Overall survival did not differ between the two groups: there were 49/309 (15.9%) deaths with dexmedetomidine versus 63/310 (20.3%) with placebo (adjusted hazard ratio [HR] 0.78, 95% CI 0.53-1.13, P = 0.187). Recurrence-free survival was improved with dexmedetomidine (68/309 [22.0%] events with dexmedetomidine versus 98/310 [31.6%] with placebo; adjusted HR 0.67, 95% CI 0.49-0.92, P = 0.012). Event-free survival was also improved with dexmedetomidine (120/309 [38.8%] events with dexmedetomidine versus 145/310 [46.8%] with placebo; adjusted HR 0.78, 95% CI 0.61-1.00, P = 0.047). Results were similar after propensity-score matching and in the subgroup of cancer patients.

Conclusions: In older patients having major noncardiac surgery mainly for cancer, intraoperative dexmedetomidine did not improve overall survival but was associated with improved recurrence-free and event-free survivals.

Trial registration: ClinicalTrials.gov NCT04111926.

Keywords: Aged; Dexmedetomidine; Neoplasms; Operative; Surgical procedures; Survival.