Effects of dexmedetomidine for postoperative delirium after joint replacement in elderly patients: a randomized, double-blind, and placebo-controlled trial

Background: Experimental evidence has indicated the benefits of dexmedetomidine for the treatment of postoperative delirium. Previously clinical trials have had no definite conclusions concerning dexmedetomidine on delirium, while some studies have shown it can reduce delirium. One study showed it cannot improve outcomes. The present study, therefore, explored whether acute dexmedetomidine treatment could reduce incidence of delirium and improve clinical outcomes. Methods: This was a randomized, double-blind, and placebo-controlled trial in three hospitals in Jiangsu and Anhui, China. This study enrolled patients aged more than 60 years old, admitted to Intensive Care Units after joint replacement surgery, with informed consent. A computer-generated randomization sequence (in a 1: 1 ratio) was used to randomly assign patients to receive either dexmedetomidine (0.1 mu g/kg per hour, from intensive care unit admission on the day of surgery) or placebos once daily for up to 3 days. Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was incidence of delirium, assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days. Analyses were performed by intention-to-treat and safety populations. Results: Between August 1, 2015, and August 1, 2017, 545 patients were assessed. A total of 453 were randomly assigned to receive either placebo (n=226) or dexmedetomidine (n=227). Incidence of postoperative delirium was significantly lower in the dexmedetomidine group (30 [13.2%] of 227 patients) than the placebo group (64 [28.3%] of 226 patients (Odds ratio [OR]=0.385, 95% CI 0.238-0.624; p<0.0001). Regarding safety, incidence of hypertension was higher with placebos (32 [14.2%] of 226 patients) than with dexmedetomidine (18 [7.9%] of 227 patients; OR=0.522, 95% CI 0.284-0.961; p=0.034). Occurrence of hypotension and bradycardia did not differ between groups. Conclusion: The current study suggests that acute dexmedetomidine treatment can reduce incidence of delirium after joint replacement. However, no evidence was found that dexmedetomidine can improve clinical outcomes. The therapy was safe. Further investigation is necessary to fully understand the potential usefulness of dexmedetomidine in older patients.