Impact of Dexmedetomidine on the Incidence of Postoperative Delirium in Patients After Cardiac Surgery: a Randomized, Double-blinded, and Placebo-controlled Clinical Trial

Delirium is a state of global cerebral dysfunction manifested by acute disturbance of consciousness, attention, cognition and perception. It develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. The reported incidences of delirium after cardiac surgery varied from 21% to 47%. The occurrence of postoperative delirium has significant harmful effects on patients' outcomes, including increased morbidity, prolonged hospital stay, increased medical cost, and higher mortality. Its occurrence is also associated with long-term cognitive decline and decreased quality of life.

The exact pathogenesis that lead to the occurrence of POD are still unclear, and possibly involves mechanisms such as inflammation, pain and sleep deprivation after surgery. Furthermore, it has been shown that anesthesia management might also have exerted some effects. Studies found that avoidance of unnecessary deep anesthesia (under the guidance of Bispectral Index monitoring) decreases the incidence of POD. Theoretically, measures that decreases the requirement of anesthetics while maintaining adequate depth of anesthesia and those that alleviates inflammation and improves postoperative analgesia as well as sleep quality will decrease the incidence of POD.

Dexmedetomidine is a highly selective alpha-2 adrenoreceptor agonists that provides anxiolysis, sedation and modest analgesia with minimal respiratory depression. Studies showed that, when used as an adjunctive anesthetics, dexmedetomidine significantly decreases the requirement of opioid analgesics and other sedatives during anesthesia. A recent study of our group found that continuous infusion of low-dose dexmedetomidine (0.2 ug/kg/h) during the first night after surgery significantly improved subjective sleep quality. Two randomized controlled trials found that, when compared with traditional sedatives (midazolam and propofol) and analgesics (such as morphine), use of dexmedetomidine in patients after cardiac surgery is associated with decreased risk of delirium. However, questions still exist as to whether dexmedetomidine prevent delirium or just does not increase its occurrence since traditional sedatives/analgesics themselves increases the risk of delirium. Furthermore, animal experiments showed that dexmedetomidine inhibits the degree of inflammation induced by endotoxins.

The investigators hypothesize that use of dexmedetomidine as an adjunctive agent during the perioperative period can decrease the incidence of postoperative delirium in patients undergoing cardiac surgery, possibly by decreasing the requirement of anesthetics during surgery, by ameliorating analgesia as well as sleep quality after surgery, and by alleviating the degree of perioperative inflammatory response.