Dexmedetomidine and Delirium in Patients After Cardiac Surgery
Condition: Delirium; C.Surgical Procedure; Cardiac; Postoperative Complications
MeSH terms: Delirium; Postoperative Complications
Study type: Interventional
Phase: Phase 4

Summary: 
      Postoperative delirium (POD) is a frequently occurring complication after cardiac surgery.
      Its occurrence is associated with worse outcomes of patients, including increased morbidity,
      prolonged hospital stay, increased medical cost, and higher mortality. It is also associated
      with long-term cognitive decline and decreased quality of life. However, until recently,
      pharmacological interventions that can effectively prevent its occurrence are still limited.
      The purpose of this study is to investigate whether perioperative dexmedetomidine use can
      decrease the incidence of postoperative delirium in patients undergoing cardiac surgery.
    

Detailed description: 
      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.
    

Intervention name(s): dexmedetomidine hydrochloride for injection; 0.9% sodium chloride for injection
Intervention type(s): Drug; Drug
Intervention description(s): Before anesthesia, dexmedetomidine hydrochloride for injection (200 ug/2 ml) will be diluted with normal saline to 50 ml (final dexmedetomidine concentration 4 ug/ml).
Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes (i.e., dexmedetomidine 0.6 μg/kg in 10 minutes), followed by continuous infusion at a rate of [0.1*kg] ml/h (i.e., dexmedetomidine at a rate of 0.4 μg /kg/h) until the end of surgery.
At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h (i.e., dexmedetomidine at a rate of 0.1 ug/kg/h) and continued until the end of mechanical ventilation after surgery.; Before anesthesia, 0.9% sodium chloride for injection 50 ml will be prepared.
Before the induction of anesthesia, a loading dose will be administered by intravenous infusion at a rate of [0.9*kg] ml/h for 10 minutes, followed by continuous infusion at a rate of [0.1*kg] ml/h until the end of surgery.
At the end of surgery, the infusion rate will be decreased to [0.025*kg] ml/h and continued until the end of mechanical ventilation after surgery.
Other intervention name(s): Aibeining (trade name); normal saline
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Delirium; Cardiac Surgical Procedures; Postoperative Complications; Dexmedetomidine; Prevention