Clinical trial NCT02267538: Dexmedetomidine and Delirium in Patients After Cardiac Surgery
Official title: Impact of Dexmedetomidine on the Incidence of Postoperative Delirium in Patients After Cardiac Surgery: a Randomized, Double-blinded, and Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Delirium
C.Surgical Procedure; Cardiac
Postoperative Complications
Keywords: Delirium
Cardiac Surgical Procedures
Postoperative Complications
Dexmedetomidine
Prevention
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
Collaborators: name: Chinese Academy of Medical Sciences, Fuwai Hospital
First posted: 2014-10-17
Enrollment: 285
Sex: ALL
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

Patients of 60 years or older who are planning to receive cardiac surgery (CABG and/or valve replacement surgery)

Exclusion Criteria:

Patients will be excluded if they meet any of the following criteria:

1. Refuse to participate;
2. Preoperative history of schizophrenia, epilepsia, Parkinson syndrome, or severe dementia;
3. Inability to communicate in the preoperative period because of severe visual/auditory dysfunction or language barrier;
4. History of brain injury or neurosurgery;
5. Preoperative sick sinus syndrome, severe bradycardia (HR \< 50 bpm), second-degree or above atrioventricular block without pacemaker;
6. Severe hepatic dysfunction (Child-Pugh class C);
7. Severe renal dysfunction (requirement of renal replacement therapy);
8. Other conditions that are considered unsuitable for participation.

Primary outcomes:
measure: Incidence of Postoperative Delirium
timeFrame: During the first five days after surgery
Secondary outcomes:
measure: Cognitive Function
timeFrame: on the sixth day after surgery, and on the 30th day after surgery
measure: Incidence of Non-delirium Complications After Surgery
timeFrame: Occurrence of non-delirium complications will be monitored until 30 days after surgery.
Other outcomes:
measure: Pain Intensity
timeFrame: During the first five days after surgery
measure: Subjective Sleep Quality
timeFrame: During the first five days after surgery
measure: Length of Stay in the Intensive Care Unit
timeFrame: From end of surgery until discharge from Intensive Care Unit or 30 days after surgery
measure: Length of Stay in Hospital After Surgery
timeFrame: From end of surgery until discharge from hospital or 30 days after surgery
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Dong-Xin Wang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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