Clinical trial NCT02237495: Dexmedetomidine and Outcomes of Cardiac Surgery (DOCS)
Official title: Perioperative Infusion of Dexmedetomidine Improves Outcomes of Cardiovascular Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heart Valve Diseases
Coronary Artery Disease
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2014-09-11
Enrollment: 1100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Cardiac surgery is associated with a high risk of cardiovascular and other complications. The investigators hypothesized that perioperative infusion of dexmedetomidine may reduce the incidence of complications and mortality following cardiovascular surgery.

Detailed description: There are about 694,000 open-heart surgeries performed in US each year. The major complication rates for valve plus coronary artery bypass graft (CABG) procedure are as high as 30.1% in Society of Thoracic Surgeons (STS) reports. Postoperative delirium, infection, acute renal failure (ARF) and major adverse cardiocerebral events (MACE) which include permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest represent the major postoperative complications. These complications translate into increased mortality and prolonged hospital stays with estimated costs exceeding $20 billion annually.6 The etiologies of these adverse events are multifactorial, but one major contributing factor is the surgical stress responses that result in increasing plasma levels of epinephrine and norepinephrine, with consequent myocardial oxygen supply demand imbalance and myocardial ischemia. More than 50% of all perioperative complications are related to adverse cardiovascular events.

The alpha-2 receptor agonists (clonidine, dexmedetomidine) currently used in clinical practice have many desirable effects that may provide myocardial protection including analgesia, anxiolysis, inhibition of central sympathetic outflow and reduction of systemic norepinephrine release that improve hemodynamic stability and positively affect myocardial oxygen supply and demand. The most widely studied alpha-2 agonist is clonidine, a long-acting partial agonist with an alpha-2 to alpha-1 selectivity ratio of 39:1. However, dexmedetomidine is a highly selective, shorter-acting intravenous alpha-2 agonist with an alpha-2 to alpha-1 selectivity ratio of 1300:1.

Multiple studies have reported that dexmedetomidine has a protective effect on specific organs including heart, brain, kidney and lungs. In addition, dexmedetomidine has been shown to have anti-inflammatory properties decreasing mortality and attenuating plasma cytokine concentrations in laboratory animals exposed to endotoxin in a dose-dependent fashion. The investigators hypothesized that dexmedetomidine may provide myocardial, brain, renal and immune function protection for cardiovascular surgical patients. The specific aim of this study was to investigate whether the perioperative use of dexmedetomidine is associated with improved outcomes and a decreased incidence in postoperative mortality, MACE or other complications in patients undergoing open-heart surgery.

Eligibility criteria: Inclusion Criteria:

* Provide written informed consent
* Are \> 18 years of age
* Elective cardiac surgery with CPB, when the surgeon plans to do valve and/or CABG surgery

Exclusion Criteria:

* Emergent cardiac surgery
* Other than CABG and/or Valve surgery
* off-pump or robotic surgery
* Surgery requiring deep hypothermic circulatory arrest or involving the thoracic aorta
* Life expectancy \< 1 year
* Preop severe liver or renal dysfunction, with replacement therapy required
* Patients with IABP or with cardiogenic shock
* Severe dehydrate or dystrophia or Hb \< 10 g/dl
* History of any alpha-2 receptor agonists allergy.
* Refuse to provide written informed consent
* Diagnosed with mental illness

Primary outcomes:
measure: 1-year all cause of mortality and major postoperative complications
timeFrame: 1 year after operation
Secondary outcomes:
measure: All cause mortality and major complications
timeFrame: The participants will be tightly observed for the duration of hospital stay, an expected average of 10 days and at 30 days after operation,
Other outcomes:
measure: postoperative hospital stay
timeFrame: the number of days between the operation and discharge, an expected average of 12 days
measure: ICU-stay
timeFrame: the number of days the patients stay in the ICU after surgery, an expected average of 3 days
measure: Incidence of prolonged ventilation
timeFrame: the duration of intubation is the time from trachea intubation to extubation, an expected average of 20 hours
Locations:
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
Study officials:
affiliation: Xijing Hospital
name: Hailong Dong, M.D., Ph.D.,
role: STUDY_CHAIR
References: