Dexmedetomidine and Outcomes of Cardiac Surgery (DOCS) (DOCS)

Perioperative Infusion of Dexmedetomidine Improves Outcomes of Cardiovascular Surgery

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Heart Valve Diseases
• Intervention / Treatment: Drug: placebo; Drug: dexmedetomidine

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.

• Study Type: Interventional
• Enrollment (Actual): 1100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; Normal saline as placebo is continuously infused right after anesthesia induction and lasts for 12 hrs with the same infusion rate as the comparator dexmedetomidine	Drug: placebo; The vehicle of dexmedetomidine, normal saline is continuously infused right after anesthesia induction and lasts for 12 hrs with the same rate of the treatment arm.
Experimental: dexmedetomidine; dexmedetomidine intravenous infusion starts right after anesthesia induction in the operating room and last for 12 hours into ICU with a infusion dose of 0.4 ug/kg/h. To avoid potential cause of bradycardia, no dexmedetomidine bolus is given.	Drug: dexmedetomidine; dexmedetomidine with the dose of 0.4 ug/kg/h is continuously infused right after anesthesia induction and lasts for 12 hrs.; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year all cause of mortality and major postoperative complications	Postoperative delirium, infection, acute renal failure (ARF) and major adverse cardiocerebral events (MACE) which includes permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest represent major postoperative complications.	1 year after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality and major complications	Infection, renal failure, need for dialysis, and major adverse cardiocerebral events (MACE) which includes permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest represent major complications	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative hospital stay	Record the time of post operative stay	the number of days between the operation and discharge, an expected average of 12 days
ICU-stay	It is the length of stay in ICU	the number of days the patients stay in the ICU after surgery, an expected average of 3 days
Incidence of prolonged ventilation	Prolonged ventilation is defined as patients remaining on the ventilator for more than 48 hours	the duration of intubation is the time from trachea intubation to extubation, an expected average of 20 hours

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: Hailong Dong, M.D., Ph.D.,, Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2014
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: August 18, 2014
• First Submitted That Met QC Criteria: September 8, 2014
• First Posted (Estimate): September 11, 2014

Study Record Updates

• Last Update Posted (Actual): July 8, 2020
• Last Update Submitted That Met QC Criteria: July 5, 2020
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Heart Valve Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 20140227-5