Xenon in Off-pump Coronary Artery Bypass Graft Surgery

The Safety and Feasibility of Administering Xenon to Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery: a Pilot Study

Purpose of this study is to test whether xenon application during off-pump-coronary artery bypass (OPCAB)-surgery is safe and feasible.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Anesthesia
• Intervention / Treatment: Drug: Xenon; Drug: sevoflurane

Detailed Description

The investigators hypothesize that xenon application during OPCAB-surgery performs non-inferiorly to the administration of the established anaesthetic sevoflurane with regard to haemodynamic stability, respiratory function, and depth of anesthesia. The evaluation of the outcome will include several secondary parameters such as the incidence of post-operative cardiovascular and neurovascular events, the incidence of organ dysfunction and further adverse events.

This study will further function as a pilot study for the evaluation of the incidence of postoperative delirium (POD) following OPCAB-surgery and xenon treatment. POD is a common complication of cardiac surgery/anaesthesia and may significantly affect the patients' mortality and outcome. Xenon possesses neuroprotective and anti-inflammatory qualities that may directly interfere with the pathogenesis of POD, as well as reducing other factors of perioperative organ injury including cardiac complications. Xenon´s favourable pharmacokinetic properties further result in rapid clearance from the brain, reducing any residual anaesthetic effects that may predispose to POD.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven

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:

• Patients with coronary artery disease scheduled for elective OPCAB- surgery
• Patients willing and able to complete the requirements of this study
• Ejection Fraction > 30%

Exclusion Criteria:

• Lack of informed consent
• Age < 18 years
• Pregnancy
• chronic obstructive pulmonary disease (COPD) GOLD > II
• Renal dysfunction defined as serum-creatinine > 1.5 mg/dl
• Acute coronary syndrome during the last 24 hours; haemodynamic instability, requirement of inotropic support
• Single vessel grafting
• Disabling neuropsychiatric disorders (severe dementia, Alzheimer's disease, schizophrenia, depression), history of stroke with residuals, significant stenosis of carotid arteries, increased intracranial pressure
• Hypersensitivity to the study medication
• Presumed uncooperativeness or legal incapacity

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug: Xenon; gaseous anesthetic, dosage: 50-60% (v/v) in oxygen, continuous application during surgery	Drug: Xenon; general anaesthesia with xenon 50-60% in oxygen (FiO2=0.4-0.5)
Active Comparator: Drug: Sevoflurane; inhalative anesthetic, dosage: 1.4% (v/v) in 50% oxygen/medical air , continuous application during surgery	Drug: sevoflurane; general anesthesia with sevoflurane 1.4% in 50% oxygen/medical air

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility/Safety of xenon anesthesia	assessed by: depth of anesthesia, perioperative hemodynamic profile, peripheral and arterial oxygen saturation	Intraoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac and cerebral events (MACCE)	death from any cause; perioperative myocardial infarction and stroke	up to six months after surgery
Incidence and duration of postoperative delirium	assessed with the Confusion Assessment Method (CAM-ICU)	up to five days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other secondary efficacy/safety measures	Perioperative blood loss	up to five days after surgery
Other secondary efficacy/safety measures	Requirement for blood (product) transfusion	up to five days after surgery
Other secondary efficacy/safety measures	Duration of postoperative intensive care unit and hospital stay	until discharge from the hospital
Other secondary efficacy/safety measures	Severity of postoperative critical illness as indicated by the sequential organ failure assessment (SOFA) score	up to five days after surgery
Other secondary efficacy/safety measures	Perioperative renal function assessed by serum-creatinine levels and calculated creatinine clearance	up to five days after surgery
other secondary efficacy/safety measures	Severity of postoperative critical illness as indicated by the new simplified acute physiology score (SAPS II)	up to five days after surgery

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Steffen Rex, PhD, UZ Leuven

Publications and helpful links

General Publications

• Al Tmimi L, Van Hemelrijck J, Van de Velde M, Sergeant P, Meyns B, Missant C, Jochmans I, Poesen K, Coburn M, Rex S. Xenon anaesthesia for patients undergoing off-pump coronary artery bypass graft surgery: a prospective randomized controlled pilot trial. Br J Anaesth. 2015 Oct;115(4):550-9. doi: 10.1093/bja/aev303.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 3, 2012
• First Submitted That Met QC Criteria: December 20, 2012
• First Posted (Estimate): December 28, 2012

Study Record Updates

• Last Update Posted (Estimate): March 26, 2014
• Last Update Submitted That Met QC Criteria: March 24, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: xenon anesthesia; sevoflurane anesthesia; off-pump coronary artery bypass graft surgery
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Sevoflurane
• Other Study ID Numbers: SR052012; 2012-002316-12 (EudraCT Number)