The Effect of Continued Mechanical Ventilation on the Occurrence of Myocardial Ischemia

Study Overview
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Brief Summary
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The goal of this study is to examine the influence of mechanical ventilation on the occurrence of myocardial ischemia in patients undergoing endo-CABG.

Detailed Description
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Coronary artery bypass grafting (CABG) surgery is one of the main treatment options for patients suffering from coronary artery disease, a condition characterized by a build-up of cholesterol in the coronary arteries of the heart that affects 126 million people worldwide each year. During this procedure, cardiopulmonary bypass (CPB) takes over the function of the heart and lungs. In recent years, there has been a huge focus on reducing surgical trauma in this procedure, leading to the emergence of minimally invasive cardiac surgery (MICS) such as endoscopic CABG (endo-CABG). In these techniques, peripheral CPB with femoral arterial cannulation is the most commonly used strategy. However, the use of retrograde arterial perfusion is not without risk. It can cause that the upper part of the body only receives deoxygenated blood. The effect on the heart is not yet fully known. The hypoxemia could cause myocardial ischemia and this could damage the heart muscle cells. It is reported in the literature that establishing adequate ventilation from the initiation of CPB to cardiac arrest can resolve this phenomenon. This approach was investigated in a recently performed double-blinded, randomized, controlled pilot study (n=10) of our research group. However, a larger randomized controlled trial was needed. Therefore, this research aims to investigate the effect of continued mechanical ventilation on the occurrence of myocardial ischemia in patients undergoing endo-CABG.

Official Title
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The Effect of Continued Mechanical Ventilation on the Occurrence of Myocardial Ischemia in Patients Undergoing Totally Endoscopic Coronary Artery Bypass Grafting

Conditions
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Cardiovascular Diseases, Coronary Artery Disease, Myocardial Ischemia, Hypoxia

Intervention / Treatment
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* Procedure: Discontinued ventilation
* Procedure: Continued ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years old Patients undergoing their first elective endo-CABG procedure using peripheral cannulation for CPB Patients who are able to give their informed consent Patients who speak Dutch or French Exclusion Criteria: Patients participating in another clinical trial Patients taking corticosteroids Patients with an ejection fraction < 25% Patients with lung diseases (chronic obstructive pulmonary disease (COPD), asthma) Patients where groin cannulation is not possible

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>Ventilation is discontinued after going on CPB and lungs are exposed to atmospheric pressure. Blood will be drawn: At baseline: before general anaesthesia, after start of CPB, after clamping the aorta, before unclamping the aorta, after the operation, 5 h after clamping the aorta, 12 hours after clamping the aorta, and 24 hours after aortic clamping | Procedure: Discontinued ventilation<br>* Ventilation is discontinued after going on CPB and lungs are exposed to atmospheric pressure<br>|
| Experimental: Ventilation group<br>Ventilation is continued from going on CPB until clamping of the ascending aorta. Blood will be drawn: At baseline: before general anaesthesia, after start of CPB, after clamping the aorta, before unclamping the aorta, after the operation, 5 h after clamping the aorta, 12 hours after clamping the aorta, and 24 hours after aortic clamping | Procedure: Continued ventilation<br>* Ventilation is continued from going on CPB until clamping of the ascending aorta with tidal volume 3ml/kg ideal body weight, Fraction of inspired oxygen (FiO2) 50%, respiratory rate 5/min and Inspiratory:Expiratory (I/E) ratio 1/2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The influence of continued mechanical ventilation on the release of cardiac troponin T (cTn-T) | Cardiac troponin T is represented in ng/L. If the value of cTn-T exceeds 14 ng/L, then cTn-T is able to detect myocardial ischemia at the predefined time points. | Until 24 hours after clamping the aorta | 
| The influence of continued mechanical ventilation on the release of creatine kinase-myocardial band (CK-MB) | Creatine kinase-myocardial (CK-MB) band is represented in µg/L. If the value of CK-MB exceeds 6.2 µg/L, then CK-MB is able to detect myocardial ischemia at the predefined time points. | Until 24 hours after clamping the aorta | 
| The influence of continued mechanical ventilation on the release of heart-type fatty acid-binding protein (hFABP) | Heart-type fatty acid-binding protein (hFABP) is represented in ng/L. If the value of hFABP exceeds 6 ng/L, then hFABP is able to detect myocardial ischemia at the predefined time points. | Until 5 hours after clamping the aorta | 
| The influence of continued mechanical ventilation on lipid peroxidation | Lipid peroxidation is measured using the malondialdehyde assay. | Until unclamping the aorta (on average until 64 minutes after clamping the aorta) | 
| The influence of continued mechanical ventilation on the redox balance | superoxide dismutase 1 and 2 (SOD1, SOD2), nuclear factor erythroid 2-related factor 2 (Nrf2), catalase (CAT), glutathione peroxidase (GPx), NADPH oxidase 2 and 4 (NOX2, NOX4), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO-1)) will be studied to determine the redox balance. | Until unclamping the aorta (on average until 64 minutes after clamping the aorta) ] | 
| The influence of continued mechanical ventilation on the partial pressure of oxygen (pO2) | pO2 is represented in mmHg. If pO2 is lower than 60 mmHg, then hypoxemia is present. | Until the end of surgery (on average until 203 minutes after the start of the surgery) | 
| The influence of continued mechanical ventilation on the partial pressure of carbon dioxide (pCO2) | pCO2 is represented in mmHg. | Until the end of surgery (on average until 203 minutes after the start of the surgery) | 
| The influence of continued mechanical ventilation on the pH | The pH will measure the acidity. | Until the end of surgery (on average until 203 minutes after the start of the surgery) | 
| The influence of continued mechanical ventilation on lactate | Lactate is represented in mmol/L. | Until the end of surgery (on average until 203 minutes after the start of the surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurence of myocardial infarction | This is based on the Fourth universal definition of myocardial infarction (2018). | Until 30 days after surgery | 
| The occurence of mortality | All-cause mortality is evaluated. | Until 30 days after surgery | 
| The occurence of neurological complications | Neurological complications include cerebrovascular accident (CVA), transient ischemic attack (TIA), delirium, epilepsy | Until 30 days after surgery | 
| The occurence of graft failure | Graft failure describes total graft occlusion that prevents blood flow through the graft to the revascularized part of the heart. | Until 30 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac surgery, Minimally invasive cardiac surgery, Endoscopic coronary artery bypass grafting, Harlequin syndrome, Ventilation