Adenosine as an Adjunct to Blood Cardioplegia

Study Overview
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Brief Summary
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Myocardial protection is a major issue in cardiac surgery, since inadequate protection increases the risk of postoperative cardiac dysfunction. The main principle of myocardial protection in cardiac surgery is to preserve myocardial function by preventing ischemia with blood cardioplegia . Previous studies have shown that adenosine as an adjunct to blood cardioplegia can be safely used in cardiac surgery. In the Amphia Hospital, adenosine is already used as standard care as an initial cardioplegic bolus in minimally invasive port access operations. Whether, adenosine as an adjunct to intermittent warm blood cardioplegia, has an added value remains unclear. Therefore the investigators would like to investigate the effect of the addition of adenosine to standard intermittent warm blood cardioplegia in patients scheduled for minimally invasive, port access operations (mitral valve surgery). Half of the participants will receive standard intermittent warm blood cardioplegia, while the other half will receive intermittent warm blood cardioplegia enriched with adenosine.

Detailed Description
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Myocardial protection is a major issue in cardiac surgery, since inadequate protection increases the risk of postoperative cardiac dysfunction. The main principle of myocardial protection in cardiac surgery is to preserve myocardial function by preventing ischemia with blood cardioplegia . Previous studies have shown that adenosine as an adjunct to blood cardioplegia can be safely used in cardiac surgery. In the Amphia Hospital, adenosine is already used as standard care as an initial cardioplegic bolus in minimally invasive port access operations. Whether, adenosine as an adjunct to intermittent warm blood cardioplegia, has an added value remains unclear. Therefore the investigators would like to investigate whether the addition of adenosine to standard intermittent warm blood cardioplegia reduces the 6-hours post-operative cardiac troponin T (cTnT) in patients scheduled for minimally invasive, port access operations (mitral valve surgery).

Official Title
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The Effect of Adenosine on Myocardial Protection in Intermittent Warm Blood Cardioplegia: A Randomized Placebo-controlled Trial

Conditions
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Pathological Processes, Cardiomyopathies

Intervention / Treatment
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* Drug: Adenosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective cardiac surgical patients minimally invasive, port access surgery (mitral valve surgery) Exclusion Criteria: All non-minimally invasive, port access surgery Theophylline or dipyridamole use up to 24 hours prior to surgery Products that contain caffeine of theobromine up to 12 hours prior to surgery (coffee, chocolate, energizing drinks (e.g. Red Bull), tea, soda (coke), etc)

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard cardioplegia<br>Delivery of cardioplegic solutions will be according to the standard protocol (Amphia hospital, Breda, the Netherlands). Oxygenated blood and cardioplegic maintenance solution is delivered in a 20:1 ratio. Cardioplegic solutions will be administered at 20-minutes intervals. The flow of the cardioplegia must be at 300 ml/min, the duration is approximately 1 minute. The cardioplegic maintenance solution consists of a 500 ml normal saline (0.9% NaCl) infusion bag. Potassiumchloride (20 mmol) and magnesiumsulphate (1000 mg) is added according to standard protocol. This arms receives standard intermittent 20:1 diluted warm blood cardioplegic solution. Intervention: n/a | |
| Experimental: adenosine enriched cardioplegia<br>Delivery of cardioplegic solutions will be according to the standard protocol (Amphia hospital, Breda, the Netherlands). Oxygenated blood and cardioplegic maintenance solution is delivered in a 20:1 ratio. Cardioplegic solutions will be administered at 20-minutes intervals. The flow of the cardioplegia must be at 300 ml/min, the duration is approximately 1 minute. The cardioplegic maintenance solution consists of a 1000 mg = 500 ml adenosine infusion bag (2 mg/ml). Potassiumchloride (20 mmol) and magnesiumsulphate (1000 mg) is added according to standard protocol. This arms receives adenosine enriched, intermittent 20:1 diluted warm blood cardioplegic solution. Intervention: Drug: Adenosine | Drug: Adenosine<br>* This group receives intermittent warm blood cardioplegia enriched with adenosine<br>* Other names: Adenocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-hour cardiac Troponin T (cTnT) release | The primary end point is 6-hour cTnT release | 6 hours post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18-hour cardiac Troponin T (cTnT) area under the curve (AUC) release | 18-hour postoperative AUC release of cardiac troponin T Routine blood samples pre-operatively from peripheral blood (T0); post-operatively, from peripheral blood, at arrival at ICU (T1) and 6 hours after arrival at ICU (T2), and 18 hours after arrival at ICU (T3). | cardiac Troponin T (cTnT) AUC will be assessed at different time points, the latest up to 18 hours after ICU arrival | 
| Incidence of myocardial injury on 12-lead ECG | Incidence of myocardial injury on 12-lead ECG New-onset Left bundle branch block (LBBB) New-onset Q wave | participants will be followed for the duration of ICU stay, an expected average of 2 days | 
| Vasoactive-inotropic score | The hourly doses of the following inotropic and vasoactive medications are recorded for the first 18 h after post-operative admission to the ICU: dopamine, dobutamine, epinephrine, norepinephrine, milrinone and vasopressin. | participants will be followed for the duration of ICU stay, an expected average of 2 days | 
| Vasoconstrictor usage | Vasoconstrictor usage yes/no | participants will be followed for the duration of ICU stay, an expected average of 2 days | 
| Incidence of new onset Atrial fibrillation (AF) | Incidence of new onset AF | participants will be followed for the duration of ICU stay, an expected average of 2 days | 
| Routine blood samples | The amount of creatine kinase MB (CK-MB) and Creatinine at different time intervals. preoperatively from peripheral blood (T0); post-operatively, from peripheral blood, at arrival at ICU (T1) and 6 hours after arrival at ICU (T2) | Routine blood samples will be assessed at different time points, the latest up to 6 hours after ICU arrival | 
| Mean arterial pressure (MAP) | Haemodynamic monitoring | participants will be followed for the duration of ICU stay, an expected average of 2 days | 
| postoperative left ventricular ejection fraction (LVEF) | 3-D transesophageal echocardiography (TEE) postoperative left ventricular ejection fraction (LVEF) after skin closure | postoperative after skin closure, an expected average of 3 hours after starting surgery | 
| Wall Motion Score Index (WMSI) | 3-D transesophageal echocardiography (TEE) Wall Motion Score Index (WMSI) after skin closure | postoperative after skin closure, an expected average of 3 hours after starting surgery | 
| Heart rate (HR) | Haemodynamic monitoring. Heart rate will be measured in beats per minute (bpm). | participants will be followed for the duration of ICU stay, an expected average of 2 days | 
| Cardiac index (CI) | Cardiac index (CI) is a haemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA) | participants will be followed for the duration of ICU stay, an expected average of 2 days | 
| Systemic vascular resistance index (SVRI) | SVRI = 80 x (MAP - RAP)/CI MAP = Mean Arterial Pressure (mmHg) RAP = Right Arterial Pressure (mmHg) CI = Cardiac Index (L/min/m2) | participants will be followed for the duration of ICU stay, an expected average of 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardioplegia, Cardiac Surgery, Adenosine, Therapeutic Uses, Intermittent warm blood cardioplegia, Minimally Invasive Surgery, minimally invasive mitral valve plasty (mini-MPL), minimally invasive mitral valve replacement (mini-MVR)