Effects of Microplegia on Transfusion Rates After Cardiac Surgery

Study Overview
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Brief Summary
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This is a prospective, randomized study that is studying the rate of red blood cell (RBC) transfusion rates after planned heart (cardiac) surgery. The study will be conducted at Barnes-Jewish Hospital. Cardioplegia refers to the method of stopping (arresting) the heart in order to perform heart surgery. However, cardioplegia has also come to refer to the solution to achieve cardiac arrest as well as the machinery in which to deliver the solution. This study will investigate our current Standard Cardioplegia (diluted 4:1 blood cardioplegia) versus Microplegia (undiluted blood cardioplegia) to determine if Microplegia reduces peri-operative blood transfusion rates as compared to Standard Cardioplegia. All forms of cardioplegia will be delivered using the MPS2 Microplegia delivery machine by Quest Medical, Inc. Patients will be randomized to receive undiluted microplegia or standard 4:1 cardioplegia. The patient and the surgeon will be blinded to the randomization. Patients will be followed for 30 days post-operatively (or until their initial standard of care post-operative follow up visit with cardiac surgery if that appointment falls outside of the 30 day post-operative window) for the development of any adverse events as well as documentation of blood products given. We will draw one tube of blood for troponin levels at four time points; 1 draw before surgery (this may be done during the intraoperative period), and 3 draws post-operatively: ICU arrival, 12 hours post-ICU arrival and 24 hours post-ICU arrival. This is to closely monitor the patient for any heart tissue injury.

Detailed Description
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Cardioplegia was first introduced as a method to protect the heart during cardiac surgery in the 1950s (1). Initially, it consisted of a crystalloid solution and in the 1970s Follette and colleagues proposed that blood was the best mode of delivery of cardioplegia as it is rich in nutrients and oxygen (2). Blood has better osmotic, buffering, and antioxidant qualities that are needed by ischemic myocardium. More recent studies comparing blood and crystalloid cardioplegias showed that there was less cardiac edema, and recovery of ventricular function was more rapid with blood based cardioplegia (3). A meta-analysis of over 5000 patients corroborated these findings and showed that blood based cardioplegia reduced the incidence of postoperative low cardiac output syndrome and was associated with less myocardial damage (4). Standard diluted blood cardioplegia can also be modified to undiluted blood cardioplegia also known as microplegia. To compare the cardioprotection of 4:1 blood:crystalloid cardioplegia to microplegia, McCann et al randomized 20 pigs to either group. Cardiac edema was measured using histologic morphometrics and echocardiogram. It was noted that both edema percentage and left ventricular mass were significantly more decreased in the microplegia group. Furthermore, all animals receiving microplegia were successfully weaned off cardiopulmonary bypass, whereas only 40% of those receiving standard cardioplegia were successfully weaned (5). More recently, Algarni et al. showed decreased prevalence of low cardiac output syndrome in patients who received microplegia (n=2,630) (6). Another study compared microplegia and standard cardioplegia in patients undergoing coronary artery bypass grafting and found that the microplegia group had lower troponin levels during the post-operative course. Moreover, microplegia resulted in lower transfusion rates and decreased length of hospital stay (7). A high rate of patients undergoing cardiac surgery require red blood cell transfusions (RBC). Red blood cell transfusions are strongly associated with both infection and ischemic postoperative morbidity, length of stay, increased early and late mortality, and overall hospital costs (8). Given that previous studies have shown that microplegia is associated with less transfusions, it would be reasonable to incorporate this into practice at Washington University.

Official Title
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Effects of Microplegia on Transfusion Rates After Cardiac Surgery: A Randomized Prospective Analysis

Conditions
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Aortic Valve Disease, Mitral Valve Disease

Intervention / Treatment
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* Drug: Cardioplegia Solution
* Drug: Microplegic Solution No. 1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are to undergo non-emergent cardiac surgery >18 years of age Willing and able to provide informed consent Exclusion Criteria: History of endocarditis Dialysis-dependent renal failure Currently on pre-operative mechanical circulatory support (i.e. ECMO, LVAD or intra-aortic balloon pump [IABP]) Contraindication to receiving a blood transfusion (i.e. Jehovah's Witness) Emergency procedures

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cardioplegia<br>4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood. | Drug: Cardioplegia Solution<br>* The microplegia solution that is standard of care for all cardiac surgery patients, and which all study subjects will receive is: Induction 240 mL Baxter Cardioplegia Solution 10. 5 mL Potassium Chloride 2 meq/ml (21 meq) 250.5 mL total volume Maintenance 747 mL Baxter Cardioplegia Solution 3.4 mL Potassium Chloride 2 meq/ml (6.75 meq) 750.4 mL total volume Subjects will be randomly assigned to 4:1 cardioplegia or nondiluted microplegia. 4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood. Nondiluted microplegia consists of all parts human blood.<br>|
| Active Comparator: Microplegia<br>Nondiluted microplegia consists of all parts human blood. | Drug: Microplegic Solution No. 1<br>* The microplegia solution that is standard of care for all cardiac surgery patients, and which all study subjects will receive is: Induction 240 mL Baxter Cardioplegia Solution 10. 5 mL Potassium Chloride 2 meq/ml (21 meq) 250.5 mL total volume Maintenance 747 mL Baxter Cardioplegia Solution 3.4 mL Potassium Chloride 2 meq/ml (6.75 meq) 750.4 mL total volume Subjects will be randomly assigned to 4:1 cardioplegia or nondiluted microplegia. 4:1 cardioplegia consists of 4 parts crystalloid intravenous fluid to one part human blood. Nondiluted microplegia consists of all parts human blood.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microplegia results in less peri-operative transfusions | To determine if use of microplegia results in less peri-operative transfusions compared to diluted 4:1 cardioplegia. | 30 days | 
| Effects of Microplegia on overall morbidity and mortality during peri-operative period | To investigate the effects of microplegia on overall morbidity and mortality during the peri-operative period. We will assess operative mortality and 30 day mortality. We will examine intra-operative and post-operative complications. A complete list of variables to be examined can be found in table 1. We will determine if microplegia results in better myocardial protection than standard cardioplegia by assessing pre-operative, intra-operative and post-operative serum troponin levels. | 30 days |