Assessing The Clinical Utility of Non-Depolarizing Cardioplegia & The Challenge Of Evidence-Based Decision Making in an Anecdotal Age of Cardioplegia Comparative Research

Abstract

PART I Background: For over forty years, depolarizing, hyperkalemic cardioplegia solutions have served as the standard of care for cardiac surgery. While effective in inducing cardiac arrest, potassium-based solutions are associated with an array of negative consequences, such as coagulopathies, conduction dysfunction, inflammation, coronary vasoconstriction, myocardial edema, and ischemic injury. Adenosine-lidocaine-magnesium, a non-depolarizing, non-potassium-containing solution, has recently entered the clinical arena. Animal research suggests that this agent may provide a method of diastolic arrest that is as effective as potassium-based cardioplegia but with improved protective benefits.Purpose: The aim is to assess the safety and efficacy of adenosine-lidocaine-magnesium as a cardioplegia solution in terms of overall patient outcomes.Methodology: In June 2014, Banner University Medical Center Tucson became the first American institution to adopt the use of PolarShot (ALM)--adenosine-lidocaine-magnesium - as a cardioplegia solution. This one-year, retrospective study compares patients receiving adenosine-lidocaine-magnesium to those receiving high-potassium/low-potassium cardioplegia during adult cardiac surgery. Cases compared in this study include isolated coronary artery bypass, isolated aortic/mitral valve repair/replacement, and combination coronary artery bypass/valve replacement surgery only. A propensity-weighted regression model was used for analysis to determine whether or not cardioplegia treatment affected clinical outcome. To assess overall clinical outcome, major morbidity and mortality and post-procedural length of stay were chosen as primary endpoints. Results: In terms of treatment (adenosine-magnesium-lidocaine vs. high-potassium/low-potassium), no statistically significant difference was found between groups in regard to major morbidity and mortality event occurrences nor was a significant difference found between post-procedural length of stay. Discussion: After comparing postoperative outcomes between cardioplegia treatment groups, PolarShot (ALM) cardioplegia produced postoperative outcomes that were statistically similar to those of high-potassium/low-potassium cardioplegia. The confidence in these results is limited by low case volume, surgical case variability, and retrospective nature of this study. Conclusion: According to this propensity-weighted regression model, PolarShot (ALM) cardioplegia appears to be a safe and effective alternative to traditional potassium-based cardioplegia for the purpose of adult cardiac surgery. More research, including prospective randomized trials, is necessary to confirm or deny the findings of this study. PART II Background: Historically, surgical cardioplegia compounding was accomplished by filling patient-tailored prescriptions on-demand. Modern day compounding has become a manufacturing process to improve quality and accommodate physician demand. Additionally, sterile compounding standards have become more stringent, further necessitating a standardized compounding approach. In 2013, scrutiny of sterile drug compounding increased with passage of the Drug Quality and Security Act (DQSA) and subsequent Federal Drug Administration oversight. This federal mandate requires all compounded sterile preparations distributed by 503B Outsourcing Facilities be tested for potency, stability, and sterility. To accomplish this, compounders must significantly reduce batched formula variability. Purpose: A review of 2014 sales data from a large 503B outsourcing facility and cardioplegia compounder will be conducted. The study will identify solution differences and detail its findings. The aim of this study is to assess cardioplegia variability on a national level. Methodology: Results will be summarized by cardioplegia strategy (Buckberg, high-potassium/low-potassium, crystalloid, del Nido, Adenocaine, and microplegia), dilution strategy (4:1 blood-crystalloid, 8:1 blood-crystalloid, 1:4 crystalloid-blood, all-blood, and all-crystalloid), formula constituents (base solutions, additives, buffers), potassium concentrations. Any observed patterns in formula usage will also be reported, geographical or otherwise. Results / Discussion: Based on institutional use, high-potassium/low-potassium (two-solution) multidose strategy was the most common. Based on solutions ordered, the most common cardioplegia ingredient was potassium chloride, present in almost ninety percent (89.64%) of all units sold. After looking at potassium content, extensive variability was noted in terms of potassium added to the bag (undiluted) and potassium to-be delivered (post-dilutional). Additionally, unique solution formulations identified in multiple institutions were often found in neighboring states or within a single state. Conclusion: The results of this analysis illustrate the extent to cardioplegia formula variability nationwide. Variability exists in both methodology and formulation on a state-to-state, institution-to-institution, even across-single-institution basis. This formula customization appears to be institution- and surgeon-specific, suggesting empirical influence in formula adaptation. Formula standardization may be necessary to combat the compounded issue of formula customization moving forward.