ABC | Volume 115, Nº2, August 2020

Original Article Custodiol®-HTK Solution vs. Cold Blood Cardioplegia for Isolated Coronary Surgery Requiring Prolonged Cross-Clamp Time: A Propensity-Matched Analysis Giuseppe Gatti, 1 Pierpaolo Taffarello, 1 Gabriella Forti, 1 Carla Gripari, 1 Gianfranco Gustin, 1 Gianluca Castaldi, 1 Ilaria Fiorica, 1 Aniello Pappalardo 1 Università degli Studi di Trieste, 1 Trieste – Italy Mailig Address: Giuseppe Gatti • Università degli Studi di Trieste - via Pietro Valdoni, 7 Trieste 34127 – Italy E-mail: gius.gatti@gmail.com Manuscript received January 18, 2019, revised masucript June 25, 2019, accepted July 17, 2019 DOI: https://doi.org/10.36660/abc.20190267 Abstract Background: Custodiol®-histidine-tryptophan-ketoglutarate (HTK) cardioplegia is widely used. Objective: To compare the outcomes of isolated coronary surgery requiring prolonged cross-clamp time (XCT) in patients receiving a single-dose HTK or multidose cold blood (MCB) cardioplegia. Methods: XCT was ≥120 minutes for 148 consecutive patients undergoing isolated coronary surgery (2009−2016). HTK and MCB cardioplegia were used in 38 and 110 cases, respectively. The two cohorts were compared on baseline characteristics, operative data, and early outcomes. Because risk profile and operative data differed significantly between the two groups, one-to-one propensity score-matched analysis was performed and 34 pairs were generated. Results: While expected operative risk was higher in the HTK than in the MCB cohort (European System for Cardiac Operative Risk Evaluation II, p=0.005), there was no significant intergroup difference regarding in-hospital mortality (p=0.573). Overall (positive) postoperative fluid balance (p=0.003), number of blood transfusions (p=0.017), rates of acute kidney injury (p=0.002) and any major complication (p=0.019) were increased in HTK patients. These results were all confirmed even after propensity matching, though the difference was significant only for fluid balance (p=0.013) and quite significant for blood transfusions (p=0.054). In the HTK cohort, intensive care unit and hospital stay were longer both for overall (p=0.016 and 0.008) and matched patients (p=0.142 and 0.198). In matched patients, peak serum levels of cardiac troponin I were lower in the HTK cohort (p=0.122); serum levels of creatinine were lower in the MCB cohort (p=0.023). Conclusion: For the patients of this study who required prolonged XCT, there was a trend towards poorer outcomes when HTK, rather than MCB cardioplegia, was used. (Arq Bras Cardiol. 2020; 115(2):241-250) Keywords: Myocardial Revascularization/complications; Heart Arrest Induced; Cardioplegic Solutions/thertapeutic use; Myocardial Reperfusion; Postoperative complications; Myocardial Infarction, Stroke; Mortality. for a period of up to three hours. 2,3 Consequently, it is generally used for myocardial protection in complex, adult 4,5 or pediatric cardiac operations 6 and for heart preservation in transplant surgery. 7,8 Actually, safe aortic cross-clamping time (XCT) using Custodiol-HTK cardioplegia has not been established yet. There are also concerns about hyponatremia that follows the rapid administration of the required high volume of this low- sodium cardioplegic solution, 9,10 as well as the adequacy of myocardial protection offered by only a single dose of cardioplegia. 7,8,11 In addition, despite its widespread use, very few clinical studies have compared Custodiol- HTK solution with conventional, blood or crystalloid cardioplegia in coronary bypass surgery. 12 The aim of this retrospective study was to compare Custodiol-HTK solution with conventional multidose cold blood (MCB) cardioplegia in patients undergoing isolated coronary surgery requiring prolonged XCT. Both myocardial protection and early outcome after surgery were reviewed. Introduction The Custodiol® histidine-tryptophan-ketoglutarate (HTK) solution (Essential Pharma, Newtown, PA, US) is classified as an intracellular, crystalloid cardioplegia because of its low sodium and calcium content. 1 Sodium depletion of the extracellular space causes hyperpolarization of the myocardial cell plasma membrane, inducing cardiac arrest in diastole. A high histidine content buffers the acidosis caused by the accumulation of anaerobic metabolites during the ischemic period; ketoglutarate improves adenosine triphosphate production during reperfusion; tryptophan stabilizes the cell membrane. 2 A single-dose of cardioplegia is claimed to offer myocardial protection 241