ABC | Volume 115, Nº2, August 2020

Original Article Gatti et al. Custodiol®-HTK solution & prolonged cross-clamp time Arq Bras Cardiol. 2020; 115(2):241-250 Results Overall series Although the HTK and MCB cohorts differed significantly in expected operative risk by EuroSCORE II (p=0.005), number of coronary anastomoses (p=0.003) and length of XCT (p=0.031), there was no statistically significant difference regardingt in-hospital mortality (p=0.573). However, overall (positive) postoperative fluid balance (p=0.003), acute kidney injury (p=0.002), number of transfused red blood cells units (p=0.017), and overall major complication rate (p=0.019) were all significantly increased in HTK-patients, who consequently experienced longer in-hospital stays (p=0.008) (Tables 1-3). PS-matched pairs A PS was estimated by logistic regression and its area under the receiver-operating characteristic curve was of 0.75 (95 %CI, 0.67–0.81). One-to-one matching resulted in 34 pairs of HTK/ MCB patients with similar baseline characteristics, risk profile and operative data, as confirmed by standardized differences being all lower than 10% (Tables 1 and 2). Overall (positive) postoperative fluid balance was significantly higher for HTK than for MCB patients (p=0.013) (Table 2). In the HTK cohort, there was a trend towards a higher number of transfused red blood cells units (p=0.054), an increased risk of acute kidney injury (p=0.150) and anymajor complication (p=0.128), as well as towards longer intensive care unit (p=0.142) and in-hospital stay (p=0.198) (Table 3). Test for interaction showed that the use of Custodiol- HTK solution in patients with renal impairment could increase the risk of any major complication after surgery (p=0.183; Table 4). Between the two cohorts, there were no significant differences in changes in blood levels of hemoglobin, platelets and electrolytes. Similarly, no significant changes were observed in the coagulation profile between the values immediately before surgery and those immediately following patient admission to ICU, whereas differences in creatinine levels were significant (p=0.023; Fig. 1). Finally, peak serum levels of cardiac troponin I were lower in the HTK than in the MCB cohort, though the difference was not quite significant (p=0.122; Fig. 2). Discussion The most relevant finding of this study was that, with respect to conventional MCB cardioplegia, Custodiol-HTK solution did not improve clinical outcomes of a limited series of patients undergoing isolated coronary operations requiring XCT of 120 minutes or longer. In effect, after propensity matching, higher blood levels of creatinine were observed in HTK patients early after surgery, as well as a trend towards a higher number of transfused red blood cells units, an increased risk of acute kidney injury (and renal replacement therapy) and any major complication, and longer intensive care unit and hospital stays. In addition, the test for interaction showed that the use of Custodiol-HTK solution in patients with renal impairment could increase the risk of any major complication after surgery. However, the poorer performance of this intracellular cardioplegia in the difficult subset of patients of the present study was not related to inadequate myocardial protection. Actually, between the HTK and MCB cohorts there were differences neither in the rates of myocardial infarction and low cardiac output nor in the rates of their surrogates, such as prolonged inotropic support, intraoperative and postoperative use of IABP. Besides, the peak levels of cardiac troponin I tended to be lower in HTK than in MCB patients. The increased need for red blood cells units, primarily during surgery, in the HTK cohort was mainly due to hemodilution, associated with administration of large volumes of crystalloid cardioplegia, as required by this method. Despite removing part of the HTK solution from the aortic root during the retrograde mode of delivering, overall (positive) postoperative fluid balance was indeed significantly higher for HTK than MCB patients, even after propensity- matched analysis. In fact, there was neither increased bleeding post-surgery nor any difference on blood coagulation profiles in HTK patients compared withMCB patients. Both hemodilution and the following need for transfusions that occurred in the HTK cohort during operation, as well as the increased positive fluid balance that ensued, could explain both the increased rate of acute kidney injury (and renal replacement therapy) in these patients and the increased risk of any major postoperative complication in HTK patients with renal impairment. Certainly, some systemic metabolic effects might be even involved. For instance, some grade of metabolic acidosis occurs frequently following the use of Custodiol-HTK solution, and must be promptly neutralized. 1-3 However, since no perioperative data on pH or lactacidemia have been reported, this hypothesis could not be confirmed in the study. On the other hand, because the Custodiol-HTK solution is being successfully used to preserve renal function in kidney transplantation surgery 16 , direct kidney injury seems unlikely. Although there was an evident difference in in-hospital mortality between the two study groups (5.6% vs. 1.8%), this difference was not significant (p=0.573), maybe owing to the limited number of study patients. However, there was no difference in in-hospital mortality (p=1.000) after propensity matching, which compensated for difference in expected operative risk in the overall cohort. No increased rate of spontaneous ventricular tachycardia or fibrillation after cross- clamp releasing was recorded. No significantly increased risk of right ventricular dysfunction was reported. No significant benefit derived from using either Custodiol-HTK or MCB cardioplegia for patients with anaemia, unstable angina, recent myocardial infarction or left ventricular dysfunction. The perioperative strict and effective control of hyponatremia, which was obtained in the study patients, could explain the low rate of any transitory neurological dysfunction that occurred in HTK cohort. The lower rate of any transitory neurological dysfunctions observed in HTK patients compared to the MCB group (albeit the difference was not quite significant) was an unexpected result for the present authors. The role of Custodiol-HTK solution in adult cardiac surgery has not been explored in depth. Generally, the authors who have investigated outcomes following minimally invasive cardiac surgery using Custodiol-HTK solution agreed that avoiding repetitive infusions may reduce the risk for coronary malperfusion due to dislodgement of the endoaortic clamp (if used) and increase the surgeon’s comfort during the procedure. 17-20 Almost all of the investigators who have compared Custodiol-HTK with cold blood cardioplegia have 243