Editorial Comment: Blood or crystalloid cardioplegia: which is better?

The accompanying paper by Viana et al. [1] compared their standard technique of blood cardioplegia with a new approach with histidine-enhanced crystalloid cardioplegia. The debate between blood and crystalloid cardioplegia continues after nearly 30 years [2, 3]. A variety of compositions, temperatures, delivery methods and additives have been tested in randomized clinical trials for both blood and crystalloid cardioplegia. Cardiac surgeons have learned to tailor their cardioplegic techniques to the individual patient and select the most appropriate approach to reduce the risks of postoperative morbidity and mortality. A propensity-matched analysis may not account for the selection bias of experienced cardiac surgeons. As suggested by the authors, a large-scale prospective randomized trial will be required to determine whether blood provides better perioperative myocardial protection than histidine-enhanced crystalloid cardioplegia. Recent clinical trials in carefully selected high-risk patients undergoing isolated coronary bypass grafting (CABG) have required thousands of patients to have sufficient power to detect a significant difference [4]. Even more patients are required to demonstrate equivalence or non-inferiority. A retrospective review of all cardiac surgical procedures may not be able to determine whether crystalloid is as safe as blood cardioplegia. Early studies with extracellular crystalloid solutions suggested that multidosing provided better protection than infrequent dosing for CABG surgery [5]. However, no randomized clinical trial has adequately compared extracellular with intracellular crystalloid solutions and no study has compared single dose with multidose protection with histidine-tryptophan-ketoglutarate (HTK, Custodiol) solution for coronary bypass surgery. The optimal technique of crystalloid cardioplegia has not been established for either isolated CABG or valve surgery. The best method of blood cardioplegic delivery depends on the cardiac procedure anticipated. Patients with diffuse coronary disease may require cooler temperatures and those with ventricular hypertrophy may require near-continuous delivery [6]. The options with blood cardioplegia include temperature (cold, warm or tepid), direction (antegrade, retrograde or combined) and continuity (intermittent or continuous). The study from Melbourne suggests that their surgeons selected an intermediate compromise between cooling and perfusion. Increasing experience with blood cardioplegia has improved the outcomes of surgery. Comparing blood with crystalloid cardioplegia is extremely difficult because the reasons for selecting alternate cardioplegic methods are not adequately determined with the usual patient demographics. Experienced cardiac surgeons tailor their myocardial protection strategies to the anticipated procedure. Mitral valve surgery is commonly accomplished expeditiously and a single dose of cold crystalloid cardioplegia may be all that is required if the ventricle is normal. In addition, multidosing may be difficult because of the need to deair the aortic root for subsequent antegrade doses. Braathen et al. [7] found that a single dose of HTK solution resulted in outcomes similar to those achieved with multidose cold-blood cardioplegia for mitral valve surgery. However, the same group found that HTK did not provide as good protection as cold-blood cardioplegia for aortic valve surgery [8]. Cardiac surgeons employ a variety of cardioplegic techniques for valve surgery, depending on the challenges of the procedure and the extent of ventricular abnormalities. Coronary artery disease presents more complex problems because of the potential for inadequate cardioplegic delivery. Prospective, randomized clinical trials are required to compare alternative cardioplegic techniques for each of these surgical procedures. Combining all cardiac surgical procedures in a single evaluation resulted in a frustrating lack of clarity. The authors claimed that HTK cardioplegia was ‘at least as safe’ as cold-blood cardioplegia. Unfortunately, they did not have a sufficient number of patients with adequate postoperative measurements to detect significant adverse effects of either cardioplegic approach. Because they did not systematically measure cardiac enzymes or determine which patients required prolonged inotropic support, they were not able to use the outcomes employed in many studies of cardioplegic additives [4–6, 9]. Postoperative cardiac enzyme release has been associated with diminished long-term survival [9] and perioperative low cardiac output syndrome has been associated with a higher incidence of complications [10]. These endpoints provide an opportunity to compare alternative strategies of myocardial protection. The incidence of postoperative balloon pump assistance, stroke and in-hospital mortality is too low after most cardiac procedures to be useful outcomes to discriminate between alternative strategies. Return for bleeding and prolonged ventilation may not reflect the adequacy of myocardial protection. Therefore, detection of significant differences between cardioplegic solutions remains a difficult undertaking. However, finding no difference between two strategies is not the same as equivalence or non-inferiority. The authors were not able to identify significant differences, but the study had insufficient power to determine important risks with either blood or crystalloid cardioplegia. The authors should be congratulated on exploring the potential of a simple technique of cardioplegic protection. However, prospective randomized trials in a uniform group of high-risk patients will be required to detect equivalence or important differences. Additives that protect against postoperative complications have not been identified despite multiple clinical trials. New methods of myocardial protection are urgently needed to preserve the low rates of morbidity and mortality despite the increasing risk profile of patients presenting for cardiac surgery.