The avoidance of unnecessary blood transfusion is a high priority; therefore, determining safe thresholds for transfusion is imperative.1,2 Among the highest recipients of red-cell transfusion are patients undergoing cardiac surgery,2-6 with a substantial proportion of the total blood supply used by this group.7,8 Whether a restrictive approach to intraoperative and postoperative transfusion in cardiac surgery safely achieves outcomes similar to those achieved by means of a more liberal approach remains unclear.9-12
The infectious and noninfectious risks associated with transfusion support a restrictive transfusion practice in several clinical settings.13-15 However, anemia, particularly in the perioperative setting, may also be detrimental.16-19 Patients who are at high perioperative risk may be more susceptible to anemia-induced tissue hypoxia,20 potentially exposing them to an increased risk of complications and death if a restrictive approach is used.21 We conducted a multicenter, randomized, controlled trial to determine whether a restrictive transfusion strategy applied throughout the perioperative period would be noninferior, in terms of major morbidities and mortality, to a liberal approach among patients undergoing cardiac surgery who had a moderate-to-high risk of death.
Trial Design and Oversight
The Transfusion Requirements in Cardiac Surgery (TRICS) III trial was an international, open-label, randomized, controlled, noninferiority trial that compared restrictive and liberal red-cell transfusion strategies in adults undergoing cardiac surgery with cardiopulmonary bypass who had a moderate-to-high predicted risk of death according to the European System for Cardiac Operative Risk Evaluation (EuroSCORE I; scores are on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery).22,23 An appropriately authorized ethics committee approved the trial in all the participating centers.
The trial was supported by the Canadian Institutes of Health Research, the Canadian Blood Services–Health Canada, the National Health and Medical Research Council of Australia, and the Health Research Council of New Zealand. The funders had no role in the trial design or conduct; in the collection, management, analysis, or interpretation of the data; or in the preparation or review of the manuscript or the approval of the manuscript for submission. The trial was designed by the executive committee and carried out by the TRICS investigators (see the Supplementary Appendix, available with the full text of this article at NEJM.org). The first author and the last four authors vouch for the data and analyses and for the fidelity of the trial to the protocol (available at NEJM.org).
We enrolled participants 18 years of age or older who were scheduled to undergo cardiac surgery with cardiopulmonary bypass and who had a preoperative additive EuroSCORE I of 6 or higher. The EuroSCORE I has been validated previously and has been shown to be predictive of an in-hospital mortality of 4% or more (see the Supplementary Appendix for a list of the EuroSCORE I components).24,25 We excluded patients if they were unable to receive blood products, declined blood products, were involved in a preoperative autologous donation program, were undergoing heart transplantation, were having surgery solely for the insertion of a ventricular assist device, or were pregnant or lactating. Written informed consent was obtained from all the participants before enrollment.