Erythrocyte Transfusion and Long-Term Mortality in Open Heart Surgery in Adults

Background Approximately 3,000 cases of cardiac surgery with cardiopulmonary bypass are performed each year in Norway. Cardiac surgery is performed to treat various disease of the heart, which includes ischemic, valvular, and congenital heart disease. Improvements in surgical and non-surgical techniques, as well as perioperative patient management have improved patient outcomes following cardiac surgery. Nevertheless, several risk factors and complications are associated with cardiac surgery, mortality being the most serious. Transfusion of red blood cells (RBC) is associated with postoperative morbidity, shortand long-term mortality in cardiac surgery. However, some investigators have found contradicting results regarding the association between RBC transfusion and long-term mortality. The observed difference in mortality between patients who receive RBC transfusion and patients who do not receive any transfusion, could be attributed to residual confounding by factors such as preoperative anaemia. Aim The aim of this thesis was to investigate the association between RBC transfusion and long-term all-cause mortality in adult patients undergoing cardiac surgery. Another aim was to compare the risk associated with RBC transfusion and preoperative anaemia on long-term all-cause mortality in adult patients undergoing cardiac surgery. Methods Data on adult patients undergoing cardiac surgery been consecutively collected from 2000 through 2017 in the Trondheim Heart Surgery Database at St. Olavs Hospital, Trondheim, Norway. We investigated the association between transfusion of at least one unit of RBC intra- or postoperatively and long-term mortality, in patients undergoing primary isolated coronary artery bypass grafting (CABG). We also investigated the association between RBC transfusion and 5-year mortality in adult patients with preoperative anaemia undergoing primary cardiac surgery. Cox regression adjusted for known risk factors for mortality and common postoperative complications following cardiac surgery was employed. To compare the association of RBC transfusion with preoperative anaemia on long-term all-cause mortality, we employed Structural equation modelling (SEM). We constructed and analysed path diagrams between known risk factors in cardiac surgery and observed mortality between 30 days and 5 years postoperatively. The total effect of preoperative anaemia on mortality was compared with the direct effect of RBC transfusion. Results From 2000 through 2014, 4,014 patients underwent primary isolated CABG, and from 2000 through 2017, 1,859 patients with preoperative anaemia underwent cardiac surgery at St. Olavs Hospital. The unadjusted hazard ratio showed a statistically significant association between RBC transfusion and long-term mortality in both groups. However, when adjusted for known risk factors and common postoperative complications, the association was no longer significant for the patients who underwent isolated CABG (Paper 1). For the patients with preoperative anaemia (Paper 2), the association was not statistically significant when adjusted for pre- and intraoperative variables. The hazard ratio was highest in the first postoperative year in this patient group. A total of 9,315 patients who underwent cardiac surgery from 2000 through 2017 were included in the SEM analysis (Paper 3). The standardized total effect coefficient of preoperative anaemia on mortality between 30 days and 5 years postoperatively was 0.10. The standardized direct effect of RBC transfusion on mortality was 0.03, which was smaller compared with preoperative anaemia. All other risk factors in the SEM analysis had larger total effect on mortality compared with RBC transfusion, except for female sex. Conclusions RBC transfusion was associated with increased long-term all-cause mortality in patients who underwent primary isolated CABG, and in cardiac surgery patients with preoperative anaemia. RBC transfusion was no longer statistically significantly associated with longterm all-cause mortality when the analyses were adjusted for known pre- and intraoperative variables, and common postoperative complications. RBC transfusion had smaller effect on 5-year mortality compared with preoperative anaemia. Most of the observed difference in mortality between patients who received RBC transfusion and patients who did not receive any transfusion, may be attributed to patient comorbidities and operative risk factors