Cardiac surgery is known to have high rates of perioperative red blood cell (RBC) transfusions which are associated with increased postoperative mortality and morbidity. Perioperative erythropoietin (EPO) has been suggested to lower perioperative RBC transfusions, and the effect on postoperative morbidity or mortality is unknown.

The registered study protocol is available on PROSPERO (CRD42022314538). We searched the Pubmed, EMbase, and Cochrane CENTRAL databases for randomized controlled trials (RCT) of EPO in cardiac surgery. Outcomes were short-term mortality, acute kidney injury (AKI), re-operation, cerebrovascular accident (CVA), perioperative myocardial infarction (MI), infectious complications, and RBC transfusions. RCT studies of perioperative EPO that reported at least one prespecified outcome of interest were included.

A total of 21 RCT’s (n = 2,763 patients) were included. Mortality analysis included 17 studies (EPO 1,272 patients, control 1,235) and showed no significant difference (risk difference (RD) 0.0004, 95%CI: −0.016, 0.009). EPO did not reduce the incidence of AKI (RD −0.006, 95% CI: −0.038, 0.026) and reoperation (RD 0.001, 95% CI: −0.013, 0.015). The incidence of CVA (RD −0.004, 95% CI: −0.015, 0.007) and perioperative MI (RD −0.008, 95% CI: −0.021, 0.005) was similar between the groups.

Although EPO had been proven to reduce perioperative RBC transfusions, we did not find that it reduces the incidence of postoperative short-term mortality, AKI, and reoperation. The study results support that perioperative EPO is also safe, with no rise in thrombotic events, including CVA and perioperative MI.