Erythropoietin to minimize perioperative blood transfusion: a systematic review of randomized trials. The International Study of Peri-operative Transfusion (ISPOT) Investigators.

Our aim was to perform a systematic review to determine the efficacy and side-effects of erythropoietin, given with or without autologous predonation, to patients undergoing orthopaedic or cardiac surgery. A number of studies have been done to determine whether erythropoietin minimizes exposure to perioperative allogeneic red cell transfusion. A systematic review of all randomized trials will provide the best estimate of the efficacy and side-effects of erythropoietin therapy. All randomized trials of erythropoietin in cardiac or orthopaedic surgery that reported the proportion of patients receiving perioperative allogeneic transfusion were included. The efficacy of erythropoietin was evaluated in subgroups of patients depending upon the route of administration, dose of erythropoietin, the type of control and the methodological quality of the study report. The odds ratio for the proportion of patients transfused with allogeneic blood in studies of erythropoietin to augment autologous donation was 0.42 (95% confidence limits 0.28-0.62; P < 0.0001) for orthopaedic surgery and 0.25 (95% CI 0.08-0.82; P = 0.02) for cardiac surgery. The odds ratio for erythropoietin alone was 0.36 (95% CI 0.24-0.56; P = 0.0001) in orthopaedic surgery and 0.25 (95% CI 0.06-1.04; P < 0.06) in cardiac surgery. The route of administration, dose of erythropoietin, type of control and methodological quality of the study report had no statistically significant effect upon the odds ratios. Although there was no convincing evidence that erythropoietin used alone increased the frequency of thrombotic complications, some studies found an excess of events in erythropoietin-treated patients, and the number of patients studied was relatively small. Erythropoietin, when given alone or to augment autologous donation, decreased exposure to perioperative allogeneic transfusion in orthopaedic and cardiac surgery. Further studies are required to definitively establish the safety of erythropoietin alone, to determine the optimal dose of perioperative erythropoietin, and to compare its efficacy and cost-effectiveness with other methods of minimizing perioperative transfusion.