Extracorporeal membrane oxygenation (ECMO) has been successful treatment (80% survival) in over 2,000 neonates with severe respiratory failure (80% predicted mortality without ECMO). Neonates on ECMO require frequent blood product replacement, which increases donor exposure (DE) and the risk of transfusion related complications. Successful, widespread usage of ECMO in neonatal respiratory failure is placing increased numbers of surviving infants at risk for acute and long-term transfusion related problems. We assessed DE rates in 21 consecutive neonatal ECMO survivors. In the first 12 patients packed red blood cell (PRBC) transfusions were administered as 10 mL/kg body weight for hematocrit less than 45%. PRBC exchange transfusions were used in patients with hematocrit less than 45% and hypervolemia. Fresh frozen plasma (FFP) and cryoprecipitate (CRYO) infusions were used empirically for evidence of hemorrhage. DE rates (donors per ECMO day, mean +/- SD) were: PRBC (2.8 +/- 0.6), FFP/CRYO (0.5 +/- 0.7), and platelet (2.0 +/- 1.0), with a total donor exposure rate of 5.3 +/- 2.0 donors per ECMO day. Mean duration of ECMO was 4.6 +/- 2.0 days and total DE per infant was 22.8 +/- 9.5 donors per ECMO run. In a protocol (n = 9) to minimize DE risks, exchange transfusions were eliminated and PRBC transfusion volumes were increased to 15 mL/kg. Empiric use of FFP and CRYO was discontinued. The blood bank divided standard units of PRBCs into four aliquots and dispensed each aliquot sequentially before dispensing blood from another unit.(ABSTRACT TRUNCATED AT 250 WORDS)