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Our objectives were to identify problems associated with the administration of fat emulsion by extracorporeal membrane oxygenation (ECMO) circuits, and gather information from other institutions on standards of practice and the complications associated with infusion of fat emulsion by ECMO to infants and children. In vitro analysis was performed using six circuits. Fat emulsion was infused into a prereservoir port at 3 ml/hour. Circuits and blood samples collected distal to the oxygenator were inspected visually for layering (separation of fat emulsion from blood), agglutination, and phase separation (formation of an oil layer) at 0.5, 1, 2, 4, 6, 12, and 24 hours. At 24 hours, samples were reevaluated and circuits dissected. All circuits showed layering and agglutination. Blood clots were present in five circuits during the simulation. There was no evidence of phase separation in the samples. Adhesion of emulsion to the equipment was present in all circuits. Five of the membrane oxygenators contained clots. One contained long strands of fat; separation of its mesh revealed an oily residue indicating disruption of the stability of the emulsion. Survey responses from 54 centers found that 78% used fat emulsion routinely in neonatal or pediatric patients receiving ECMO. Most used both ECMO and separate venous access for the infusion, depending on availability. Twenty-two (52%) of the 42 centers using fat emulsion had a policy in place regarding site selection. Of those, 73% preferred central venous access, another 18% used a prereservoir port of the ECMO circuit. The most frequently reported problems with administration through the circuit were cracking of stopcocks, clogging and malfunction of the membrane oxygenator, agglutination of the emulsion, and increase in blood clot formation. Our results suggest that fat emulsion should be infused through a separate intravenous site whenever possible. Based on these results and current practices of most ECMO centers, a clinical trial is currently being conducted to provide additional information.