Development of simulated and ovine models of extracorporeal life support to improve understanding of circuit-host interactions

Background: Extracorporeal life support (ECLS) is a lifesaving technology that is being increasingly used in patients with severe cardiorespiratory failure. However, ECLS is not without risks. The biosynthetic interface between the patient and the circuit can significantly alter inflammation, coagulation, pharmacokinetics and disposition of trace elements. The relative contributions of the pump, disease and patient in propagating these alterations are difficult to quantify in critically ill patients with multiple organ failure. Objective: To design a model where the relevance of individual components could be assessed, in isolation and in combination. Design and subjects: Four ECLS models were developed and tested - an in-vitro simulated ECLS circuit; and ECLS in healthy sheep, sheep with acute lung injury (ALI), and sheep with ALI together with transfusion of old or new blood. Main outcome measures: Successful design of in-vitro and in-vivo models. Results: We successfully conducted multiple experiments in the simulated circuits and ECLS runs in healthy and ALI sheep. We obtained preliminary data on inflammation, coagulation, histology, pharmacokinetics and trace element disposition during ECLS. Conclusions: The establishment of in-vitro and in-vivo models provides a powerful means for enhancing knowledge of the pathophysiology associated with ECLS and identification of key factors likely to influence patient outcomes. A clearer description of the contribution of disease and therapeutic interventions may allow improved design of equipment, membranes, medicines and physiological goals for improved patient care