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.
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 illpatients 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.
Authors: Kiran Shekar; Jason A Roberts; Charles I Mcdonald; Sussan Ghassabian; Chris Anstey; Steven C Wallis; Daniel V Mullany; Yoke L Fung; John F Fraser Journal: Crit Care Date: 2015-04-14 Impact factor: 9.097
Authors: Saul Chemonges; Kiran Shekar; John-Paul Tung; Kimble R Dunster; Sara Diab; David Platts; Ryan P Watts; Shaun D Gregory; Samuel Foley; Gabriela Simonova; Charles McDonald; Rylan Hayes; Judith Bellpart; Daniel Timms; Michelle Chew; Yoke L Fung; Michael Toon; Marc O Maybauer; John F Fraser Journal: Biomed Res Int Date: 2014-03-25 Impact factor: 3.411
Authors: Kiran Shekar; Jason A Roberts; Susan Welch; Hergen Buscher; Sam Rudham; Fay Burrows; Sussan Ghassabian; Steven C Wallis; Bianca Levkovich; Vin Pellegrino; Shay McGuinness; Rachael Parke; Eileen Gilder; Adrian G Barnett; James Walsham; Daniel V Mullany; Yoke L Fung; Maree T Smith; John F Fraser Journal: BMC Anesthesiol Date: 2012-11-28 Impact factor: 2.217
Authors: Kiran Shekar; Jason A Roberts; Charles I Mcdonald; Stephanie Fisquet; Adrian G Barnett; Daniel V Mullany; Sussan Ghassabian; Steven C Wallis; Yoke L Fung; Maree T Smith; John F Fraser Journal: Crit Care Date: 2012-10-15 Impact factor: 9.097
Authors: David G Platts; Andrew Hilton; Sara Diab; Charles McDonald; Matthew Tunbridge; Saul Chemonges; Kimble R Dunster; Kiran Shekar; Darryl J Burstow; John F Fraser Journal: Intensive Care Med Exp Date: 2014-02-06
Authors: Kristine Estensen; Kiran Shekar; Elissa Robins; Charles McDonald; Adrian G Barnett; John F Fraser Journal: Intensive Care Med Exp Date: 2014-11-22
Authors: Kiran Shekar; Jason A Roberts; Adrian G Barnett; Sara Diab; Steven C Wallis; Yoke L Fung; John F Fraser Journal: Crit Care Date: 2015-12-15 Impact factor: 9.097