Kiran Shekar

The ECMO PK project : Understanding PK/PD on ECMO to improve patient outcomes

Extracorporeal membrane oxygenation (ECMO) is a supportive therapy and its success depends on optimal drug therapy along with other supportive care. Emerging evidence suggests significant interactions between the drug and the device resulting in altered pharmacokinetics (PK) of vital drugs which may be further complicated by the PK changes that occur in the context of critical illness. Such PK alterations are complex and challenging to investigate in critically ill patients on ECMO and necessitate mechanistic research. The aim of this project is to investigate each of circuit, drug and critical illness factors that affect drug PK during ECMO.

Cardiac protection during veno-arterial extracorporeal membrane oxygenation

Advances in medical therapies in the last three decades have failed to improve mortality from cardiogenic shock (CS). This is despite the rapid uptake of TCS technologies, most notably V-A ECMO and percutaneous ventricular assist devices. Encouraging outcomes have been reported in selected group of CS patients with the use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO). However, the CS population supported with V-A ECMO is quite heterogenous. While approximately 60% of patients have sufficient cardiac recovery to wean from V-A ECMO, 40% of patients survive to hospital discharge and this attrition is largely due to persistent heart failure. Most acute CS patients are not candidates for durable MCS or heart transplant, and therefore it is of critical importance to minimise secondary cardiac injury and maximise cardiac recovery during V-A ECMO. However, the current setup and use of V-A ECMO results in increased LV workload, potentially leading to progressive LV distension, loss of aortic valve opening, intra-cardiac blood stasis and thrombosis, with subendocardial ischemic injury and compromised cardiac recovery. Equally, significant impairment of microcirculation seen in CS and V-A ECMO patients, combined with blood component damage and activation of the endothelium, as well as coagulation and inflammatory systems may all lead to further cardiac injury. Therefore, merely replacing the native pump (patient’s own heart) with a non-pulsatile, continuous flow pump (V-A ECMO), without optimising the microcirculation and unloading the LV, may result in suboptimal outcomes.

To overcome this, we may have to look beyond traditional haemodynamic monitoring and measurements to achieve this goal. In the future, holistic monitoring during V-A ECMO may include continuous monitoring of cardiac mechanics and output, pulmonary pressures, haemostasis, microcirculation and brain tissue oxygenation. Defining CS patient populations that stand to benefit most in clinical studies, thereby enriching those studies is also a key priority moving forward. Equally, measuring quality and process metrics for ECMO is critical to making improvements in an ECMO program. This project takes a holistic look at V-A ECMO to systematically investigate this eveolving area to improve patient outcomes.

Lung protection during venovenous extracorporeal membrane oxygenation

Although minimizing risks of ventilator-induced lung injury on venovenous ECMO is paramount, the risks/benefits of strategies employed to minimize ventilator-induced lung injury also merit due consideration. This research involves systematic invetsigation of topics espcially the use of partial or total liquid ventilation to minimsie iatrogenic lung injury on V-V ECMO and to provide best lung healing conditions.

Standardising ECMO education to bridge the variability in global ECMO outcomes

Please contact A/Prof Kiran Shekar further details