The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology

Abstract

Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing short-term mechanical support to the heart, lungs or both. Over the last decade, the number of centres offering ECMO has grown rapidly. At the same time, the indications for its use have also been broadened. In part, this trend has been supported by advances in circuit design and in cannulation techniques. Despite the widespread adoption of extracorporeal life support techniques, the use of ECMO remains associated with significant morbidity and mortality. A complication witnessed during ECMO is the inflammatory response to extracorporeal circulation. This reaction shares similarities with the systemic inflammatory response syndrome (SIRS) and has been well-documented in relation to cardiopulmonary bypass. The exposure of a patient's blood to the non-endothelialised surface of the ECMO circuit results in the widespread activation of the innate immune system; if unchecked this may result in inflammation and organ injury. Here, we review the pathophysiology of the inflammatory response to ECMO, highlighting the complex interactions between arms of the innate immune response, the endothelium and coagulation. An understanding of the processes involved may guide the design of therapies and strategies aimed at ameliorating inflammation during ECMO. Likewise, an appreciation of the potentially deleterious inflammatory effects of ECMO may assist those weighing the risks and benefits of therapy.

Keywords: Coagulation; ECMO; Extracorporeal membrane oxygenation; Inflammation; SIRS.

Fig. 1

The inflammatory response to extracorporeal membrane oxygenation (ECMO). During ECMO, the complement and contact systems are activated as a result of blood-biomaterial interaction. The alternative complement pathway (AP) is primarily responsible for producing the anaphylatoxins C3a and C5a and the membrane attack complex (MAC). This occurs as the result of increased hydrolysis of C3 on the biomaterial surface. The contact system is responsible for producing activated factor XII (FXIIa), which induces the intrinsic coagulation pathway, leading to thrombin formation. Products produced by each of these systems, promote the production of pro-inflammatory cytokines and have direct effects on leukocytes, platelets and the vascular endothelium. In particular, neutrophils are activated, leading to increased neutrophilic infiltration of tissue and eventual organ damage