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.

The inflammasome of circulatory collapse: single cell analysis of survival on extracorporeal life support

“…Although the CD8+ naïve T cells constituted a 5 small cell population, these cells can proliferate rapidly when they encounter their target antigens. The extensive synthetic surfaces of the VA-ECLS circuit can induce significant inflammatory responses (19). The presence of CD8+ naïve T cells with activating gene signatures among non-surviving patients-as identified here-may be indicative of an immune system poised to have a maladaptive inflammatory response to VA-ECLS.…”

“…VA-ECLS is a powerful stimulator of the immune response against a background of already tenuous perfusion and end organ function (24). Whether this immune response is adaptive or mal-adaptive remains unclear.…”

“…For some patients, VA-ECLS support provides life support while failing organs recover and regain function, while in others it provides 5 a life support bridge until definitive intervention-such as organ transplantation or mechanical assist devices-can be achieved. VA-ECLS continues to be associated with mortality rates of around 60% (18), due mainly to unrelenting progression of the underlying disease process, but also complication of VA-ECLS itself (19).…”

COVID-19 and ECMO: the interplay between coagulation and inflammation—a narrative review

“…The two principal mechanisms of activation of coagulation are supraphysiological shear stress and interactions between the foreign material and blood components [19][20][21][22]. The latter creates an inflammatory reaction, as already reported in the systemic inflammatory response syndrome, that involves leukocytes, platelet endothelial cells, intrinsic and extrinsic coagulation, cytokines, and complement system [23]. The result is an unbalance between pro-coagulant and anticoagulant factors, e.g., fibrinogen contributes to thrombus formation, while loss of high molecular vWF causes a bleeding tendency [24].…”

Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report

“…Concerns were recently raised that ECMO may contribute to the lymphopenia observed in COVID-19 patients thereby deteriorating the patient's cellular immune response and ability to clear the SRAS-CoV-2 pathogen effectively [14]. The extra-corporeal circuit has been shown to exaggerate an already dysfunctional immune system [25] and this adverse effect may negatively impact the outcomes of COVID-19 patients [14]. The role of immunemodulating therapies in the setting of advanced COVID-19 infections in mitigating the "cytokine storm" leading to hyperinflammation and adverse outcomes is a topic of intense ongoing investigation [25][26][27][28].…”