Preserving the Membrane Lung: An Ongoing ECMO Challenge

Abstract

We read with interest the article by Mang et al. 1 Indeed, oxygenator thrombosis remains a common reason for circuit exchange, the risk of which increases with the duration of extracorporeal membrane oxygenation (ECMO) support. 2 Coinciding with the pandemic's unprecedented increase of ECMO disposable demand, judicious use of limited supply was warranted. While we applaud the authors for their clever approach, we would like to add words of caution regarding their strategy.Catheter-directed regional thrombolysis using a slow thrombolytic infusion is well established, and similarly, the strategy of Mang et al. 1 is to deliver the thrombolytic to the site of the thrombus to maximize its local exposure, while minimizing systemic effects. 3 This strategy achieves a favorable risk-benefit profile by 1) maximizing thrombus-drug exposure through heightened local drug concentrations; 2) reducing nonlocal side effects as the half-life of alteplase is short (~5 minutes) and agent washout is limited due to vascular occlusion; and 3) limit bleeding complications as compared to bolus thrombolytics application. 3 In the absence of detailed thrombolytic dosing rates by Mang et al. 1 it is not possible to ascertain whether a sustained extended infusion or a bolus strategy was employed. If the rapid administration of alteplase was applied, it may provide an explanation for why three of the four patients required multiple thrombolytic administrations and one patient receiving nine separate administrations. This presumed bolus administration pattern may increase the risk of devastating bleeding complications. Of additional concern was that patient 1, the lone discharge survivor, had ECMO circuit flow adjusted lower by over 50% throughout the course of eight injections, which may have clouded the pressure drop effects of thrombolysis. This is due to the physical effects of a decreased pressure drop with decreasing flows across the oxygenator.Further, we ask: should the approach to membrane lung preservation rely on rescuing an exhausted device, or rather focus on implementing preventative strategies? Mang et al. reported heparin anticoagulation titrated to an activated partial thromboplastin time of 45-55 seconds, a modest level of anticoagulation. In standard venovenous (VV)-ECMO circuits, this may be sufficient, however, higher anticoagulation levels may be needed in coronavirus disease 2019 (COVID-19) patients due to an underlying hypercoagulable state. 4 Furthermore, Mang et al. 1 do not report any intensification of anticoagulation in an attempt slow the increasing rate of pressure drop. Finally, one might consider direct thrombin inhibitors as first-line anticoagulants in VV-ECMO patients to mitigate these deposits. Indeed, in aggregate analyses of non-COVID-19 ECMO patients, bivalirudin use was associated with reduced circuitrelated thrombotic events when compared to heparin. 5 This may be due to pharmacologic differences between the agents. Specifically, heparin only exerts an antithrombotic effect on freely circulating throm...

Preserving the Membrane Lung Without Jeopardizing Patients’ Safety

“…Another of Wieruszewski et al 1 concerns is that lowering ECMO blood flow in between multiple rtPA injections might have obscured pressure drops in one particular patient. We chose to define pump head efficiency ƞ (ml of conveyed blood per pump head revolution) exactly to avoid such clouding.…”

“…In their letter, 1 they advise against a systemic bolus application of rtPA for oxygenator thrombolysis since its application through a local catheter directed to the site of the thrombus will provide a superior risk-benefit ratio. In contrast to localized deep vein thrombosis or occlusive pulmonary embolism (PE), thrombi in an ECMO oxygenator will be concentrated to the basal sites of the inflow part, 3 making it difficult to place a catheter in proximity.…”

“…We thank Wieruszewski et al 1 for their critical evaluation of our manuscript 2 demonstrating increased extracorporeal membrane oxygenator (ECMO) half-life through administration of recombinant tissue plasminogen activator (rtPA) and would like to address several points made by the authors:…”