Paralysis Secondary to Intracranial Venous Hypertension Following VV ECMO Dual-Lumen Jugular Cannulation: A Sentinel Report

Study: Severe COVID-19 infection results in pulmonary and cardiac compromise, often requiring extracorporeal oxygenation and mechanical circulatory support (MCS). Accompanying severe COVID-19 is a burst of hyperinflammatory cytokines referred to as "cytokine storm." Prior studies have shown MCS shear forces alter circulating protein structure and function, e.g. von Willebrand factor, yet it is unknown what effect MCS device flow and shear has on COVID-19-associated cytokines. We hypothesize that MCS-generated flow alters cytokine binding, structure, or function. Utilizing a closed loop in vitro we investigated alterations of COVID-19-associated cytokines following circulation with MCS (Impella 5.5 or CentriMag). Methods: CentriMag or Impella 5.5 were affixed in a Tygon closed loop. Impella was positioned with outflow cannula in a 1-inch tube region and maintained at 60 mmHg pressure. Porcine platelet poor plasma (PPP) obtained via centrifugation of fresh, anticoagulated (10% ACD) whole blood was the circulating fluid. Cytokines alone or "COVID-19 cocktail'' containing porcine IL-6 (4.5 ng/mL), IL-1β (0.5 ng/mL), IL-8 (2.7 ng/mL), and TNFα (1 ng/mL) were added to PPP prior to filling loops. Loops were run at 5 L/min and sampled at 0, 1, and 4 hrs for analysis of cytokine binding via ELISA, compared to resting. Results: Cytokine-antibody binding was altered following circulation, indicative of flow-mediated modulation of cytokine epitope availability. After 4 hrs, an increase in IL-6 antibody binding was observed with Impella, and a similar increase in IL-8 detected with CentriMag. No significant change was noted for IL-1β or TNFα after 4 hrs circulation with either system. Interestingly, when cytokines were combined, changes in antibody binding were no longer evident. Future investigation, e.g. with whole blood, is required to define additional mechanistic aspects of these cytokine alterations to offer potential clinical utility for informing improved therapy.