Abstract 113: Effects of Anticoagulation and Thrombolytic Therapy in a Porcine Model of Prolonged Out-of-hospital Cardiac Arrest Treated with ECPR

Abstract

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has been used in patients with refractory out-of-hospital cardiac arrest (OHCA). However, recovery of organ function and survival are potentially impaired due to microvascular coagulation causing a “no-reflow” phenomenon. Hypothesis: Early anticoagulant therapy (argatroban) during CPR and/or thrombolytic therapy (streptokinase) at ECPR onset improves recovery of organ function in an OHCA porcine model. Methods: In a blinded and randomized study, 48 swine (40±5kg) were subjected to 8min of ventricular fibrillation cardiac arrest (CA) followed by 30min of goal directed CPR (gdCPR), and 8h of ECPR (33°C) with heparin anticoagulation during ECPR. Animals (n=12) were randomized to one of 4 groups with 350mg/kg argatroban (Arg) or placebo (20mL NSS) given 12min after CA onset and 1.5 MU streptokinase (STK) or placebo (50mL NSS) given at ECPR initiation: Group 1 (placebo and placebo); Group 2 (Arg and placebo); Group 3 (placebo and STK); and Group 4 (Arg and STK). Recovery of cardiac function measured by a cardiac resuscitablity score (CRS), see Table. Recovery of neurologic function measured by amplitude recovery of cortical somatosensory evoked potentials (cSSEP). Data analysis: Kruskal Wallis and single factor ANOVA tests with ( p <0.05 significant). Results: Average CRS and cSSEP recovery were not significantly different between groups. However, the combined average CRS of the argatroban groups (2&4) was 3.2±2.1 compared to 2.0±1.6 for the groups without it (1&3), p =0.03 single factor ANOVA. Furthermore, more animals in groups 2&4 (n=8) achieved a robust recovery in cSSEP amplitude (≥30% amplitude return) than in groups 1&3 (n=4). Discussion: These results provide evidence that argatroban given early during CPR potentially improves early recovery of cardiac and neurological function in a porcine model of OHCA. However, the impact of these therapies on long term recovery remains to be determined.