Abstract 02: Intravenous Oxygen Microparticles as Resuscitative Fluid Improves Outcomes in a Swine Model of Asphyxial Cardiac Arrest

Abstract

Introduction: Asphyxia-induced cardiac arrest (ACA) can lead to organ damage and death within minutes, with a reported survival rate of 25-38%. It is the leading cause of in-hospital cardiac arrest in children and elderly and the second in adults. The direct injection of oxygen as a rescue therapy for ACA is not yet possible. Methods: We manufactured immediate-release intravenous oxygen (IVO 2 ) microparticles with a shell composed of biocompatible dextran polymers formed by nanoprecipitation. Following intravenous injection, the hydrophobic shell transitions from a crystalline state to a rapidly dissolving, fluid shell based on pH (A). IVO 2 was manufactured following Good Manufacturing Practice control over particle size, chemical purity, and sterility. Following instrumentation, Yorkshire swine (n=10 control, n=6 IVO 2 ) underwent complete asphyxia by endotracheal tube occlusion for 12 minutes (B). ACLS was performed whenever SBP<40 mmHg. At minute 6, 8 and 10 of asphyxia, IVO 2 or placebo (20 mL/kg fluid phase) was administered. Animals were then survived for 4 days in an ICU environment, followed by brain MRI and neurohistology. Results: Animals receiving IVO 2 exhibited increased arterial oxygen saturation during asphyxia (p<0.05, C), with less CPR time (p<0.001, D) and higher ROSC (p=0.011, E). Three out of 6 IVO 2 animals vs 0/3 surviving controls were successfully extubated (p=0.035). IVO 2 treatment was associated with increased survival (p=0.037, F) with improved swine neurologic deficit scores (p<0.05, G). MRI (H) and pathology (I) demonstrated devastating hypoxic-ischemic injury in all surviving controls, endpoints that were significantly improved with IVO 2 . No significant adverse effects were noted in hematologic, coagulation, hepatic, or renal function due to IVO 2 . Conclusion: Treatment of ACA with IVO 2 may diminish critical oxygen deficit, resulting in improved survival and neurological outcomes.