Abstract 194: A Combination of Metabolic Strategies and Cardiopulmonary Bypass Allows Improved Short-Term Resuscitation from Prolonged Lethal Cardiac Arrest

Abstract

Background: The metabolic or late phase of cardiac arrest is highly lethal. Emergency cardiopulmonary bypass (ECPB) can resuscitate many patients even after prolonged cardiac arrest and provides immediate vascular access for correction of metabolic derangement during the reperfusion process. We developed a rodent model of ECPB resuscitation which showed the superiority of ECPB over conventional CPR, especially when combined with hypothermia. For this study we examined a metabolic strategy against ischemia/reperfusion (MS-I/R) injury that included: leukoreduction, low Ca2+, Mg, buffered pH, red blood cells and a colloid. We tested whether ECPB plus MS-I/R and/or hypothermia reduced reperfusion injury and showed better outcomes compared to our standard ECPB reperfusate. Methods: Using a 2x2 factorial design we tested ECPB with (a) MS-I/R versus standard solution, and (b) hypothermia versus normothermia in our rat model (n=38). The four reperfusion strategies included: (1) MS-I/R reperfusate plus hypothermia, (2) MS-I/R with normothermia, (3) standard plasmalyte reperfusate plus hypothermia, or (4) plasmalyte plus normothermia. Animals underwent 12 min of untreated asphyxial arrest and were resuscitated with ECPB with one of the strategies for 30 min. Thereafter ECPB was stopped and ICU-like support was provided for 3 hours, while hemodynamic, perfusion and other metrics were serially measured. Results: All rats achieved ROSC with ECPB. Significant differences emerged after 3 hrs, the best outcomes were in animals with MS-I/R perfusate plus hypothermia (lactate: 1.0±0.3 mmol/L; MAP: 84±12 mm Hg, seizures: 0/10), while the worst outcomes were with standard plasmalyte reperfusate and normothermia (lactate: 8.8±4.3 mmol/L, MAP: 36±13 mm Hg, seizures: 7/10, P<0.001). The outcomes of the other two groups (hypothermia only; MS-I/R reperfusate only) were intermediate. Both hypothermia and MS-I/R reperfusate independently improved outcome. Conclusions: While most human ECPB is applied without a MS-I/R reperfusate, we observed that in rodents the addition of a MS-I/R reperfusate plus hypothermia to ECPB resuscitation resulted in short-term benefit after prolonged arrest. Future long-term and translational survival studies are warranted.