A combination of metabolic strategies plus cardiopulmonary bypass improves 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 injury (MS-IR) that included: leukoreduction, low Ca(2+), Mg(2+), buffered pH, red blood cells and a colloid. We tested whether ECPB plus MS-IR and/or hypothermia improves short-term hemodynamic outcomes compared to a standard ECPB reperfusate.

Methods: Using a 2×2 factorial design we tested ECPB with (a) MS-IR versus a standard crystalloid solution; and (b) hypothermia versus normothermia in our rat model. The four reperfusion strategies included: (1) MS-IR plus hypothermia, (2) MS-IR with normothermia, (3) standard plasma-lyte (STD) reperfusate plus hypothermia, or (4) STD plus normothermia. Animals underwent 12 min of untreated asphyxial arrest and were resuscitated with ECPB and one of the four strategies for 30 min. Thereafter, ECPB was discontinued and ventilatory support was provided for 3 hours, while hemodynamic, perfusion and other metrics were serially measured.

Results: All rats achieved ROSC with ECPB. Significant differences between the groups emerged after 3 hrs: the best outcomes were in animals with MS-IR plus hypothermia (lactate: 1.1 ± 0.1 mmol/L; MAP: 83 ± 4 mm Hg, seizures: 0/10), while the worst outcomes were with STD and normothermia (lactate: 8.9 ± 1.4 mmol/L, MAP: 36 ± 4 mm Hg, seizures: 7/10, p < 0.001). The outcomes of the other two groups (MS-IR only; hypothermia only) were intermediate. MS-IR and hypothermia improved outcome in an additive fashion.

Conclusions: While most human ECPB is applied with a normothermic crystalloid priming solution, we observed that in rodents the addition of MS-IR plus hypothermia resulted in considerable short-term benefit after prolonged arrest. Future long-term and translational survival studies are warranted to optimize ECPB resuscitation methods.