Comparison of norepinephrine with a combined non-catecholaminergic therapy in a porcine model of refractory cardiac arrest resuscitated with VA-ECMO

INTRODUCTION: Post-cardiac arrest syndrome (PCAS) under veno-arterial ECMO (VA-ECMO) is frequently complicated by severe vasoplegia and microcirculation failure. Conventional resuscitation relies heavily on catecholamines and crystalloids loading, which may exacerbate endothelial dysfunction and oxidative stress. We evaluated whether a multimodal non-catecholaminergic strategy (vasopressin, methylene blue, albumin, and hypothermia) could improve hemodynamics and microcirculation compared to standard therapy with norepinephrine. METHODS: Twenty pigs underwent surgically induced ischemic cardiac arrest and were resuscitated with VA-ECMO after 30 min of CPR. Animals were randomized (1:1) to receive either standard care (norepinephrine and crystalloids) or optimized treatment combining vasopressin, methylene blue, 20% albumin, and moderate hypothermia (34 °C). Hemodynamic, metabolic, and microcirculatory parameters were monitored for 6 h. Sublingual microcirculation was assessed using sidestream dark field (SDF) imaging. RESULTS: Eighteen animals completed the protocol (9 per group). The optimized group required significantly less norepinephrine (7 mg [0-20] vs 78 mg [58-126], p = 0.0046) and fluid loading (4.5 L [4-5] vs. 14 L [13-18.5], p = 0.0007). Microcirculatory perfusion was markedly improved in the optimized group (PPV 88% vs. 28%, p < 0.001; MFI 2.25 vs. 0.25, p < 0.01). Lactate clearance did not differ significantly. Histological analysis showed less intestinal ischemic injury (Chiu/Park score 1 [0-1] vs. 4 [3-4], p = 0.003). CONCLUSION: In a porcine model of refractory cardiac arrest resuscitated with VA-ECMO, a multimodal non-catecholaminergic resuscitation strategy reduced vasopressor and fluid requirements and preserved microcirculation. These findings support multimodal, catecholamine-sparing approaches to limit endothelial dysfunction in ECMO-treated PCAS.