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

Abstract 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.