The Microcirculatory Response to Endotoxemia and Resuscitation Is a Marker of Regional Renal Perfusion, Renal Metabolic Stress, and Tubular Injury.

Aims: We sought to investigate the relationship between macrohemodynamic resuscitation and microcirculatory parameters with the response of microcirculatory flow, tissue-specific parameters of metabolic stress and injury. We hypothesized that early resuscitation based on macrohemodynamic parameters does not prevent the development of organ dysfunction in a porcine model of endotoxemic shock, and that sublingual microcirculatory parameters are associated with markers of tissue metabolic stress and injury. Results: Both resuscitation groups had significant increases in creatinine and neutrophil gelatinase-associated lipocalin as compared with baseline. Neither the macrovascular response to endotoxemia or resuscitation, nor group allocation predicted the development of acute kidney injury (AKI). Only a microvascular flow index (MFI) <2.5 was associated with the development of renal tubular injury and AKI, and with increased renal, liver, peritoneal, and sublingual lactate/pyruvate (L/P) ratio and lactate. Among systemic parameters, only partial pressure of carbon dioxide (PCO ₂ ) gap >6 and P(a-v)CO ₂ /C(v-a)O ₂ >1.8 were associated with increased organ L/P ratio and AKI. Innovation and Conclusion: Our findings demonstrate that targeting macrohemodynamics to guide resuscitation during endotoxemic shock failed to predict tissue metabolic stress and the response of the microvasculature to resuscitation, and was unsuccessful in preventing tubular injury and AKI. Mechanistically, our data suggest that loss of hemodynamic coherence and decoupling of microvascular flow from tissue metabolic demand during endotoxemia may explain the lack of association between macrohemodynamics and perfusion goals. Finally, we demonstrate that MFI, PCO ₂ gap, and P(v-a)CO ₂ /C(a-v)O ₂ ratio outperformed macrohemodynamic parameters at predicting the development of renal metabolic stress and tubular injury, and therefore, that these indices merit further validation as promising resuscitation targets. Antioxid. Redox Signal . 35, 1407-1425.