The microcirculatory response to endotoxemia and resuscitation is a marker of regional renal perfusion, renal metabolic stress and tubular injury.

Document Type

Article

Publication Date

2-15-2021

Publication Title

Antioxidants & redox signaling

Keywords

washington; spokane; pshmc

Abstract

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 NGAL as compared to baseline. Neither the macrovascular response to endotoxemia or resuscitation, nor group allocation predicted the development of AKI. Only an MFI < 2.5 was associated with the development of renal tubular injury and AKI, and with increased renal, liver, peritoneal and sublingual Lactate to Pyruvate ratio (L/P) and lactate. Amongst systemic parameters, only PCO2 gap > 6 and P(a-v)CO2/C(v-a)O2 >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 at preventing tubular injury and AKI. Mechanistically, our data suggests 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, PCO2 gap and P(v-a)CO2/C(a-v)O2 ratio outperformed marcohemodynamic parameters at predicting renal metabolic stress and tubular injury development, and therefore, that these indices merit further validation as promising resuscitation target.

Clinical Institute

Kidney & Diabetes

Department

Nephrology

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