Abstract
Septic shock is a medical emergency and is one of the main causes of mortality in critically ill patients. Given the pathophysiological complexity of sepsis spectrum and progression in clinical settings, animal models become essential tools to improve patient care, and to understand key mechanisms that may remain masked from the heterogeneity of clinical practice. Our aim was to verify whether the metabolic constellations we previously reported for septic shock patients appear also in our septic shock swine model as systemic markers of early disturbances in energy metabolism and hepatic homeostasis. Septic shock was induced in anesthetized, instrumented, and ventilated adult swines by polymicrobial peritonitis. Hemodynamic and serial measurements of arterial and mixed venous blood gasses were made. Laboratory measurements and mass spectrometry-based targeted quantitative plasma metabolomics were performed in blood samples collected at baseline, at shock and at fully resuscitation after fluids and vasopressors administration. Data elaboration was performed by multilevel and multivariate analysis. Changes in hemodynamic, blood chemistry, and inflammatory markers were in line with a septic shock phenotype. Time course alteration of systemic metabolites were characterized by marked decreased in phosphatidylcholines and lysophosphatidylcholines species, altered alanine-glucose cycle and inter-organ amino acid metabolism, pointing toward an early hepatic impairment similarly to what we previously reported for septic shock. This is the first study in which an experimental swine model of septic shock recapitulates the main metabolic derangements reported in a clinical setting of shock. These events occur within hours from infections and may act as early metabolic features to assist in evaluating subclinical hepatic alterations and pave the way to improve the management of septic shock.
Highlights
Septic shock is a life threatening condition that can develop subsequent to infection
We aim to verify whether such metabolic constellations occurring in septic shock patients appear in the septic shock swine model as systemic markers of early disturbances in energy metabolism and hepatic homeostasis, where liver acts as inflammatory barrier, but as organ actively involved in energy pathways
Values are reported as median (25th, 75th) percentile; HR, heart rate; DAP rad, diastolic arterial pressure from radial artery; MAP rad, mean arterial pressure from radial artery; CO, cardiac output; T, body temperature; PaCO2, arterial carbon dioxide partial pressure: PaO2, arterial oxygen partial pressure; Sat O2, oxygen content; BE, base excess; Hct, hematocrit; anion gap measured as AG = Na+ – (Cl− + HCO3−)
Summary
Septic shock is a life threatening condition that can develop subsequent to infection. It is a subset of sepsis with underlying circulatory and cellular/metabolic abnormalities associated with higher mortality rates (Angus et al, 2001; Singer et al, 2016). Septic shock causes progressive failure of vital homeostatic mechanisms culminating in immunosuppression, coagulopathy and microvascular dysfunction, which can lead to refractory hypotension, organ failure and death. Mortality rate for septic shock may reach 40% even in the era of early recognition and treatment with today’s poor prognosis, mainly related to multi-organ dysfunction syndrome (MODS) (Rhee et al, 2017). The multiple organ involvement, which can lead to death within a few days, suggests that this concomitant process is systemic in nature and initiated in parallel with inflammatory response
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