• Pablo Tapia, Dagoberto Soto, Alejandro Bruhn, Leyla Alegría, Nicolás Jarufe, Cecilia Luengo, Eduardo Kattan, Tomás Regueira, Arturo Meissner, Rodrigo Menchaca, María Ignacia Vives, Nicolas Echeverría, Gustavo Ospina-Tascón, Jan Bakker, and Glenn Hernández.
• Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. patapiab@gmail.com.
• Crit Care. 2015 Jan 1;19:188.

IntroductionAlthough the prognostic value of persistent hyperlactatemia in septic shock is unequivocal, its physiological determinants are controversial. Particularly, the role of impaired hepatic clearance has been underestimated and is only considered relevant in patients with liver ischemia or cirrhosis. Our objectives were to establish whether endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock.MethodsAfter anesthesia, 12 sheep were subjected to hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to lipopolysaccharide (LPS) (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a three-hour study period. After 60 minutes of shock, animals were fluid resuscitated to normalize mean arterial pressure. Repeated series of measurements were performed immediately after fluid resuscitation (point B), and one (point C) and two hours later (point D). Monitoring included systemic and regional hemodynamics, blood gases and lactate measurements, and ex-vivo hepatic mitochondrial respiration at point D. Parallel exogenous lactate and sorbitol clearances were performed at points B and D. Both groups included an intravenous bolus followed by serial blood sampling to draw a curve using the least squares method.ResultsSignificant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 (3.1 to 6.7) versus 1.8 (1.5 to 3.7) mmol/L), increasing to 10.2 (7.8 to 12.3) mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. No within-group difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (point D: 915 (773 to 1,046) versus 655 (593 to 1,175) ml/min), mitochondrial respiration, liver enzymes or sorbitol clearance was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 (30 to 180) versus 1,212 (743 to 2,116) ml/min, P < 0.01; point D: 113 (65 to 322) versus 944 (363 to 1,235) ml/min, P < 0.01).ConclusionsEndotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion.

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