Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion

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, Glenn Hernández

Although 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 considered relevant only in patients with liver ischemia or cirrhosis. Our objectives were to establish if endotoxemia impairs whole body net lactate clearance, and to explore a potential role for total liver hypoperfusion during the early phase of septic shock. After anesthesia twelve sheep were subjected to a hemodynamic/perfusion monitoring including hepatic and portal catheterization, and a hepatic ultrasound flow probe. After stabilization (point A), sheep were alternatively assigned to LPS (5 mcg/kg bolus followed by 4 mcg/kg/h) or sham for a 3 h study period. After 60 min of shock, animals were fluid resuscitated to normalize MAP. 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. In both cases the procedure included an IV bolus followed by serial blood sampling to draw a curve using the least squares method. A significant hyperlactatemia was already present in LPS as compared to sham animals at point B (4.7 [3.1-6.7] vs. 1.8 [1.5-3.7] mmol/L) increasing to 10.2 [7.8-12.3] mmol/L at point D. A significant increase in portal and hepatic lactate levels in LPS animals was also observed. However, no difference in hepatic DO2, VO2 or O2 extraction, total hepatic blood flow (915 [773-1046] vs. 655 [593-1175] ml/min at point D), mitochondrial respiration, liver enzymes or sorbitol clearance within groups was found. However, there was a highly significant decrease in lactate clearance in LPS animals (point B: 46 [30-180] vs. 1212 [743-2116] ml/min, p < 0.01; point D: 113 [65-322] vs. 944 [363-1235] ml/min, p < 0.01). Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion.