title: Impairment of exogenous lactate clearance in experimental hyperdynamic septic shock is not related to total liver hypoperfusion.
abstract: BACKGROUND
  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 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.
  
  
  METHODS
  After 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.
  
  
  RESULTS
  Significant 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).
  
  
  CONCLUSIONS
  Endotoxemia induces an early and severe impairment in lactate clearance that is not related to total liver hypoperfusion.
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. patapiab@gmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Tapia
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. dasoto@illinois.edu.
authors.forename: Dagoberto
authors.initials: D
authors.lastname: Soto
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. abruhn@med.puc.cl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bruhn
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. lmalegri@gmail.com.
authors.forename: Leyla
authors.initials: L
authors.lastname: Alegría
authors.affiliation: Departamento de Cirugía Digestiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. njarufe@med.puc.cl.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Jarufe
authors.affiliation: Unidad de Pacientes Críticos, Hospital Clínico Universidad de Chile, Santos Dumont 999, Santiago, 8380000, Chile. celuengomed@gmail.com.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Luengo
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. e.kattan@gmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Kattan
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. tregueira@gmail.com.
authors.forename: Tomás
authors.initials: T
authors.lastname: Regueira
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. aameissner@uc.cl.
authors.forename: Arturo
authors.initials: A
authors.lastname: Meissner
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. ramenchaca@uc.cl.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Menchaca
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. mivives@uc.cl.
authors.forename: María Ignacia
authors.initials: MI
authors.lastname: Vives
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. nicolasecheverria1979@gmail.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Echeverría
authors.affiliation: Intensive Care Medicine Department, Fundación Valle del Lili - Universidad ICESI, Avenida Simón Bolívar Carrera 98, Cali, 76001000, Colombia. gusospin@gmail.com.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ospina-Tascón
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. jan.bakker@erasmusmc.nl.|Department of Intensive Care Adults, Erasmus MC University Medical Centre, PO Box 2040, Room H625, Rotterdam, CA, 3000, The Netherlands. jan.bakker@erasmusmc.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: Bakker
authors.affiliation: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. glennguru@gmail.com.
authors.forename: Glenn
authors.initials: G
authors.lastname: Hernández
mesh_terms: D000818:Animals; D006439:Hemodynamics / Q000502:physiology*; D065906:Hyperlactatemia / Q000097:blood* / Q000473:pathology; D019344:Lactic Acid / Q000097:blood* / Q000494:pharmacology; D008099:Liver / Q000098:blood supply / Q000187:drug effects; D008107:Liver Diseases / Q000097:blood* / Q000473:pathology; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D012772:Shock, Septic / Q000097:blood* / Q000473:pathology
chemical_list: D019344:Lactic Acid