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Critical care (London, England)
Apr 22, 2015;19 188.

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
Author Information
  1. Pablo Tapia: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. patapiab@gmail.com.
  2. Dagoberto Soto: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. dasoto@illinois.edu.
  3. Alejandro Bruhn: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. abruhn@med.puc.cl.
  4. Leyla Alegría: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. lmalegri@gmail.com.
  5. Nicolás Jarufe: Departamento de Cirugía Digestiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. njarufe@med.puc.cl.
  6. Cecilia Luengo: Unidad de Pacientes Críticos, Hospital Clínico Universidad de Chile, Santos Dumont 999, Santiago, 8380000, Chile. celuengomed@gmail.com.
  7. Eduardo Kattan: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. e.kattan@gmail.com.
  8. Tomás Regueira: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. tregueira@gmail.com.
  9. Arturo Meissner: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. aameissner@uc.cl.
  10. Rodrigo Menchaca: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. ramenchaca@uc.cl.
  11. María Ignacia Vives: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. mivives@uc.cl.
  12. Nicolas Echeverría: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. nicolasecheverria1979@gmail.com.
  13. Gustavo Ospina-Tascón: Intensive Care Medicine Department, Fundación Valle del Lili - Universidad ICESI, Avenida Simón Bolívar Carrera 98, Cali, 76001000, Colombia. gusospin@gmail.com.
  14. Jan Bakker: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. jan.bakker@erasmusmc.nl.
  15. Glenn Hernández: Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, 8320000, Chile. glennguru@gmail.com.
PMID: 25898244 DOI: 10.1186/s13054-015-0928-3

Abstract

INTRODUCTION: 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.

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MeSH Term

Animals
Hemodynamics
Hyperlactatemia
Lactic Acid
Liver
Liver Diseases
Metabolic Clearance Rate
Sheep
Shock, Septic

Chemicals

Lactic Acid
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

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