Skip to main content
SpringerLink
Log in

Myths and Facts Regarding Lactate in Sepsis

  • Chapter
Annual Update in Intensive Care and Emergency Medicine 2016

Part of the book series: Annual Update in Intensive Care and Emergency Medicine ((AUICEM))

Abstract

Lactate has a questionable reputation amongst professionals caring for patients with sepsis. The concern is partly justified, as lactate is indeed a sentinel marker of shock and poor prognosis in sepsis [1]. Traditionally, elevated serum lactate is synonymous of tissue hypoxia, in particular when associated with metabolic acidosis and frequently clinicians guide fluid resuscitation or inotrope/vasopressor use based on that premise [2]. The concept is based on the distinction between two types of glycolysis: aerobic and anaerobic (insufficient oxygen availability for mitochondrial ATP production), the latter being regarded as the main source of increased lactate [2, 3]. In this chapter, we argue that such a view of pathophysiology in sepsis is more a “habit of mind” then a real phenomenon and has limited clinical relevance [4]. We will argue that lactate is a crucial molecule in energy metabolism, acid base homeostasis and cellular signaling in sepsis largely independent of tissue oxygenation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bakker J, Coffernils M, Leon M, Gris P, Vincent JL (1991) Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest 99:956–962

    Article  CAS  PubMed  Google Scholar 

  2. Jones AE, Shapiro NI, Trzeciak S et al (2010) Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 303:739–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW (2013) Etiology and therapeutic approach to elevated lactate levels. Mayo Clin Proc 88:1127–1140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schurr A (2014) Cerebral glycolysis: a century of persistent misunderstanding and misconception. Front Neurosci 8:360

    Article  PubMed  PubMed Central  Google Scholar 

  5. Robergs RA, Ghiasvand F, Parker D (2004) Biochemistry of exercise-induced metabolic acidosis. Am J Physiol Regul Integr Comp Physiol 287:R502–R516

    Article  CAS  PubMed  Google Scholar 

  6. Board M, Humm S, Newsholme EA (1990) Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. Biochem J 265:503–509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Robergs RA (2011) Nothing ‘evil’ and no ‘conundrum’ about muscle lactate production. Exp Physiol 96:1097–1098

    Article  PubMed  Google Scholar 

  8. Halestrap AP (2013) Monocarboxylic acid transport. Compr Physiol 3:1611–1643

    Article  PubMed  Google Scholar 

  9. Elustondo PA, White AE, Hughes ME, Brebner K, Pavlov E, Kane DA (2013) Physical and functional association of lactate dehydrogenase (LDH) with skeletal muscle mitochondria. J Biol Chem 288:25309–25317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kane DA (2014) Lactate oxidation at the mitochondria: a lactate-malate-aspartate shuttle at work. Front Neurosci 8:366

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rogatzki MJ, Ferguson BS, Goodwin ML, Gladden LB (2015) Lactate is always the end product of glycolysis. Front Neurosci 9:22

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bergersen LH (2015) Lactate transport and signaling in the brain: potential therapeutic targets and roles in body-brain interaction. J Cereb Blood Flow Metab 35:176–185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gladden LB (2008) A “lactatic” perspective on metabolism. Med Sci Sports Exerc 40:477–485

    Article  CAS  PubMed  Google Scholar 

  14. Fencl V, Jabor A, Kazda A, Figge J (2000) Diagnosis of metabolic acid base disturbances in critically ill patients. Am J Respir Crit Care Med 162:2246–2251

    Article  CAS  PubMed  Google Scholar 

  15. Levy B, Desebbe O, Montemont Ch, Gibot S (2008) Increased aerobic glycolysis through beta-2 stimulation is a common mechanism involved in lactate formation during shock states. Shock 4:417–421

    Article  Google Scholar 

  16. Haji-Michael PG, Ladrière L, Sener A, Vincent JL, Malaisse WJ (1999) Leukocyte glycolysis and lactate output in animal sepsis and ex vivo human blood. Metabolism 48:779–785

    Article  CAS  PubMed  Google Scholar 

  17. Newsholme EA, Crabtree B, Ardawi MS (1985) The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci Rep 5:393–400

    Article  CAS  PubMed  Google Scholar 

  18. Carré JE, Singer M (2008) Cellular energetic metabolism in sepsis: the need for a systems approach. Biochim Biophys Acta 1777:763–771

    Article  PubMed  Google Scholar 

  19. Ronco JJ, Fenwick JC, Tweeddale MG et al (1993) Identification of the critical oxygen delivery for anaerobic metabolism in critically iii septic and nonseptic humans. JAMA 270:1724–1730

    Article  CAS  PubMed  Google Scholar 

  20. Bauer DE, Harris MH, Plas DR et al (2004) Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demand. FASEB 18:1303–1305

    CAS  Google Scholar 

  21. Febbraio MA, Lambert DL, Starkie RL, Proietto J, Hargreaves M (1998) Effect of epinephrine on muscle glycogenolysis during exercise in trained men. J Appl Physiol 84:465–470

    CAS  PubMed  Google Scholar 

  22. James JH, Luchette FA, McCarter FD, Fischer JE (1999) Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 354:505–508

    Article  CAS  PubMed  Google Scholar 

  23. Levy B, Desebbe O, Montemont C, Gibot S (2008) Increased aerobic glycolysis through beta-2 stimulation is a common mechanism involved in lactate formation during shock states. Shock 4:417–421

    Article  Google Scholar 

  24. Michalek RD, Gerriets VA, Jacobs SR et al (2011) Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 186:3299–3303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. MacIver NJ, Jacobs SR, Wieman HL, Wofford JA, Coloff JL, Rathmell JC (2008) Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival. J Leukoc Biol 84:949–957

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chen X, Qian Y, Wu S (2015) The Warburg effect: Evolving interpretations of an established concept. Free Radic Biol Med 79C:253–263

    Article  Google Scholar 

  27. Meszaros K, Bojta J, Bautista AR, Lang CH, Spitzer JJ (1991) Glucose utilisation by Kupffer cells, endothelial cells and granulocytes in endotoxemic rat liver. Am J Physiol 1260:G7–G12

    Google Scholar 

  28. Tannahill GM, Curtis AM, Adamik J et al (2013) Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496:238–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yang L, Xie M, Yang M et al (2014) PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis. Nat Commun 5:4436

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Cheng SC, Quintin J, Cramer RA et al (2014) mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684

    Article  PubMed  PubMed Central  Google Scholar 

  31. Durrbach A, Francois H (2013) Intracellular lactate flux: a new regulator of the allogenic immune response. Transpl Int 26:20–21

    Article  PubMed  Google Scholar 

  32. Fischer K, Hoffmann P, Voelkl S et al (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109:3812–3819

    Article  CAS  PubMed  Google Scholar 

  33. Parnell GP, Tang BM, Nalos M et al (2013) Identifying key regulatory genes in the whole blood of septic patients to monitor underlying immune dysfunctions. Shock 40:166–174

    Article  CAS  PubMed  Google Scholar 

  34. Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ (2014) Lactate reduces liver and pancreatic injury in Toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. Gastroenterology 146:1763–1774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bui T, Thompson CB (2006) Cancer's sweet tooth. Cancer Cell 9:419–420

    Article  CAS  PubMed  Google Scholar 

  36. Richardson RS, Noyszewski EA, Leigh JS, Wagner (1998) Lactate efflux from exercising human skeletal muscle: role of intracellular PO2. J Appl Physiol 85:627–634

    CAS  PubMed  Google Scholar 

  37. Mason S, Johnson RS (2007) The role of HIF-1 in hypoxic response in the skeletal muscle. Adv Exp Med Biol 618:229–244

    Article  PubMed  Google Scholar 

  38. Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci 95:11715–11720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Semenza GL (2002) HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol Med 8:S62–S67

    Article  CAS  PubMed  Google Scholar 

  40. Zhang H, Bosch-Marce M, Shimoda LA et al (2008) Mitochondrial autophagy is a HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283:10892–10903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mason SD, Howlett RA, Kim MJ et al (2004) Loss of skeletal muscle HIF-1alpha results in altered exercise endurance. PLoS Biol 2:e288

    Article  PubMed  PubMed Central  Google Scholar 

  42. Regueira T, Djafarzadeh S, Brandt S et al (2012) Oxygen transport and mitochondrial function in porcine septic shock, cardiogenic shock, and hypoxaemia. Acta Anaesthesiol Scand 56:846–859

    Article  CAS  PubMed  Google Scholar 

  43. Ortega A, Fernández A, Arenas MI et al (2013) Outcome of acute renal injury in diabetic mice with experimental endotoxemia: role of hypoxia-inducible factor-1 α. J Diabetes Res 2013:254529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bateman RM, Tokunaga C, Kareco T, Dorscheid DR, Walley KR (2007) Myocardial hypoxia-inducible HIF-1alpha, VEGF, and GLUT1 gene expression is associated with microvascular and ICAM-1 heterogeneity during endotoxemia. Am J Physiol Heart Circ Physiol 293:H448–H456

    Article  CAS  PubMed  Google Scholar 

  45. Hagen T, Taylor CT, Lam F, Moncada S (2003) Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science 302:1975–1978

    Article  CAS  PubMed  Google Scholar 

  46. Emhoff CA, Messonnier LA, Horning MA, Fattor JA, Carlson TJ, Brooks GA (2013) Direct and indirect lactate oxidation in trained and untrained men. J Appl Physiol 115:829–838

    Article  CAS  PubMed  Google Scholar 

  47. Glenn TC, Martin NA, Horning MA et al (2015) Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects. J Neurotrauma 32:820–832

    Article  PubMed  PubMed Central  Google Scholar 

  48. Garcia-Alvarez M, Marik P, Bellomo R (2014) Sepsis-associated hyperlactatemia. Crit Care 18:503

    Article  PubMed  PubMed Central  Google Scholar 

  49. Duburcq T, Favory R, Mathieu D et al (2014) Hypertonic sodium lactate improves fluid balance and hemodynamics in porcine endotoxic shock. Crit Care 18:467

    Article  PubMed  PubMed Central  Google Scholar 

  50. Somasetia DH, Setiati TE, Sjahrodji AM et al (2014) Early resuscitation of dengue shock syndrome in children with hyperosmolar sodium-lactate: a randomized single-blind clinical trial of efficacy and safety. Crit Care 18:466

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Intensive Care Medicine, Nepean Hospital, 2751, Penrith, NSW, Australia

    M. Nalos & A. S. McLean

  2. Department of Intensive Care Medicine, University of Sydney, Nepean Clinical School, 2751, Penrith, Australia

    M. Nalos, A. S. McLean & B. Tang

  3. Centre for Immunology and Allergy Research, Westmead Millennium Institute, Sydney, NSW, Australia

    B. Tang

Authors
  1. M. Nalos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. S. McLean
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Nalos .

Editor information

Editors and Affiliations

  1. Université libre de Bruxelles Dept. of Intensive Care, Erasme Hospital, Brussels, Belgium

    Jean-Louis Vincent

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Nalos, M., McLean, A.S., Tang, B. (2016). Myths and Facts Regarding Lactate in Sepsis. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2016. Annual Update in Intensive Care and Emergency Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-27349-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-27349-5_7

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-27348-8

  • Online ISBN: 978-3-319-27349-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation