Abstract
Purpose
During septic shock, muscle produces lactate and pyruvate by way of an exaggerated Na+, K+-ATPase-stimulated aerobic glycolysis associated with epinephrine stimulation. We hypothesized that patients with sepsis without shock and increased epinephrine levels or an increased muscle-to-serum lactate gradient are likely to evolve towards septic shock. Thus, in sepsis patients, we investigated (1) whether muscle produces lactate and pyruvate, and (2) whether muscle lactate production is linked to epinephrine levels and the severity of the patient's condition.
Methods
We studied 40 ventilated patients with sepsis without shock or hyperlactatemia and a control group of 10 ICU patients without infection. A microdialysis probe was inserted into the quadriceps muscle. Plasma lactate and pyruvate concentrations were measured in both the dialysate fluid and arterial blood samples every 6 h.
Results
There was no gradient between muscle and arterial levels for lactate and pyruvate in the control group. In the sepsis group, muscle lactate and pyruvate concentrations were consistently higher than the arterial levels (P < 0.01). Plasma epinephrine concentrations were also elevated (P < 0.05). A total of 15/40 patients further developed septic shock, and on admission these patients had significantly higher musculo-arterial gradients of lactate (2.9 ± 0.3 vs. 0.7 ± 0.2 mmol/l) (P < 0.05) and pyruvate (740 ± 60 vs. 200 ± 20 μmol/l) (P < 0.05), and higher levels of epinephrine concentrations (6.2 ± 0.7 vs. 2.5 ± 0.24 nmol/l) (P < 0.05). Both the lactate gradient and epinephrine concentrations measured on admission were good predictors of the evolution towards septic shock.
Conclusions
Muscle produces lactate and pyruvate during sepsis, and this production is highly correlated with plasma epinephrine secretion and severity of illness.
Similar content being viewed by others
References
Cohen RD, Woods HF (1983) Lactic acidosis revisited. Diabetes 32:181–191
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
Kompanje EJ, Jansen TC, van der Hoven B, Bakker J (2007) The first demonstration of lactic acid in human blood in shock by Johann Joseph Scherer (1814–1869) in January 1843. Intensive Care Med 33:1967–1971
James JH, Fang CH, Schrantz SJ, Hasselgren PO, Paul RJ, Fischer JE (1996) Linkage of aerobic glycolysis to sodium-potassium transport in rat skeletal muscle. Implications for increased muscle lactate production in sepsis. J Clin Invest 98:2388–2397
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
James JH, Wagner KR, King JK, Leffler RE, Upputuri RK, Balasubramaniam A, Friend LA, Shelly DA, Paul RJ, Fischer JE (1999) Stimulation of both aerobic glycolysis and Na+-K+-ATPase activity in skeletal muscle by epinephrine or amylin. Am J Physiol 277:E176–E186
Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE (2005) Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet 365:871–875
Levy B (2006) Lactate and shock state: the metabolic view. Curr Opin Crit Care 12:315–321
Leverve XM (1999) Energy metabolism in critically ill patients: lactate is a major oxidizable substrate. Curr Opin Clin Nutr Metab Care 2:165–169
Levy B, Desebbe O, Montemont C, Gibot S (2008) Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states. Shock 30:417–421
Barth E, Albuszies G, Baumgart K, Matejovic M, Wachter U, Vogt J, Radermacher P, Calzia E (2007) Glucose metabolism and catecholamines. Crit Care Med 35:S508–S518
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International sepsis definitions conference. Crit Care Med 31:1250–1256
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 345:1368–1377
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60
Rosdahl H, Ungerstedt U, Henriksson J (1997) Microdialysis in human skeletal muscle and adipose tissue at low flow rates is possible if dextran-70 is added to prevent loss of perfusion fluid. Acta Physiol Scand 159:261–262
Daniel AM, Shizgal HM, MacLean LD (1978) The anatomic and metabolic source of lactate in shock. Surg Gynecol Obstet 147:697–700
Clausen T, Flatman JA (1980) Beta 2-adrenoceptors mediate the stimulating effect of adrenaline on active electrogenic Na-K-transport in rat soleus muscle. Br J Pharmacol 68:749–755
Bearn AG, Billing B, Sherlock S (1951) The effect of adrenaline and noradrenaline on hepatic blood flow and splanchnic carbohydrate metabolism in man. J Physiol 115:430–441
Gladden LB (2004) Lactate metabolism—a new paradigm for the third millennium. J Physiol 558:5–30
Bakker J, Jansen TC (2007) Don’t take vitals, take a lactate. Intensive Care Med 33:1863–1865
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Levy, B., Perez, P., Gibot, S. et al. Increased muscle-to-serum lactate gradient predicts progression towards septic shock in septic patients. Intensive Care Med 36, 1703–1709 (2010). https://doi.org/10.1007/s00134-010-1938-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-010-1938-x