Clinical use of lactate monitoring in critically ill patients

Jan Bakker, Maarten Wn Nijsten, Tim C Jansen, Jan Bakker, Maarten Wn Nijsten, Tim C Jansen

Abstract

Increased blood lactate levels (hyperlactataemia) are common in critically ill patients. Although frequently used to diagnose inadequate tissue oxygenation, other processes not related to tissue oxygenation may increase lactate levels. Especially in critically ill patients, increased glycolysis may be an important cause of hyperlactataemia. Nevertheless, the presence of increased lactate levels has important implications for the morbidity and mortality of the hyperlactataemic patients. Although the term lactic acidosis is frequently used, a significant relationship between lactate and pH only exists at higher lactate levels. The term lactate associated acidosis is therefore more appropriate. Two recent studies have underscored the importance of monitoring lactate levels and adjust treatment to the change in lactate levels in early resuscitation. As lactate levels can be measured rapidly at the bedside from various sources, structured lactate measurements should be incorporated in resuscitation protocols.

Figures

Figure 1
Figure 1
Lactate at the cellular level. Usually not oxygen shortage per se, but acute energy requirements is a key determinant of lactate levels. a Under stable conditions, glucose is converted to pyruvate, generating 2 ATP, and pyruvate is then subsequently fully oxidized to CO2 generating ~36 ATP. b Under stress, glycolysis can increase by a factor 100 to 1,000, provided that glucose is present and pyruvate is converted to lactate. Irrespective of optimal mitochondrial function and oxygenation, such a rate of pyruvate production will saturate the mitochondrial tricarboxylic acid cycle and oxidative phosphorylation (OxPhos). c During recovery, lactate is converted back to pyruvate and fully oxidized.
Figure 2
Figure 2
Lactate at the physiological level. The flexible use of glucose and lactate as fuels on the cellular level is mirrored at the organism level. All living tissues can consume glucose. From the glucose/lactate point of view, three sorts of tissues/cells exist: 1) cells that must produce lactate because they lack mitochondria, e.g., red blood cells; 2) tissues or cells that either produce or consume lactate depending on circumstances, i.e., all mitochondria-containing cells; 3) tissues that can perform gluconeogenesis and export glucose that is resynthesized from lactate. The liver and the kidneys can only perform gluconeogenesis and export glucose. Only this so-called Cori cycle (denoted by *) carries an energy penalty, whereas the other shuttles do not lead to “waste” of energy.
Figure 3
Figure 3
1,745 combined measurements of arterial pH and arterial lactate in 171 critically ill patients. Horizontal and vertical lines represent suggested definition of lactic acidosis [8]. For lactate levels ≥ 5.0 mmol/L, a significant linear regression analysis reveals a R2 = 0.28 (p < 0.001).
Figure 4
Figure 4
Lactate levels and LDH levels in a patient with a lymphoma admitted to the ICU because of respiratory failure. Following diagnosis, treatment with chemotherapy was started. The effect of the first and second chemotherapy on lactate and LDH is shown.

References

    1. Kompanje EJ, Jansen TC, van der Hoven B, Bakker J. The first demonstration of lactic acid in human blood in shock by Johann Joseph Scherer (1814–1869) in January 1843. Intensive Care Med. 2007;3(11):1967–1971. doi: 10.1007/s00134-007-0788-7.
    1. Araki T. Ueber die Bildung von Milchsäure und Glycose im Organismus bei Sauerstoffmangel. Z Physiol Chem. 1891;3:335–370.
    1. Leverve XM. Energy metabolism in critically ill patients: lactate is a major oxidizable substrate. Curr Opin Clin Nutr Metab Care. 1999;3(2):165–169. doi: 10.1097/00075197-199903000-00013.
    1. Brooks GA. Lactate shuttles in nature. Biochem Soc Trans. 2002;3(2):258–264.
    1. Zilva JF. The origin of the acidosis in hyperlactataemia. Ann Clin Biochem. 1978;3(1):40–43.
    1. Stewart PA. Modern quantitative acid–base chemistry. Can J Physiol Pharmacol. 1983;3(12):1444–1461. doi: 10.1139/y83-207.
    1. Gunnerson KJ, Saul M, He S, Kellum JA. Lactate versus non-lactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients. Crit Care. 2006;3(1):R22. doi: 10.1186/cc3987.
    1. Fall PJ, Szerlip HM. Lactic acidosis: from sour milk to septic shock. J Intensive Care Med. 2005;3(5):255–271. doi: 10.1177/0885066605278644.
    1. Cain SM. Appearance of excess lactate in anesthetized dogs during anemic and hypoxic hypoxia. Am J Physiol. 1965;3:604–608.
    1. Zhang H, Vincent JL. Oxygen extraction is altered by endotoxin during tamponade-induced stagnant hypoxia in the dog. Circ Shock J1 - CS. 1993;3(3):168–176.
    1. Bakker J, Vincent J-L. The oxygen supply dependency phenomenon is associated with increased blood lactate levels. J Crit Care. 1991;3:152–159. doi: 10.1016/0883-9441(91)90006-F.
    1. Ronco JJ, Fenwick JC, Tweeddale MG, Wiggs BR, Phang PT, Cooper DJ, Cunningham KF, Russell JA, Walley KR. Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans. JAMA. 1993;3(14):1724–1730. doi: 10.1001/jama.1993.03510140084034.
    1. Friedman G, De Backer D, Shahla M, Vincent JL. Oxygen supply dependency can characterize septic shock. Intensive Care Med. 1998;3(2):118–123. doi: 10.1007/s001340050531.
    1. De Backer D, Creteur J, Dubois MJ, Sakr Y, Koch M, Verdant C, Vincent JL. The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects. Crit Care Med. 2006;3(2):403–408. doi: 10.1097/01.CCM.0000198107.61493.5A.
    1. Leverve XM. From tissue perfusion to metabolic marker: assessing organ competition and co-operation in critically ill patients? Intensive Care Med. 1999;3(9):890–892. doi: 10.1007/s001340050976.
    1. Levy B, Sadoune LO, Gelot AM, Bollaert PE, Nabet P, Larcan A. Evolution of lactate/pyruvate and arterial ketone body ratios in the early course of catecholamine-treated septic shock [see comments] Crit Care Med. 2000;3(1):114–119. doi: 10.1097/00003246-200001000-00019.
    1. Levy B, Bollaert PE, Charpentier C, Nace L, Audibert G, Bauer P, Nabet P, Larcan A. Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study. Intensive Care Med. 1997;3(3):282–287. doi: 10.1007/s001340050329.
    1. Weil MH, Tang W. Forty-five-year evolution of stat blood and plasma lactate measurement to guide critical care. Clin Chem. 2009;3(11):2053–2054. doi: 10.1373/clinchem.2009.133553.
    1. Griffith FR Jr, Lockwood JE, Emery FE. Adrenalin lactacidemia: proportionality with dose. Am J Physiol. 1939;3(3):415–421.
    1. Zborowska-Sluis DT, Dossetor JB. Hyperlactatemia of hyperventilation. J Appl Physiol J1 - JAP. 1967;3(4):746–755.
    1. McMahon M, Gerich J, Rizza R. Effects of glucocorticoids on carbohydrate metabolism. Diabetes Metab Rev. 1988;3(1):17–30. doi: 10.1002/dmr.5610040105.
    1. Warburg O. On respiratory impairment in cancer cells. Science. 1956;3(3215):269–270.
    1. Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet. 2005;3(9462):871–875. doi: 10.1016/S0140-6736(05)71045-X.
    1. Levy B, Desebbe O, Montemont C, Gibot S. Increased aerobic glycolysis through beta-2 stimulation is a common mechanism involved in lactate formation during shock states. Shock. 2008;3(4):417–421. doi: 10.1097/SHK.0b013e318167378f.
    1. Taylor DJ, Faragher EB, Evanson JM. Inflammatory cytokines stimulate glucose uptake and glycolysis but reduce glucose oxidation in human dermal fibroblasts in vitro. Circ Shock. 1992;3(2):105–110.
    1. McCarter FD, Evans JA, Luchette FA, Friend LA, James JH, Davis K, Frame SB. Concurrent reduction of glycogenolysis, glycolysis, and Na(+)/K(+) pump activity after hemorrhagic shock. Curr Surg. 2000;3(6):639.
    1. Luchette FA, Friend LA, Brown CC, Upputuri RK, James JH. Increased skeletal muscle Na+, K+-ATPase activity as a cause of increased lactate production after hemorrhagic shock. J Trauma. 1998;3(5):796–801. doi: 10.1097/00005373-199805000-00010. discussion 801–793.
    1. Haji-Michael PG, Ladriere L, Sener A, Vincent JL, Malaisse WJ. Leukocyte glycolysis and lactate output in animal sepsis and ex vivo human blood. Metabolism. 1999;3(6):779–785. doi: 10.1016/S0026-0495(99)90179-8.
    1. Brealey D, Brand M, Hargreaves I, Heales S, Land J, Smolenski R, Davies NA, Cooper CE, Singer M. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet. 2002;3(9328):219–223. doi: 10.1016/S0140-6736(02)09459-X.
    1. Crouser ED, Julian MW, Blaho DV, Pfeiffer DR. Endotoxin-induced mitochondrial damage correlates with impaired respiratory activity. Crit Care Med. 2002;3(2):276–284. doi: 10.1097/00003246-200202000-00002.
    1. Didwania A, Miller J, Kassel D, Jackson EVJ, Chernow B. Effect of intravenous lactated Ringer’s solution infusion on the circulating lactate concentration: Part 3. Results of a prospective, randomized, double-blind, placebo-controlled trial. Crit Care Med. 1997;3(11):1851–1854. doi: 10.1097/00003246-199711000-00024.
    1. Levraut J, Ciebiera JP, Jambou P, Ichai C, Labib Y, Grimaud D. Effect of continuous venovenous hemofiltration with dialysis on lactate clearance in critically ill patients. Crit Care Med. 1997;3(1):58–62. doi: 10.1097/00003246-199701000-00013.
    1. Cole L, Bellomo R, Baldwin I, Hayhoe M, Ronco C. The impact of lactate-buffered high-volume hemofiltration on acid–base balance. Intensive Care Med. 2003;3(7):1113–1120. doi: 10.1007/s00134-003-1812-1.
    1. Bollmann MD, Revelly JP, Tappy L, Berger MM, Schaller MD, Cayeux MC, Martinez A, Chiolero RL. Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure. Intensive Care Med. 2004;3(6):1103–1110. doi: 10.1007/s00134-004-2251-3.
    1. Lalau JD, Lacroix C, Compagnon P, de Cagny B, Rigaud JP, Bleichner G, Chauveau P, Dulbecco P, Guerin C, Haegy JM. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care. 1995;3(6):779–784. doi: 10.2337/diacare.18.6.779.
    1. Marinella MA. Lactic acidosis associated with propofol. Chest. 1996;3(1):292. doi: 10.1378/chest.109.1.292.
    1. Lonergan JT, Behling C, Pfander H, Hassanein TI, Mathews WC. Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens. Clin Infect Dis. 2000;3(1):162–166. doi: 10.1086/313912.
    1. Claessens YE, Cariou A, Monchi M, Soufir L, Azoulay E, Rouges P, Goldgran-Toledano D, Branche F, Dhainaut JF. Detecting life-threatening lactic acidosis related to nucleoside-analog treatment of human immunodeficiency virus-infected patients, and treatment with L-carnitine. Crit Care Med. 2003;3(4):1042–1047. doi: 10.1097/01.CCM.0000053649.69377.08.
    1. Naidoo DP, Gathiram V, Sadhabiriss A, Hassen F. Clinical diagnosis of cardiac beriberi. S Afr Med J. 1990;3(3):125–127.
    1. Morgan TJ, Clark C, Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate. Crit Care Med. 1999;3(10):2177–2179. doi: 10.1097/00003246-199910000-00017.
    1. Brindley PG, Butler MS, Cembrowski G, Brindley DN. Falsely elevated point-of-care lactate measurement after ingestion of ethylene glycol. CMAJ. 2007;3(8):1097–1099.
    1. Leverve XM, Boon C, Hakim T, Anwar M, Siregar E, Mustafa I. Half-molar sodium-lactate solution has a beneficial effect in patients after coronary artery bypass grafting. Intensive Care Med. 2008;3(10):1796–1803. doi: 10.1007/s00134-008-1165-x.
    1. Almenoff PL, Leavy J, Weil MH, Goldberg NB, Vega D, Rackow EC. Prolongation of the half-life of lactate after maximal exercise in patients with hepatic dysfunction. Crit Care Med. 1989;3(9):870–873. doi: 10.1097/00003246-198909000-00004.
    1. Mustafa I, Roth H, Hanafiah A, Hakim T, Anwar M, Siregar E, Leverve XM. Effect of cardiopulmonary bypass on lactate metabolism. Intensive Care Med. 2003;3(8):1279–1285. doi: 10.1007/s00134-003-1860-6.
    1. Vary TC. Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate. Shock. 1996;3(2):89–94. doi: 10.1097/00024382-199608000-00002.
    1. Stacpoole PW, Wright EC, Baumgartner TG, Bersin RM, Buchalter S, Curry SH, Duncan CA, Harman EM, Henderson GN, Jenkinson S. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. N Engl J Med. 1992;3(22):1564–1569. doi: 10.1056/NEJM199211263272204.
    1. Aduen J, Bernstein WK, Khastgir T, Miller J, Kerzner R, Bhatiani A, Lustgarten J, Bassin AS, Davison L, Chernow B. The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations. JAMA. 1994;3(21):1678–1685. doi: 10.1001/jama.1994.03520210062033.
    1. Brinkert W, Rommes JH, Bakker J. Lactate measurements in critically ill patients with a hand-held analyser. Intensive Care Med. 1999;3(9):966–969. doi: 10.1007/s001340050990.
    1. Weil MH, Michaels S, Rackow EC. Comparison of blood lactate concentrations in central venous, pulmonary artery, and arterial blood. Crit Care Med. 1987;3(5):489–490.
    1. Younger JG, Falk JL, Rothrock SG. Relationship between arterial and peripheral venous lactate levels. Acad Emerg Med. 1996;3(7):730–734. doi: 10.1111/j.1553-2712.1996.tb03502.x.
    1. Fauchere JC, Bauschatz AS, Arlettaz R, Zimmermann-Bar U, Bucher HU. Agreement between capillary and arterial lactate in the newborn. Acta Paediatr. 2002;3(1):78–81. doi: 10.1111/j.1651-2227.2002.tb01645.x.
    1. Noordally O, Vincent JL. Evaluation of a new, rapid lactate analyzer in critical care. Intensive Care Med. 1999;3(5):508–513. doi: 10.1007/s001340050889.
    1. Astles R, Williams CP, Sedor F. Stability of plasma lactate in vitro in the presence of antiglycolytic agents. Clin Chem. 1994;3(7 Pt 1):1327–1330.
    1. Andersen O, Haugaard SB, Jorgensen LT, Sorensen S, Nielsen JO, Madsbad S, Iversen J. Preanalytical handling of samples for measurement of plasma lactate in HIV patients. Scand J Clin Lab Invest. 2003;3(6):449–454. doi: 10.1080/00365510310005128.
    1. Jansen TC, van Bommel J, Bakker J. Blood lactate monitoring in critically ill patients: a systematic health technology assessment. Crit Care Med. 2009;3(10):2827–2839. doi: 10.1097/CCM.0b013e3181a98899.
    1. Bakker J, Gris P, Coffernils M, Kahn RJ, Vincent JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg. 1996;3(2):221–226. doi: 10.1016/S0002-9610(97)89552-9.
    1. Jansen TC, van Bommel J, Woodward R, Mulder PG, Bakker J. Association between blood lactate levels, sequential organ failure assessment subscores, and 28-day mortality during early and late intensive care unit stay: a retrospective observational study. Crit Care Med. 2009;3(8):2369–2374. doi: 10.1097/CCM.0b013e3181a0f919.
    1. Jansen TC, van Bommel J, Mulder PG, Rommes JH, Schieveld SJ, Bakker J. The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital setting: a pilot study. Crit Care. 2008;3(6):R160. doi: 10.1186/cc7159.
    1. Bakker J, Coffernils M, Leon M, Gris P, Vincent J-L. Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest. 1991;3(4):956–962. doi: 10.1378/chest.99.4.956.
    1. Howell M, Donnino M, Clardy P, Talmor D, Shapiro N. Occult hypoperfusion and mortality in patients with suspected infection. Intensive Care Med. 2007;3(11):1892–1899. doi: 10.1007/s00134-007-0680-5.
    1. Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, Weiss JW. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005;3(5):524–528. doi: 10.1016/j.annemergmed.2004.12.006.
    1. Hernandez G, Bruhn A, Castro R, Regueira T. The holistic view on perfusion monitoring in septic shock. Curr Opin Crit Care. 2012;3(3):280–286. doi: 10.1097/MCC.0b013e3283532c08.
    1. Vincent JL, Ince C, Bakker J. Clinical review: circulatory shock - an update: a tribute to Professor Max Harry Weil. Crit Care. 2012;3(6):239.
    1. Polonen P, Ruokonen E, Hippelainen M, Poyhonen M, Takala J. A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients. Anesth Analg. 2000;3(5):1052–1059. doi: 10.1097/00000539-200005000-00010.
    1. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;3(8):739–746. doi: 10.1001/jama.2010.158.
    1. Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, Willemsen SP, Bakker J. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;3(6):752–761. doi: 10.1164/rccm.200912-1918OC.
    1. James JH, Luchette FA, McCarter FD, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet. 1999;3(9177):505–508. doi: 10.1016/S0140-6736(98)91132-1.
    1. Vincent JL, Dufaye P, Berre J, Leeman M, Degaute JP, Kahn RJ. Serial lactate determinations during circulatory shock. Crit Care Med. 1983;3(6):449–451. doi: 10.1097/00003246-198306000-00012.
    1. Lewis RJ. Disassembling goal-directed therapy for sepsis: a first step. JAMA. 2010;3(8):777–779. doi: 10.1001/jama.2010.203.
    1. Zhang H, Spapen H, Benlabed M, Vincent JL. Systemic oxygen extraction can be improved during repeated episodes of cardiac tamponade. J Crit Care. 1993;3(2):93–99. doi: 10.1016/0883-9441(93)90013-B.
    1. Spronk PE, Ince C, Gardien MJ, Mathura KR, Oudemans-van Straaten HM, Zandstra DF. Nitroglycerin in septic shock after intravascular volume resuscitation. Lancet. 2002;3(9343):1395–1396. doi: 10.1016/S0140-6736(02)11393-6.
    1. Lima A, van Genderen M, Van Bommel J, Bakker J. Nitroglycerine dose-dependent improves peripheral perfusion in patients with circulatory shock: results of a prospective cross-over study. Intensive Care Med. 2012;3(Suppl 1):S127.
    1. Boerma EC, Koopmans M, Konijn A, Kaiferova K, Bakker AJ, van Roon EN, Buter H, Bruins N, Egbers PH, Gerritsen RT. Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial. Crit Care Med. 2010;3(1):93–100. doi: 10.1097/CCM.0b013e3181b02fc1.
    1. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;3(19):1368–1377. doi: 10.1056/NEJMoa010307.

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