Download PDF
Semin Respir Crit Care Med 2021; 42(05): 650-661
DOI: 10.1055/s-0041-1733915
Review Article

What Is the Utility of Measuring Lactate Levels in Patients with Sepsis and Septic Shock?

Jeremy Weinberger
1   Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
2   Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
,
Michael Klompas
1   Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
3   Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
,
Chanu Rhee
1   Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts
› Author Affiliations Funding J.W. received support from the National Heart Lung and Blood Institute of the National Institutes of Health (T32HL007633).
› Further Information
    Permissions and Reprints

Abstract

Elevations in blood lactate concentrations have been studied in sepsis and other disease states for decades and are well known to be associated with increased mortality. Many studies have also demonstrated the prognostic accuracy of serial lactate levels, and some have suggested that lactate clearance may be a useful therapeutic target for resuscitation. Lactate measurements have therefore gained an increasingly prominent role in sepsis definitions, screening protocols, management guidelines, and quality measures over the past two decades. The heavy emphasis on lactate monitoring, however, has also generated controversy and concerns. Lactate is not specific to infection and its frequent use for sepsis screening and diagnosis may therefore trigger unnecessary broad-spectrum antibiotic use in some patients. Because hyperlactatemia does not always reflect fluid-responsive hypoperfusion, titrating resuscitation to lactate clearance can also lead to unnecessary fluid and volume overload. More broadly, there is a lack of high-quality evidence demonstrating that initial and serial lactate monitoring leads to better patient-centered outcomes. Indeed, a recent randomized controlled trial comparing resuscitation strategies based on lactate clearance versus normalizing capillary refill time showed no benefit and potential harm with lactate-guided therapy. In this article, we review the basic pathobiology of lactate metabolism and delineate why the traditional paradigm that hyperlactatemia reflects tissue hypoxia is overly simplistic and incomplete. We then review the evidence behind the diagnostic, prognostic, and therapeutic uses of lactate monitoring and place this in the context of evolving sepsis diagnosis and management guidelines.

Keywords

lactate - lactic acidosis - hyperlactatemia - sepsis - septic shock - lactate clearance


Publication History

Article published online:
20 September 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Pepper DJ, Sun J, Cui X, Welsh J, Natanson C, Eichacker PQ. Antibiotic- and fluid-focused bundles potentially improve sepsis management, but high-quality evidence is lacking for the specificity required in the Centers for Medicare and Medicaid Service's Sepsis Bundle (SEP-1). Crit Care Med 2019; 47 (10) 1290-1300
    CrossrefPubMedSearch in Google Scholar
  • 2 Han X, Edelson DP, Snyder A. et al. Implications of Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock Early Management Bundle and initial lactate measurement on the management of sepsis. Chest 2018; 154 (02) 302-308
    CrossrefPubMedSearch in Google Scholar
  • 3 Rhee C, Murphy MV, Li L, Platt R, Klompas M. Centers for Disease Control and Prevention Prevention Epicenters Program. Lactate testing in suspected sepsis: trends and predictors of failure to measure levels. Crit Care Med 2015; 43 (08) 1669-1676
    CrossrefPubMedSearch in Google Scholar
  • 4 Whippy A, Skeath M, Crawford B. et al. Kaiser Permanente's performance improvement system, part 3: multisite improvements in care for patients with sepsis. Jt Comm J Qual Patient Saf 2011; 37 (11) 483-493
    PubMedSearch in Google Scholar
  • 5 Dettmer M, Holthaus CV, Fuller BM. The impact of serial lactate monitoring on emergency department resuscitation interventions and clinical outcomes in severe sepsis and septic shock: an observational cohort study. Shock 2015; 43 (01) 55-61
    CrossrefPubMedSearch in Google Scholar
  • 6 Spiegel R, Gordon D, Marik PE. The origins of the Lacto-Bolo reflex: the mythology of lactate in sepsis. J Thorac Dis 2020; 12 (Suppl. 01) S48-S53
    CrossrefPubMedSearch in Google Scholar
  • 7 Ferguson BS, Rogatzki MJ, Goodwin ML, Kane DA, Rightmire Z, Gladden LB. Lactate metabolism: historical context, prior misinterpretations, and current understanding. Eur J Appl Physiol 2018; 118 (04) 691-728
    CrossrefPubMedSearch in Google Scholar
  • 8 Phypers B, Pierce JT. Lactate physiology in health and disease. Contin Educ Anaesth Crit Care Pain 2006; 6: 128-132
    CrossrefPubMedSearch in Google Scholar
  • 9 Connor H, Woods HF. Quantitative aspects of L(+)-lactate metabolism in human beings. Ciba Found Symp 1982; 87: 214-234
    PubMedSearch in Google Scholar
  • 10 Dienel GA. Brain lactate metabolism: the discoveries and the controversies. J Cereb Blood Flow Metab 2012; 32 (07) 1107-1138
    CrossrefPubMedSearch in Google Scholar
  • 11 Stanley WC. Myocardial lactate metabolism during exercise. Med Sci Sports Exerc 1991; 23 (08) 920-924
    CrossrefPubMedSearch in Google Scholar
  • 12 van Hall G. Lactate kinetics in human tissues at rest and during exercise. Acta Physiol (Oxf) 2010; 199 (04) 499-508
    CrossrefPubMedSearch in Google Scholar
  • 13 Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care 2014; 18 (05) 503
    CrossrefPubMedSearch in Google Scholar
  • 14 Mazzeo RS, Brooks GA, Schoeller DA, Budinger TF. Disposal of blood [1-13C]lactate in humans during rest and exercise. J Appl Physiol (1985) 1986; 60 (01) 232-241
    CrossrefPubMedSearch in Google Scholar
  • 15 Miller BF, Fattor JA, Jacobs KA. et al. Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion. J Physiol 2002; 544 (03) 963-975
    CrossrefPubMedSearch in Google Scholar
  • 16 Hui S, Ghergurovich JM, Morscher RJ. et al. Glucose feeds the TCA cycle via circulating lactate. Nature 2017; 551 (7678): 115-118
    CrossrefPubMedSearch in Google Scholar
  • 17 Meyerhof O. The chemistry of muscular contraction. Lancet 1930; 216: 1415-1422
    CrossrefPubMedSearch in Google Scholar
  • 18 Wasserman K, McIlroy MB. Detecting the threshold of anaerobic metabolism in cardiac patients during exercise. Am J Cardiol 1964; 14: 844-852
    CrossrefPubMedSearch in Google Scholar
  • 19 Glancy B, Kane DA, Kavazis AN, Goodwin ML, Willis WT, Gladden LB. Mitochondrial lactate metabolism: history and implications for exercise and disease. J Physiol 2021; 599 (03) 863-888
    CrossrefPubMedSearch in Google Scholar
  • 20 Friedman G, De Backer D, Shahla M, Vincent JL. Oxygen supply dependency can characterize septic shock. Intensive Care Med 1998; 24 (02) 118-123
    CrossrefPubMedSearch in Google Scholar
  • 21 Astiz ME, Rackow EC, Kaufman B, Falk JL, Weil MH. Relationship of oxygen delivery and mixed venous oxygenation to lactic acidosis in patients with sepsis and acute myocardial infarction. Crit Care Med 1988; 16 (07) 655-658
    CrossrefPubMedSearch in Google Scholar
  • 22 James JH, Luchette FA, McCarter FD, Fischer JE. Lactate is an unreliable indicator of tissue hypoxia in injury or sepsis. Lancet 1999; 354 (9177): 505-508
    CrossrefPubMedSearch in Google Scholar
  • 23 Mira JP, Fabre JE, Baigorri F. et al. Lack of oxygen supply dependency in patients with severe sepsis. A study of oxygen delivery increased by military antishock trouser and dobutamine. Chest 1994; 106 (05) 1524-1531
    CrossrefPubMedSearch in Google Scholar
  • 24 Ronco JJ, Fenwick JC, Wiggs BR, Phang PT, Russell JA, Tweeddale MG. Oxygen consumption is independent of increases in oxygen delivery by dobutamine in septic patients who have normal or increased plasma lactate. Am Rev Respir Dis 1993; 147 (01) 25-31
    CrossrefPubMedSearch in Google Scholar
  • 25 Boekstegers P, Weidenhöfer S, Kapsner T, Werdan K. Skeletal muscle partial pressure of oxygen in patients with sepsis. Crit Care Med 1994; 22 (04) 640-650
    CrossrefPubMedSearch in Google Scholar
  • 26 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; 365 (9462): 871-875
    CrossrefPubMedSearch in Google Scholar
  • 27 Opdam H, Bellomo R. Oxygen consumption and lactate release by the lung after cardiopulmonary bypass and during septic shock. Crit Care Resusc 2000; 2 (03) 181-187
    PubMedSearch in Google Scholar
  • 28 Sair M, Etherington PJ, Peter Winlove C, Evans TW. Tissue oxygenation and perfusion in patients with systemic sepsis. Crit Care Med 2001; 29 (07) 1343-1349
    CrossrefPubMedSearch in Google Scholar
  • 29 Hayes MA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994; 330 (24) 1717-1722
    CrossrefPubMedSearch in Google Scholar
  • 30 Bouglé A, Mira JP. Short-acting β-blocker administration in patients with septic shock. JAMA 2014; 311 (07) 736-737
    CrossrefPubMedSearch in Google Scholar
  • 31 Morelli A, Ertmer C, Westphal M. et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 2013; 310 (16) 1683-1691
    CrossrefPubMedSearch in Google Scholar
  • 32 Barth E, Albuszies G, Baumgart K. et al. Glucose metabolism and catecholamines. Crit Care Med 2007; 35 (9, Suppl): S508-S518
    CrossrefPubMedSearch in Google Scholar
  • 33 Garcia-Alvarez M, Marik P, Bellomo R. Stress hyperlactataemia: present understanding and controversy. Lancet Diabetes Endocrinol 2014; 2 (04) 339-347
    CrossrefPubMedSearch in Google Scholar
  • 34 Goodwin ML, Pennington Z, Westbroek EM, Cottrill E, Ahmed AK, Sciubba DM. Lactate and cancer: a “lactatic” perspective on spinal tumor metabolism (part 1). Ann Transl Med 2019; 7 (10) 220
    CrossrefPubMedSearch in Google Scholar
  • 35 Kumar A, Schupp E, Bunnell E, Ali A, Milcarek B, Parrillo JE. Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock. Crit Care 2008; 12 (02) R35
    CrossrefPubMedSearch in Google Scholar
  • 36 Levy B, Dusang B, Annane D, Gibot S, Bollaert PE. College Interregional des Réanimateurs du Nord-Est. Cardiovascular response to dopamine and early prediction of outcome in septic shock: a prospective multiple-center study. Crit Care Med 2005; 33 (10) 2172-2177
    CrossrefPubMedSearch in Google Scholar
  • 37 Wutrich Y, Barraud D, Conrad M. et al. Early increase in arterial lactate concentration under epinephrine infusion is associated with a better prognosis during shock. Shock 2010; 34 (01) 4-9
    CrossrefPubMedSearch in Google Scholar
  • 38 Singer M. Mitochondrial function in sepsis: acute phase versus multiple organ failure. Crit Care Med 2007; 35 (9, Suppl): S441-S448
    CrossrefPubMedSearch in Google Scholar
  • 39 Lanni A, Moreno M, Goglia F. Mitochondrial actions of thyroid hormone. Compr Physiol 2016; 6 (04) 1591-1607
    CrossrefPubMedSearch in Google Scholar
  • 40 Alamdari N, Constantin-Teodosiu D, Murton AJ. et al. Temporal changes in the involvement of pyruvate dehydrogenase complex in muscle lactate accumulation during lipopolysaccharide infusion in rats. J Physiol 2008; 586 (06) 1767-1775
    CrossrefPubMedSearch in Google Scholar
  • 41 Hotchkiss RS, Karl IE. Reevaluation of the role of cellular hypoxia and bioenergetic failure in sepsis. JAMA 1992; 267 (11) 1503-1510
    CrossrefPubMedSearch in Google Scholar
  • 42 Brealey D, Brand M, Hargreaves I. et al. Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet 2002; 360 (9328): 219-223
    CrossrefPubMedSearch in Google Scholar
  • 43 Levraut J, Ciebiera JP, Chave S. et al. Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction. Am J Respir Crit Care Med 1998; 157 (4, Pt 1): 1021-1026
    CrossrefPubMedSearch in Google Scholar
  • 44 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; 17 (09) 870-873
    CrossrefPubMedSearch in Google Scholar
  • 45 Legouis D, Ricksten SE, Faivre A. et al. Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality. Nat Metab 2020; 2 (08) 732-743
    CrossrefPubMedSearch in Google Scholar
  • 46 Stacpoole PW, Wright EC, Baumgartner TG. et al; The Dichloroacetate-Lactic Acidosis Study Group. A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. N Engl J Med 1992; 327 (22) 1564-1569
    CrossrefPubMedSearch in Google Scholar
  • 47 Moskowitz A, Donnino MW. Thiamine (vitamin B1) in septic shock: a targeted therapy. J Thorac Dis 2020; 12 (Suppl. 01) S78-S83
    CrossrefPubMedSearch in Google Scholar
  • 48 Fujii T, Luethi N, Young PJ. et al; VITAMINS Trial Investigators. Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the VITAMINS randomized clinical trial. JAMA 2020; 323 (05) 423-431
    CrossrefPubMedSearch in Google Scholar
  • 49 Kraut JA, Madias NE. Lactic acidosis. N Engl J Med 2014; 371 (24) 2309-2319
    CrossrefPubMedSearch in Google Scholar
  • 50 Bone RC, Balk RA, Cerra FB. et al; The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992; 101 (06) 1644-1655
    CrossrefPubMedSearch in Google Scholar
  • 51 Levy MM, Fink MP, Marshall JC. et al; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31 (04) 1250-1256
    CrossrefPubMedSearch in Google Scholar
  • 52 Yealy DM, Kellum JA, Huang DT. et al; ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014; 370 (18) 1683-1693
    CrossrefPubMedSearch in Google Scholar
  • 53 Peake SL, Delaney A, Bailey M. et al; ARISE Investigators, ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014; 371 (16) 1496-1506
    CrossrefPubMedSearch in Google Scholar
  • 54 Mouncey PR, Osborn TM, Power GS. et al; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 2015; 372 (14) 1301-1311
    CrossrefPubMedSearch in Google Scholar
  • 55 Inpatient Hospitals Specifications Manual. Accessed July 10, 2021 at: https://www.qualitynet.org
  • 56 Rivers E, Nguyen B, Havstad S. et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345 (19) 1368-1377
    CrossrefPubMedSearch in Google Scholar
  • 57 Singer M, Deutschman CS, Seymour CW. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315 (08) 801-810
    CrossrefPubMedSearch in Google Scholar
  • 58 Dellinger RP, Carlet JM, Masur H. et al; Surviving Sepsis Campaign Management Guidelines Committee. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32 (03) 858-873
    CrossrefPubMedSearch in Google Scholar
  • 59 Rhodes A, Evans LE, Alhazzani W. et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017; 43 (03) 304-377
    CrossrefPubMedSearch in Google Scholar
  • 60 Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Crit Care Med 2018; 46 (06) 997-1000
    CrossrefPubMedSearch in Google Scholar
  • 61 Rhee C, Filbin MR, Massaro AF. et al; Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program. Compliance with the National SEP-1 Quality Measure and Association with Sepsis Outcomes: a multicenter retrospective cohort study. Crit Care Med 2018; 46 (10) 1585-1591
    CrossrefPubMedSearch in Google Scholar
  • 62 Bakker J, Coffernils M, Leon M, Gris P, Vincent JL. Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. Chest 1991; 99 (04) 956-962
    CrossrefPubMedSearch in Google Scholar
  • 63 Cady Jr LD, Weil MH, Afifi AA, Michaels SF, Liu VY, Shubin H. Quantitation of severity of critical illness with special reference to blood lactate. Crit Care Med 1973; 1 (02) 75-80
    CrossrefPubMedSearch in Google Scholar
  • 64 Casserly B, Phillips GS, Schorr C. et al. Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign database. Crit Care Med 2015; 43 (03) 567-573
    CrossrefPubMedSearch in Google Scholar
  • 65 del Portal DA, Shofer F, Mikkelsen ME. et al. Emergency department lactate is associated with mortality in older adults admitted with and without infections. Acad Emerg Med 2010; 17 (03) 260-268
    CrossrefPubMedSearch in Google Scholar
  • 66 Green JP, Berger T, Garg N, Shapiro NI. Serum lactate is a better predictor of short-term mortality when stratified by C-reactive protein in adult emergency department patients hospitalized for a suspected infection. Ann Emerg Med 2011; 57 (03) 291-295
    CrossrefPubMedSearch in Google Scholar
  • 67 Howell MD, Donnino M, Clardy P, Talmor D, Shapiro NI. Occult hypoperfusion and mortality in patients with suspected infection. Intensive Care Med 2007; 33 (11) 1892-1899
    CrossrefPubMedSearch in Google Scholar
  • 68 Mikkelsen ME, Miltiades AN, Gaieski DF. et al. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009; 37 (05) 1670-1677
    CrossrefPubMedSearch in Google Scholar
  • 69 Phua J, Koay ESC, Lee KH. Lactate, procalcitonin, and amino-terminal pro-B-type natriuretic peptide versus cytokine measurements and clinical severity scores for prognostication in septic shock. Shock 2008; 29 (03) 328-333
    CrossrefPubMedSearch in Google Scholar
  • 70 Shapiro NI, Howell MD, Talmor D. et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005; 45 (05) 524-528
    CrossrefPubMedSearch in Google Scholar
  • 71 Tang Y, Choi J, Kim D. et al. Clinical predictors of adverse outcome in severe sepsis patients with lactate 2-4 mM admitted to the hospital. QJM 2015; 108 (04) 279-287
    CrossrefPubMedSearch in Google Scholar
  • 72 Trzeciak S, Dellinger RP, Chansky ME. et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007; 33 (06) 970-977
    CrossrefPubMedSearch in Google Scholar
  • 73 Shankar-Hari M, Phillips GS, Levy ML. et al; Sepsis Definitions Task Force. Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315 (08) 775-787
    CrossrefPubMedSearch in Google Scholar
  • 74 Nguyen HB, Rivers EP, Knoblich BP. et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004; 32 (08) 1637-1642
    CrossrefPubMedSearch in Google Scholar
  • 75 Arnold RC, Shapiro NI, Jones AE. et al; Emergency Medicine Shock Research Network (EMShockNet) Investigators. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2009; 32 (01) 35-39
    CrossrefPubMedSearch in Google Scholar
  • 76 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; 171 (02) 221-226
    CrossrefPubMedSearch in Google Scholar
  • 77 Bruno RR, Wernly B, Binneboessel S. et al. Failure of lactate clearance predicts the outcome of critically ill septic patients. Diagnostics (Basel) 2020; 10 (12) 1105
    CrossrefPubMedSearch in Google Scholar
  • 78 Chertoff J, Chisum M, Simmons L, King B, Walker M, Lascano J. Prognostic utility of plasma lactate measured between 24 and 48 h after initiation of early goal-directed therapy in the management of sepsis, severe sepsis, and septic shock. J Intensive Care 2016; 4: 13
    CrossrefPubMedSearch in Google Scholar
  • 79 Haas SA, Lange T, Saugel B. et al. Severe hyperlactatemia, lactate clearance and mortality in unselected critically ill patients. Intensive Care Med 2016; 42 (02) 202-210
    CrossrefPubMedSearch in Google Scholar
  • 80 Herwanto V, Lie KC, Suwarto S, Rumende CM. Role of 6-hour, 12-hour, and 24-hour lactate clearance in mortality of severe sepsis and septic shock patients. Crit Care 2014; 18: 2
    CrossrefPubMedSearch in Google Scholar
  • 81 Levraut J, Ichai C, Petit I, Ciebiera J-P, Perus O, Grimaud D. Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients. Crit Care Med 2003; 31 (03) 705-710
    CrossrefPubMedSearch in Google Scholar
  • 82 Lokhandwala S, Andersen LW, Nair S, Patel P, Cocchi MN, Donnino MW. Absolute lactate value vs relative reduction as a predictor of mortality in severe sepsis and septic shock. J Crit Care 2017; 37: 179-184
    CrossrefPubMedSearch in Google Scholar
  • 83 Marty P, Roquilly A, Vallée F. et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann Intensive Care 2013; 3 (01) 3
    CrossrefPubMedSearch in Google Scholar
  • 84 Masyuk M, Wernly B, Lichtenauer M. et al. Prognostic relevance of serum lactate kinetics in critically ill patients. Intensive Care Med 2019; 45 (01) 55-61
    CrossrefPubMedSearch in Google Scholar
  • 85 Nichol A, Bailey M, Egi M. et al. Dynamic lactate indices as predictors of outcome in critically ill patients. Crit Care 2011; 15 (05) R242
    CrossrefPubMedSearch in Google Scholar
  • 86 Puskarich MA, Trzeciak S, Shapiro NI. et al. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest 2013; 143 (06) 1548-1553
    CrossrefPubMedSearch in Google Scholar
  • 87 Ryoo SM, Ahn R, Shin TG. et al; Korean Shock Society (KoSS) Investigators. Lactate normalization within 6 hours of bundle therapy and 24 hours of delayed achievement were associated with 28-day mortality in septic shock patients. PLoS One 2019; 14 (06) e0217857
    CrossrefPubMedSearch in Google Scholar
  • 88 Vincent J-L, Quintairos E Silva A, Couto Jr L, Taccone FS. The value of blood lactate kinetics in critically ill patients: a systematic review. Crit Care 2016; 20 (01) 257
    CrossrefPubMedSearch in Google Scholar
  • 89 Yang CS, Qiu HB, Huang YZ. et al. [Prospective research on the prognosis of septic shock based on the change of lactate concentration in arterial blood]. Zhonghua Wai Ke Za Zhi 2009; 47 (09) 685-688
    PubMedSearch in Google Scholar
  • 90 Zhang Z, Xu X. Lactate clearance is a useful biomarker for the prediction of all-cause mortality in critically ill patients: a systematic review and meta-analysis*. Crit Care Med 2014; 42 (09) 2118-2125
    CrossrefPubMedSearch in Google Scholar
  • 91 Marik P, Bellomo R. Lactate clearance as a target of therapy in sepsis: a flawed paradigm. OA Critical Care 2013; 1
    CrossrefPubMedSearch in Google Scholar
  • 92 Jansen TC, van Bommel J, Schoonderbeek FJ. et al; LACTATE Study Group. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med 2010; 182 (06) 752-761
    CrossrefPubMedSearch in Google Scholar
  • 93 Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Emergency Medicine Shock Research Network (EMShockNet) Investigators. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010; 303 (08) 739-746
    CrossrefPubMedSearch in Google Scholar
  • 94 Lyu X, Xu Q, Cai G, Yan J, Yan M. [Efficacies of fluid resuscitation as guided by lactate clearance rate and central venous oxygen saturation in patients with septic shock]. Zhonghua Yi Xue Za Zhi 2015; 95 (07) 496-500
    Search in Google Scholar
  • 95 Tian HH, Han SS, Lv CJ. et al. [The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia]. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2012; 24 (01) 42-45
    PubMedSearch in Google Scholar
  • 96 Yu B, Tian HY, Hu ZJ. et al. [Comparison of the effect of fluid resuscitation as guided either by lactate clearance rate or by central venous oxygen saturation in patients with sepsis]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2013; 25 (10) 578-583
    PubMedSearch in Google Scholar
  • 97 Ding XF, Yang ZY, Xu ZT. et al. Early goal-directed and lactate-guided therapy in adult patients with severe sepsis and septic shock: a meta-analysis of randomized controlled trials. J Transl Med 2018; 16 (01) 331
    CrossrefPubMedSearch in Google Scholar
  • 98 Lu Y, Zhang H, Teng F, Xia WJ, Sun GX, Wen AQ. Early goal-directed therapy in severe sepsis and septic shock: a meta-analysis and trial sequential analysis of randomized controlled trials. J Intensive Care Med 2018; 33 (05) 296-309
    CrossrefPubMedSearch in Google Scholar
  • 99 Hernández G, Ospina-Tascón GA, Damiani LP. et al; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN). Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28-day mortality among patients with septic shock: the ANDROMEDA-SHOCK randomized clinical trial. JAMA 2019; 321 (07) 654-664
    CrossrefPubMedSearch in Google Scholar
  • 100 Lara B, Enberg L, Ortega M. et al. Capillary refill time during fluid resuscitation in patients with sepsis-related hyperlactatemia at the emergency department is related to mortality. PLoS One 2017; 12 (11) e0188548
    CrossrefPubMedSearch in Google Scholar
  • 101 Lima A, Jansen TC, van Bommel J, Ince C, Bakker J. The prognostic value of the subjective assessment of peripheral perfusion in critically ill patients. Crit Care Med 2009; 37 (03) 934-938
    CrossrefPubMedSearch in Google Scholar
  • 102 Kattan E, Hernández G, Ospina-Tascón G, Valenzuela ED, Bakker J, Castro R. ANDROMEDA-SHOCK Study Investigators and the Latin America Intensive Care Network (LIVEN). A lactate-targeted resuscitation strategy may be associated with higher mortality in patients with septic shock and normal capillary refill time: a post hoc analysis of the ANDROMEDA-SHOCK study. Ann Intensive Care 2020; 10 (01) 114
    CrossrefPubMedSearch in Google Scholar
  • 103 Zampieri FG, Damiani LP, Bakker J. et al. Effects of a resuscitation strategy targeting peripheral perfusion status versus serum lactate levels among patients with septic shock. A Bayesian reanalysis of the ANDROMEDA-SHOCK trial. Am J Respir Crit Care Med 2020; 201 (04) 423-429
    CrossrefPubMedSearch in Google Scholar
  • 104 Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care 2015; 19: 251
    CrossrefPubMedSearch in Google Scholar
  • 105 Andrews B, Semler MW, Muchemwa L. et al. Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. JAMA 2017; 318 (13) 1233-1240
    CrossrefPubMedSearch in Google Scholar
  • 106 Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 2011; 39 (02) 259-265
    CrossrefPubMedSearch in Google Scholar
  • 107 Maitland K, Kiguli S, Opoka RO. et al; FEAST Trial Group. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364 (26) 2483-2495
    CrossrefPubMedSearch in Google Scholar
  • 108 Sakr Y, Rubatto Birri PN, Kotfis K. et al; Intensive Care Over Nations Investigators. Higher fluid balance increases the risk of death from sepsis: results from a large international audit. Crit Care Med 2017; 45 (03) 386-394
    CrossrefPubMedSearch in Google Scholar
  • 109 Corl KA, Prodromou M, Merchant RC. et al. The Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock (RIFTS): a randomized pilot study. Crit Care Med 2019; 47 (07) 951-959
    CrossrefPubMedSearch in Google Scholar
  • 110 Hjortrup PB, Haase N, Bundgaard H. et al; CLASSIC Trial Group, Scandinavian Critical Care Trials Group. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med 2016; 42 (11) 1695-1705
    CrossrefPubMedSearch in Google Scholar
  • 111 Andersen LW, Mackenhauer J, Roberts JC, Berg KM, Cocchi MN, Donnino MW. Etiology and therapeutic approach to elevated lactate levels. Mayo Clin Proc 2013; 88 (10) 1127-1140
    CrossrefPubMedSearch in Google Scholar
  • 112 Rhee C, Kadri SS, Dekker JP. et al; CDC Prevention Epicenters Program. Prevalence of antibiotic-resistant pathogens in culture-proven sepsis and outcomes associated with inadequate and broad-spectrum empiric antibiotic use. JAMA Netw Open 2020; 3 (04) e202899
    CrossrefPubMedSearch in Google Scholar
  • 113 Chen H, Zhao C, Wei Y, Jin J. Early lactate measurement is associated with better outcomes in septic patients with an elevated serum lactate level. Crit Care 2019; 23 (01) 351
    CrossrefPubMedSearch in Google Scholar
  • 114 Pruinelli L, Westra BL, Yadav P. et al. Delay within the 3-hour surviving sepsis campaign guideline on mortality for patients with severe sepsis and septic shock. Crit Care Med 2018; 46 (04) 500-505
    CrossrefPubMedSearch in Google Scholar
  • 115 Seymour CW, Gesten F, Prescott HC. et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 2017; 376 (23) 2235-2244
    CrossrefPubMedSearch in Google Scholar
  • 116 Singer AJ, Taylor M, LeBlanc D, Williams J, Thode Jr HC. ED bedside point-of-care lactate in patients with suspected sepsis is associated with reduced time to iv fluids and mortality. Am J Emerg Med 2014; 32 (09) 1120-1124
    CrossrefPubMedSearch in Google Scholar
  • 117 Gu W-J, Zhang Z, Bakker J. Early lactate clearance-guided therapy in patients with sepsis: a meta-analysis with trial sequential analysis of randomized controlled trials. Intensive Care Med 2015; 41 (10) 1862-1863
    CrossrefPubMedSearch in Google Scholar
  • 118 Pan J, Peng M, Liao C, Hu X, Wang A, Li X. Relative efficacy and safety of early lactate clearance-guided therapy resuscitation in patients with sepsis: a meta-analysis. Medicine (Baltimore) 2019; 98 (08) e14453
    CrossrefPubMedSearch in Google Scholar