Normal-Range Blood Lactate Concentration in Septic Shock Is Prognostic and Predictive

We hypothesized that lactate levels even within the normal range are prognostic and that low lactate levels predict a beneficial response to vasopressin infusion in septic shock. We conducted a retrospective analysis using the Vasopressin in Septic Shock Trial (VASST) as a derivation cohort (n = 665), then validated using another single-center septic shock cohort, St Paul’s Hospital (SPH) cohort (n = 469). Lactate levels were divided into quartiles. The primary outcome variable was 28-day mortality in both cohorts. We used receiver operating characteristic (ROC) curve analysis to compare the prognostic value of lactate concentrations versus Acute Physiology and Chronic Health Evaluation II scores. We then explored whether lactate concentrations might predict beneficial response to vasopressin compared with noradrenaline in VASST. Normal lactate range is less than 2.3 mmol/L. At enrolment, patients in the second quartile (1.4 < lactate < 2.3 mmol/L) had significantly increased mortality and organ dysfunction compared with patients who had lactate ⩽1.4 mmol/L (quartile 1) (P < 0.0001). Quartile 2 outcomes were as severe as quartile 3 (2.3 ⩽ lactate < 4.4 mmol/L) outcomes. Baseline lactate values (area under the ROC curve = 0.63, 0.66; VASST, SPH) were as good as Acute Physiology and Chronic Health Evaluation II scores (area under the ROC curve = 0.66, 0.73; VASST, SPH) as prognostic indicators of 28-day mortality. Lactate concentrations of 1.4 mmol/L or less predicted a beneficial response in those randomized to vasopressin compared with noradrenaline in VASST (P < 0.05). Lactate concentrations within the “normal” range can be a useful prognostic indicator in septic shock. Furthermore, patients whose lactate level is less than or equal to 1.4 mmol/L may benefit from vasopressin infusion. ABBREVIATIONS APACHE—Acute Physiology and Chronic Health Evaluation ATP—adenosine triphosphate COPD — chronic obstructive pulmonary disease ScvO2—central venous oxygen saturation SPH—St Paul’s Hospital VASST—Vasopressin and Septic Shock Trial

[1]  C. Sprung,et al.  Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock 2012 , 2013, Critical care medicine.

[2]  Michael Bailey,et al.  Dynamic lactate indices as predictors of outcome in critically ill patients , 2011, Critical care.

[3]  O. Okorie,et al.  Lactate: biomarker and potential therapeutic target. , 2011, Critical care clinics.

[4]  Clifton Callaway,et al.  Prehospital serum lactate as a predictor of outcomes in trauma patients: a retrospective observational study. , 2011, The Journal of trauma.

[5]  J. Bakker,et al.  Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. , 2010, American journal of respiratory and critical care medicine.

[6]  Michael Bailey,et al.  Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study , 2010, Critical care.

[7]  Alan E. Jones,et al.  Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. , 2010, JAMA.

[8]  Munish Goyal,et al.  Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock* , 2009, Critical care medicine.

[9]  J. Bakker,et al.  Prognostic value of blood lactate levels: does the clinical diagnosis at admission matter? , 2009, The Journal of trauma.

[10]  Jason Phua,et al.  LACTATE, PROCALCITONIN, AND AMINO-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE VERSUS CYTOKINE MEASUREMENTS AND CLINICAL SEVERITY SCORES FOR PROGNOSTICATION IN SEPTIC SHOCK , 2008, Shock.

[11]  Sangeeta Mehta,et al.  Vasopressin versus norepinephrine infusion in patients with septic shock. , 2008, The New England journal of medicine.

[12]  M. Levy,et al.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 , 2007, Intensive Care Medicine.

[13]  M. Nagino,et al.  HYPERLACTEMIA CAN PREDICT THE PROGNOSIS OF LIVER RESECTION , 2007, Shock.

[14]  B. Levy.  Lactate and shock state: the metabolic view , 2006, Current opinion in critical care.

[15]  Larry A Nathanson,et al.  Serum lactate as a predictor of mortality in emergency department patients with infection. , 2005, Annals of emergency medicine.

[16]  K. Walley,et al.  The association of interleukin 6 haplotype clades with mortality in critically ill adults. , 2005, Archives of internal medicine.

[17]  A. Coquerel,et al.  Erythropoietin and renin as biological markers in critically ill patients , 2004, Critical care.

[18]  G. Jacobsen,et al.  Early lactate clearance is associated with improved outcome in severe sepsis and septic shock* , 2004, Critical care medicine.

[19]  G. Friedman,et al.  Occult hypoperfusion is associated with increased mortality in hemodynamically stable, high-risk, surgical patients , 2004, Critical care.

[20]  Michael D Sharpe,et al.  Bench-to-bedside review: Microvascular dysfunction in sepsis –hemodynamics, oxygen transport, and nitric oxide , 2003, Critical care.

[21]  K. Jablonski,et al.  Serum lactate, not base deficit, rapidly predicts survival after major burns. , 2002, Burns : journal of the International Society for Burn Injuries.

[22]  E. Ivers,et al.  Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock , 2001 .

[23]  M. Ba.  Hyperlactatemia in acute liver failure: decreased clearance versus increased production. , 2001 .

[24]  B. Mizock.  The hepatosplanchnic area and hyperlactatemia: A tale of two lactates. , 2001, Critical care medicine.

[25]  B. Mizock.  Hyperlactatemia in acute liver failure: decreased clearance versus increased production. , 2001, Critical care medicine.

[26]  E. Ruokonen,et al.  Acute respiratory distress syndrome: frequency, clinical course, and costs of care. , 1999, Critical care medicine.

[27]  G. Bernard,et al.  A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. , 1997, Chest.

[28]  J. Vincent,et al.  Serial blood lactate levels can predict the development of multiple organ failure following septic shock. , 1996, American journal of surgery.

[29]  H. Werner,et al.  Myocardial oxygen extraction ratio is decreased during endotoxemia in pigs. , 1995, Journal of applied physiology.

[30]  J. Vincent,et al.  Combined measurements of blood lactate concentrations and gastric intramucosal pH in patients with severe sepsis. , 1995, Critical care medicine.

[31]  W. Sibbald,et al.  Round table conference on clinical trials for the treatment of sepsis. , 1995, Critical care medicine.

[32]  W. Sibbald,et al.  Roundtable Conference on Clinical Trials for the Treatment of Sepsis. Brussels, March 12-14, 1994. , 1995, Chest.

[33]  J. E. Carceller.  American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis , 1992, Critical care medicine.

[34]  J. Vincent,et al.  Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock. , 1991, Chest.

[35]  J. Dhainaut,et al.  Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock. , 1987, Circulation.

[36]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[37]  A. Gimson,et al.  Lactic acidosis in fulminant hepatic failure. Some aspects of pathogenesis and prognosis. , 1985, Journal of hepatology.