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The association of early lactate clearance with inflammatory biomarkers in severe sepsis and septic shock


Patients presenting to the hospital with sepsis with evidence of hypoperfusion have a greater risk of developing organ dysfunction and higher mortality [1]. Early recognition of hypoperfused states and implementation of strategies to resolve global tissue hypoxia as reflected by early lactate clearance correlate with improved outcome and mortality [2]. This study is a secondary analysis comparing early lactate clearance with serum biomarkers among a cohort of patients collected during the Early Goal Directed Therapy Trial (EGDT).


Lactate levels were drawn on patients presenting with severe sepsis and septic shock upon hospital presentation and at 6 hours after resuscitation. Lactate clearance was defined as the decrease in blood lactate concentration from the baseline to the 6-hour value, expressed as a percentage of the baseline value [2]. Biomarkers were examined at baseline, 6, 12, 24, 36, 48, 60 and 72 hours after hospital presentation. Biomarkers were determined by immunoassay independently performed by Biosite®, Inc. (San Diego, CA, USA). The Kruskal-Wallis statistic was used to detect differences in mean (0–72 hours) biomarker levels among patients stratified by lactate clearance quartiles. Chi-square analysis and Kaplan-Meier mortality estimation were used to compare outcome among the lactate clearance quartiles. The Student two-sample t test, Wilcoxon rank sum test, chi-square and Kruskal-Wallis statistics were employed to compare hospital survivors versus nonsurvivors. A two-tailed probability level < 0.05 was accepted as statistically significant.


Two hundred and forty-three patients were stratified into quartiles by their level of lactate clearance after 6 hours. There was a statistically significant inverse relationship between patients' lactate clearance and the mean levels of each biomarker (TNF-α, IL-1 receptor antagonist and caspase-3) over the first 72 hours of hospitalization (P < 0.035). There was also a statistically significantly higher hospital 28-day and 60-day mortality for each quartile of decreasing lactate clearance (P < 0.010).


Early resolution of global tissue hypoxia or greater lactate clearance is associated with a corresponding decrease in inflammatory mediators and mortality. The exact mechanism by which early hemodynamic optimization modulates inflammation requires further study.


  1. Rivers E, Nguyen B, Havstad S, et al.: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345: 1368-1377. 10.1056/NEJMoa010307

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  2. Nguyen HB, Rivers EP, Knoblich , et al.: Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004, 32: 1637-1642. 10.1097/01.CCM.0000132904.35713.A7

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Otero, R., Rivers, E., Nguyen, H. et al. The association of early lactate clearance with inflammatory biomarkers in severe sepsis and septic shock. Crit Care 10 (Suppl 1), P83 (2006).

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