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

Introduction

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).

Methods

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.

Results

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).

Conclusion

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.