Early Aggressive Therapy to Reduce Serum Lactate Levels Improves Outcomes in Critically Ill Patients

Abstract & Commentary

By David J. Pierson, MD, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle. Dr. Pierson reports no financial relationships relevant to this field of study.This article originally appeared in the January 2011 issue of Critical Care Alert. It was peer reviewed by William Thompson, MD. Dr. Thompson is Associate Professor of Medicine, University of Washington. Dr. Thompson reports no financial relationships relevant to this field of study.

Synopsis: In a multicenter study, critically ill patients with initial hyperlactatemia had improved outcomes (including shorter ICU stays and lower adjusted mortality) compared to control patients when they were managed for the first 8 hours with a resuscitation protocol targeted at reducing the lactate level by at least 20% every 2 hours.

Source: Jansen TC, 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;182:752-761.

Carried out in four icus in the netherlands, this study evaluated the effects of a serum lactate-guided resuscitation protocol during initial management of critically ill patients with elevated lactate levels, as compared to standard management not guided by serial lactate measurements. Adult patients with admission lactate levels of 3.0 mEq/L or greater were enrolled during a 2-year period. Patients with conditions that might either generate more lactate (such as grand mal seizures) or affect its clearance (such as severe liver disease) were excluded. Patients were randomized on admission to the ICU, and were managed either according to the protocol or without serum lactate guidance for the initial 8 hours; thereafter, their management was according to the judgment of their treating intensivists.

Patients in the control group had management targeted at a mean arterial pressure > 60 mm Hg, heart rate < 100/min, central venous pressure 8-12 mm Hg (12-15 mm Hg in ventilated patients), urine output at least 0.5 mL/kg/hr, hemoglobin at least 7 g/dL, and arterial oxygen saturation at least 92%. In this group, central venous oxygen saturation (ScvO2) monitoring was allowed at the discretion of the managing intensivist, but lactate levels were not made available during the 8-hour intervention period. In the intervention (lactate-guided) group, the above management goals were the same, with the addition of a targeted reduction in serum lactate of at least 20% every 2 hours until the level was 2.0 mEq/L or less, and the goal of achieving and maintaining a ScvO2 value of at least 70%. Arterial blood was preferentially used for lactate measurement, but the use of venous or capillary blood also was allowed; measurement was by means of a hand-held point-of-care device (Accutrend®, Roche Diagnostics; Mannheim, Germany), which was provided for the study by the manufacturer.

There were 177 patients in the control group and 171 patients in the lactate-targeted group. Their ages, demographics, admission diagnoses, APACHE II scores (mean ~23), and sequential organ failure assessment (SOFA) scores (mean ~9) were comparable. Most of the patients were admitted to the ICU within 6 hours of hospital admission, and median time from ICU admission to randomization was less than 1 hour. The lactate group received more fluids and vasodilators, although there were no differences between the groups with respect to the patients' lactate levels themselves. Hospital mortality in the control group was 43.5% as compared to 33.9% in the lactate group, a nonsignificant difference (P = 0.067). However, when adjusted for predefined risk factors, mortality was lower in the lactate group (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87; P = 0.006). SOFA scores were lower between 9 and 72 hours after starting the study in the lactate patients; they also had fewer hours of vasopressor therapy, shorter periods of mechanical ventilation, and shorter ICU stays. The authors conclude that lactate-guided initial fluid and hemodynamic management among critically ill patients with initial hyperlactatemia is beneficial.

Commentary

In this multicenter, open-label randomized controlled study, the use of a serum lactate-guided resuscitation protocol during the initial 8 hours in the ICU, aimed at reducing lactate levels by at least 20% every 2 hours until they were 2 mEq/L or less, reduced ICU length of stay and also — after adjustment for various factors — both ICU and hospital mortality. Although the mechanism is unclear, blood lactate levels correlate inversely with prognosis in critically ill patients, irrespective of the type of critical illness or the presence of either shock or organ failure. Attention has thus naturally focused on the possible effects on patient outcomes of measures to reduce serum lactate, particularly in the early hours of treatment for critical illness. Current evidence indicates that mortality relates to the primary disease process generating the increased serum lactate (primarily through tissue hypoxia) rather than the lactate molecule itself, and reducing lactate levels by infusing dichloroacetate does not reduce mortality.

Although the setting was somewhat different and only about 40% of the patients had severe sepsis or septic shock, this study supports the findings of the widely heralded, single-center, emergency department study of Rivers et al in patients with sepsis,1 which has been used as the basis for broad application of early goal-directed therapy in critically ill patients. The findings of Jansen et al will likely be used to support wider use of lactate monitoring in the ICU, in addition to the use of ScvO2 monitoring and the hemodynamic and other components of early goal-directed therapy for severe sepsis and septic shock.

If past critical care experience is any guide, these things also may begin to be used in clinical settings different from those in which the results were obtained. Based on its findings, the current study supports a lactate-guided strategy of fluid and hemodynamic management in critically ill patients starting immediately on presentation to the ICU and continuing for the next 8 hours. Whether additional benefit might accrue from the use of this strategy beyond 8 hours, or if it is initiated later in the course of the patient's illness, is unknown and must await the results of additional studies.

Reference

1. Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-1377.