The LACTATE trial: Early lactate-guided therapy in intensive care patients [Classics Series]

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1. Therapy aimed at reducing lactate levels by 20% every 2 hours during the first 8 hours of ICU admission led to decreased in-hospital mortality and shorter ICU stays.

2. Patients in the early lactate-guided therapy group received more fluids and started on vasopressors earlier than in the control group, but did not have a faster reduction rate of lactate levels.

Original Date of Publication: September 15, 2010

Study Rundown: Elevated blood lactate levels are a known prognostic factor for morbidity and mortality in the intensive care unit (ICU). This multi-center, open-label, randomized controlled trial compared standard early goal-directed therapy (EGDT) to EGDT combined with early lactate-guided therapy in patients admitted to the ICU with increased lactate levels. The goal of early lactate-guided therapy was to reduce the lactate level by at least 20% every 2 hours during the first 8 hours of admission in hopes of reducing end-organ damage and improving outcomes in the ICU. Lactate-guided therapy significantly reduced in-hospital mortality (HR 0.61; 95%CI 0.43-0.87) and led to shorter periods of time on mechanical ventilation and for ICU stay. There was no difference in the time to stopping vasopressors or in the initiation of renal replacement therapy.

In summary, this study demonstrates that frequent monitoring of lactate levels (every 2 hours), with the goal of reducing levels by 20% per 2 hours, during the initial 8 hours of admission to the ICU is beneficial to patients with regards to in-hospital mortality and shorter ICU stays. Of note, there was no difference in the rate of lactate reduction between the two groups, despite more aggressive fluid and vasopressor resuscitation in the lactate group. This suggests that trending lactate levels early on may be useful as an indicator of improvement, or lack thereof, in a patient undergoing aggressive resuscitation in the ICU.

Click to read the study in AJRCCM

In-Depth [randomized, controlled study]: Originally published in 2010, this trial was conducted at 4 mixed intensive care units across the Netherlands between 2006 and 2008. Eligible patients were all patients above the age of 18 who were admitted to the ICU with a lactate level at or above 3.0 mEq/L on admission. The study excluded patients with liver failure or post-liver surgery, recent epileptic seizures, a contraindication for a central venous catheterization, an evident aerobic cause of hyperlactatemia, or those with a do-not-resuscitate status. Patients were randomized into two groups: 1) the experimental group where therapy was aimed to decrease lactate levels by at least 20% every 2 hours, or 2) the control group with standard therapy, where the team only had the admission lactate level. Treatment period was first 8 hours of ICU admission. Patients were followed up until hospital discharge or death. Primary endpoint was in-hospital mortality, with significant reduction in in-hospital mortality in the lactate-guided therapy group after adjustment for age, sex, and initial assessment of organ failure by APACHE and SOFA scores (HR 0.61; 95%CI 0.43-0.87). There was also a decrease in ICU stay in the lactate-guided therapy group (HR 0.65; 95%CI 0.50-0.85) compared to the standard therapy group.

By Milana Bogorodskaya and Andrew Cheung, M.D.

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