Clinical Trial: Early Lactate-Directed Therapy in the Intensive Care Unit (ICU)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Early Lactate-Directed Therapy on the ICU: A Randomized Controlled Trial

Brief Summary: Blood lactate levels have long been related to tissue hypoxia, a severe condition in critically ill patients associated with the development of organ system failure and subsequent death. Increased blood lactate levels and failure to normalize blood lactate levels during treatment have been associated with increased morbidity and mortality. However, evidence of improved clinical outcome of lactate-directed therapy is limited and difference in the use of blood lactate monitoring in the intensive care unit exists between hospitals. This warrants a study on the efficacy of early blood lactate-directed therapy. In this study the efficacy of 8 hours of early lactate-directed therapy (therapy aimed at resolving tissue hypoxia that is guided by serial blood lactate levels) will be compared with 8 hours of control group therapy (without lactate measurement).

Detailed Summary:

Tissue hypoxia can be defined as a state in which tissue oxygen demand is not met by tissue oxygen delivery (DO2). The presence and persistence of tissue hypoxia is related to the development of organ system failure and subsequent death. However, definite clinical indicators of tissue hypoxia are lacking. In experimental conditions, a mismatch between oxygen delivery and oxygen demand, resulting from either a progressive decrease of any of the components of oxygen delivery (hemoglobin level, arterial oxygen saturation and cardiac output) or an increase in oxygen demand, leads to increases in blood lactate levels. However, as lactate is a normal end product of metabolism, other processes not related to tissue hypoxia have also been linked to increases in blood lactate levels. In clinical conditions increased blood lactate levels and a failure to normalize blood lactate levels during treatment have been associated with increased morbidity and mortality. Even in hemodynamically stable patients with hyperlactatemia, a condition referred to as compensated shock or occult hypoperfusion, lactate levels are related to morbidity and mortality. In our retrospective pilot study, performed in the general ICU of the Erasmus MC (n= 931), we found 40% mortality in patients with blood lactate levels of 3 mmol/l or higher in the early hours of ICU admission. Blow at al. implemented a treatment protocol to increase oxygen delivery, guided by blood lactate levels, in hemodynamically stable trauma patients with occult hypoperfusion. Failure to correct hyperlactatemia after lactate-directed therapy correlated with increased mortality. Rossi et al. studied lactate-directed therapy in children undergoing congenital heart surgery. However, while showing a reduction in morbidity and mortality, they used a historical control group. Only one randomized controlled trial has been performed evaluating lactate-directed therapy. This study of Polonen e
Sponsor: Erasmus Medical Center

Current Primary Outcome: In-hospital mortality

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • ICU mortality
  • Day-28 mortality
  • APACHE II,SOFA and hemodynamic variables
  • Use of health care resources
  • Pre-specified subgroup analyses within non-sepsis stratum:
  • Neuro critical care (traumatic brain injury, neurovascular conditions, neuro-oncological conditions)
  • Cardiac arrest
  • Remaining group (without neuro critical care and cardiac arrest)
  • Pre-specified subgroup analyses within sepsis stratum:
  • Sepsis and severe sepsis
  • Septic shock


Original Secondary Outcome:

  • ICU mortality
  • Day-28 mortality
  • APACHE II,SOFA and hemodynamic variables
  • Use of health care resources


Information By: Erasmus Medical Center

Dates:
Date Received: December 23, 2005
Date Started: February 2006
Date Completion:
Last Updated: April 24, 2008
Last Verified: April 2008