The Multi-Center Endotoxin Detection in Critical illness (MEDIC) trial was a multi-center, prospective observational study, performed in 10 Intensive Care Units (ICUs) of academic hospital settings in North America and Europe. The presence of endotoxemia was evaluated on the first day of the patients ICU stay to determine the odds of developing severe sepsis within 24 hours of ICU admission.  The target population for the Risk Assessment Study included all eligible patients (N=857) enrolled in the MEDIC trial on first day of ICU admission who had evaluable samples. 

We have found that endotoxemia is common in a highly heterogeneous population of critically ill patients on the day of their admission to an intensive care unit:  almost half of all patients have circulating endotoxin levels more than 2 standard deviations above those detected in healthy control subjects.  Yet only 4% of the study cohort had gram-negative infections based on the criteria of the Centers for Disease Control.  While this discrepancy may reflect the intrinsic challenge of documenting infection in a critically ill patient its sheer magnitude suggests that exposure to endotoxin can also derive from other sources.

Patients who had intermediate or high levels of endotoxin on the day of ICU admission were clearly a sicker population, as reflected in higher admission APACHE II scores, and a greater prevalence of severe sepsis. Moreover patients with the highest levels of circulating endotoxin had a significantly increased risk of dying while in the ICU.  Thus the presence of endotoxemia identifies a high risk subpopulation of critically ill patients.

Rule –out of Gram Negative Infection

The EAA™ is an endotoxin activity with a numeric cut-off to rule-out Gram negative infection set at 0.40. In the MEDIC trial, invasive Gram negative infection was identified by culture in 36 of 465 (8%) of evaluable patients. Results less than 0.40 (0.00-0.39) support the absence of Gram negative infection for ICU patients with suspicion of infection.

Whole blood chemiluminescence offers the following advantages: it is simple, sensitive and allows neutrophil function to be studied in the ambient blood milieu. The EAA™ produces less artifacts and more accurately represents the results of in vivo mediator interactions.  By providing the caregiver with reliable, time critical information, the EAA™ assists physicians in stratifying patients at high risk for severe sepsis who may benefit from early goal-directed therapy.