Combining Intermediate Levels of the Endotoxin Activity Assay (EAA) with Other Biomarkers in the Assessment of Patients with Sepsis: Results of an Observational Study

Introduction: The Endotoxin Activity Assay (EAA) is a useful test to risk stratify patients with severe sepsis and assess for Gram negative infection. However, the significance of intermediate levels of EAA (0.4-0.59) at the bedside has not been well elucidated. The purpose of this study was to interpret intermediate EAA levels in clinical practice.

Methods: This retrospective observational study included all adult patients with suspected sepsis admitted to our medico-surgical intensive care unit (ICU) in whom EAA was measured from July 2008 to September 2011. Data collected included EAA, white blood cell (WBC) count and differential, C-reactive protein (CRP), procalcitonin (PCT) and bacterial cultures. Data were analyzed by comparative statistics.

Results: Two hundred and ten patients were studied. Ninety two (43%) patients had culture documented gram negative infection. Patients with Gram-negative organisms in cultures had significantly higher EAA levels (0.47, IQR 0.27) than those without any Gram-negative organisms in cultures (0.34, IQR 0.22) (p < 0.0001). For patients with intermediate EAA levels (0.40 to 0.59), PCT levels and presence of left shift of WBC significantly differed between patients with Gram negative organisms in their blood or other cultures and those who had no organisms in any of the cultures (4.9 versus 1.7 ng/mL, p < 0.05; 57.9 versus 18.9%, p < 0.0004, respectively).

Conclusions: We confirm that high levels of EAA in our cohort of patients with suspected sepsis are strongly associated with gram negative infection. In those patients with intermediate elevation in EAA levels, use of PCT and WBC differential can provide additional diagnostic value to clinicians at the bedside.