Increased endotoxin activity is associated with clinical deterioration in moderate-severity emergency department sepsis patients: a pilot study

Abstract

Background: High levels of endotoxin activity are associated with increased mortality in ICU patients. Objectives: To assess endotoxin activity in emergency department (ED) patients with normotensive sepsis to determine the ability of the endotoxin activity assay (EAA) measurement and its change over 24 hours to predict progressive organ dysfunction. Methods: Design: Prospective observational study. Setting: A singlecenter prospective observational study in an urban, academic medical center. Participants: Adult ED patients with suspected infection admitted to a medical floor and receiving IV antibiotics with either elevated lactate (2.0-3.9 mM) or transient hypotension (sBP <90 mmHg). EAA was measured at enrollment and again at 24 hours and results were divided based on benchmark cutoffs for “low” (1 point, mechanical ventilation or vasopressor utilization) within 72 hours of admission or in-hospital mortality. Results: We enrolled 57 patients over a 12-month period. The primary outcome was met in 63% of the cohort and 33% were transferred to the ICU from their initial medical floor admissions. Patients with the outcome of increased organ failure had no difference in initial lactate, age, MAP, or exposure to hypotension. Patients meeting primary outcome had a higher ICU transfer rate (42% vs 19%, p=0.15) and increased ICU (2 vs 0) and hospital lengths of stay (13 vs 8). Outcome patients had similar endotoxin levels at enrollment compared to those not meeting outcome (0.61 vs 0.51, p=0.075) with increased levels at 24 hours (0.73 vs. 0.47, p=0.005). An increased incidence of the primary outcome was seen with each category increase in EAA. An increasing endotoxin level over 24 hours had a 71% specificity and 72% PPV in predicting the primary outcome. Conclusion: Within this sepsis cohort, physiologic data in the ED were unable to differentiate those with progressive organ dysfunction over 72 hours, while endotoxin levels were higher at 24 hours. A high or increasing EAA as a predictor of progressive organ dysfunction can supplement clinical decision-making to aid clinicians in identifying highrisk patients from this homogeneous sepsis population.