Importance of Endotoxin Clearance in Endotoxemic Septic Shock: An Analysis From the Evaluating Use of PolymyxinB Hemoperfusion in a Randomized Controlled Trial of Adults Treated for Endotoxemic Septic Shock (EUPHRATES) Trial.

UNLABELLED

To investigate the relationship between survival and treatment-related reduction in endotoxin activity for patients in the Evaluating Use of PolymyxinB Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic shock trial with baseline endotoxin activity assay greater than or equal to 0.60 to less than 0.90 units.

DESIGN

Post hoc analysis of a multicenter randomized controlled clinical trial.

SETTING

Fifty-five tertiary hospitals in North America.

PATIENTS

Patients with septic shock and endotoxin activity assay level greater than or equal to 0.60 to less than 0.90 and multiple organ dysfunction syndrome greater than 9.

INTERVENTIONS

Two polymyxin B hemoperfusion treatments or Sham.

MEASUREMENTS AND MAIN RESULTS

One-hundred ninety-four patients were included (88 polymyxin B and 106 Sham). We evaluated the impact of changes in endotoxin activity assay based on comparison to the median reduction from baseline to day 3 and a second method where a target post-treatment endotoxin activity assay level (day 3) was established. The population median reduction in endotoxin activity assay level was 10.4%. In patients with a greater than median reduction, there was trend toward lower mortality with polymyxin B (17.1% vs 33.3%; = 0.07) and a significant increase in mechanical ventilation-free days (20 vs 13.5; = 0.04). The pressure adjusted heart rate showed a significant improvement in the polymyxin B group ( = 0.02). For patients who achieved an endotoxin activity assay of less than 0.65 at day 3, the polymyxin B treated group had a trend toward a mortality reduction compared to Sham (16% vs 33%; = 0.06) and a significant increase in ventilation-free day (20 vs 16; = 0.05). Kaplan-Meier analysis showed a 17% reduction in mortality with polymyxin B ( = 0.04).

CONCLUSIONS

These findings suggest that reducing endotoxin activity assay levels with polymyxin B as measured by comparison to a median reduction or when a treatment target is established, may result in improvements in mortality and organ function outcomes. This article is the first to report endotoxin activity assay measurements in response to polymyxin B use versus Sham in patients with septic shock and elevated endotoxin activity assay. These findings are considered to be hypothesis generating and will need to be prospectively validated.