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Sepsis

Star Research Presentations: Sepsis

Combination of Endotoxin Activity and SOFA Defines Severity in Septic Shock

Sunday, February 23, 2025
9:45am – 10:45am Eastern Time
Location: Connections Central Theater 1

  • Mark A. Tidswell, MD

    Baystate Medical Center

    Disclosure(s): AstraZeneca: Clinical Trial Investigator (Terminated), Scientific Advisory Board (Terminated); Direct Biologics: Scientific Advisory Board (Ongoing); Dompe Pharmaceuticals: Clinical Trial Investigator (Ongoing), Consulting fees or other remuneration (Ongoing); Frontier Biotechnologies: Advisory Board (Terminated); Novartis: Clinical Trial Investigator (Ongoing); Shionogi: Advisory Board (Terminated); Spectral Medical: Clinical Trial Investigator (Ongoing), Scientific Advisory Board (Ongoing)

  • AA

    Ali Al-Khafaji, MD

    Professor of Critical Care Medicine and Surgery; Director, Transplant Intensive Care Unit
    University of Pittsburgh School of Medicine

    Disclosure information not submitted.

  • Danielle Davison, MD

    Associate Professor, Director of Intensive Care
    George Washington University Medical Center

    Disclosure information not submitted.

  • CG

    Claude Galphin, MD

    Director of Clinical Research
    Southeastern Renal Reseach Institute

    Disclosure information not submitted.

  • LM

    Luca Molinari, MD

    Physician
    Università del Piemonte Orientale, Department of Translational Medicine, Novara Italy

    Disclosure information not submitted.

  • JK

    John A. Kellum, MD

    Chief Medical Officer, Spectral Medical Inc.; and Professor of Medicine
    The Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh School of Medicine

    Disclosure information not submitted.

Disclosure(s):
Mark A. Tidswell, MD: AstraZeneca: Clinical Trial Investigator (Terminated), Scientific Advisory Board (Terminated); Direct Biologics: Scientific Advisory Board (Ongoing); Dompe Pharmaceuticals: Clinical Trial Investigator (Ongoing), Consulting fees or other remuneration (Ongoing); Frontier Biotechnologies: Advisory Board (Terminated); Novartis: Clinical Trial Investigator (Ongoing); Shionogi: Advisory Board (Terminated); Spectral Medical: Clinical Trial Investigator (Ongoing), Scientific Advisory Board (Ongoing)
Introduction: High endotoxin activity may represent an endotype of septic shock. However, risk of death from sepsis is also related to organ failure and an ongoing randomized trial testing endotoxin removal with polymyxin B hemoadsorption uses both endotoxin activity and organ failure scores as enrollment criteria. We sought to test the hypothesis that the combination of endotoxin activity and sequential organ failure assessment (SOFA) scores using pre-defined cutoffs, would identify patients at highest risk of death from sepsis.


Methods: We conducted a prospective observational study in four centers in the US and enrolled patients with septic shock after obtaining informed consent. On the day of enrollment, we measured endotoxin activity using the Endotoxin Activity Assay (EAA) according to the manufacturer’s specifications and collected clinical information necessary to calculate SOFA. Based on prior literature we set an EAA cutoff of ≥ 0.6 and SOFA >11 to define the high severity phenotype. We followed patients until day 28 for survival. We compared across four groups based on EAA and SOFA using a chi-squared/Fischer’s exact test and calculated relative risk for mortality at day 28 considering significance as p < 0.05.


Results: We enrolled 90 patients. After excluding 2 (2.2%) who were lost to follow-up and 4 (4.4%) with non-reactive EAA our primary analysis included 84 patients. EAA ≥ 0.6 and SOFA >11 was present in 20 (23.8%) patients and these patients had a 60% mortality. EAA ≥ 0.6 and SOFA ≤ 11 occurred in 29 (34.5%), mortality 13.8%. Patient with low EAA ( < 0.6) mainly had low SOFA (≤ 11), 29 (34.5%) patients and low mortality (17.2%). Only 6 patients (7.1%) had low EAA and high SOFA and none died. Compared to other patients with septic shock, those with endotoxic septic shock (EAA ≥ 0.6 and SOFA >11) had significantly higher mortality (60% vs 14.1%, p < 0.001); Relative risk: 4.27 (95% CI 2.11-8.62) p < 0.001).


Conclusions: Endotoxic septic shock, defined by the combination of endotoxin activity ≥ 0.6 and SOFA >11 identifies patients with the highest risk of death from sepsis. Such patients are most appropriate for trials testing anti-endotoxin therapy for improving survival.