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Predicting Organ Dysfunction in Septic and Critically Ill Patients: A Prospective Cohort Study Using Rapid Ex Vivo
Abigail M Samuelsen1, E Scott Halstead2, Erik B Lehman3
1Penn State Department of Anesthesiology and Perioperative Medicine, Hershey, PA.
Critical Care Explorations
|June 25, 2024
Summary
Early immune response profiling in critically ill patients can predict organ dysfunction. This rapid assay helps identify patients at risk for severe outcomes, aiding timely intervention.
Area of Science:
- Immunology
- Critical Care Medicine
- Translational Research
Background:
- Cytokine response patterns are crucial for immune responses but are often dysregulated in sepsis and critical illness.
- Immunological deficits in critical illness may be quantifiable through ex vivo whole blood stimulation assays.
- These deficits may indicate subsequent organ dysfunction.
Purpose of the Study:
- To investigate the hypothesis that quantifiable immunological deficits, identified through ex vivo whole blood stimulation assays, predict subsequent organ dysfunction in critically ill patients.
- To explore the relationship between early cytokine production and organ dysfunction.
- To assess the utility of a rapid immune profiling technique for early prediction and management of organ dysfunction.
Main Methods:
- Prospective observational study involving adult septic and critically ill nonseptic patients.
- Quantification of cytokine responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin using a rapid ex vivo assay.
- Measurement of organ dysfunction using the Sequential Organ Failure Assessment score on day 3 (SOFAd3).
Main Results:
- Elevated tumor necrosis factor and interleukin-6 levels post-endotoxin challenge were inversely correlated with SOFAd3.
- Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients.
- Clustering analysis identified two distinct immune phenotypes based on differential responses to LPS and anti-CD3/anti-CD28 stimulation.
Conclusions:
- A rapid immune profiling technique shows promise for the early prediction and management of organ dysfunction in critically ill patients.
- This method can provide crucial information for early intervention strategies.
- The findings suggest potential for preventing irreversible organ damage during the acute phase of critical illness.

