Acetaminophen and Clinical Outcomes in Sepsis: A Retrospective Propensity Score Analysis of the Ibuprofen in Sepsis Study.

Summary

A retrospective propensity-matched analysis of 276 matched patients from the ISS trial found that early acetaminophen exposure was associated with lower 30-day mortality (HR 0.58; 95% CI 0.40–0.84) and more ventilator-free days in adults with sepsis.

Key Findings

• Retrospective propensity-matched analysis included 276 matched patients from the ISS trial.
• Acetaminophen exposure in the first 2 study days was associated with lower 30-day mortality (HR 0.58; 95% CI 0.40–0.84).
• Acetaminophen use was associated with more days alive and free of mechanical ventilation.

Clinical Implications

While not practice-changing yet, these data support prioritizing randomized trials of acetaminophen in sepsis and may encourage thoughtful use when fever control is indicated.

Limitations

• Observational, retrospective design with potential residual confounding
• Dose, timing, and indication for acetaminophen not randomized or standardized

Future Directions

Conduct adequately powered RCTs testing acetaminophen vs. standard care in sepsis, and explore mechanistic biomarkers of hemoprotein reduction.