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Acetaminophen in Sepsis Treatment: A Comprehensive Study Reveals New Insights

Sepsis, a life-threatening condition that surfaces from the body’s reaction to infection, stands as a formidable challenge in the field of critical care medicine. Recently, a Phase 2b randomized, double-blind clinical trial published in JAMA set out to evaluate the potential benefits of using acetaminophen – also known as paracetamol – in sepsis treatment. The use of acetaminophen has been investigated owing to its proficiency in inhibiting cell-free hemoglobin-induced oxidation of lipids and other substrates, which can help lower the risk of organ dysfunction, a common complication in sepsis patients.

The trial under discussion, termed ‘Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial,’ was conducted from October 2021 to April 2023, and it involved a follow-up period of 90 days post-trial. The participants of the study were adults suffering from sepsis with either respiratory or circulatory organ dysfunction, and they were selected from 40 academic hospitals across the United States.

The primary aim of this study was to ascertain if the intravenous administration of 1g of acetaminophen every 6 hours over a 5-day period could enhance the number of days the patients spent alive and free from organ support, compared to a placebo group. The study yielded some vital results. Notably, while intravenous acetaminophen proved safe, it failed to significantly boost the primary outcome in terms of days spent alive and free from organ support.

The trial, however, didn’t solely focus on this primary outcome. It further evaluated several secondary clinical outcomes, including the counts of ventilator-free days, vasopressor-free days, and mortality rates after 28 and 90 days. It also monitored safety outcomes, including potential hepatic injuries and adverse events.

Riding on the participation of 447 enrolled patients, the trial confirmed the safety of intravenous acetaminophen, although the primary outcome did not show considerable improvement. Worth mentioning are several promising trends spotted among secondary outcomes. Patients who received acetaminophen exhibited lower rates of developing acute respiratory distress syndrome (ARDS) and improvements in certain elements of the Sequential Organ Failure Assessment (SOFA) score, which monitors organ dysfunction or failure.

Meanwhile, the trial investigated the potential predictive value of baseline plasma cell-free hemoglobin levels – a biomarker linked to sepsis severity – in determining the effectiveness of acetaminophen treatment. A posthoc analysis suggested a potential treatment benefit in patients with higher baseline hemoglobin levels, despite no significant interaction being observed between these levels and treatment outcome.

The study, nevertheless, bore limitations, including its intermediate size for a Phase 2 study and limited power to examine heterogeneous treatment effects. Also, the duration for administering the study drug was shorter than initially planned due to apprehensions about its hemodynamic effects.

Despite these limitations, this study contributes to the ongoing discussion on sepsis treatment’s complexities, underscoring the need for further research to unearth therapeutic strategies that can enhance patient outcomes in this critical condition. Intravenous acetaminophen’s safety in treating critically ill sepsis patients and the promising trends observed in some secondary outcomes – even though it didn’t significantly enhance survival or lessen the need for organ support – highlight the worthiness of pursuing further related investigations. In particular, the potential predictive value of plasma cell-free hemoglobin levels in guiding acetaminophen therapy in sepsis deserves additional attention.

Source: https://www.infectioncontroltoday.com/view/acetaminophen-sepsis-recent-study-examines-efficacy-safety

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