Acetaminophen Shown Beneficial in Patients with Sepsis

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An NIH-supported clinical trial found that intravenous acetaminophen reduced sepsis patients’ risk of having organ injury or developing acute respiratory distress syndrome, a serious condition that allows fluid to leak into the lungs. Sepsis is the body’s uncontrolled and extreme response to an infection.

While the trial did not improve mortality rates in all patients with sepsis regardless of severity, researchers found that acetaminophen gave the greatest benefit to the patients most at risk for organ damage. With the therapy, those patients needed less assisted ventilation and experienced a slight, though statistically insignificant, decrease in mortality. The study was published in JAMA.

In sepsis, red blood cells become injured and die at abnormally high rates, releasing “cell-free hemoglobin” into the blood. The body becomes overwhelmed and can’t remove this excess hemoglobin; this can lead to organ damage. Previous work from Dr. Lorraine Ware at Vanderbilt University, first author of the current study, showed that acetaminophen, in addition to relieving pain and reducing fevers, can block the harmful effects of cell-free hemoglobin on the lungs, which are at major risk of injury during sepsis.

To test the therapeutic potential of acetaminophen more fully in a mid-stage clinical trial, researchers enrolled 447 adults with sepsis and respiratory or circulatory organ dysfunction at 40 U.S. academic hospitals from October 2021 to April 2023. Patients were randomized to receive either acetaminophen or a placebo intravenously every six hours for five days. The researchers then followed the patients for 28 days to see how they fared.

Researchers found that intravenous acetaminophen was safe for all the sepsis patients, with no difference in liver injury, low blood pressure or other adverse events compared to the placebo group. Among secondary outcomes, they also found that organ injury was significantly lower in the acetaminophen group, as was the rate of acute respiratory distress syndrome onset within seven days of hospital admission.

More research is needed to uncover the mechanisms and validate these results.