0
0
A National Institutes of Health (NIH)-supported clinical trial has revealed that intravenous acetaminophen can reduce the risk of organ injury and the development of acute respiratory distress syndrome (ARDS) in sepsis patients. The findings were published in the Journal of the American Medical Association (JAMA).
Sepsis is a life-threatening condition caused by the body’s extreme and uncontrolled response to an infection. This response can lead to organ failure and death. The recent trial, however, did not show an overall improvement in mortality rates among all sepsis patients, regardless of severity. Researchers discovered that acetaminophen provided the most significant benefit to patients at the highest risk for organ damage. Those patients required less assisted ventilation and experienced a slight, though not statistically significant, decrease in mortality.
The study, titled “Phase 2b Randomized Trial of Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Sepsis Patients,” was led by Dr. Lorraine Ware, professor of medicine, pulmonary, and critical care at Vanderbilt University, and Dr. Michael Matthay, professor of medicine and anesthesia at the University of California, San Francisco.
During sepsis, red blood cells are damaged and die at high rates, releasing “cell-free hemoglobin” into the bloodstream. The body struggles to clear this excess hemoglobin, which can lead to organ damage. Previous research by Dr. Ware suggested that acetaminophen not only relieves pain and reduces fevers but also blocks the harmful effects of cell-free hemoglobin on the lungs, which are particularly vulnerable during sepsis.
The trial, conducted between October 2021 and April 2023, involved 447 adults with sepsis and respiratory or circulatory organ dysfunction across 40 U.S. academic hospitals. Participants were randomized to receive either intravenous acetaminophen or a placebo every six hours for five days. They were monitored for 28 days to assess their outcomes, with a specific focus on those with high levels of cell-free hemoglobin.
Results showed that intravenous acetaminophen was safe, with no significant differences in adverse events compared to the placebo group. Notably, the acetaminophen group experienced significantly lower rates of organ injury and ARDS within seven days of hospital admission.
For patients with higher cell-free hemoglobin levels, only 8% of those in the acetaminophen group required assisted ventilation, compared to 23% in the placebo group. Additionally, 12% of patients in the acetaminophen group had died after 28 days, compared to 21% in the placebo group, although this difference was not statistically significant.
“While the anticipated effects of acetaminophen therapy were not realized for all sepsis patients, this study shows that it still holds promise for the most critically ill,” said Dr. James Kiley, director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, part of NIH. “More research is needed to uncover the mechanisms and validate these results.”
Dr. Ware and Dr. Matthay plan to conduct a larger clinical trial focusing on patients with higher cell-free hemoglobin levels to further explore the potential benefits of acetaminophen in sepsis treatment.
For more information, refer to the study: “Phase 2b Randomized Trial of Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Sepsis Patients,” JAMA (2024).
