According to the National Heart, Lung and Blood Institute, results from a recent clinical trial substantiate the use of acetaminophen administered intravenously in patients with sepsis to help reduce the risk of organ damage or the development of acute respiratory distress syndrome (ARDS). The researchers, whose study was published in JAMA, found this approach to be the greatest benefit to at-risk patients. Patients who received this treatment required less assisted ventilation and demonstrated a slightly lower, though statistically insignificant, rate of mortality.
Lorraine Ware, MD, first author of the study and professor of medicine, pulmonary and critical care at Vanderbilt University in Nashville, Tennessee, had previously discovered that, in addition to relieve pain and reducing fever, acetaminophen could block the harmful effects of cell-free hemoglobin on the lungs. Patients who have sepsis are at high risk of lung damage. Additional research suggests that acetaminophen is especially beneficial for patients with severe sepsis, who are further susceptible to ARDS and death.
Senior study author Michael Matthay, MD, professor of medicine and anesthesia at the University of California, San Francisco, is hopeful that these findings will eventually lead to the creation of a biomarker to identify high levels of cell-free hemoglobin. This breakthrough could help determine early on which sepsis patients might benefit from treatment with acetaminophen.
The NIH-supported trial enrolled 447 adults who had sepsis and respiratory or circulatory organ dysfunction at 40 U.S. academic hospitals between October 2021 and April 2023. Patients randomly received either acetaminophen or a placebo intravenously every six hours for five consecutive days. The research team continued to monitor the patients for 28 days post-treatment.
The scientists confirmed that intravenous acetaminophen therapy was safe for all sepsis patients, with no major adverse events compared to those patients who received the placebo. They also found that patients in the acetaminophen group showed a significantly lower rate of organ injury and a reduced risk of developing ARDS within seven days of hospitalization.
Within a subset of patients who had higher levels of cell-free hemoglobin, only 8% of patients who had acetaminophen required assisted ventilation compared to 23% of patients who had the placebo. At the end of the 28-day period, 21% of patients in the placebo group had died, compared to 12% in the acetaminophen group.
“While the anticipated effects of acetaminophen therapy were not realized for all sepsis patients, this study shows it still holds promise for the most critically ill,” said James Kiley, PhD, director of the Division of Lung Diseases at the National Heart, Lung and Blood Institute.
The research team said the results trend positive for this population of critically ill patients, and they plan to conduct a larger clinical trial, particularly evaluating the acetaminophen therapy in patients with higher levels of cell-free hemoglobin.
