Acetaminophen Fails to Prevent Organ Dysfunction Among Sepsis Patients: Study

Although sepsis patients are often prescribed acetaminophen, which is the active ingredient in Tylenol and a number of other pain medications, the results of a new study suggest that the drug fails to help improve respiratory, circulatory or kidney dysfunction among those critically ill patients.

Sepsis is a life-threatening infection that requires urgent medical care to prevent tissue damage, organ failure, and death. Symptoms can include decreased blood pressure, fever, increased heart rate, confusion, shortness of breath, and weakness. Sepsis is responsible for one in five deaths worldwide.

Organ dysfunction is a condition where one or more organs fail to perform their normal functions. This can occur due to a variety of reasons, including sepsis, disease, injury, or chronic health conditions. Organ dysfunction can range from mild impairment to complete failure and can affect any organ in the body, such as the heart, lungs, kidneys, liver, or brain.

Due to acetaminophen’s ability to successfully reduce pain, fever, and inflammation, as well as prevent hemoglobin-induced oxidation, it has been widely thought to be beneficial in treating sepsis, as well as organ dysfunction, by preventing the damaging effects of cell-free hemoglobin. However, in findings published this week in the medical journal JAMA Network Open, researchers warns that acetaminophen does not appear to improve survival rates or prevent organ dysfunction for critically ill patients with sepsis.

Acetaminophen Ineffective in Preventing Organ Dysfunction

Researchers from Vanderbilt University Medical Center conducted a  randomized, double-blind clinical trial from October 2021 to April 2023, involving 40 academic hospitals in the U.S.; specifically in emergency departments or intensive care units (ICU). The trial evaluated the efficacy of treatment in a larger group of patients, while still focusing on safety and dosage.

The study enrolled 447 adults with a mean age of 64 years, who presented with sepsis and had either respiratory or circulatory organ dysfunction. These patients were enrolled within 36 hours of their presentation to the hospital. Patients were randomly assigned to receive either 1 gram of acetaminophen intravenously, with 227 receiving acetaminophen intravenously every 6 hours, while 220 received a placebo. This treatment regimen lasted for five days.

The data indicates that acetaminophen was safe to use, as there were no significant differences observed in liver enzyme levels, incidence of hypotension, or fluid balance compared to placebo. However, the study did not show a meaningful difference in the number of days patients remained alive and free of organ support after 28 days of follow-up.

This suggests that while acetaminophen did not worsen outcomes, it also did not provide a significant clinical benefit in terms of reducing the need for organ support in critically ill patients with sepsis-related organ dysfunction, the researchers concluded.

Acetaminophen Liver Damage Concerns

The findings come after the U.S. Food and Drug Administration (FDA) issued an acetaminophen liver injury warning in February, cautioning against overuse of the pain killer. The advisory underscored the ease with which individuals can inadvertently exceed the recommended dosage, especially when treating conditions such as colds or flu, prompting the FDA to emphasize the importance of carefully reading drug labels for all products used.

The current maximum recommended adult daily dose of acetaminophen is 4,000 milligrams per day, according to the FDA.

Acetaminophen, including brand names like Tylenol, has been identified by experts as a leading cause of liver injury, contributing to approximately 50,000 emergency room visits annually in the U.S., with 25,000 resulting in hospitalizations and over 450 deaths.

The manufacturer of Tylenol faced approximately 500 lawsuits last year, alleging that acetaminophen use during pregnancy could heighten the risk of autism and attention deficit hyperactivity disorder (ADHD) in offspring.

However, a federal judge presiding over a multidistrict litigation recently excluded plaintiffs’ Tylenol expert witnesses, ruling that their scientific methodologies and studies lacked sufficient credibility to be presented to a jury. As a result, the plaintiffs currently lack evidence to establish causation, potentially leading to the dismissal of these cases unless overturned on appeal, effectively concluding the litigation.