New guidelines address management of acetaminophen poisoning

Key takeaways:

• New guidelines define acute ingestion as an ingestion period of less than 24 hours.
• They recommend an acetylcysteine regimen of at least 300 mg/kg during the first 20 to 24 hours.

A panel of experts chosen by four leading United States and Canadian clinical toxicology societies have developed clinical recommendations for the management of acetaminophen poisoning in ED settings.

According to Richard C. Dart, MD, PhD, a professor of emergency medicine-medical toxicology and pharmacology at the University of Colorado School of Medicine, and colleagues, acetaminophen poisoning can occur either as self-harm or during repeated consumption of doses for pain or fever.

More than 80,000 cases involving an acetaminophen product were reported to U.S. poison control centers in 2021, the authors wrote in a consensus statement published in JAMA Network Open. However, no formal clinical guidelines were previously published on the management of acetaminophen poisoning in the U.S. and Canada.

“The need for more standardized care of acetaminophen poisoning is pressing,” they wrote. “The past 25 years have witnessed numerous changes in acetaminophen poisoning, such as the introduction of products that contain greater amounts of acetaminophen, extended-release preparations, and new combination drugs of acetaminophen with opioids or other ingredients.”

So, America’s Poison Centers, the American Academy of Clinical Toxicology, the American College of Medical Toxicology and the Canadian Association of Poison Control Centers commissioned Dart and other panel members to conduct a review of 84 guidelines and 278 publications and develop recommendations for ED management of single or repeated acetaminophen consumption.

A key difference from the current U.S. practice was defining an acute ingestion as an ingestion period from 4 to 24 hours, according to the guideline authors. In contrast, they defined repeated supratherapeutic ingestion as an ingestion occurring in a period of more than 24 hours.

Meanwhile, a high-risk ingestion was labeled as ingestion of more than 30 g of acetaminophen, or an acetaminophen concentration above the high-risk line on the nomogram.

For the administration of acetylcysteine, the panel recommended an oral or IV regimen of at least 300 mg/kg delivered during the first 20 to 24 hours of treatment. They also determined that acetylcysteine administration should continue until the stopping criteria is met, as opposed to the “common clinical error” of administrating treatment for 20 to 21 hours and then stopping without reassessment.

The guidelines additionally recommend that supratherapeutic ingestion management be based on the patients’ presentation.

“If the acetaminophen concentration is greater than 20 g/mL, or the aspartate aminotransferase or alanine aminotransferase level is abnormal, acetylcysteine should be administered until stopping criteria are met,” Dart and colleagues wrote.

Several special issues were also addressed, with the panel determining that:

• management of poison in patients weighing more than 100 kg is the same as that for any acetaminophen product, with the calculation of acetylcysteine dose being capped at 100 kg of body weight;
• management of poison in patients aged younger than 6 years is the same as that for older patients, but clinicians should contact their poison center or clinical toxicologist if the child receives a single IV acetaminophen dose of 90 mg/kg body weight or a cumulative dose of more than 150 mg/kg body weight during 24 hours; and
• assessment and management of poison is the same for a pregnant patient, and although some clinicians prefer IV delivery, there are no data suggesting oral delivery is less effective during pregnancy.

The authors noted that an inaccurate estimation of ingestion time “can lead to the erroneous conclusion that acetylcysteine is not needed or can be discontinued prematurely.”

“This mistake is potentially fatal; thus, it is recommended that if there is any doubt about the history, the patient receive acetylcysteine,” they wrote.

Additionally, although there are 15 acetylcysteine regimens recommended by the literature, there were not enough data comparing the effectiveness of these regimens, resulting in the decision to recommend a minimum adequate dose of acetylcysteine.

Dart and colleagues concluded that future research “should focus on refining critical elements of history-taking in poisoned patients, comparative effectiveness and safety research on various acetylcysteine regimens, and refining the clinical roles of fomepizole and hemodialysis in acetaminophen poisoning.”