OCTOBER 3, 2023
Originally published by our sister publication Specialty Pharmacy Continuum
By Myles Starr
Although more than 80,000 cases involving acetaminophen were reported to U.S. poison centers in 2021, there is no national standard for managing poisoning with the drug. A consensus statement published in JAMA Network Open creates a framework for treating acetaminophen poisoning that responds to current trends in how the drug is prescribed and taken over the counter (2023;6[8]:e2327739).
“The
Originally published by our sister publication Specialty Pharmacy Continuum
By Myles Starr
Although more than 80,000 cases involving acetaminophen were reported to U.S. poison centers in 2021, there is no national standard for managing poisoning with the drug. A consensus statement published in JAMA Network Open creates a framework for treating acetaminophen poisoning that responds to current trends in how the drug is prescribed and taken over the counter (2023;6[8]:e2327739).
“The guidelines were needed due to wide discrepancies in how the patients with acetaminophen poisoning are diagnosed and managed,” said study author Richard Dart, MD, PhD, the director of the Rocky Mountain Poison and Drug Center, in Denver. “We created a common ground for clinicians and also for researchers to use in future studies.”
After conducting a literature review, 21 experts developed the guidelines using a modified Delphi method. The touchstone of the group’s recommendations was a decision to revise the Rumack-Matthew nomogram (RMN), a tool that helps doctors interpret serum acetaminophen concentrations in relation to time since a patient’s ingestion. The modified RMN includes only lines that guide clinical action. Under the new guidelines, acetylcysteine is only administered to patients whose serum acetaminophen concentration is higher than the treatment line on the nomogram.
Additionally, the experts agreed that:
• Acute ingestion is “any ingestion period of less than 24 hours regardless of the ingestion pattern,” for which an acetylcysteine regimen that delivers at least 300 mg/kg orally or intravenously during the first 20 to 24 hours of treatment is recommended.
• A high-risk ingestion is an “ingestion of at least 30 g of acetaminophen or an acetaminophen concentration above the high-risk line on the nomogram.” Such cases may require administration of activated charcoal longer than four hours post ingestion, additional laboratory testing, and an increased dosage of acetylcysteine after consultation with a toxicology specialist.
• Supratherapeutic ingestion is defined as “multiple ingestions for a period greater than 24 hours.” In the case of acetaminophen concentrations greater than 20 mcg/mL or abnormal aspartate aminotransferase or alanine aminotransferase levels, “acetylcysteine should be administered until stopping criteria are met.”
• In patients who ingested acetaminophen along with anticholinergic or opioid agonist medications, further diagnostics are potentially indicated. In these patients, when acetaminophen concentration is greater than 10 mcg/mL but below the treatment line on the RMN (measured four to 24 hours after ingestion) in conjunction with the presence of anticholinergic or opioid clinical effects, another measurement should be taken four to six hours after the first measurement. Clinicians should follow dosing and duration for acetylcysteine treatments based on that reading.
• Calculation of acetylcysteine dose should be capped at 220 lb of body weight.
• In children under 6 years of age, a toxicologist should be consulted if a child receives an intravenous dose of acetaminophen of 90 mg/kg body weight or a cumulative dose of greater than 150 mg/kg body weight during 24 hours.
• In patients with an acetaminophen concentration of 900 mcg/mL or greater with acidosis or altered consciousness due to acetaminophen, hemodialysis and acetylcysteine are recommended.
• Liver transplant should be considered in cases with progressive increases in aspartate aminotransferase or alanine aminotransferase and coagulation abnormalities. Transplant should also be considered for patients with encephalopathy or multisystem failure after acetylcysteine treatment.
The main limitation of these guidelines is that insufficient information was available in the literature to address the question of what the best acetylcysteine administration regimen is, Dr. Dart said. “This is why the consensus panel chose to specify a dose, and not the specific regimen by which the acetylcysteine is administered,” he explained.
Dr. Dart reported no relevant financial disclosures.
