What is the appropriate initial therapy for acetaminophen (paracetamol) overdose?

From the Guidelines

N-acetylcysteine (NAC) is the appropriate initial therapy for acetaminophen overdose, and it should be started as soon as possible, ideally within 8 hours of ingestion. The standard regimen involves a 21-hour intravenous protocol: an initial loading dose of 150 mg/kg over 1 hour, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1. Alternatively, an oral regimen can be used: 140 mg/kg initially, followed by 70 mg/kg every 4 hours for 17 doses. Treatment decisions should be guided by the patient's serum acetaminophen level plotted on the Rumack-Matthew nomogram, along with the time since ingestion. NAC works by replenishing glutathione stores, which are depleted during acetaminophen metabolism. Glutathione is essential for detoxifying N-acetyl-p-benzoquinone imine (NAPQI), the toxic metabolite of acetaminophen that causes liver damage.

Some key points to consider when treating acetaminophen overdose include:

• The importance of early treatment, as delays can lead to increased morbidity and mortality 1
• The use of the Rumack-Matthew nomogram to guide treatment decisions, although it should not be used to exclude possible toxicity due to multiple doses over time, or altered metabolism in the alcoholic or fasting patient 1
• The potential benefits of NAC in reducing the incidence of severe hepatotoxicity and mortality, even when started later than 8 hours after ingestion 1
• The need for supportive care, including intravenous fluids, antiemetics for nausea, and close monitoring of liver function tests

It is also worth noting that NAC has been shown to be effective and safe for the treatment of acetaminophen overdose, with few side effects, such as nausea, vomiting, and rare urticaria or bronchospasm 1. Overall, the evidence supports the use of NAC as the initial therapy for acetaminophen overdose, and it should be started as soon as possible to minimize the risk of liver damage and improve patient outcomes.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION General Regardless of the quantity of acetaminophen reported to have been ingested, administer acetylcysteine solution immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen. The following procedures are recommended:

1. The stomach should be emptied promptly by lavage or by inducing emesis with syrup of ipecac.
2. Administer the loading dose of acetylcysteine, 140 mg per kg of body weight.

The appropriate initial therapy for acetaminophen overdose is:

• Immediate administration of acetylcysteine solution if 24 hours or less have elapsed from the reported time of ingestion
• Stomach emptying by lavage or inducing emesis with syrup of ipecac
• Loading dose of acetylcysteine, 140 mg per kg of body weight 2

From the Research

Initial Therapy for Acetaminophen Overdose

The appropriate initial therapy for acetaminophen (paracetamol) overdose is a crucial aspect of treatment. According to the available evidence:

• N-acetylcysteine (NAC) is the treatment of choice for acetaminophen poisoning, with standard 72-h oral or 21-h intravenous protocols being most frequently used 3, 4, 5, 6.
• Prompt treatment with acetylcysteine, regardless of dose, can prevent hepatotoxicity in high-risk paracetamol ingestion 3.
• The use of activated charcoal may also be beneficial in reducing paracetamol absorption, although its clinical benefit is unclear 5, 6.

Treatment Protocols

Different treatment protocols have been evaluated, including:

• Standard-dose acetylcysteine (300 mg/kg over 21 h in divided doses) 3.
• High-dose acetylcysteine, which has shown mixed results in prior studies 3.
• Oral NAC protocol, which may preserve more hepatocytes than the 21-h intravenous protocol 4.
• A 3-day modified regimen of intravenous N-acetylcysteine, which has been reported to be safe and efficacious in severe paracetamol poisoning 7.

Key Considerations

When treating acetaminophen overdose, it is essential to consider the following:

• Prompt treatment is critical in preventing hepatotoxicity 3, 4.
• The selection criteria for N-acetylcysteine treatment are not clear, and no single regime has been shown to be more effective than others 5, 6.
• Liver transplantation may be life-saving in patients with fulminant hepatic failure, but further refinement of selection criteria and evaluation of long-term outcomes are required 5, 6.