From the Guidelines
Paracetamol (acetaminophen) overdose requires prompt medical attention and treatment with N-acetylcysteine (NAC), which should be administered as soon as possible, ideally within 8 hours of ingestion, to reduce the risk of liver failure and other complications. The management of acetaminophen overdose involves a step-by-step approach, starting with risk assessment based on the amount ingested, time since ingestion, and serum paracetamol levels plotted on a treatment nomogram 1.
Risk Assessment and Treatment
For patients requiring treatment, NAC is administered in a three-step protocol:
- An initial loading dose of 150 mg/kg over 60 minutes,
- Followed by 50 mg/kg over 4 hours, and
- Then 100 mg/kg over 16 hours. In total, this 21-hour regimen provides 300 mg/kg of NAC 1.
Supportive Care
Supportive care includes monitoring liver function tests, coagulation parameters, and kidney function. Activated charcoal can be given if the patient presents within 1 hour of ingestion to reduce absorption 1.
Mechanism of Action
NAC works by replenishing glutathione stores, which are depleted during paracetamol metabolism. Glutathione is essential for detoxifying N-acetyl-p-benzoquinone imine (NAPQI), the toxic metabolite of paracetamol that causes hepatocellular damage. Without adequate glutathione, NAPQI binds to liver cells, causing necrosis. Early treatment significantly reduces the risk of liver failure, which is the most serious complication of paracetamol overdose 1.
Key Considerations
- The Rumack-Matthew nomogram is used to determine the risk of hepatotoxicity based on serum acetaminophen concentrations and the time of ingestion 1.
- Patients with repeated supratherapeutic ingestions or extended-release preparations may require individualized treatment plans due to the lack of systematic data on risk stratification for hepatotoxicity in these situations 1.
- NAC may still be beneficial when started more than 8 hours after ingestion, and its use should be considered in all cases of suspected acetaminophen overdose, even if the time of ingestion is unknown or the patient presents with hepatotoxicity 1.
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 stomach should be emptied promptly by lavage or by inducing emesis with syrup of ipecac. Draw blood for predetoxification acetaminophen plasma assay and baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes. Administer the loading dose of acetylcysteine, 140 mg per kg of body weight. Determine subsequent action based on predetoxification plasma acetaminophen information.
The management and treatment of acetaminophen overdose involves:
- 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
- Blood tests for predetoxification acetaminophen plasma assay and baseline liver function tests
- Loading dose of acetylcysteine, 140 mg per kg of body weight
- Subsequent treatment based on predetoxification plasma acetaminophen information, which may include additional doses of acetylcysteine 2 Additionally, supportive treatment may include:
- Maintaining fluid and electrolyte balance
- Treating hypoglycemia
- Administering vitamin K1 or fresh frozen plasma if necessary 2
From the Research
Management of Acetaminophen Overdose
The management of acetaminophen (paracetamol) overdose involves several key steps, including:
- Assessment of the patient's risk of hepatotoxicity using a nomogram 3, 4
- Administration of activated charcoal to reduce absorption 4, 5
- Treatment with intravenous acetylcysteine (NAC) for patients at risk of hepatotoxicity 3, 4, 6, 7
Treatment Regimens
Different treatment regimens for acetaminophen overdose have been studied, including:
- A 3-phase NAC infusion regimen 3
- A 2-bag acetylcysteine infusion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h) 4
- A simplified 2-infusion protocol 7
- Oral and intravenous NAC regimens 6
Special Considerations
Certain patient populations require special consideration, including:
- Pregnant women, who should be treated with either oral or intravenous NAC according to regular protocols 6
- Children, who may require testing of liver enzyme levels if they have received more than 75 mg/kg/day of paracetamol for more than 24 hours 6
- Patients with modified release paracetamol overdoses, large or massive overdoses, or repeated supratherapeutic ingestions, who may require different management strategies 4
Controversies and Uncertainties
There are still some controversies and uncertainties in the management of acetaminophen overdose, including: