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Acetaminophen overdose is defined as the ingestion of a dose of acetaminophen that exceeds the recommended limit, typically > 4 g within a 24-hour period or excessive doses over several days.
The pathophysiology of acetaminophen overdose involves its action as a dose-dependent hepatotoxin, causing acute pericentral liver injury. Acetaminophen is metabolized in the liver, and in overdose situations, its toxic metabolite can cause hepatocellular necrosis. In some cases, renal insufficiency can also occur, attributed to cytochrome P-450 mixed function oxidase isoenzymes present in the kidney.
In 2021, US poison control centers recorded over 80,000 cases related to acetaminophen products. The incidence of acetaminophen overdose in Iceland is estimated at 16 per 100,000 person-years.
Clinical manifestations of acetaminophen overdose can include symptoms such as nausea, vomiting, abdominal pain, and in severe cases, mental status changes. Hepatotoxicity is indicated by elevated liver enzymes, and in severe cases, it can lead to ALF, characterized by encephalopathy and coagulopathy.
Prognosis and risk of recurrence
The severity of liver damage, as indicated by laboratory tests such as serum transaminases and coagulation profile, is a key determinant of prognosis. The prognosis in acetaminophen-related ALF is related to the degree of encephalopathy, coagulopathy, and acidosis.
The following summarized guidelines for the evaluation and management of acetaminophen overdose are prepared by our editorial team based on guidelines from the American Academy of Family Physicians (AAFP 2024), the American College of Gastroenterology (ACG 2023), the American Association for the Study of Liver Diseases (AASLD 2022), the Treatment of Paracetamol Poisoning Writing Group (TPPWG 2020), the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP 2014), and the American Association of Poison Control Centers (AAPCC 2006).
1.Screening and diagnosis
Diagnosis: as per AASLD 2022 guidelines, recognize that acetaminophen is a dose-dependent hepatotoxin causing acute pericentral liver injury when doses of > 4 g are ingested within a 24-hour period or excessive doses over several days.
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2.Classification and risk stratification
Prognosis: recognize that the prognosis in acetaminophen-related ALF is related to the degree of encephalopathy, coagulopathy, and acidosis.
History of ingestion: elicit history including the patient's age and intent, specific formulation and dose of acetaminophen, ingestion pattern, duration of ingestion, and concomitant medications ingested.
Setting of care: refer patients with stated or suspected self-harm or recipients of a potentially malicious administration of acetaminophen to an emergency department regardless of the amount ingested.
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As per AAFP 2024 guidelines:
Consider administering a single dose of activated charcoal PO or by nasogastric tube if the ingestion of a potentially toxic amount of medication occurred within 1 hour of presentation. Do not administer activated charcoal in patients without an intact or protected airway.
Insufficient evidence to support the use of cathartics, including ipecac syrup, in poisoning.
Extracorporeal treatment: consider initiating ECTR in patients with any of the following:
N-acetylcysteine is not administered and acetaminophen concentration is > 1,000 mg/L or > 800 mg/L
N-acetylcysteine is not administered, the patient presents with altered mental status, metabolic acidosis, elevated lactate, and acetaminophen concentration is > 700 mg/L or > 500 mg/L
N-acetylcysteine is administered, the patient presents with altered mental status, metabolic acidosis, elevated lactate, and acetaminophen concentration is > 900 mg/L or > 800 mg/L
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Consult a liver transplant unit if any of the following criteria are met:
INR > 3.0 at 48 hours or > 4.5 at any time
oliguria or creatinine > 200 mcmol/L
persistent acidosis (pH < 7.3) or arterial lactate > 3 mmol/L
systolic hypotension with BP < 80 mmHg, despite resuscitation
hypoglycemia, severe thrombocytopenia, or encephalopathy of any degree
any alteration of consciousness (GCS < 15) not associated with sedative co-ingestions
Do not administer clotting factors unless the patient is bleeding or after discussion with a liver transplant unit.
Pediatric patients: as per TPPWG 2020 guidelines, measure serum acetaminophen concentration at least 2 hours after ingestion in < 6 years old pediatric patients with suspected ingestion of > 200 mg/kg of liquid acetaminophen. Do not administer N-acetylcysteine if the 2-4-hour acetaminophen concentration is < 150 mg/L. Repeat measurement of acetaminophen concentration 4 hours after ingestion if the 2-hour acetaminophen concentration is > 150 mg/L and administer N-acetylcysteine if the 4-hour concentration is ≥ 150 mg/L.
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9.Follow-up and surveillance
Indications for poison center consultation: consult a poisons information center in the following situations:
very large overdoses - immediate-release or modified-release acetaminophen overdoses of ≥ 50 g or 1 g/kg (whichever is less)
high acetaminophen concentration, more than triple the nomogram line
IV acetaminophen errors or overdoses, as the treatment threshold is lower
patients with hepatotoxicity (ALT > 1,000 IU/L)
neonatal acetaminophen poisonings
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Assessment of treatment response