From the Guidelines
The most significant risk of mortality from acetaminophen (paracetamol) overdose is liver failure.
Key Points
- Acetaminophen overdose can cause severe liver damage, leading to liver failure and death 1.
- The risk of liver failure and mortality increases with the dose and duration of acetaminophen use 1.
- Early treatment with N-acetylcysteine (NAC) can help prevent liver failure and reduce mortality in patients with acetaminophen overdose 1.
- The standard treatment for acetaminophen overdose is administration of NAC, which can be given orally or intravenously 1.
- The evidence suggests that NAC is effective in reducing mortality and liver failure in patients with acetaminophen overdose, with a significant reduction in mortality rates compared to placebo 1.
Important Details
- The dose of NAC for treatment of acetaminophen overdose is typically 140 mg/kg orally or 150 mg/kg intravenously, followed by maintenance doses 1.
- The treatment should be started as early as possible, ideally within 8-10 hours of ingestion, but can still be effective if started later 1.
- The risk of liver failure and mortality from acetaminophen overdose can be increased in patients with pre-existing liver disease, chronic alcohol use, or other underlying medical conditions 1.
From the FDA Drug Label
Warnings Liver warning This product contains acetaminophen Severe liver damage may occur if: an adult takes more than 6 doses in 24 hours, or greater than 4000 mg of acetaminophen, the maximum daily amount Overdose warning Taking more than the recommended dose (overdose) may cause liver damage. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222). Quick medical attention is critical for adults as well as children even if you do not notice any signs or symptoms.
The most significant risk of mortality from acetaminophen (paracetamol) overdose is liver damage.
- Severe liver damage may occur with overdose, and
- quick medical attention is critical to prevent serious outcomes, including mortality 2.
From the Research
Risk of Mortality from Acetaminophen Overdose
The most significant risk of mortality from acetaminophen (paracetamol) overdose is related to the development of hepatotoxicity and subsequent liver failure. Key factors contributing to this risk include:
- Delay in hospital admission and treatment, which can lead to delayed administration of antidotes like acetylcysteine 3
- Massive ingestion of paracetamol, leading to early lactic acidosis and coma 4
- Established liver failure, resulting in reduced hepatic clearance of lactate and potentially contributing to peripheral anaerobic respiration in shocked patients 4
- Cardiovascular collapse with rapidly progressive resistant hypotension and/or cardiac arrest, particularly in older patients without cerebral oedema 5
Mechanisms and Risk Factors
The mechanisms of paracetamol-induced hepatotoxicity involve the formation of toxic metabolites, such as N-acetyl-p-benzo-quinone imine, which can inhibit electron transfer in the mitochondrial respiratory chain and lead to cellular injury 4. Risk factors for severe hepatotoxicity include:
- Male gender
- Alcohol abuse
- Ingested paracetamol dose
- Time span from ingestion to hospital admission 3
- Age, with older patients being at higher risk of early mortality without cerebral oedema 5
Treatment and Prevention
Effective treatment of paracetamol overdose involves the administration of acetylcysteine as an antidote 6. Prevention measures include better identification of high-risk overdoses, improved treatment regimens, and legislative changes targeting large overdoses and modified-release paracetamol formulations 6.