What is the monitoring protocol for Paracetamol (Acetaminophen) toxicity?

From the Guidelines

Paracetamol toxicity monitoring protocol involves prompt administration of N-acetylcysteine (NAC) and close monitoring of liver function.

Key Monitoring Steps

• Admit patients with suspected paracetamol overdose to an ICU for frequent monitoring 1
• Draw acetaminophen levels in all patients presenting with acute liver failure (ALF), as paracetamol is a leading cause of ALF 1
• Use the standard acetaminophen toxicity nomogram to determine the likelihood of serious liver damage, but do not rely solely on this to exclude possible toxicity 1
• Monitor for very high aminotransferases (serum levels exceeding 3,500 IU/L), which are highly correlated with acetaminophen poisoning 1

NAC Administration

• Administer NAC as early as possible, but it may still be of value 48 hours or more after ingestion 1
• Give NAC orally (140 mg/kg by mouth or nasogastric tube diluted to 5% solution, followed by 70 mg/kg by mouth q 4 h for 17 doses) or intravenously (loading dose is 150 mg/kg in 5% dextrose over 15 minutes; maintenance dose is 50 mg/kg given over 4 hours followed by 100 mg/kg administered over 16 hours) 1
• Consider giving activated charcoal (1g/kg orally, in a slurry) just prior to NAC administration if ingestion occurred within 4 hours of presentation 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 monitoring protocol for Paracetamol (Acetaminophen) toxicity involves:

• Immediate medical attention in case of overdose
• Contacting a Poison Control Center right away at 1-800-222-1222
• Quick medical attention is critical for adults and children, even if no signs or symptoms are noticed 2

From the Research

Monitoring Protocol for Paracetamol (Acetaminophen) Toxicity

The monitoring protocol for paracetamol toxicity involves several key steps:

• Patients who present early should be given activated charcoal to prevent absorption of the drug 3, 4
• Patients at risk of hepatotoxicity should receive intravenous acetylcysteine, which has been shown to prevent hepatic damage in most cases if started within 10 hours from ingestion 3, 5, 6
• The paracetamol nomogram is used to assess the need for treatment in acute immediate release paracetamol ingestions with a known time of ingestion 3, 5, 6
• Cases that require different management include modified release paracetamol overdoses, large or massive overdoses, accidental liquid ingestion in children, and repeated supratherapeutic ingestions 3

Treatment Regimens

Different treatment regimens have been studied, including:

• A two-bag acetylcysteine infusion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h) which has similar efficacy but significantly reduced adverse reactions compared with the previous three-bag regimen 3
• A novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate, which has been shown to result in a similar exposure to NAC 7
• A modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg bodyweight loading dose, which has been associated with significantly fewer adverse reactions compared with the traditional three-bag 20.25-hour regimen 4

Special Considerations

Special considerations include:

• Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine 3
• All potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine 3
• Patients ingesting ≥ 30 g or ≥ 500 mg/kg should receive increased doses of acetylcysteine 3
• Children who have received more than 75 mg/kg/day of paracetamol for more than 24 hours during febrile illness should have liver enzyme levels tested, and treated with NAC when transaminase levels are elevated 5