Summary statement: new guidelines for the management of paracetamol poisoning in Australia and New Zealand

The NACSTOP Trial: A Multicenter, Cluster‐Controlled Trial of Early Cessation of Acetylcysteine in Acetaminophen Overdose

“…The inclusion criteria were as follows: Age 16 years or older; Acute single or staggered (i.e., over 1 hour) acetaminophen ingestion, requiring acetylcysteine as per the Australian and New Zealand acetaminophen guidelines (i.e., above 150 mg/L at 4‐hour treatment nomogram line for single ingestions) ( ) ; Serum ALT less than the local laboratory upper limit of normal (40 IU/L) on presentation and after 12 hours of acetylcysteine infusion; Serum acetaminophen concentration less than 20 mg/L (132 μmol/L, the upper therapeutic concentration) after 12 hours of acetylcysteine infusion; and Serum creatinine within normal laboratory limits on presentation and after 12 hours of acetylcysteine infusion. …”

“…Those requiring treatment with acetylcysteine and excluded from the study received management as per the guideline. ( )…”

“…( ) The decision to treat cases of single acute acetaminophen overdose with acetylcysteine is based on a timed acetaminophen concentration plotted on a treatment nomogram. ( ) The standard acetylcysteine treatment regimen, used for several decades, calls for 300 mg/kg infused over a fixed interval of 20 to 21 hours (i.e., 150 mg/kg of acetylcysteine intravenously [IV] over 15‐60 minutes, followed by 50 mg/kg of acetylcysteine over 4 hours and 100 mg/kg of acetylcysteine over 16 hours). ( ) To simplify acetylcysteine dosing and reduce adverse reactions during the rapid initial load, ( ) we recently instituted a two‐bag acetylcysteine regimen consisting of 200 mg/kg over 4 hours followed by a further 100 mg/kg over 16 hours.…”

Paracetamol poisoning in children

“…preparation, but are very rare. The regimens for oral or IV administration of NAC are [17][18][19][20][21][22][23][24] : • Oral -a standard 72-hour oral course of NAC is given as a 140 mg/kg loading dose followed by 17 doses of 70 mg/kg every four hours (total dose 1330 mg/kg) Acetylcystein is cornerstone therapy of acute paracetamol poisoning, with proven safety and eficacy in children. Loading dose -150 mg/kg in 100 mL of diluent given IV over 60 minutes; Second dose -50 mg/kg in 250 mL of diluent given IV over 4 hours (12.5 mg/kg NAC per hour); Third dose -100 mg/kg in 500 mL of diluent administered over 16 hours (6.25 mg/kg NAC per hour) c) Patients ≥ 40 kg may receive IV NAC as recommended for adults: Loading dose -150 mg/kg in 200 ml of diluent over 15 to 60 minutes; Second dose-50 mg/kg in 500 ml of diluent over 4 hours; Third dose -100 mg/kg in 1000 mL of diluent administered over 16 hours (6.25 mg/kg NAC per hour).…”

“…Because of low toxicity and potential beneficial effects, even consider early treatment with N-acetylcysteine (NAC) when acetaminophen toxicity is a likely contributor of liver dysfunction 17 . Treatment is indicated with administering the antidote, NAC in adolescents and children [17][18][19][20] : a) when the plasma paracetamol concentration exceeds the treatment line in the RumackMatthew nomogram ( Figure 3); b) a suspected single ingestion of greater than 150 mg/kg (7.5 g total dose regardless of weight) in a patient for whom the serum paracetamol concentration will not be available until more than eight hours from the time of the ingestion; c) patients with an unknown time of ingestion beyond 24 hours and a serum paracetamol concentration > 10 mg/L (66 µmol/L); d) patients with delayed presentation (> 24 hours after ingestion) consisting of laboratory evidence of hepatotoxicity (from mildly elevated aminotransferases to fulminant hepatic failure) and a history of excessive paracetamol ingestion.…”