see also: [[N-acetyl-cysteine|NAC]] [Murray paracetamol overdose](x-devonthink-item://C8AE745C-C96E-4AEF-9010-D441840C6DF4?page=333) [Austin](https://www.austin.org.au/Assets/Files/Paracetamol%20Acute%20Single%20Ingestion%202022%20FINAL.pdf) > [!Key Points] > - **risk dose:** >10 g or >200 mg/kg > - Antidote:: [[N-acetyl-cysteine|NAC]] # Toxicokinetics ![[Pasted image 20230531165646.png]] # Diagnosis ALT <50 # clinical phases ![[Pasted image 20240411085018.png]] # Symptoms - GI symptoms (often resolve and become asymptomatic) - then hepatic and renal dysfunction begins - [[hypoglycaemia|hypoglycemia]] - [[Liver Failure]] # Treatment ## Acute Overdose **Nomogram** ![[Pasted image 20230531171812.png]] > [[N-acetyl-cysteine]]: > INFUSION 1: [200mg/kg](x-devonthink-item://2D6928BB-F280-49A9-B6CF-8A537BF2FE72) NAC in 500 mL 5% dextrose over 4 hours (infant 100mL) > INFUSION 2: 100 mg/kg NAC in 1000 mL 5% dextrose over 16 hour (infant 250mL) **if you start NAC within 8 hours, treatment success is 100%** ### Acute overdose presenting >8 hours Patients presenting >8 hours after ingestion; who have an unknown time of ingestion; or whose paracetamol level will not be available within 8 hours are commenced on N-acetylcysteine immediately until the biochemical risk assessment (serum paracetamol and hepatic transaminase (ALT) levels) is available. ## Staggered acute overdose - In patients presenting with a history of more than one paracetamol overdose over several hours, a worst-case scenario can be adopted. - **assume that the total dose of paracetamol was ingested as a single-dose at the earliest possible ingestion time** and the total ingested dose was greater than 200 mg/kg. - The serum paracetamol concentration is plotted on the nomogram based on this time point. Treatment is initiated if it is above the nomogram line. ## Repeated supratherapeutic ingestion see: [Murray repeated supratherapeutic ingestion](x-devonthink-item://DA1896AC-D57C-4A67-B2C7-65B1D27BB53E?page=345) - acute OD nomogram not applicable - Risk based on history (see table below) and biochemical markers - ==ALT ≥50 U/L or paracetamol level ≥20 mg/L (≥132 micromol/L):== - Patients at higher risk of developing significant hepatotoxicity. - Commence NAC pending further evaluation > - Patients with clear evidence of resolving hepatotoxicity (undetectable paracetamol, falling ALT, INR <2 and who are clinically well) do not require further NAC and are fit for medical discharge. > - Patients with fulminant hepatic failure require management in an intensive care unit and referral to a liver transplant service (see [[#Liver transplant king's college|Kings College]] criteria) ![[Pasted image 20230702232016.png]] ![[Pasted image 20250224222356.png]] ## Sustained release paracetamol aka modified-release paracetamol or slow-release paracetamol (eg panadol osteo) see: [Austin modified release Paracetamol](x-devonthink-item://C2AC6B87-8C10-4E9F-B3BA-730B5EE1AF9A) - if taken toxic amount (>200mg/kg), ==start NAC, no role for nomogram== - If ≥ 30 g or 500mg/kg, second bag NAC double-dose - if non-toxic amount (<200mg/kg), take paracetamol level at 4 hours and 8 hours, plot on nomogram, if either above treatment line, then give NAC give activated charcoal (if safe to do so) for sustained release paracetamol presenting ≤ 4 hours ![[Pasted image 20250207065204.png]] ## Massive paracetamol overdose Applies regardless of whether modified release or IR; note above flow chart for MR massive overdose - Patients with a massive ingestion (e.g. **≥30 g or ≥500 mg/kg**) and a paracetamol level > double the nomogram line should receive an increased dose of N-acetylcysteine. - likely second NAC bag (usually 100mg/kg over 16 hours) double to 200mg/kg per austin tox; discuss with toxicology if dose >50g ## Extended NAC treatment [Extended NAC Rx 2022](x-devonthink-item://474B0403-CD47-41DD-9058-2A361A341DF4) # Children there are [no reports of death following single acute non-intentional paracetamol exposure in children under 8 years of age](x-devonthink-item://C8AE745C-C96E-4AEF-9010-D441840C6DF4?page=335&start=1212&length=8&search=Children). Ingestion of <200 mg/kg as a single dose or over a period of <8 hours does not warrant decontamination, referral to hospital, serum paracetamol level, liver function tests, antidote treatment or follow-up. ## liquid paracetamol OD in children <6 > Paediatric liquid preparations are absorbed rapidly and a 2 (to 4) hour level below the 4-hour nomogram treatment line allows safe early discharge. In children under 6 years of age where ingestion of more than 200 mg/kg of liquid paracetamol is suspected, a serum paracetamol concentration should be measured at least ==2 hours after ingestion.== - If the 2–4-hour concentration is below 150 mg/L (1000 μmol/L), acetylcysteine is not required and can be discharged. - If the 2-hour paracetamol concentration is greater than 150 mg/L (1000 μmol/L), this should be repeated 4 hours after ingestion and NAC commenced if this is 150 mg/L or more (1000 μmol/L). A 2-hour concentration should only be used in a well child under 6 years of age with isolated liquid paracetamol ingestion. In all other cases, a 4-hour concentration should be performed. Further, for children who present later than 4 hours after ingestion or in children older than 6 years of age, treatment is as per adult protocol. # When to stop NAC - after finishing infusion if started <8 hours - ALT falling and no detectable level in delayed presentation - anaphylaxis # Liver transplant king's college when to transfer to liver transplant centre mnemonic:: **HE CRASH** Hypotension <80 Encephalopathy (any) Coagulopathy INR >3 at 24 hours or >4.5 at any stage Renal failure Cr >200 or oliguria Acidosis pH <7.3 or lactate >3 after resuscitation Severe thrombocytopenia <50 Hypoglcyaemia # when to dialyse - renal failure / anuria - severe acidosis - uraemia with end stage liver failure / encephalopathy # Related Questions ## paracetamol overdose - [ ] 5Q: [Paracetamol Overdose](x-devonthink-item://FE3157C2-07B3-43F2-9ECE-AFACE1355E13?page=61) -- [Answer](x-devonthink-item://DDC959EB-0C1E-448A-8380-C397BF734322?page=30) - [ ] 6Q: [Paracetamol Overdose](x-devonthink-item://3D57C3FE-3B52-42E0-9FBD-E4034F60C5B7?page=6) -- [Answer](x-devonthink-item://75D8E35B-EE77-4D1B-A665-438451C976AE?page=22) # OSCE - [Monash 2021 st 5 SCBD pregnant paracetamol eclampsia](x-devonthink-item://9DFE0939-6D28-4F5A-A099-470328566260)