Source: Fvasconcellos, https://en.wikipedia.org/wiki/Paracetamol_toxicity#/media/File:Paracetamol_metabolism.svg!
Covalent binding to proteins!Oxidative stressCalcium and signal transduction!Mitochondrial damageATP depletion!Nucleic acid degradation
Clinical features
Phase 1!<24h!
Asymptomatic!N&V
Phase 2!1-3d!
RUQ pain!Hepatotoxicity!
Phase 3!3-4d!
Fulminant hepatic failure!MODS!
Phase 4!4d-2wk!
Recovery phase!
SINGLE INGESTION <8h
“At risk” (>10g or >200mg/kg)!No charcoal >2h!
APAP level after 4h!Plot on nomogram (<8h)!
N-Acetylcysteine IV!
150 mg/kg in 200 mL D5W over 15 min!50 mg/kg in 500 mL D5W over 4h!
100 mg/kg in 1000 mL D5W over 16h!
Good outcome if NAC started within 8h from ingestion!
!Stop infusion at 20h, !
no blood tests needed!
SINGLE INGESTION <8-24h
“At risk” (>10g or >200mg/kg)!No charcoal >2h!Start NAC (>8h)!
Check APAP level & AST/ALT
SINGLE INGESTION >24h
“At risk” (>10g or >200mg/kg)!No charcoal >2h!Start NAC (>8h)!
Check APAP level & AST/ALT
As >24h, continue NAC until:!!
Asymptomatic!ALT/AST stable/declining!
APAP <10 mg/L (<66 umol/L)
No role for nomogram!
REFER TO LIVER CENTER
INR >3.0 at 48h or >4.5 any time oliguria or Cr >200 μmol/L
persistent acidosis (pH < 7.3) or arterial lactate >3 mmol/L
SBP <80 mmHg, despite resus hypoglycaemia
severe thrombocytopenia encephalopathy
OTHER SCENARIOS:Unknown time of ingestion!
Staggered ingestions!Repeated supra-therapeutic
ingestion (RSI)!Modified release tablets!
Liquid and IV formulations!