paracetamol toxicity
TRANSCRIPT
PARACETAMOL TOXICITY
Chris Nickson FACEM FCICM Intensivist, The Alfred ICU
Financial Conflicts of Interest NO !
http://litfl.org/CONCEPTOS
N-acetyl-p–aminophenol (APAP)!
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
Necrosis!
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!
ResusRSI DEAD
SCENARIO 120y F (60kg)!
Single ingestion 5h ago!Paracetamol 18g (300mg/kg)!
SINGLE INGESTION <8h
“At risk” (>10g or >200mg/kg)!No charcoal >2h!
APAP level after 4h!Plot on nomogram (<8h)!
TREAT!
N-Acetylcysteine PO!
140 mg/kg loading dose!70 mg/kg q4h for 72h!
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!
SCENARIO 220y F (60kg)!
Single ingestion 10h ago!Paracetamol 21g (350mg/kg)!
SINGLE INGESTION <8-24h
“At risk” (>10g or >200mg/kg)!No charcoal >2h!Start NAC (>8h)!
Check APAP level & AST/ALT
TREAT!
As >8h, continue NAC until:!!
Asymptomatic!ALT/AST stable/declining!
APAP <10 mg/L (<66 umol/L)!
SCENARIO 320y F (60kg)!
Single ingestion 30h ago!Paracetamol 24g (40mg/kg)!
N&V and RUQ pain!
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!
SCENARIO 420y F (60kg)!
Single ingestion 4h ago!Paracetamol 30g (50mg/kg)!
TREAT!
MASSIVE INGESTION
>30g or level 2x Rx line!Charcoal up to 4h!
Start NAC!Run at 200 mg/h over 16h
Continue NAC until!
Asymptomatic!ALT/AST stable/declining!
APAP <10 mg/L (<66 umol/L)
SCENARIO 4 at 48h:INR 3.5!
lactate 4 mmol/L!
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
Role of liver transplantation for paracetamol toxicity is
controversial
OTHER SCENARIOS:Unknown time of ingestion!
Staggered ingestions!Repeated supra-therapeutic
ingestion (RSI)!Modified release tablets!
Liquid and IV formulations!
Don’t underestimate paracetamol overdose!
Use guidelines and know !when to use a nomogram
Call a toxicologist for advice with difficult cases
http://litfl.org/CONCEPTOS