Paracetamol toxicity
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Slides for a talk by Chris Nickson at the Toxicology Workshop at CONCEPTOS 2016 in Chile. See also: http://lifeinthefastlane.com/ccc/conceptos/
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Paracetamol toxicity
- 1. PARACETAMOL TOXICITY Chris Nickson FACEM FCICM Intensivist, The Alfred ICU
- 5. Covalent binding to proteins! Oxidative stress Calcium and signal transduction! Mitochondrial damage ATP depletion! Nucleic acid degradation
- 6. Necrosis!
- 7. 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!
- 9. SCENARIO 1 20y F (60kg)! Single ingestion 5h ago! Paracetamol 18g (300mg/kg)!
- 10. SINGLE INGESTION <8h “At risk” (>10g or >200mg/kg)! No charcoal >2h! APAP level after 4h! Plot on nomogram (<8h)!
- 13. TREAT!
- 14. N-Acetylcysteine PO ! 140 mg/kg loading dose! 70 mg/kg q4h for 72h!
- 15. 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!
- 17. Good outcome if NAC started within 8h from ingestion! ! Stop infusion at 20h, ! no blood tests needed!
- 18. SCENARIO 2 20y F (60kg)! Single ingestion 10h ago! Paracetamol 21g (350mg/kg)!
- 19. SINGLE INGESTION <8-24h “At risk” (>10g or >200mg/kg)! No charcoal >2h! Start NAC (>8h)! Check APAP level & AST/ALT
- 20. TREAT!
- 21. As >8h, continue NAC until:! ! Asymptomatic! ALT/AST stable/declining! APAP <10 mg/L (<66 umol/L)!
- 22. SCENARIO 3 20y F (60kg)! Single ingestion 30h ago! Paracetamol 24g (40mg/kg)! N&V and RUQ pain!
- 23. SINGLE INGESTION >24h “At risk” (>10g or >200mg/kg)! No charcoal >2h! Start NAC (>8h)! Check APAP level & AST/ALT
- 24. As >24h, continue NAC until:! ! Asymptomatic! ALT/AST stable/declining! APAP <10 mg/L (<66 umol/L) No role for nomogram!
- 25. SCENARIO 4 20y F (60kg)! Single ingestion 4h ago! Paracetamol 30g (50mg/kg)!
- 26. TREAT!
- 27. MASSIVE INGESTION >30g or level 2x Rx line! Charcoal up to 4h! Start NAC! Run at 200 mg/h over 16h
- 28. Continue NAC until ! Asymptomatic! ALT/AST stable/declining! APAP <10 mg/L (<66 umol/L)
- 29. SCENARIO 4 at 48h: INR 3.5! lactate 4 mmol/L!
- 30. 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
- 31. Role of liver transplantation for paracetamol toxicity is controversial
- 32. OTHER SCENARIOS: Unknown time of ingestion! Staggered ingestions! Repeated supra-therapeutic ingestion (RSI)! Modified release tablets! Liquid and IV formulations!
- 34. Use guidelines and know ! when to use a nomogram
- 35. Call a toxicologist for advice with difficult cases