Paracetamol Poisoning

Metabolism

Paracetamol - glucorination, sulfonation - nontoxic products
When glutathione is depleted, paracetamol is converted into NAPQI by cytochromes

Toxic doses > 200 mg/kg
Recommended doses less than 90 mg/kg

4 stages of paracetamol poisoning

Stage	Duration	Features	Lab findings
1	0-24 hrs	Anorexia, vomiting, malaise	Labs - normal
2	24-48 hrs	Right upper quadrant pain	Elevated transaminase
3	3-5 days	Liver failure, multiorgan failure	Peak transaminases
4	5d - 2 weeks	Clinical recovery followed by histological recovery	Resolution of liver function

Paracetamol levels after 4 hours of ingestion

4 categories

Category	Management
CATEGORY 1 Normal transaminases	Prophylaxis If PCM levels known - Rumack - Matthew nomogram If possibility of toxicity - start NAC NAC oral > IV Oral - 24 hr dose - 140 mg/kg loading followed by 70 mg/kg q4h IV (3%) - 21 hours - 150 mg/kg loading - 50mg/kg over the first 4 hours - 100 mg/ kg over the next 16 hours - To be given in case of vomiting, hepatic failure, pregnancy Repeat transaminases at the end of treatment If elevated move to category 2
CATEGORY 2 Raised transaminases	Can cause hepatocellular necrosis Order of elevation of enzymes - AST > ALT > INR Start NAC treatment Stop when NAC "tend towards" normal
CATEGORY 3 Acute liver failure	Do liver transplant - KINGS COLLEGE CRITERIA pH < 7.3 Serum creatinine > 3.3 mg/dl INR > 6 Serum Lactic acid > 3 mmol/lit (not part of KINGS criteria, but helpful) Transaminases has no role
CATEGORY 4 Repeated subtherapeutic ingestion	Rumack's nomogram not helpful 1. Asymptomatic (AST - N, PCM <10 mcg/ml) - no therapy 2. Asymptomatic (AST - N, PCM elevated) - NAC till PCM levels not detected 3. Asymptomatic (AST raised) - Category 2 4. Right upper quadrant pain, vomiting, jaundice - Empirically NAC till Lab comes