May 23, 2024
Prognosis
The second most common cause of liver transplants worldwide; a safe therapeutic dose of 4 g/24 hours; a toxic dose of 7.5 g–10 g/24 hours; and a toxic metabolite of NAPQI. N acetyl para-benzoquinone imine; Conversion reaction-mediated metabolism.
Five to ten percent of paracetamol pass via P450. The particular enzyme involved in the metabolism of paracetamol is CYP2E1. The building block of glutathione production is cysteine. The toxicity of paracetamol is greatest when glutathione or cysteine are depleted.
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Stage Time post ingestion Characteristics I 0-24 h Anorexia, nausea, vomiting. Hepatic transaminases may start to rise II 24-72 h May see improvement in clinical findings, some patients may report right upper quadrant abdominal pain. Elevated AST, ALT, bilirubin, INR. III 72-96 h Hepatic failure, acidosis, sometimes renal failure and pancreatitis. Peak AST, ALT, bilirubin and INR levels IV >5days Progression to multiple organ failure (sometimes fatal) Resolution of hepatotoxicity in survivors
The histological hallmark of paracetamol poisoning
Drugs that result in necrosis of the centrilobulus - Paracetamol; INH; Hydralazine; Halothane; Cytolysis.
Baseline LFT, RFT; Repeating LFT, RFT, and ABG at 8 hours; Therapeutic: 2 hours after exposure.
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When the blood paracetamol level drops below the therapeutic range, NAC is administered. Available in an injectable and oral form. The Rumack-Matthew Nomogram carries a liver damage risk. Treatment line: 25% lower than the Rumack-Matthew line; Time/blood paracetamol levels; Chooses which patients to treat.
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More than 3.4 mg/dL of creatinine; Blood pH below 7.3 even with sufficient hydration with fluids. An INR of more than 6.5 or a prothrombin time more than 1.8 times control A poor prognosis; The onset of grade 3 or 4 encephalopathy.
Liver transplantation
To lower the chance of dying. The acute liver failure criteria of Kings College.
Paracetamol |
Non – paracetamol |
pH<7.3* or Arterial lactate >3.5 mmol at 4 h or Arterial lactate >3.0 mmil/l at 12 h* or PT >100 s (INR >6.5) Serum creatinine >300 mmol (3.4 mg/dl) Grade 3 or 4 encephalopathy |
Prothrombin time greater than 100 s (INR>6.5) (irrespective of grade of encephalopathy) or any three of the following 1. Age less than 11 years or greater than 40 years 2. Aetiology of non-A / non -B hepatitis, halothane hepatitis, or idiosyncratic drug reactions. 3. Duration of jaundice of more than 7 days before onset of encephalopathy 4. Prothrombin time greater than 50 s (INR>3.5) 5. Serum bilirubin level greater than 17 mg /dl (300 μmol/l) |
Adapted (with permission) from O’Grady, et al and Bernal, et al. *After fluid resuscitation. INR, International Normalised Ratio |
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