Paracetamol Metabolism After Liver Surgery

Observational Study Assessing Cytochrome P450 Dependant Paracetamol Metabolites Following Liver Resection.

This observational study will assess the metabolic pathways of paracetamol that are utilised after liver resection.

Paracetamol is normally metabolised by the glucuronidation and sulfation of paracetamol to non toxic end products. If paracetamol is administered in supra-therapeutic doses this pathway becomes saturated and an alternative pathway is utilised. This results in a toxic metabolite called N-acetyl-p-benzoquinone imine (NAPQI). If NAPQI is not metabolised by glutathione to cysteine and mercapturic acid, then NAPQI bind to hepatic cells resulting in necrosis and hepatotoxicity.

Therefore the investigators plan to measure the levels of the paracetamol metabolites in patient undergoing liver resection.

Patients will undergo liver resection according to their onco-surgical requirements. As part of the normal post operative care they will receive 1g paracetamol every six hours unless stated otherwise by the operating surgeon. Urinary samples will be taken for the first 4 post operative days and used for analysis of the urinary paracetamol metabolite levels.

Inclusion Criteria:

• Patients undergoing liver surgery

Exclusion Criteria:

• Contra-indication to paracetamol
• Inability to give written, informed consent.
• Jaundice (Bilirubin > 100 μmol/L).
• Liver resection combined with secondary surgical procedure.
• Age < 18 years.
• Pregnant women.