ToxicityLiver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).
Risk factorsIf the patient• is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's wort or other drugs that induce liver enzymes, or• is likely to be glutathione depleted e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after administration and clinical symptoms generally culminate after 4 to 6 days. Abnormalities of glucose metabolism and metabolic acidosis may occur.In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Management Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of clinically significant early symptoms, patients should be referred urgently to hospital for immediate medical attention. This is because early symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines - see BNF overdose section.As concentrations soon after paracetamol ingestion are unreliable, plasma paracetamol concentration should be measured at 4 hours or later after the initial administration. Treatment with N-acetylcysteine may be used for up to 24 hours after administration of paracetamol; however, the maximum protective effect is only obtained up to 8 hours post-administration. The effectiveness of this antidote declines sharply after this 8 hour time period. If required, the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, then oral methionine may be a suitable alternative for remote areas, outside hospital. Management of those patients presenting with serious hepatic dysfunction 24 hours after paracetamol administration should be discussed with the National Poisons Information Centre (NPIS) or a liver unit.