General Management of Acute Poisoning

Specific Poisonings

Paracetamol

Toxicity stems from its saturable metabolism. In therapeutic doses, 60-90% is conjugated to inactive sulphates and glucuronides. Saturation of the sulphation path after OD diverts an increased fraction to the reactive/toxic species NABQI (N-acetyl-benzoquinoneimine) whose detoxification rapidly depletes hepatic glutathione stores.

Presentation

• Apart from mild nausea, vomiting and anorexia, patients presenting within 24 hrs of ingestion are generally asymptomatic.
• Hepatic necrosis becomes apparent at 24-36 hrs with right subchondral pain/tenderness, reappearance of vomiting and neuroglycopenia. Encephalopathy deepens over the next 72 hrs.

Complications

• The predictable consequences of liver failure i.e. metabolic acidosis, hypoglycaemia, cerebral oedema, cardiac arrhythmias and GI bleeding.
• 10% of patients develop renal impairment from acute tubular necrosis which occasionally is seen in the absence of hepatic failure.
• Very rarely patients with G6PD deficiency develop methaemoglobinaemia and haemolysis.

Prognostic features

• Untreated, the fatal dose in adults is usually >10g but may be lower in chronic alcoholics or subjects with underlying liver disease.
• A PT of 20s at 24 hrs indicates significant hepatocellular damage and the more rapid the rise in PT thereafter the poorer the prognosis.
• Patients developing hepatic failure. A poor prognosis is suggested by: (1) arterial pH <7.3; (2) prothrombin time >100s; (3) creatinine of >300 mol/l. They should be considered for early liver transplantation.

Management

• Ipecac/gastric lavage within 4 hrs of ingestion.
• Paracetamol levels checked at 4hrs. Compare to treatment curve (200mg/1 or 1.32mmol/l at 4h joined to with 6mg/1 or 0.04mmol/l at 24h. Some 60% of patients above the line develop severe liver damage i.e. AST >1000.
• Patients on or above the line should be given IV N-acetylcysteine*

* up to 10% have a rash, bronchospasm or hypotension during the IVI (acts as a mast cell releaser). Stopping and giving chlorpheniramine IV usually allows the IVI to be safely restarted.