Paracetamol overdose

Learning objectives

Paracetamol is a mild analgesic and antipyretic medication and is safe if used in therapeutic doses
Most medication overdoses, either accidentally or intentionally, are due to paracetamol overdose
The most common cause of acute liver failure in the western world
A dose of ≥ 150 mg/kg can cause liver damage and this threshold might be lower in people with chronic alcohol abuse or anorexia
The preferred treatment is an n-acetylcysteine infusion

Hepatic effects	Acute liver failure Hepatoxicity may also occur with doses within the therapeutic range secondary to deficiencies in glutathione, because of inadequate nutrition, P450 enzyme induction by chronic alcohol excess, or concomitant use of other medications
Renal effects	Thought to have only minor effects on renal function Rare effects observed after an acute overdose or chronic abuse include: Acute kidney injury (AKI) Acute tubular necrosis Interstitial nephritis
Gastro-inestinal effects	Paracetamol can be associated with: Nausea and vomiting Dyspepsia Abdominal pain Bloating Acute pancreatitis (rarely)
Hemodynamic effects	Hypotension (rare) Increased skin blood flow
Respiratory effects	Difficulty breathing Bronchospasm Paracetamol may causally linked with the development of asthma
Hematological/oncological effects effects	Very rare: Thrombocytopenia Leucopenia Neutropenia Methamoglobinemia
Dermatological effects	Extremely rare: Erythema Flushing Peripheral edema and pruritus Bullous erythema Purpura fulminans Toxic epidermal necrolysis (TEN) Stevens-Johnson syndrome Acute generalized exanthematous pustolis

The SNAP (Scottish & Newcastle Acetylcysteine Protocol)-12 protocol is preferred over the classic 21-hour regimen for intravenous N-acetylcysteine (NAC) infusion as this has some advantages:
- Simple to use
- Fewer adverse drug reactions
- A shortened length of hospital stay for most patients
Clinical judgment is important:
- Ensure that there is no doubt about the time of ingestion or the type of drug
- Some patients have chronically raised ALT/INR
- If ALT is abnormal despite a normal paracetamol concentration, consider treating for an overdose
- If uncertain, treat and review