What are the symptoms and treatment of paracetamol (acetaminophen) poisoning?

Symptoms of Paracetamol Poisoning

Clinical Presentation by Time Course

Paracetamol poisoning typically presents in four distinct phases, with symptoms evolving over hours to days after ingestion, and early recognition is critical as liver damage may not be apparent until 24-72 hours post-ingestion. 1

Phase 1: First 24 Hours Post-Ingestion

• Patients are often asymptomatic or have only mild, nonspecific symptoms including nausea, vomiting, malaise, and pallor 1, 2
• Right upper quadrant tenderness may be variably present 1
• The absence of symptoms during this phase does not exclude serious poisoning 3, 4

Phase 2: 24-72 Hours Post-Ingestion

• Right upper quadrant pain and tenderness develop 1
• Elevated liver enzymes (AST, ALT) begin to rise, potentially reaching levels >1,000 U/L or even >3,500 U/L in severe cases 1, 5
• Jaundice may appear 1
• Patients may still feel relatively well despite biochemical evidence of liver injury 4

Phase 3: 72-96 Hours Post-Ingestion (Peak Hepatotoxicity)

• Maximum liver damage occurs, with AST/ALT levels potentially reaching thousands of units per liter 1, 3
• Jaundice becomes prominent 1
• Coagulopathy develops (elevated INR/prothrombin time) 1, 5
• Hepatic encephalopathy may develop with altered mental status and asterixis (flapping tremor) 1, 6
• Acute liver failure manifests with inability to palpate the liver (indicating massive hepatocyte loss) or hepatomegaly in early stages 1
• Renal failure may occur 5
• Metabolic derangements including hypoglycemia, elevated lactate, and arterial blood gas abnormalities 1

Phase 4: 4 Days to 2 Weeks (Recovery or Progression)

• Either gradual recovery with normalization of liver function over weeks, or progression to irreversible liver failure requiring transplantation 1, 7

Critical Warning Signs Requiring Immediate Intervention

Very high aminotransferase levels (AST/ALT >3,500 U/L) are highly correlated with paracetamol poisoning and should raise suspicion even without clear overdose history 5, 8

Signs of Acute Liver Failure

• Altered mental status or hepatic encephalopathy 1, 6
• Coagulopathy (elevated INR) 1, 5
• Hypoglycemia 1
• Elevated arterial lactate 1
• Renal dysfunction (elevated creatinine) 1

Important Clinical Caveats

• Paracetamol overdose does not cause focal neurological deficits such as bilateral lower limb motor and sensory deficits—these symptoms suggest alternative diagnoses including spinal cord compression, compartment syndrome from rhabdomyolysis, or unrelated neurological conditions 6
• Physical examination findings are often unremarkable in the first 24 hours despite potentially lethal ingestion 1, 3
• History may be unreliable or unavailable, particularly in cases of altered mental status or intentional self-harm 1
• Chronic alcoholics may develop severe hepatotoxicity with doses as low as 4-5 g/day, well below typical toxic thresholds 1, 8

Toxic Dose Thresholds

• Acute single ingestions exceeding 150 mg/kg or 10 grams (whichever is less) are considered potentially hepatotoxic 8, 2
• Severe hepatotoxicity has been documented with ingestions ranging from 10-65 grams, with survival reported even after massive 60-gram ingestions 8, 9
• In high-risk populations (chronic alcoholics, malnourished patients, those with pre-existing liver disease), severe hepatotoxicity can occur with doses as low as 4-5 g/day 1, 8
• Repeated supratherapeutic ingestions of ≥6 grams per day for 48 hours or longer are potentially toxic 8

Essential Laboratory Monitoring

Initial laboratory assessment must include: 1

• Serum paracetamol level (drawn at least 4 hours post-ingestion for nomogram interpretation) 5, 3
• AST, ALT, alkaline phosphatase, total bilirubin 1
• Prothrombin time/INR 1
• Creatinine and blood urea nitrogen 1
• Arterial blood gas and arterial lactate 1
• Glucose 1
• Complete blood count 1

Treatment Implications

N-acetylcysteine (NAC) should be administered immediately when paracetamol poisoning is suspected, as early treatment (within 8 hours) prevents hepatotoxicity in most cases, while delayed treatment beyond 15 hours is associated with liver damage and death 1, 5, 3, 7