Definition

Paracetamol (Acetaminophen) overdose is one of the most common poisonings in the Western world. It causes hepatotoxicity through accumulation of a toxic metabolite (NAPQI) and can lead to acute liver failure (ALF) and death.

The "Silent Killer" Phase

Patients are often asymptomatic in the first 24 hours despite ongoing liver damage. This "latent period" is dangerous as patients may present late when significant hepatic necrosis has occurred.

Key Facts (High Yield for Exams)

Clinical Pearls

1. Never assume low paracetamol level means safety – timing matters. A low level at 2 hours may be rising.
2. Staggered overdoses are extremely dangerous – treat with NAC immediately; nomogram is invalid.
3. ALT is more sensitive than AST for paracetamol hepatotoxicity.
4. INR is the best prognostic marker – rising INR after 48h indicates severe injury.
5. NAC should never be withheld if there is doubt – it is safe and potentially life-saving.

General Inspection

• Level of consciousness (GCS) – Early encephalopathy may be subtle.
• Jaundice (Scleral icterus appears first).
• Asterixis (Hepatic flap) – Test for metabolic encephalopathy.
• Stigmata of chronic liver disease (unlikely in acute overdose unless underlying cirrhosis).

Abdominal Examination

• RUQ Tenderness – Suggests hepatic inflammation/capsular stretch.
• Hepatomegaly – Common in acute hepatitis.
• Ascites – Late sign, indicates severe hepatic decompensation.

Neurological Examination

• Orientation – Early encephalopathy causes confusion.
• GCS – Serial assessment.
• Papilloedema – May indicate cerebral oedema in severe ALF.

Signs of Coagulopathy

• Bruising (spontaneous or from venepuncture).
• Bleeding from gums or IV sites.
• Petechiae.

With Early Treatment (NAC <8 hours)

• Hepatotoxicity prevented in >95%.
• Mortality <1%.

With Delayed Treatment (NAC >24 hours)

• Hepatotoxicity rate increases significantly.
• Mortality 5-10% even with NAC.

Acute Liver Failure

• Without transplant: 80% mortality if King's Criteria met.
• With transplant: Survival ~70%.

Overall Mortality

• ~0.4% of all paracetamol overdoses result in death.
• Higher in staggered overdoses (often present late, cannot use nomogram).

NICE / TOXBASE Guidelines (UK)

• Use the 100 mg/L treatment line at 4 hours.
• Staggered overdose: Treat with NAC; do NOT use nomogram.
• High-risk patients: Lower threshold for treatment.

Key Studies

What is Paracetamol Overdose?

"Paracetamol is a very common painkiller. In normal doses, it's very safe. But if you take too much, it can damage your liver. The liver is the organ that breaks down paracetamol. If overwhelmed, a toxic substance builds up and kills liver cells."

Why Do I Feel Fine?

"It's very common to feel okay for the first 24 hours after a paracetamol overdose. This does NOT mean you are safe. Liver damage happens silently. That's why we take blood tests and may give you an antidote even if you feel well."

What Treatment Will I Get?

"If the blood test shows you are at risk, we will give you a medicine called NAC (N-Acetylcysteine) through a drip. This medicine protects your liver by helping it break down the toxic substance. It works best if given early."

Will I Be Okay?

"If we catch it early and give NAC, the chance of serious liver damage is very low (<5%). Most people recover completely. But without treatment, severe overdoses can cause liver failure, which can be life-threatening."

Common Exam Questions

1. "A patient presents 6 hours after taking 20g of paracetamol. Paracetamol level is 120 mg/L. What do you do?"

• Answer: Plot 120 mg/L at 6 hours on the nomogram. The treatment line at 6h is ~66 mg/L. 120 is ABOVE the line. Start NAC immediately.

2. "What is NAPQI and why is it toxic?"

• Answer: N-Acetyl-p-benzoquinone imine. It is a reactive metabolite from CYP2E1 metabolism of paracetamol. Normally detoxified by Glutathione. In overdose, GSH is depleted, and NAPQI binds to hepatocyte proteins causing centrilobular necrosis.

3. "Why can you NOT use the nomogram for staggered overdoses?"

• Answer: The nomogram assumes single-time-point ingestion with predictable kinetics. Staggered ingestion means paracetamol levels don't follow the expected decay curve, and hepatotoxicity can occur even at lower levels. Always treat with NAC.

Common Mistakes

• ❌ Taking paracetamol level too early: Must be ≥4 hours post-ingestion.
• ❌ Using nomogram for staggered overdose: Treat with NAC immediately; nomogram is invalid.
• ❌ Stopping NAC because patient "feels fine": Hepatotoxicity is silent in first 24h.
• ❌ Withholding NAC for anaphylactoid reaction: Pause, give antihistamine, restart slower.
• ❌ Thinking low paracetamol level = safe: Timing matters. Late presentation with low level can still have severe injury.

Viva Points

Scenario 1: The Staggered Overdose

"A patient took 10 paracetamol tablets at 6pm, then another 20 at midnight. They present at 8am. What do you do?" Answer: "This is a staggered overdose. I cannot use the nomogram. I would start NAC immediately. I would check LFTs, INR, Creatinine as baseline and repeat at 12-24 hours."

Scenario 2: The Late Presenter

"A patient presents 48 hours after a 25g paracetamol overdose. ALT is 8000, INR 4.5, Creatinine 200. Paracetamol level is undetectable. Should you give NAC?" Answer: "Yes. Even though paracetamol is undetectable, the patient has established hepatotoxicity. Late NAC still improves outcomes in ALF. I would also check King's College Criteria for transplant referral."

Advanced MCQ Bank

Case 1: The Nomogram Paracetamol level 80 mg/L at 8 hours post-ingestion. Question: What is the action?

• A) Discharge, below treatment line
• B) Give NAC
• C) Recheck level in 4 hours
• D) Give Activated Charcoal Correct: B. At 8 hours, treatment line is ~50 mg/L. Level 80 is ABOVE. Give NAC.

Case 2: King's Criteria A patient has pH 7.25, INR 8.0, Creatinine 350, and Grade II encephalopathy. Question: Do they meet King's College Criteria?

• A) Yes (pH <7.30 alone)
• B) No (Encephalopathy not Grade III/IV)
• C) Yes (All three of INR, Creatinine, Encephalopathy)
• D) Cannot determine Correct: A. pH <7.30 after resuscitation is sufficient alone. (B is also met by INR+Creat+Enceph but Encephalopathy is only Grade II, so that arm is not quite met).

Case 3: The "Anaphylactoid" Reaction A patient on NAC Bag 1 develops urticaria, flushing, and mild wheeze. Question: What do you do?

• A) Stop NAC permanently, record allergy
• B) Stop NAC, give Adrenaline IM
• C) Pause NAC, give Chlorpheniramine, restart at slower rate
• D) Continue NAC, ignore symptoms Correct: C. Anaphylactoid reactions to NAC are common (non-IgE mediated). Management is pause, antihistamine, restart slowly. This is NOT a true allergy.

Last Reviewed: 2025-12-27 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists. This information is not a substitute for professional medical advice, diagnosis, or treatment.