Paracetamol Overdose

Paracetamol (acetaminophen) OD causes hepatic necrosis via NAPQI accumulation when glutathione stores depleted. Treatment: N-acetylcysteine (NAC) neutralises NAPQI. Treatment line on Rumack-Matthew nomogram: paracetamol level vs time since…

MHRA NAC Treatment Protocol / Rumack-Matthew Nomogram

The pathway

1 · History & timing

Time of ingestion (critical for nomogram)
Dose (mg/kg)
Staggered vs single acute
Other substances?
Any symptoms: RUQ pain (liver), nausea, pallor
Current medication (enzyme inducers)
Mental health history, social circumstances

2 · Investigations

Paracetamol level at 4 hours post-ingestion (earlier levels unreliable)
If presentation >8h: take level immediately and start NAC while awaiting result
LFTs, INR (rising INR = significant hepatotoxicity), U&E, creatinine, FBC, venous blood gas
Repeat LFTs at 24h

3 · Nomogram interpretation

Plot paracetamol level (mmol/L or mg/L) against time since ingestion on Rumack-Matthew nomogram
Treat if level above treatment line (100mg/L at 4h, falls to 15mg/L at 15h)
Staggered OD, unknown time, or risk factors: treat empirically without nomogram

4 · NAC protocol — 3-bag regimen

Bag 1: 150mg/kg in 200ml 5% dextrose over 1 hour
Bag 2: 50mg/kg in 500ml 5% dextrose over 4 hours
Bag 3: 100mg/kg in 1L 5% dextrose over 16 hours
Total 21 hours
Common side effect: anaphylactoid reaction (flushing, urticaria, bronchospasm) — slow infusion, chlorphenamine if mild, stop if severe

5 · End of NAC assessment

At 21 hours: check LFTs, INR, creatinine
If LFTs normal and INR <1.3: discharge safe
If LFTs rising or INR >2: continue NAC (200mg/kg over 16h), refer liver team
King's College Criteria for transplant if: pH <7.3, INR >6.5, creatinine >300, grade 3–4 encephalopathy

6 · Safeguarding & mental health

All intentional ODs need mental health assessment before discharge
Safe prescribing review
SSRI/psychiatric follow-up
Do not discharge without mental health clearance — contact liaison psychiatry early

Drugs

Drug	Dose	Route	Notes
N-acetylcysteine (NAC)	150mg/kg → 50mg/kg → 100mg/kg	IV in 5% dextrose	3-bag 21-hour regimen. Check weight before prescribing. Most effective <8h from ingestion.
Chlorphenamine	10mg	IV slow	For anaphylactoid reaction to NAC — slow infusion first, then antihistamine.
Activated charcoal	50g	Oral	If <1h since ingestion and airway protected. Rarely applicable on ward.

When to escalate

Rising INR or LFTs not settling at end of NAC → liver team urgently,INR >2 at 24h → continue NAC, consider liver unit transfer,pH <7.3 or INR >6.5 or creatinine >300 → King's College Criteria, transplant assessment,Grade 3–4 hepatic encephalopathy → ITU, liver unit,All intentional ODs → liaison psychiatry before discharge

Reference: MHRA NAC guidelines 2012 / TOXBASE / British National Formulary

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