Paracetamol overdose 2 days ago, now INR 3.8, confused, glucose 2.1 — INR ≥1.5 + encephalopathy = acute liver failure. NAC for everyone, transplant call early.
ABCDE
NAC immediately (all causes, not just paracetamol); correct hypoglycaemia with 10% dextrose; minimal sedation; head-up 30°; early transfer discussion with transplant centre.
Define: INR ≥1.5 + any encephalopathy in acute liver injury without prior cirrhosis = ALF; grade encephalopathy I–IV (asterixis → coma)
NAC for ALL: 150 mg/kg over 1 h → 50 mg/kg over 4 h → 100 mg/kg over 16 h — benefits even non-paracetamol ALF (improves transplant-free survival)
Find the cause: paracetamol level (can be undetectable — treat anyway), viral serologies, autoimmune, Wilson (young + haemolysis), ischaemic hepatitis, DILI, pregnancy (HELLP/fatty liver)
Protect the brain: grade III–IV → intubate for airway; head up 30°, quiet room, avoid suction clusters; treat seizures; NH₃ >150 → ICP risk — hypertonic saline/mannitol if signs; prophylactic hypertonic saline to target Na 145–155 mmol/L in grade III–IV encephalopathy (Stravitz/Lee 2022)
Metabolic guard: glucose q1–2 h with 10% dextrose infusion (hepatic glucose output fails); replace phosphate/Mg/K; lactate — falling is good, rising ominous
Transplant criteria: King's College — paracetamol: pH <7.25 or (INR >6.5 + Cr >300 + grade III–IV); non-paracetamol: INR >6.5 or any 3 of (age <10/>40, aetiology, jaundice-encephalopathy >7 d, INR >3.5, bili >300) — transfer EARLY
Order set
- NAC infusion protocol
- 10% dextrose infusion + glucose q1–2 h
- Serial INR q6–12 h, lactate, NH₃
- Viral hepatitis screen, autoimmune, ceruloplasmin
- Paracetamol level (undetectable ≠ excluded)
- Head-up 30°, minimise stimulation
- Discuss transplant centre TODAY
Monitor
- q1–2 hCapillary glucose — hypoglycaemia is constant threat
- q6–12 hINR trend (prognostic), lactate, NH₃
- HourlyEncephalopathy grade, GCS, pupillary responses
- DailyPhosphate (high = regeneration, low = poor prognosis), renal function
Escalate / ICU
- Encephalopathy grade III–IV — intubate
- NH₃ >150 µmol/L or ICP signs
- King's College criteria met — transfer now
- AKI / oliguria — early CRRT (preferred over intermittent HD even if haemodynamically stable when NH₃ >150 µmol/L or cerebral-oedema risk — Stravitz/Lee 2022)
Criteria
AdmitAll ALF → ICU/HDU, transplant centre if criteria approached
NACEvery ALF patient regardless of cause
IntubateGrade III–IV encephalopathy, agitation, ICP signs
TransplantKing's College criteria — list super-urgent (UNOS Status 1A)
Never
- Give FFP to 'correct' the INR unless bleeding or a procedure — you destroy the best prognostic marker
- Sedate before grading encephalopathy — masks deterioration
- Wait for a paracetamol level before starting NAC
Key
- Phosphate paradox: LOW phosphate = liver regenerating well; HIGH = massive necrosis, poor prognosis
- Avoid NSAIDs, sedatives, and protein loads; lactulose has NO role in ALF encephalopathy
- Hypoglycaemia + rising INR + rising NH₃ = the triad that phones the transplant centre
Clinical detail — differentials, red flags, pitfalls, disposition
Red flags
- INR rising over days, not hours
- Confusion/agitation (grade II)
- Glucose <3 mmol/L repeatedly
- NH₃ >150 µmol/L
Differentials
- Paracetamol (commonest in UK/US)
- Viral hepatitis A/B/E
- Autoimmune, Wilson, Budd-Chiari
- DILI (isoniazid, herbals), mushroom poisoning
Common mistakes
- Stopping NAC at 21 h while still acidotic/encephalopathic (continue until improving)
- Normal paracetamol level = false reassurance at late presentation
- Prophylactic FFP
- Missing hypoglycaemia as the cause of 'encephalopathy worsening'
- Choosing intermittent HD over CRRT when NH₃ >150 µmol/L
Disposition & follow-up
ICU + early transplant centre liaison; if survives with native liver — full recovery usual; psychiatry follow-up after overdose; vaccinations vs triggers.
💊 Treatment detail — doses & preparation
N-acetylcysteine (NAC)paracetamol antidote
Dose150 mg/kg in 200 mL D5W over 1 h → 50 mg/kg in 500 mL over 4 h → 100 mg/kg in 1 L over 16 h (150/50/100 protocol); continue if still acidotic/INR rising
Preparation200 mg/mL ampoules — dilute in D5W as above; weight-capped at 110 kg
MonitorAnaphylactoid reactions (flush/wheeze — slow/stop, antihistamine, restart slower); INR, glucose
Dextrose 10% infusionhypoglycaemia/ALF
Dose100–200 mL/h of 10% titrated to glucose 5–8 mmol/L
Preparation500 mL/1 L bags; give with thiamine in at-risk patients
MonitorCapillary glucose q1–2 h in liver failure
Hypertonic saline 3%severe hyponatraemia/ICP
DoseSymptomatic hypoNa: 100–150 mL of 3% over 10–20 min, repeat ×2–3 until symptoms settle (target Na +4–6 in first 6 h). ICP: 250 mL bolus
Preparation3% NaCl via pump, central or large peripheral vein
MonitorNa⁺ q2–4 h — max rise 8–10 mmol/L/24 h (osmotic demyelination)
Mannitol 20%osmotic diuretic (ICP)
Dose0.25–1 g/kg IV bolus over 10–20 min for ICP crisis
Preparation20% (200 mg/mL) 500 mL bag via filter needle (crystals); may repeat q6–8h
MonitorSerum osmolality (keep <320), Na⁺, volume; effect wanes after 48 h
Vitamin K (phytomenadione)warfarin reversal
DoseMajor bleed: 5–10 mg slow IV + PCC 25–50 U/kg; non-urgent: 1–3 mg PO/IV
Preparation10 mg/mL ampoule in 50 mL D5W over 20–30 min (anaphylaxis if fast)
MonitorINR at 4–6 h; re-warfarinisation window
📖 King's College criteria; AASLD ALF guidance + Stravitz/Lee ALF Update 2022 + textbook Ch.45Reviewed July 2026