Paracetamol Toxicity — Viva Defence

Long Case Viva Defence

The scenario

A 38-year-old man presents 14 hours after a single large paracetamol ingestion during an alcohol binge. He is drowsy, icteric, and tender in the right upper quadrant, with a liver flap. AST and ALT are in the thousands, INR 3.4, creatinine 180 micromol/L, arterial pH 7.32, arterial lactate 4.2 mmol/L, glucose 3.1 mmol/L, paracetamol 90 mg/L. ^[17]

Opening statement (SASPOP)

"This is a late single acute paracetamol overdose with established hepatotoxicity — transaminitis, coagulopathy, hypoglycaemia, mild encephalopathy, acute kidney injury — in a man with alcohol use disorder. The nomogram still describes a single known-time ingestion, but he is already injured so I am not waiting on a plot: I start intravenous acetylcysteine now, extend it while injury persists, and triage transplant using O'Grady's pH, prothrombin time and creatinine plus Bernal lactate. Chronic alcohol is a comorbidity, not a second nomogram line." ^{[17][7][3][5][13]}

Problem list

1. Late single acute overdose with established hepatotoxicity. ^[17][1]
2. Alcohol use disorder — withdrawal and nutrition; Rumack found no consistent chronic-alcohol difference in hepatotoxicity. ^[13]
3. Transplant triage — pH 7.32 is not yet below 7.30; lactate 4.2 mmol/L is above Bernal's early 3.5 mmol/L threshold. ^[3][5]
4. Deliberate self-harm — psychiatry once medically stable. ^[17]

Integrated management plan

Antidote: Start NAC now. ANZ current: Chiew two-bag 200 mg/kg over 4 hours then 100 mg/kg over 16 hours. Classic three-bag remains the exam comparator: 150 mg/kg over 15 minutes or 1 hour, 50 mg/kg over 4 hours, 100 mg/kg over 16 hours. Keays continued until recovery from encephalopathy or death; survival 48% versus 20%. Charcoal is futile at 14 hours (position paper: consider up to one hour, not routinely). ^{[11][7][4][12]}

Monitoring: Prothrombin time, creatinine, arterial pH, lactate, glucose. O'Grady poor prognosis: pH below 7.30, prothrombin time greater than 100 s, creatinine greater than 300 micromol/L. Bernal lactate identified non-survivors at a median 4 versus 10 hours. ^[3][5]

Reactions: Yarema 8.2% of 6,455 courses; 75.4% cutaneous; 95.4% in the first 5 hours; antihistamine in 92% of treated reactions. Stop, treat, restart slower. ^[10]

Probing questions

Q: Urticaria and wheeze during the first bag? Stop the infusion, treat the anaphylactoid reaction, restart more slowly. Yarema: most reactions are cutaneous and early; higher paracetamol concentrations were associated with fewer reactions (OR 0.79). ^[10]

Q: pH 7.28, prothrombin time greater than 100 s, creatinine 310, grade 3 encephalopathy? He now meets O'Grady poor-prognosis markers. Urgent liver-unit referral; continue NAC (Keays). Do not convert the 1989 paper into an unsourced "INR above 6.5". ^[3][4]

Q: How does lactate help? Validation-sample thresholds 3.5 mmol/L early (67%/95%) and 3.0 mmol/L after fluids (76%/97%); earlier identification than KCH criteria (4 versus 10 hours). ^[5]

Q: Staggered over three days instead? Nomogram invalid. UK CHM: treat all staggered and uncertain ingestions. Craig: 24.3% of a severe-injury cohort were staggered, mortality 37.3% versus 27.8%; consider early specialist transfer. ^[8][6][11]

Q: Activated charcoal? Fifty grams in volunteer data; consider up to one hour if the airway is protected; not routine; no evidence of improved clinical outcome. ^[12]