Diagnosis: Acute Liver Failure Secondary to Paracetamol (Acetaminophen) Toxicity
This patient has acute liver failure (ALF) due to paracetamol overdose, evidenced by the classic triad of jaundice, coagulopathy (implied by asterixis and altered mental status), and hepatic encephalopathy in a patient with no prior liver disease and a clear history of excessive paracetamol consumption. 1
Clinical Reasoning and Diagnostic Criteria
The diagnosis is established by the following key features:
Classic triad present: Jaundice (yellowish discoloration of eyes and skin), hepatic encephalopathy (altered sensorium, drowsiness, disorientation, asterixis/flapping tremors), and coagulopathy (implied by encephalopathy development) 1
Temporal relationship: The 2-5 day interval between paracetamol consumption and symptom development is characteristic of paracetamol-induced hepatotoxicity 1
Absence of chronic liver disease: No prior history of liver disease, jaundice, or chronic alcohol intake—a critical diagnostic criterion for ALF 2, 1
Clinical examination findings: The inability to palpate the liver suggests decreased liver volume from massive hepatocyte loss, which is indicative of acute hepatic necrosis 2
Hepatic encephalopathy markers: GCS 12/15 with asterixis (flapping tremors) confirms Grade II-III hepatic encephalopathy 1
Immediate Management Algorithm
N-acetylcysteine (NAC) must be administered immediately without waiting for laboratory confirmation, as it reduces mortality from 80% to 52% in fulminant hepatic failure regardless of time since ingestion. 1, 3
NAC Dosing Protocol
The intravenous regimen should be initiated urgently 2, 1, 4:
- Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 2, 4
- Second dose: 50 mg/kg over 4 hours 2, 4
- Third dose: 100 mg/kg over 16 hours 2, 4
- Continue NAC until transaminases are declining and INR normalizes 1
Critical Actions Required
Contact a liver transplant center immediately—this is mandatory as the patient meets criteria for potential transplantation. 1
King's College Hospital criteria for transplantation in paracetamol-induced ALF include: arterial pH <7.3 after resuscitation, OR all three of INR >6.5, creatinine >300 μmol/L, and Grade III-IV encephalopathy 1
ICU admission required: Patients with ALF require intensive monitoring for complications including worsening encephalopathy, coagulopathy, renal failure, and metabolic derangements 2, 3
Essential Laboratory Investigations
Obtain immediately 2:
- Prothrombin time/INR
- AST, ALT, alkaline phosphatase, total bilirubin, albumin
- Creatinine, blood urea nitrogen
- Arterial blood gas and arterial lactate
- Serum paracetamol level (even if delayed presentation—low or absent levels do NOT rule out paracetamol poisoning) 3
- Complete blood count
- Glucose (to monitor for hypoglycemia) 5
- Arterial ammonia
- Viral hepatitis serologies (anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV)
- Pregnancy test
Important Clinical Caveats
Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with paracetamol poisoning and should prompt immediate NAC treatment even when history is inadequate. 3
Staggered overdoses (repeated supratherapeutic ingestions for pain relief) are associated with worse outcomes despite lower total ingested doses, with mortality rates of 37.3% versus 27.8% for single time-point overdoses 6
Delayed presentation beyond 24 hours post-overdose independently predicts death/liver transplantation (OR 2.25) and is associated with increased multi-organ failure risk 6
The Rumack-Matthew nomogram does NOT apply to this patient due to staggered/repeated ingestion pattern and delayed presentation 3
Supportive Care Priorities
Monitor and manage complications aggressively 2, 7:
- Neuroprotective measures: Consider hypertonic saline to reduce intracranial hypertension risk if encephalopathy worsens 7
- Renal replacement therapy: High-dose hemofiltration may be needed to reduce ammonia levels and manage acute kidney injury (decreased urine output present) 7
- Fluid resuscitation: Address hypotension (BP 100/60 mmHg) carefully 7
- Broad-spectrum antimicrobials: Consider empiric coverage given risk of infection in ALF 7
- Avoid benzodiazepines and psychotropic drugs in hepatic encephalopathy 8
- Do not routinely correct coagulopathy unless active bleeding occurs 8
Prognosis
With aggressive critical care and specialized transplant center input, outcomes can be favorable 7. One-year survival is 76.7% and 5-year survival is 66% in patients who undergo liver transplantation for paracetamol-induced ALF 1. However, liver transplant is reserved for those unlikely to survive with medical treatment alone based on prognostic criteria 7.