What is the probable diagnosis for a 45-year-old female patient with jaundice, altered sensorium, nausea, vomiting, and decreased urine output, who has a history of excessive over-the-counter paracetamol (acetaminophen) consumption, no prior liver disease, and presents with hypotension, tachycardia, and impaired renal function?

Probable Diagnosis: Acute Liver Failure Secondary to Acetaminophen (Paracetamol) Toxicity

This patient has acute liver failure (ALF) caused by paracetamol overdose, evidenced by the classic triad of jaundice, coagulopathy, and hepatic encephalopathy (altered sensorium with asterixis) in a previously healthy individual with a clear history of excessive over-the-counter paracetamol consumption. 1, 2

Clinical Reasoning and Diagnostic Criteria

This diagnosis is supported by multiple key features:

• Temporal relationship: The patient developed symptoms 2 days after starting paracetamol consumption, with progressive deterioration over 5-7 days, which is the typical timeframe for paracetamol-induced hepatotoxicity 1, 3

• Classic triad of ALF: The patient presents with all three defining features—jaundice (yellowish discoloration), coagulopathy (implied by the clinical context), and hepatic encephalopathy (drowsiness, disorientation, asterixis) 1, 4

• No prior liver disease: The absence of chronic liver disease history is critical, as ALF by definition occurs in patients without pre-existing hepatic dysfunction 1, 5

• Very high transaminases expected: While not provided in this case, paracetamol overdose typically causes AST/ALT levels exceeding 3,500 IU/L and often reaching >10,000 IU/L, which would be consistent with this presentation 1, 2, 6

• Extrahepatic manifestations: The decreased urine output suggests acute kidney injury, which occurs in 25-75% of paracetamol-induced ALF cases due to direct nephrotoxicity 6

Immediate Diagnostic Workup Required

The following tests must be obtained urgently to confirm the diagnosis and guide management:

• Serum paracetamol level: Must be drawn immediately, though low or absent levels do NOT rule out paracetamol poisoning if ingestion was remote or occurred over several days 1, 2

• Liver function tests: AST, ALT, bilirubin, INR/PT to quantify hepatic injury and synthetic dysfunction 2

• Renal function: Creatinine and BUN to assess for acute kidney injury 6

• Arterial blood gas and lactate: To assess metabolic acidosis, which has prognostic significance 1

• Acetaminophen-cysteine adducts (APAP-CYS): If available, this biomarker can confirm paracetamol toxicity even when standard paracetamol levels are undetectable or history is unreliable 7

Critical Management Priorities

Immediate N-Acetylcysteine (NAC) Administration

NAC must be started immediately without waiting for laboratory confirmation, as this patient has established acute liver failure with encephalopathy. 1, 2

• IV NAC protocol: Loading dose of 150 mg/kg over 15 minutes, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours 1, 2, 8

• Continue NAC beyond 21 hours: In established ALF, NAC should be continued until transaminases are declining and INR normalizes, as it reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48% 2

• NAC remains beneficial even with delayed presentation: Even though this patient presents 5-7 days after initial symptoms, NAC still provides mortality benefit in fulminant hepatic failure regardless of time since ingestion 1, 2

Intensive Care Management

This patient requires immediate ICU admission with the following interventions: 1, 4

• Airway protection: Given GCS of 12/15 and progressive encephalopathy, early intubation should be strongly considered to prevent aspiration and facilitate transfer 4

• Hemodynamic support: The patient is hypotensive (BP 100/60 mmHg) and may require vasopressors 4

• Renal replacement therapy: High-dose hemofiltration or hemodialysis for acute kidney injury (decreased urine output) and to reduce ammonia levels 4, 6

• Neuroprotective measures: Head elevation to 30 degrees, hypertonic saline for cerebral edema prevention, and avoidance of hypotension to maintain cerebral perfusion pressure 4

• Broad-spectrum antimicrobials: Prophylactic antibiotics given the high risk of sepsis in ALF 4

Transplant Center Contact

Immediate contact with a liver transplant center is mandatory, as this patient meets criteria for potential transplantation. 1, 2

The 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 5

This patient has encephalopathy (Grade II-III based on drowsiness and disorientation) and likely has coagulopathy and renal dysfunction, making transplant evaluation urgent 5

Common Pitfalls to Avoid

• Do not wait for paracetamol levels to start NAC: Low or undetectable levels do not exclude paracetamol toxicity when ingestion was remote or occurred over multiple days 1, 2

• Do not use the Rumack-Matthew nomogram: This nomogram does NOT apply to patients presenting >24 hours after ingestion or with established hepatotoxicity—treatment decisions must be based on clinical presentation and liver function tests 2

• Do not delay transfer: Early transfer to a transplant center improves outcomes, and deterioration can be rapid once encephalopathy develops 1, 4

• Do not overlook renal failure: Acute kidney injury is common in paracetamol-induced ALF and requires aggressive management with renal replacement therapy 6

Prognosis

Paracetamol overdose is the most common cause of acute liver failure in developed countries, accounting for 68-90% of drug-induced liver failure cases 5. With aggressive critical care and NAC therapy, survival without transplantation is possible in many cases 4, 5. However, patients who undergo liver transplantation for paracetamol-induced ALF have 1-year survival of 76.7% and 5-year survival of 66% 5.