Ischaemic Hepatitis After Surgery

Ischaemic hepatitis (shock liver, hypoxic hepatitis) is a rapid rise in serum aminotransferases (over 20 times the upper limit of normal, often over 1,000 units/L) after circulatory failure or hypoxia, with exclusion of other causes, and a fall within 7 to 10 days.

Epidemiology. It occurs in about 1% to 2% of intensive care admissions and a minority after major cardiac, vascular and abdominal surgery. In hospital mortality is about 50% to 60%, driven by the underlying cause.

Causes. Cardiogenic shock and heart failure, hypotension, septic shock, haemorrhage, hypoxaemia, respiratory failure, arrhythmia, cardiac arrest, hepatic artery or portal vein thrombosis, and hepatic vein outflow obstruction.

Risk factors. Chronic liver disease, right heart failure with venous congestion, cirrhosis, sepsis and hypotension over 1 hour.

Pathophysiology.

Reduced hepatic oxygen delivery causes centrilobular (zone 3) necrosis because that zone has the lowest oxygen tension. Passive venous congestion in heart failure adds to hypoxic injury. Reperfusion injury follows restoration of flow.

Often few liver specific symptoms because shock dominates. Possible: jaundice, right upper quadrant discomfort, hepatomegaly, coagulopathy, hypoglycaemia, encephalopathy, and oliguria.

Red flags.

• Hypoglycaemia (glucose under 4 mmol/L).
• INR over 2.0 with encephalopathy (acute liver failure).
• Persistent rise beyond 7 days.

Aspartate and alanine aminotransferase rise within 24 hours to over 1,000 units/L (peaks 1 to 3 days), lactate dehydrogenase raised markedly (ratio of alanine aminotransferase to lactate dehydrogenase under 1.5), bilirubin modestly raised, INR prolonged. Aminotransferases fall by 50% daily after recovery of perfusion. Liver ultrasound with Doppler excludes vascular occlusion. Exclude viral hepatitis, drug injury (paracetamol), autoimmune disease and biliary obstruction.

Differential diagnosis.

• Paracetamol toxicity.
• Acute viral hepatitis.
• Drug induced liver injury (halothane, other agents).
• Biliary obstruction.
• Hepatic artery thrombosis.
• Budd-Chiari syndrome.
• Autoimmune hepatitis.

Treat the cause: restore perfusion and oxygenation, with mean arterial pressure at 65 mmHg or more, cardiac output optimisation, treatment of sepsis and arrhythmia, and haemoglobin over 70 g/L.

• Fluid and vasopressor titration: noradrenaline 0.05 to 0.5 microgram/kg/min IV; maximum 1 microgram/kg/min; monitor arterial pressure, lactate and urine output.
• Oxygen to saturation of 94% to 98%.
• Glucose: monitor every 1 to 2 hours; give 10% glucose 150 to 200 mL IV until glucose is over 4 mmol/L; maximum directed by repeat glucose.

Stop hepatotoxic and unnecessary drugs, dose adjust renally and hepatically cleared agents, and avoid paracetamol over 2 g daily until recovery.

• N-acetylcysteine: 150 mg/kg IV over 1 hour, then 12.5 mg/kg/h for 4 hours, then 6.25 mg/kg/h for 16 hours; in non-paracetamol acute liver failure with encephalopathy; maximum within the product label limit; monitor anaphylactoid reaction and fluid; reduce rate in fluid overload.

Liver transplant is considered if acute liver failure develops (INR over 2 and encephalopathy), which is rare.

Monitoring. Aminotransferases, bilirubin, INR, glucose, lactate, creatinine, ammonia and neurological state daily until recovery.

Referral and escalation. Hepatology and critical care for coagulopathy, encephalopathy or persisting rise. Transplant centre referral for acute liver failure.