Medicine Selection in Decompensated Cirrhosis

Decompensated cirrhosis is cirrhosis complicated by ascites, variceal bleeding, hepatic encephalopathy or jaundice. Medicines in this setting must treat complications, prevent infection and bleeding, and avoid triggering acute kidney injury, encephalopathy or acute-on-chronic liver failure.

Common iatrogenic triggers. Non-steroidal anti-inflammatory drugs, overdiuresis, large-volume paracentesis without albumin, sedatives, opioids, aminoglycosides, contrast, and hypotension from beta blockers or vasodilators.

Physiology. Splanchnic vasodilation leads to low effective arterial volume, activation of the renin, sympathetic and vasopressin systems, and kidney dependence on these responses. Drugs that block these responses, such as angiotensin converting enzyme inhibitors, cause hypotension and kidney injury.

Ascites. Spironolactone first line; furosemide added; amiloride 10 to 40 mg daily as an alternative to spironolactone in painful gynaecomastia. Avoid angiotensin converting enzyme inhibitors, angiotensin receptor blockers and alpha blockers.

Varices. Carvedilol or propranolol for prevention of bleeding. Vasoactive drug plus antibiotic for acute bleeding.

Encephalopathy. Lactulose first line; rifaximin added after recurrence.

Infection prophylaxis. Norfloxacin, ciprofloxacin or co-trimoxazole for spontaneous bacterial peritonitis prophylaxis in selected patients.

Hepatorenal syndrome with acute kidney injury. Terlipressin with albumin. Noradrenaline with albumin in intensive care when terlipressin is unsuitable.

Drugs to avoid. - Non-steroidal anti-inflammatory drugs and selective COX-2 inhibitors. - Aminoglycosides. - Benzodiazepines, except lorazepam or oxazepam for alcohol withdrawal. - Tramadol, codeine and pethidine. - Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in ascites. - Acarbose and sulphonylureas with long half-life such as glibenclamide. - Statins in Child-Pugh C.

Diuretics. Spironolactone 100 mg orally once daily plus furosemide 40 mg orally once daily, increased every 3 to 5 days to a maximum of 400 mg and 160 mg daily. Target weight loss up to 0.5 kg daily, or 1 kg daily with peripheral oedema.

Large-volume paracentesis. Give albumin 8 g for each litre removed when more than 5 litres are drained, as 20% albumin intravenously after the procedure.

Non-selective beta blockers. Carvedilol 6.25 mg once daily, increased to 6.25 mg twice daily after 3 days; maximum 12.5 mg daily. In refractory ascites, reduce or stop if systolic blood pressure is under 90 mmHg, sodium under 130 mmol/L or kidney injury develops.

Acute variceal bleeding. - Terlipressin 2 mg intravenously every 4 hours until bleeding is controlled, then 1 mg every 4 hours, for 2 to 5 days. - Or octreotide 50 micrograms intravenous bolus, then 50 micrograms/hour infusion for 2 to 5 days. - Plus ceftriaxone 1 g intravenously once daily for up to 7 days.

Hepatic encephalopathy. Lactulose 20 to 30 mL orally 2 to 3 times daily, titrated to 2 to 3 soft stools daily. Rifaximin 550 mg orally twice daily for secondary prevention.

Spontaneous bacterial peritonitis prophylaxis. Norfloxacin 400 mg orally once daily, or ciprofloxacin 500 mg orally once daily, or co-trimoxazole 960 mg orally once daily, long term while risk persists.

Hepatorenal syndrome with acute kidney injury. Albumin 1 g/kg (maximum 100 g) daily for 2 days first. Then terlipressin 1 mg intravenously every 4 to 6 hours or 2 mg daily by continuous infusion, increased to a maximum of 12 mg daily if creatinine has not fallen by 25% at day 3, for up to 14 days; with albumin 20 to 40 g daily.

Special groups. - Kidney impairment: adjust ciprofloxacin and co-trimoxazole to creatinine clearance. - Older adults: lower diuretic increments and closer sodium checks. - Pregnancy: terlipressin is contraindicated; spironolactone avoided.

Monitoring. Daily weight, creatinine, sodium and potassium during diuretic titration and in hospital. Oxygen saturation and fluid status during terlipressin and albumin, given the risk of pulmonary oedema.

Terlipressin stop rules. Do not start if oxygen saturation is under 90%, or in severe ischaemic heart or peripheral vascular disease. Stop for respiratory failure, ischaemia, severe hyponatraemia or arrhythmia.

Lactulose. Reduce if more than 3 stools daily, dehydration or hypernatraemia develop.

Referral and escalation. Refer every decompensated patient for transplant assessment. Escalate to high dependency care for bleeding, grade 3 to 4 encephalopathy, hepatorenal syndrome or organ failure.