Ascites Pharmacotherapy

Ascites is pathological fluid in the peritoneal cavity, most often from cirrhosis with portal hypertension, where renal sodium retention is driven by renin, aldosterone and sympathetic activation. It is graded as grade 1 (mild, seen on ultrasound only), grade 2 (moderate, symmetrical distension) and grade 3 (large or tense). Diagnostic paracentesis should be performed in every new ascites and every admission with cirrhosis and ascites.

Serum ascites albumin gradient. A gradient of 11 g/L or more indicates portal hypertension.

Peritoneal fluid neutrophils. A count of 250 cells/mm3 or more indicates spontaneous bacterial peritonitis.

Cause-specific therapy. Alcohol abstinence, antiviral therapy for hepatitis B and C, and treatment of heart failure or tuberculous peritonitis can resolve ascites.

Sodium restriction. About 2 g of sodium (88 mmol) daily. Do not restrict fluids unless sodium is under 125 mmol/L.

Grade 2 ascites. Spironolactone 100 mg orally once daily in the morning, increased every 3 to 5 days to a maximum of 400 mg daily.

Grade 3, recurrent or refractory to spironolactone alone. Add furosemide 40 mg orally once daily, keeping the 100 to 40 ratio, increased every 3 to 5 days to a maximum of 160 mg daily with 400 mg spironolactone.

Weight loss target. Up to 0.5 kg daily without peripheral oedema and up to 1 kg daily with peripheral oedema.

Alternatives. Amiloride 10 to 40 mg orally daily in place of spironolactone for painful gynaecomastia. Torsemide may replace furosemide in diuretic resistance, with equivalent potency set by response.

Large-volume paracentesis. - Remove the whole volume of fluid in one session when the patient is stable. - Give 20% or 25% albumin 8 g intravenously for each litre removed when more than 5 litres are drained, and consider it for smaller volumes in kidney impairment or acute-on-chronic liver failure.

Refractory ascites. Defined as ascites not mobilised or recurring early despite maximal diuretics and sodium restriction, or diuretic complications that prevent adequate dosing. Options are repeated large-volume paracentesis with albumin, transjugular intrahepatic portosystemic shunt, and transplant. Midodrine 7.5 mg orally three times daily has been used to improve blood pressure and diuretic response, though evidence is limited.

Hyponatraemia. - Sodium 126 to 135 mmol/L: no change in diuretics unless the patient is symptomatic. - Sodium 121 to 125 mmol/L: stop or reduce diuretics and restrict fluid to 1 to 1.5 litres daily. - Sodium 120 mmol/L or less: stop diuretics, give albumin 1 g/kg intravenously (maximum 100 g), and arrange specialist care. - Avoid tolvaptan in cirrhosis because of hepatotoxicity.

Muscle cramps. Check electrolytes and consider albumin. Baclofen 5 to 10 mg orally at night may be used, with a maximum of 30 mg daily; watch for sedation and encephalopathy.

Spontaneous bacterial peritonitis. Treat with cefotaxime 2 g intravenously every 8 hours or ceftriaxone 2 g intravenously once daily for 5 to 7 days, with albumin 1.5 g/kg intravenously within 6 hours (maximum 150 g) and 1 g/kg on day 3 (maximum 100 g). Prophylaxis is with norfloxacin 400 mg or ciprofloxacin 500 mg or co-trimoxazole 960 mg orally once daily.

Hepatorenal syndrome. Albumin 1 g/kg (maximum 100 g) daily for 2 days, then terlipressin 1 mg intravenously every 4 to 6 hours (maximum 12 mg daily) with albumin 20 to 40 g daily, for up to 14 days.

Drugs to avoid. Non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, alpha blockers and aminoglycosides.

Hyperkalaemia and hypokalaemia. Spironolactone and amiloride raise potassium, particularly with kidney impairment; furosemide lowers it.

Pregnancy. Spironolactone and angiotensin converting enzyme inhibitors are avoided. Paracentesis with albumin is the main treatment.

Breastfeeding. Spironolactone is compatible at usual doses; furosemide may reduce milk supply.

Older adults. Increase diuretics in smaller steps and check electrolytes twice weekly during titration.

Kidney impairment. Reduce or stop diuretics when creatinine rises by 50% or to over 133 micromol/L.

East Africa. Differentiate tuberculous peritonitis, which gives a low gradient with lymphocytic fluid and high adenosine deaminase, and consider schistosomal and hepatitis B causes.

Interactions. Spironolactone with trimethoprim, potassium supplements or angiotensin converting enzyme inhibitors raises potassium. Non-steroidal anti-inflammatory drugs blunt diuretic effect.

Monitoring. Daily weight, urine output, creatinine, sodium and potassium every 2 to 3 days at the start and with each dose increase, then monthly. Blood pressure at every review.

Stopping thresholds. - Sodium under 125 mmol/L. - Acute kidney injury or creatinine over 133 micromol/L. - Worsening encephalopathy. - Potassium under 3 mmol/L (stop furosemide) or over 6 mmol/L (stop spironolactone). - Severe disabling cramps.

Referral and escalation. Refer to hepatology for grade 3 or refractory ascites, hyponatraemia under 125 mmol/L, hepatorenal syndrome, or fever and abdominal pain, and refer for transplant assessment.