What medications should be prescribed for a patient with liver cirrhosis to manage ascites, portal hypertension, variceal bleed prophylaxis, hepatic encephalopathy, spontaneous bacterial peritonitis prophylaxis, and supportive care?

Medications for Liver Cirrhosis Management

For patients with liver cirrhosis, the medication regimen should include spironolactone (100-400 mg daily) with or without furosemide (40-160 mg daily) for ascites, lactulose for hepatic encephalopathy, norfloxacin or ciprofloxacin for spontaneous bacterial peritonitis prophylaxis in high-risk patients, and carvedilol or propranolol for variceal bleeding prevention. 1, 2

Ascites Management

First-Line Diuretic Therapy

• For first presentation of moderate ascites: Start spironolactone monotherapy at 100 mg daily, titrating up to 400 mg as needed 1

• For recurrent or severe ascites requiring hospitalization: Initiate combination therapy with spironolactone (100 mg, up to 400 mg) plus furosemide (40 mg, up to 160 mg) from the start 1

  • This combination approach achieves faster diuresis and higher resolution rates (76% vs 56%) compared to sequential therapy 2
  • The combination also reduces hyperkalemia risk (4% vs 18%) compared to sequential initiation 2

• Critical monitoring requirement: Nearly half of patients on diuretics develop adverse events requiring dose reduction or discontinuation 1

  • Monitor electrolytes, renal function, and blood pressure closely, especially in the first week 3
  • Check electrolytes weekly for the first month, then monthly if stable 3

Adjunctive Therapy for Refractory Ascites

• Midodrine may be considered on a case-by-case basis for refractory ascites to help maintain blood pressure 1, 3

Dietary Sodium Restriction

• Restrict sodium intake to 5-6.5 g daily (87-113 mmol), which translates to a no-added-salt diet with avoidance of precooked meals 1
• Provide nutritional counseling on sodium content 1

Large Volume Paracentesis Protocol

Albumin Replacement

• For paracentesis >5 L: Administer albumin (20% or 25% solution) at 8 g per liter of ascites removed after the procedure is completed 1

  • This prevents post-paracentesis circulatory dysfunction 1
  • Alternative plasma expanders (dextran-70, polygeline) are less effective than albumin for large volumes 1

• For paracentesis <5 L: Albumin can be considered in patients with acute-on-chronic liver failure or high risk of acute kidney injury 1

Spontaneous Bacterial Peritonitis (SBP) Management

Treatment of Active SBP

• Immediate empirical antibiotic therapy: Cefotaxime is widely studied, but choice should be guided by local resistance patterns and whether infection is community-acquired or healthcare-associated 1

• Albumin administration: Give 1.5 g/kg within 6 hours of diagnosis, followed by 1 g/kg on day 3 in patients with increased or rising serum creatinine 1

  • This reduces mortality risk 1

Secondary Prophylaxis (After SBP Episode)

• Norfloxacin 400 mg once daily OR
• Ciprofloxacin 500 mg once daily OR
• Co-trimoxazole (800 mg sulfamethoxazole/160 mg trimethoprim) daily 1

Primary Prophylaxis

• Indicated for high-risk patients: Ascitic protein <1.5 g/dL 1
• Also indicated: Patients with gastrointestinal bleeding and ascites should receive prophylactic antibiotics (cefotaxime or based on local data) to prevent SBP 1

Important caveat: Antibiotic prophylaxis increases risk of multidrug-resistant organisms, so restrict to highest-risk patients only 4

Hepatic Encephalopathy

• Lactulose is first-line therapy for improving mental status 5, 2

  • Reduces mortality (8.5% vs 14% with placebo) in trials of 705 patients 2
  • Reduces recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in trials of 1,415 patients 2

• Protein restriction is no longer recommended 5

Variceal Bleeding Prophylaxis

• Carvedilol or propranolol (non-selective beta-blockers) are first-line for preventing variceal bleeding 2
  • In a 3-year trial of 201 patients with portal hypertension, these reduced decompensation or death (16% vs 27% with placebo) 2

Management in Refractory Ascites

• Refractory ascites is NOT a contraindication to non-selective beta-blockers 1
• However, monitor closely and consider dose reduction or discontinuation if hypotension or acute/progressive renal dysfunction develops 1

Hepatorenal Syndrome

• Terlipressin improves reversal of hepatorenal syndrome (39% vs 18% with placebo in 300 patients) 2

Critical Drug Safety Considerations

Medications to AVOID or Use with Extreme Caution

• NSAIDs: Should be used cautiously or not at all in advanced cirrhosis due to risk of renal failure and gastrointestinal bleeding 6

• Proton pump inhibitors: Linked to increased risk of SBP in cirrhosis; use with care 6

• Nephrotoxic agents: Avoid aminoglycosides, ACE inhibitors, angiotensin receptor blockers 7

Safe Analgesic Use

• Acetaminophen/Paracetamol: Can be used safely at 2-3 g or less per day for short durations; recommended as first-line for pain 6

Electrolyte Management Protocols

Hyponatremia Management

• For hypovolemic hyponatremia during diuretic therapy: Discontinue diuretics and expand plasma volume with normal saline 1

• Fluid restriction to 1-1.5 L/day: Reserved only for clinically hypervolemic patients with severe hyponatremia (sodium <125 mmol/L) 1

• Hypertonic saline (3%): Reserved for severely symptomatic patients with acute hyponatremia; correct sodium slowly 1

Hospitalization Requirements

When to Initiate Therapy in Hospital

• Spironolactone initiation in cirrhosis with ascites should occur in the hospital to monitor for sudden alterations in fluid and electrolyte balance that may precipitate hepatic encephalopathy and coma 8, 9

• Start with lowest initial dose and titrate slowly in patients with cirrhosis due to reduced clearance 8

Transjugular Intrahepatic Portosystemic Shunt (TIPS)

• Consider TIPS for refractory ascites 1

• Exercise caution if: Age >70 years, bilirubin >50 μmol/L, platelets <75×10⁹/L, MELD score ≥18, current hepatic encephalopathy, active infection, or hepatorenal syndrome 1

Symptom Management

• Hydroxyzine for sleep dysfunction 2
• Pickle brine or taurine for muscle cramps 2
• Tadalafil for sexual dysfunction in men 2