What are the major complications of ascites and how should they be managed?

Major Complications of Ascites in Cirrhosis

The major complications of ascites include spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), dilutional hyponatremia, acute kidney injury, hepatic hydrothorax, and abdominal hernias—all of which significantly worsen prognosis and require prompt recognition and specific management strategies. 1

Spontaneous Bacterial Peritonitis (SBP)

Diagnosis and Clinical Significance

• SBP occurs in 10-15% of hospitalized cirrhotic patients with ascites and carries an in-hospital mortality of approximately 20%, with 1-year survival after an episode only 30-50%. 1, 2
• Diagnosis is confirmed when ascitic fluid neutrophil count exceeds 250 cells/mm³ in the absence of a surgically treatable intra-abdominal source. 1
• Perform diagnostic paracentesis immediately in any cirrhotic patient with ascites who develops fever, abdominal pain, altered mental status, worsening renal function, gastrointestinal bleeding, leukocytosis, or unexplained clinical deterioration. 1, 2
• Each hour of delay in diagnostic paracentesis after admission increases in-hospital mortality by 3.3%. 1

Management Protocol

• Start empiric third-generation cephalosporin (cefotaxime 2g IV every 8 hours) immediately when ascitic neutrophil count exceeds 250 cells/mm³, without awaiting culture results. 1, 2
• Inoculate 10 mL of ascitic fluid into blood culture bottles at the bedside to maximize bacterial recovery. 1, 2
• In patients with SBP showing renal impairment (creatinine >1 mg/dL, BUN >30 mg/dL, or total bilirubin >4 mg/dL), administer albumin 1.5 g/kg within 6 hours of diagnosis, followed by 1.0 g/kg on day 3 to prevent hepatorenal syndrome and reduce mortality. 1, 2, 3

Secondary Prophylaxis

• After recovery from a first SBP episode, initiate lifelong secondary prophylaxis with norfloxacin 400 mg daily (or ciprofloxacin 500 mg daily), which reduces recurrence from 68% to 20%. 2
• Be aware that long-term quinolone prophylaxis is associated with a 79% increase in gram-positive infections, including MRSA. 2
• All patients who experience SBP should be evaluated for liver transplantation, as 2-year survival is only 25-30%. 2

Hepatorenal Syndrome (HRS)

Epidemiology and Prognosis

• HRS accounts for 3.2% of all cirrhosis-related hospital discharges and is associated with approximately 46% inpatient mortality. 1
• HRS represents the most life-threatening type of acute kidney injury in cirrhotic patients. 4
• The number of HRS discharges in the United States has increased significantly over the past two decades. 1

Pathophysiology

• HRS results from severe effective arterial underfilling due to splanchnic vasodilation, leading to activation of vasoconstrictor systems (renin-angiotensin) and antidiuretic factors (arginine vasopressin). 1
• Portal hypertension increases sinusoidal hydrostatic pressure and gut permeability, allowing bacterial translocation that further contributes to HRS development. 1

Management

• The most appropriate medical treatment for HRS is the administration of vasoconstrictors (terlipressin, midodrine plus octreotide, or norepinephrine) combined with albumin infusion. 4
• Volume expansion with albumin and cautious diuresis are recommended. 5
• Patients developing HRS should be prioritized for liver transplantation evaluation. 1

Dilutional Hyponatremia

Definition and Clinical Impact

• Hyponatremia in cirrhosis is defined as serum sodium <130 mmol/L, as complications increase significantly below this threshold. 1
• Complications include increased risk of SBP (OR 3.40), HRS (OR 3.45), and hepatic encephalopathy (OR 2.36). 1

Management Algorithm Based on Severity

For serum sodium 126-135 mmol/L with normal renal function:

• Continue diuretics with close electrolyte monitoring; water restriction is not required. 2

For serum sodium 121-125 mmol/L with normal renal function:

• Reduce or temporarily discontinue diuretics. 2

For serum sodium 121-125 mmol/L with elevated creatinine (>150 µmol/L or rising):

• Stop diuretics immediately and provide volume expansion with colloid or saline. 2

For serum sodium <120 mmol/L:

• Stop diuretics, give volume expansion, and correct serum sodium cautiously—limit the rise to 4-6 mmol/L per 24 hours, not exceeding 8 mmol/L per 24 hours to prevent osmotic demyelination syndrome (ODS). 1, 2
• Reserve hypertonic saline for severely symptomatic hyponatremia (seizures, coma, cardiorespiratory distress). 2

Special Considerations

• Severe hyponatremia (<120 mmol/L) at time of liver transplantation increases the risk of ODS; multidisciplinary coordinated care may mitigate this risk. 1

Hepatic Hydrothorax (HH)

Epidemiology and Prognosis

• HH occurs in 4-12% of cirrhotic patients and is typically unilateral (73% right-sided, 17% left-sided, 10% bilateral). 1
• Mortality at 90 days after hospitalization with HH is 74% despite a mean MELD of 14, which would otherwise predict only 6-8% mortality—indicating HH carries a prognosis worse than predicted by MELD score alone. 1
• 9% of HH patients do not have clinically apparent ascites. 1

Diagnosis

• A serum to pleural fluid albumin gradient >1.1 g/dL is suggestive of HH. 1
• Consider alternative diagnoses (infection, pancreatitis, malignancy, cardiopulmonary causes) if the gradient is ≤1.1 g/dL, if the effusion is left-sided, or in the absence of ascites. 1

Management

• First-line therapy consists of dietary sodium restriction (90 mmol/day) and diuretics plus thoracentesis as required. 1
• Thoracentesis can be performed without transfusion of platelets or plasma. 1
• If ascites is present, large-volume paracentesis with IV albumin may improve ventilatory function, but thoracentesis is generally also required. 1
• TIPS can be considered in selected patients as second-line treatment for refractory HH. 1
• Chest tube insertion for HH should be avoided, but indwelling tunneled catheters may be considered in carefully selected patients who do not respond to medical therapy and are not candidates for TIPS. 1
• All patients with HH should be considered for liver transplantation and may receive additional priority for transplant. 1

Complications

• Complications include spontaneous bacterial empyema, progressive respiratory failure, trapped lung, and complications of thoracentesis (pneumothorax, bleeding). 1
• Patients with indwelling pleural catheters are at risk for protein depletion and malnutrition. 1
• Chemical pleurodesis often leads to loculated collections and is not recommended. 1

Abdominal Hernias

Epidemiology and Pathophysiology

• Umbilical hernias develop in approximately 20% of cirrhotic patients. 1
• Increased abdominal pressure from ascites, weakened abdominal muscles, and poor nutrition lead to rapidly enlarging hernias. 1

Complications

• Hernias may present with incarceration, pressure necrosis, rupture, evisceration, and peritonitis. 1
• A rapid decline in ascitic fluid volume (e.g., after large-volume paracentesis) can paradoxically cause incarceration. 1

Management Strategy

• Patients who are candidates for liver transplantation in the near future should defer hernia repair until during or after transplantation. 1
• For patients with low MELD scores in whom transplantation is not imminent, elective herniorrhaphy may be offered after careful risk-benefit assessment, with laparoscopic approaches preferred. 1
• Clinically apparent ascites should be controlled before elective herniorrhaphy. 1
• Postoperatively, control of ascites and optimization of nutrition are key determinants of successful outcome; restrict sodium intake to 2 g/day (90 mmol/day) and eliminate or minimize IV maintenance fluids. 1
• In high-risk patients with refractory ascites, elective preoperative TIPS can be considered before surgery. 1
• Emergent surgery for strangulated or ruptured umbilical hernia should be performed by a surgeon experienced in cirrhosis care, in consultation with a hepatologist for postoperative ascites control; TIPS placement may be considered postoperatively if ascites cannot be controlled medically. 1

Acute Kidney Injury (AKI)

Clinical Significance

• AKI is a common complication in patients with ascites and is associated with poor prognosis. 1
• Portal hypertension and bacterial translocation contribute to renal injury through direct hemodynamic effects. 1
• Structural kidney damage can follow severe and/or repeated episodes of renal events. 1

Prevention and Management

• Avoid nephrotoxic medications: NSAIDs, ACE inhibitors, angiotensin-II receptor blockers, α₁-adrenergic blockers, and aminoglycosides. 2
• Monitor renal function closely during diuretic therapy and after large-volume paracentesis. 2
• For large-volume paracentesis >5 liters, mandatory albumin replacement at 8 g per liter of ascites removed prevents post-paracentesis circulatory dysfunction and reduces the risk of AKI. 6, 2

Refractory Ascites

Definition

• Refractory ascites is defined as ascites that cannot be mobilized or recurs rapidly despite maximal diuretic therapy (spironolactone ≤400 mg/day and furosemide ≤160 mg/day) with sodium restriction, or ascites that cannot be treated due to diuretic-induced complications. 1, 2
• Once ascites becomes refractory, mortality rises to 50% within 6 months. 2

Management

• Repeated large-volume paracentesis with albumin supplementation (8 g per liter removed for volumes >5 L) is the standard first-line approach. 2
• TIPS should be considered in patients requiring ≥3 therapeutic paracenteses per month, after careful risk-benefit assessment. 2
• TIPS provides superior long-term control but may precipitate hepatic encephalopathy and heart failure; it is contraindicated in patients with MELD >18. 2
• All patients with refractory ascites should be evaluated for liver transplantation. 1, 2

Prognostic Implications

• Development of ascites reduces 5-year survival from 80% to 30% and represents an indication for liver transplantation evaluation. 1, 2
• Patients with ascites are prone to additional complications including bacterial infections, electrolyte abnormalities, HRS, and nutritional imbalances, leading to further clinical decline. 1
• When appropriate, patients with ascites and related complications should be considered for palliative care consultation. 1