Ascites

Ascites is the abnormal accumulation of fluid within the peritoneal cavity and is a common complication of portal hypertension (e.g., due to liver cirrhosis, acute liver failure) and/or hypoalbuminemia (e.g., due to nephrotic syndrome). Other conditions resulting in ascites include chronic heart failure, inflammation of abdominal viscera (e.g., pancreatitis), and malignancies. Clinical features include progressive abdominal distention, shifting dullness, and a positive fluid wave test. Abdominal pain may be present in ascites due to an acute inflammatory etiology. Diagnostics are aimed at identifying the underlying etiology and determining whether the ascitic fluid is infected. They include imaging (e.g., with abdominal ultrasound or CT abdomen and pelvis), which is used to identify free intraperitoneal fluid and possibly the underlying cause, and diagnostic paracentesis with ascitic fluid analysis. The serum-ascites albumin gradient (SAAG), or the difference between albumin levels in serum and ascitic fluid, is essential to determine the underlying etiology. A high SAAG indicates that the ascites is secondary to portal hypertension. An ascitic fluid neutrophil count ≥ 250 cells/mm³ indicates spontaneous bacterial peritonitis (SBP), which should be urgently managed with empiric antibiotic therapy. Management of ascites involves identifying and managing the underlying cause as well as dietary sodium restriction and diuretic therapy. Additionally, tense ascites and refractory ascites require therapeutic paracentesis. Liver transplant is a treatment option for patients with cirrhosis who develop ascites. Transjugular intrahepatic portosystemic shunts (TIPS) and peritoneovenous shunts are advanced treatment options for refractory ascites, which carries a high risk of mortality.

• The etiology can be determined using the serum-ascites albumin gradient (SAAG) based on Starling's law.
• SAAG = (albumin levels in serum) - (albumin levels in ascitic fluid)

Remember, exudative ascitic fluid is high in protein, like eggs.

References:^[1][2][3]

• Progressive abdominal distention ; symptoms associated with increased abdominal distention include
  • Early satiety
  • Weight gain
  • Dyspnea
  • Diarrhea, which, if chronic, may be associated with features of malnutrition
• Fluid wave test: wave produced by tapping one side of the abdomen in a patient in supine position; this wave will be transmitted to the other side via ascitic fluid.
• Shifting dullness: change of resonance from dull to tympanic resonance when patient changes from supine to lateral decubitus position.
• Flank dullness: typically elicited only if > 1.5 L of ascitic fluid is present ^[4]
• Abdominal pain may be present
• Abdominal wall hernias (e.g., umbilical, inguinal, or incisional hernias)
• Peripheral or generalized edema
• Signs of underlying disease
  • Enlarged liver, jaundice, spider angioma, palmar erythema: chronic liver disease
  • Elevated jugular venous pressure: heart failure
  • Virchow's node; and weight loss: upper abdominal malignancy

References:^[2]

Chylous ascites

• Definition: collection of lymph in the abdominal cavity, which is characteristically triglyceride-rich and has a milky appearance
• Etiology: : malignancy (e.g., lymphoma), hepatic cirrhosis, or other lymph disorders (e.g., lymphatic hyperplasia) which result in increased lymph production

Bloody ascites

• Definition: ascitic fluid with RBC > 50,000 mm³
• Etiology: : may be spontaneous (e.g., due to peritoneal carcinomatosis or a malignant mass eroding into vessels) or iatrogenic (e.g., following paracentesis or biopsy in patients with cirrhosis)

Diagnostics are used to confirm the presence of ascites, assess its severity, determine the underlying etiology, and evaluate for complications. ^[5]

Imaging ^[6][7]

Abdominal ultrasound (initial study of choice)

• Indications
  • Clinical suspicion of new-onset ascites
  • Evaluation for an underlying condition (e.g., cirrhosis, intraabdominal malignancy) ^[6]
  • Ultrasound-guided paracentesis
• Supportive findings
  • Free intraperitoneal fluid
    • Uncomplicated nonhemorrhagic ascites typically appears hypoechoic/anechoic
    • Internal echoes, debris, and septations are suggestive of exudates. ^[7]
  • Features of underlying etiology (e.g., liver cirrhosis, hepatocellular carcinoma, Budd-Chiari syndrome, ovarian tumors; see respective articles for details)

CT abdomen (and pelvis) ^[5]

• Indications: to work up for the underlying cause as needed; examples include ^[5][6]
  • GI perforation in patients with postoperative or traumatic ascites
  • Secondary peritonitis
  • Malignancy
• Findings
  • Free intraperitoneal fluid
  • Fluid density depends on the type of ascites

Laboratory studies ^[6]

The choice of laboratory studies should be guided by the pretest probability of the suspected underlying etiology.

• CBC: abnormalities related to an underlying condition
• Coagulation panel: Thrombocytopenia and coagulopathy are signs of advanced liver disease.
• Liver chemistries
  • Elevated transaminases suggest liver disease.
  • Serum albumin (for SAAG calculation)
• BMP
  • Elevated creatinine and BUN: Acute kidney injury is common in patients with decompensated cirrhosis. ^[8]
  • Serum electrolytes: hypervolemic hypotonic hyponatremia (as a complication of cirrhosis) ^[9]
• Additional evaluation for the underlying condition: E.g., see “Diagnostics for hepatic cirrhosis.”

Diagnostic paracentesis ^[5][6][10]

Indications

• All patients with new-onset ascites (to identify the underlying etiology) ^[4][5][10]
• To detect spontaneous bacterial peritonitis (SBP) or other peritoneal infections in the following situations:
  • Clinical suspicion
  • Hospitalization for any cause in patients with cirrhosis and ascites (to identify occult SBP) ^[4][6][11]

Occult SBP is common in patients with ascites and cirrhosis and delays in diagnosis result in increased mortality. ^[12]

Ascitic fluid analysis ^[6][10]

Routine studies

• Gross appearance: can provide supportive evidence of the underlying cause or complications
  • Transparent to yellow: uncomplicated ascites
  • Cloudy: infection or malignancy
  • Bloody: trauma or malignancy
  • Milky: chylous ascites
  • Dark brown: suggestive of a biliary leak (e.g., gallbladder perforation)
• Cell count and differential: A neutrophil count ≥ 250 cells/mm³ indicates spontaneous bacterial peritonitis.
• Ascitic fluid albumin: for SAAG calculation (obtain same-day serum and ascitic fluid samples) ^[6]
• Ascitic fluid total protein
  • To differentiate cirrhosis from cardiac etiologies in high SAAG ascites
  • To differentiate SBP (typically ≤ 1 g/dL) from secondary peritonitis (typically > 1 g/dL) ^[6][13]

Additional studies (based on the pretest probability of the underlying etiology)

• Suspected infection
  • Microbiology: ascitic fluid culture; in blood culture bottles (aerobic and anaerobic) and Gram stain ^[6]
  • Studies to differentiate SBP from secondary spontaneous peritonitis: LDH, glucose, CEA, alkaline phosphatase (see “Spontaneous bacterial peritonitis” for details)
  • Acid-fast bacilli smear and mycobacterial cultures (low sensitivity): only if there is clinical suspicion or a high risk of tuberculous peritonitis
• Suspected malignancy (e.g., peritoneal carcinomatosis)
  • Ascitic fluid cytology
  • Ascitic fluid tumor markers: not routinely recommended for the assessment of malignancy-related ascites
    • Cancer antigen 125 (CA-125): elevated in most patients with ascites regardless of etiology
    • Carcinoembryonic antigen (CEA): potentially of diagnostic and prognostic value in patients with gastric and intestinal carcinoma ^[6]
• Suspected chylous ascites (milky ascitic fluid): Ascitic fluid triglyceride levels; levels > 200 mg/dL indicate chylous ascites ^[14]
• Suspected pancreatic ascites or bowel perforation: Ascitic fluid amylase levels; elevated levels provide supportive evidence of pancreatitis or bowel perforation ^[15]

The International Ascites Club classifies the severity classification of ascites as follows: ^[2]

• Mild ascites (grade 1): ascites only detectable by ultrasound
• Moderate ascites (grade 2): moderate abdominal distention
• Large ascites (grade 3): marked abdominal distention

Approach ^[5][6][10]

• All patients: Identify and treat the underlying condition.
  • Cirrhotic ascites: treatment of cirrhosis, including sodium restriction, diuretics, and avoidance of certain medications, such as NSAIDs and ACE inhibitors ^[6]
  • Noncirrhotic ascites: e.g., surgery or radiochemotherapy for malignancy, antibiotics for tuberculosis
• Tense or large ascites: therapeutic paracentesis (first-line); followed by diuretic therapy and dietary sodium restriction ^[6]
• Refractory ascites ^[16]
  • Ascites that does not respond to dietary sodium restriction and high-dose diuretic therapy or that recurs within 1 month after initial therapeutic paracentesis.
  • Rule out transient refractoriness to diuretic therapy.
  • Consider the following treatment options: ^[2][16]
    • Optimize medications and ensure adherence to a low-sodium diet.
    • Serial paracentesis (with IV albumin for large-volume paracentesis)
    • Evaluate for advanced therapies (e.g., TIPS, liver transplant).

Medical and supportive therapy ^[6][10][17]

This section details only the management of ascites due to portal hypertension (e.g., cirrhosis, heart failure, some patients with malignancy-related ascites). See “Treatment of cirrhosis” for management of cirrhosis and its complications. Medical and/or supportive management of other etiologies can be found in the articles dedicated to these conditions.

Salt and fluid restriction

• Dietary sodium restriction: 2 g/day or 88 mEq/d (2 g of sodium = 5 g of salt)
  • Recommended for all patients
  • Advise patients to restrict the amount of salt in home-cooked meals and to avoid precooked and prepackaged food.
  • Consider referral to a nutritionist for counselling.
• Fluid restriction: 1 L/day (only if serum Na⁺ < 125 mEq/L)

Diuretics

• Monotherapy with spironolactone may be preferable for new-onset ascites, mild ascites, moderate ascites, and outpatients.
• Combination therapy with spironolactone; PLUS furosemide in a 10:4 ratio may be preferable for recurrent gross ascites or when faster resolution of ascites is required (e.g., in hospitalized patients).
• Once ascites is under control, taper to the minimum effective dose to reduce side effects.

Combination diuretic therapy is associated with more rapid ascites reduction and a lower risk of potassium imbalance than monotherapy. ^[6][17]

Diuretics should be used with caution in patients with severe hyponatremia, hepatic encephalopathy, and/or renal function deterioration.

Empiric antibiotic therapy ^[6][10]

Antibiotic therapy for patients with cirrhosis and ascites is recommended in the following situations:

• Patients with GI bleed due to cirrhosis: Ceftriaxone or a fluoroquinolone such as norfloxacin for 7 days
• SBP: See “Empiric antibiotic therapy for SBP.”

Monitoring ^[6]

• Monitor weight, blood pressure, nutritional status, serum electrolytes, and renal function.
• Goals of diuretic therapy
  • Patients without peripheral edema: weight loss of up to 0.5 kg/day
  • Patients with significant peripheral edema
    • No limit to daily weight loss goal until edema is resolved ^[6][17]
    • Once edema has resolved, daily weight loss should not exceed 0.5 kg/day
• Discontinue or adjust the dosage of diuretics if adverse effects develop (e.g., hyponatremia, hyperkalemia, renal dysfunction)

Therapeutic paracentesis ^[6][17][18]

• Indications
  • Tense ascites (first-line)
  • Refractory ascites (can be repeated every ∼ 2 weeks)
  • Malignancy-related ascites
  • Contraindications for diuretic therapy
• Important considerations
  • Consider performing the procedure under ultrasound guidance to minimize the risk of complications.
  • A predetermined limit to the removed volume is usually not necessary. ^[19]
  • Administer albumin in patients undergoing large-volume paracenteses (> 5 L). ^[6][18]

Fresh frozen plasma is not routinely recommended before paracentesis in patients with increased INR, as procedure-related hemorrhage is uncommon. ^[6]

Advanced therapies ^{[6][10][16][17]}

• Evaluate for invasive management options in consultation with specialists.
  • Liver transplant: cirrhosis with new-onset ascites
  • Transjugular intrahepatic portosystemic shunt (TIPS): refractory ascites ^[6][10]
  • Peritoneovenous shunt: patients with refractory ascites who are not candidates for paracenteses, TIPS, or liver transplant
  • Hernia surgery: Elective hernia surgery after control of ascites with medical management is preferred when feasible. ^[6]
• Optimization of medications for refractory ascites
  • Patients who are on beta-blockers:
    • Monitor blood pressure and renal function.
    • Consider dosage adjustment or discontinuation of beta-blockers if severe hypotension or renal dysfunction develops.
  • Consider midodrine or a vaptan on a case-by-case basis. ^[6][10][20]
  • Consider discontinuing diuretic therapy if urine Na⁺ excretion is < 30 mEq/d. ^[17]
  • Consider prophylaxis for SBP.

21% of patients who develop refractory ascites die within 6 months. Do not delay referral for surgical management. ^[6]

• Abdominal hernias (especially umbilical hernias)
• Spontaneous bacterial peritonitis (ascitic fluid infection): abdominal tenderness, fever, altered mental status
• Hepatorenal syndrome
• Hepatic hydrothorax
• Large-volume paracentesis can precipitate hepatic encephalopathy.

We list the most important complications. The selection is not exhaustive.

• One-Minute Telegram 11-2020-3/3: A lesson well learned, but so easily forgotten?

Interested in the newest medical research, distilled down to just one minute? Sign up for the One-Minute Telegram in “Tips and links” below.