ASCITES/ ASCITIC FLUID
Ascites refers to the collection of fluid in the peritoneal cavity. It may be impossible to appreciate small volumes (less than 1 liter) of ascites on physical examination and therefore many cases may go undiagnosed. Large volumes of ascites manifest as increasing abdominal girth which may be evident on physical exam as a puddle sign, fluid wave, and/or shifting dullness to percussion. When there is any doubt as to the existence of ascites, ultrasonography is helpful in establishing its presence and to allow a quick assessment of the liver for any gross pathology. The majority of cases are associated with hepatic cirrhosis. Ascites may occur concomitant with other complications of cirrhosis such as esophageal varices and hepatic encephalopathy. Patients with cirrhosis and ascites are at risk of developing associated renal failure, a condition known as the hepatorenal syndrome, or spontaneous bacterial peritonitis (SBP). Other causes of ascites include hypothyroidism (myxedema), Meig’s syndrome and other ovarian cancers, congestive heart failure, constrictive pericarditis, pancreatitis, nephrotic syndrome, systemic lupus erythematosus, POEMS syndrome, peritoneal tuberculosis, peritoneal malignancy, and hepatic vein thrombosis (Budd-Chiari syndrome).
As part of the initial work up it is prudent to screen patients with a TSH, lipase and PPD or gamma interferon assay. If either are positive, then work-up for myxedema, pancreatitis, or tuberculosis, respectively. If these tests are negative, then the next step is the calculation of the serum-ascites albumin gradient (SAAG) which helps to determine if the ascites occurred as the result of portal hypertension. If the SAAG (calculated by subtracting the ascites albumin value from the serum albumin) is greater than or equal to 1.1 gm/dL, then underlying portal hypertension may be diagnosed with approximately 97% accuracy. Conditions associated with portal hypertension induced ascites include cirrhosis, heart failure, constrictive pericarditis, restrictive cardiomyopathy, alcoholic hepatitis, metastatic disease and Budd-Chiari syndrome. Patients with an ascitic fluid total protein concentration less than 1.5 g/dL are considered at risk for ascitic fluid infection. If the SAAG is less than 1.1, then decreased oncotic pressure (hypoproteinemia or hypoalbuminemia), peritoneal malignancy, or peritoneal tuberculosis should be suspected. Laparoscopy may be required to confirm a tuberculous or malignant etiology.
Patients with ascites secondary to cirrhosis should undergo a complete physical examination, standard liver testing, abdominal ultrasonography (evaluate for hepatocellular carcinoma and portal venous system patency), esophagogastricduodenoscopy (evaluate for esophageal varices), and diagnostic paracentesis. Appropriate biochemical testing should be performed to determine the etiology of cirrhosis. If biochemical testing is unrevealing, liver biopsy may be considered (this procedure may be performed via a transjugular approach in patients with an associated cirrhotic coagulopathy). Diagnostic testing on ascitic fluid should include total protein concentration, albumin concentration, and cell count.
If the absolute neutrophil count (ANC) of the ascitic fluid is greater than or equal to 250 cells/mm3 then spontaneous bacterial peritonitis may be diagnosed. The ANC should be adjusted in hemorrhagic ascites by subtracting one from the ANC for every 250 RBCs. If underlying infection is suspected or if the ANC reveals SBP, ascitic fluid culture should be performed in blood culture bottles. However, the culture yield is 50% at best even in cases where the diagnosis is established by the ANC. Therefore, if the ANC is consistent with SBP even if cultures are negative (culture-negative neutrocytic ascites), therapy should be started with cefotaxime (2 gm intravenously every 8 hours) for five to ten days. After effective therapy to clear the infection, therapy with double-strength trimethoprim-sulfamethoxazole or norfloxacin (400 mg) should be administered daily to prevent recurrence. Another condition in which antibiotics should be considered is monomicrobial nonneutrocytic bacterascites in which ascitic fluid culture yields a single infectious organism but the ANC is not consistent with infection (<250 cells/mm3). In cases of monomicrobial nonneutrocytic bacterascites a second paracentesis should be performed in 24 to 72 hours or if symptoms indicate the possibility of infection. Before starting antibiotics blood and urine cultures should also be obtained. SBP should be considered in any cirrhotic patient with ascites who suffers any sudden impairment in their medical condition especially if there is an associated fever. Risk factors associated with ascitic fluid infection include severe liver disease, ascitic fluid total protein content less than 1.5 gm/dL, esophageal varices, gastrointestinal bleeding, previous SBP, and iatrogenic introduction of infection (urinary catheters or intravenous catheters).
When tuberculous or carcinomatous peritonitis is suspected, an acid fast bacillus (AFB) smear/culture and cytology may be ordered; however, these tests are expensive and often unrevealing. Persons from countries with a high incidence of tuberculosis who develop ascites should undergo PPD or QUANTiferon-TB Gold testing. Laparoscopy or celiotomy with peritoneal biopsy may be required to establish the diagnosis in tuberculous ascites or in ascites secondary to peritoneal malignancy. This procedure should be considered in patients without an identifiable etiology for their ascites after common causes have been excluded. Measurement of the ascitic fluid adenosine deaminase level may help establish the diagnosis of tuberculous peritonitis. An ascitic fluid adenosine deaminase level greater then 33 U/L is highly suggestive of this diagnosis. If ovarian carcinoma is suspected, paracentesis is contraindicated. Rather, pelvic ultrasonography with CA-125 measurement is used to suggest the diagnosis. If the findings are positive for possible ovarian malignancy then referral to a gynecologic oncologist is prudent.
It is important to remember that pancreatic ascites may occur in the absence of pancreatic pain or a marked elevation of the serum amylase or lipase. It is often associated with the presence of pancreatic pseudocysts, and the most effective means of establishing the diagnosis is the finding of a greatly elevated ascitic fluid amylase level. Chylous ascites is diagnosed when the triglyceride level is greater than 110 mg/dL. In the pediatric population, most cases of chylous ascites are due to congenital lymphatic anomalies. In adults, the most common cause of chylous ascites is lymphoma, with trauma, adhesions, abdominal carcinoma, tuberculosis, parasitic infection and hepatic cirrhosis also in the differential diagnosis. Lymphoma should be suspected if the ascitic fluid cell count reveals a greatly elevated lymphocyte count, and the diagnosis may be confirmed by demonstrating a monoclonal proliferation of ascitic fluid lymphocytes with flow cytometry. If an etiology other than cirrhosis is found, appropriate treatment of the underlying condition usually results in resolution of the ascites.
Therapy for ascites secondary to hepatic cirrhosis includes appropriate restrictions (alcohol and sodium intake), diuretics, serial large volume paracentesis, transjugular intrahepatic portosystemic shunting (TIPS) and in severe cases liver transplantation. Dietary sodium intake should be limited to less than 2 gm/day. If sodium restriction fails, diuresis with aldactone should be initiated at a dosage of 50-100 mg/day as a single dose and then titrated to effect or complications. Furosemide 20-40 mg/day is often added when aldactone fails as a single agent or is complicated by hyperkalemia. If diuresis is still not initiated, then the furosemide dose may be adjusted upwards, and if this still proves ineffective, metolazone therapy 5-10 mg/day may be added. When there is associated edema, the patient may be allowed to lose as much weight as therapy allows. Once edema resolves, diuretics should be adjusted to limit weight loss to 0.5 kg/day. Diuretics should be discontinued if the patient develops encephalopathy, symptoms consistent with hypovolemia, hyponatremia less than 120 mmol/L, or if the serum creatinine rises from the patients baseline. If patients have symptomatic tense ascitis, large volume paracentesis of four to six liters may be performed to relieve symptoms. These patients should then be evaluated for the need for the above mentioned therapies to prevent reaccumulation of ascitis. Large volume paracentesis may be followed by intravenous albumin administration in an attempt to expand plasma volume and prevent the circulatory changes that occur postparacentesis and cause a greater risk of repeat ascites formation and mortality.
When ascites is complicated by severe hyponatremia, water restriction is the only intervention necessary in most cases. If this fails to correct the hyponatremia, a trial of a vasopressin receptor antagonist may correct the abnormality. In this instance, the hyponatremia is a dilutional event. Administration of intravenous saline solutions should be avoided as it will further worsen ascitic fluid formation. When ascities is refractory to diuretics, therapeutic interventions include liver transplantation, repeated large volume paracentesis (removal of approximately 8 liters every 2 weeks), TIPS, or peritoneovenous (LeVeen or Denver) shunts.