Causes of ascites
The most common cause is portal hypertension secondary to cirrhosis. This accounts for for 90% of cases. In 10% of cases, there is a nonhepatic cause such as malignancy, heart failure, constrictive pericarditis, tuberculosis, nephrotic syndrome, hemodialysis, pancreatitis, bile leak and other rare causes. Table 1
History and exam
Ascites usually develops insidiously over the course of weeks. The main symptoms are increased abdominal girth along with lower extremity edema. In patients with a large and tense ascites, the respiratory function and physical activity may be impaired. Dyspnea occurs as a consequence of increasing abdominal distention or due to pleural effusions. Patients with ascites and spontaneous bacterial peritonitis (SBP) can present with fever, chills, abdominal pain, hepatic encephalopathy, and rebound abdominal tenderness. However, only a minority of patients with SBP present with these symptoms. The diagnosis of SBP always requires an examination of the peritoneal fluid.
Aside of examining the patient for stigmata of chronic liver disease, a detailed physical exam needs to be performed. Jugular venous distension can be seen in patients with heart failure. Kussmaul’s sign is seen in patients with constrictive pericarditis. Anasarca can be associated with nephrotic syndrome and congestive heart failure. Firm lymphadenopathy is found in patients with an underlying malignancy.
Patients need at least 1,500 mL of peritoneal fluid to be detected reliably by physical examination. Ultrasonography can detect as little as 100 mL of abdominal fluid and should be used for obese individuals and for patients in whom the physical examination is unreliable.
There are several techniques available for diagnosing ascites on physical examination, with the most accurate being flank dullness; without this, the patient has a <10% likelihood of having ascites. Shifting dullness also is a useful diagnostic manuever; if ascites is present, percussion of the lateral aspect of the right flank demonstrates a shift in the location of the dullness when the patient is percussed in the supine, followed by the right lateral decubitus position.
Standard electrolyte, hematological, liver, and coagulation tests should be ordered. A urine sodium (UNA) is of key importance in directing therapy as patients with severe sodium retention—UNA <10 mEq/L—have a poor response to diuretics.
Abdominal ultrasonography with Doppler should be performed to evaluate the liver parenchyma, rule out hepatocellular carcinoma, and evaluate the patency of the portal venous system; ultrasonography of the kidneys can be performed simultaneously.
If cardiac disease is suspected, echocardiography should be ordered. It should be noted that in the presence of ascites, a percutaneous liver biopsy is contraindicated as its presence increases the risk of complications; however, a transjugular approach can be used to obtain a biopsy if one is warranted.
A diagnostic paracentesis of at least 30 mL of fluid is essential to fully elucidate the etiology of the ascites. It also should be performed in all patients requiring hospitalization and in those with any evidence of clinical deterioration such as fever, abdominal pain, hypotension, or encephalopathy. Diagnostic paracentesis is required in all patients regardless of their INR value in order to exclude other causes different of cirrhosis and portal hypertension.
Baseline parameters to be determined in ascitic fluid are cell count, culture in blood culture bottles, albumin, and total protein. Glucose, lactate dehydrogenase, amylase, bilirubin, triglyceride, tuberculosis smear, and cytological analyses of the fluid are optional and provide important information in the differential diagnosis of ascites in cases where causes other than portal hypertension are considered (
The cell count is the most useful test in determining bacterial infection. The diagnosis of SBP is made when the fluid sample has a polymorphonuclear count >250/mm.
The difference between serum albumin concentration and ascites albumin concentration (serum-ascites albumin gradient) in patients with cirrhosis and ascites is usually ≥1.1 g/dL. Values <1.1 g/dL suggest a cause of ascites other than cirrhosis. Most patients with cirrhosis have a total ascitic fluid protein concentration <1.5 g/dL, and these individuals have a greater risk of developing SBP. An elevated fluid protein is found in patients with cardiac ascites.
All patients should have a chest x-ray performed to rule out pleural effusions which can occur in the context of ascites. In addtion all patients need an upper endoscopy to assess for the presence of esophageal or gastric varices.
Causes of ascites
|Portal Hypertension Related|
|Fulminant hepatic failure|
|Budd-Chiari syndrome and hepatic veno-occlusive disease|
|Malignancy (peritoneal carcinomatosis and mesothelioma)|
|Tuberculosis and other fungal infections|
|Ovarian disease (tumor, ovarian hyperstimulation syndrome)|
|Protein losing enteropathy|
Therapy of ascites
As discussed above the most common cause of ascites is cirrhosis and portal hypertension. The recommendations for the management of ascites in cirrhosis are discussed below. A mainstay of therapy is a sodium-restricted diet of approximately 90mmol/day (2-3 g/day). Fluid restriction is not necessary unless patients have dilutional hyponatremia (serum sodium < 130 meg/L). An important aspect in the management of patients with cirrhosis and ascites is evaluation for liver transplantation in suitable candidates.
The current classification of ascites divides patients in three groups. Patients with grade 1 ascites are those in whom ascites is detected only by ultrasonography; these patients do not require any specific treatment, but they should be warned about avoiding foods with large amounts of salt. Patients with grade 2 ascites are those in which ascites causes moderate distension of the abdomen associated with mild/moderate discomfort. Patients with grade 3 ascites have large amounts of ascitic fluid causing marked abdominal distension and associated with significant discomfort. Patients with refractory ascites are those that do not respond to high doses of diuretics or develop side effects that preclude their use.
Recommendations for the management of ascites are summarized in
Management of patients with ascites and cirrhosis.
|Patients with cirrhosis and moderate volume (grade 2) ascites|
|Start with a low-sodium diet (2grs of salt/ day), spironolactone (50-100 mg/day) and furosemide 20-40 mg/day to reach goal of weight loss: 300-500 gm/day. If needed, doses to be increased every 5-7 days up to 400 mg/day of spironolactone and 160 mg/day of furosemide.|
|Patients with cirrhosis and large volume (grade 3) ascites|
|Total paracentesis plus intravenous albumin (8 gm per liter of ascites removed) followed by a low-sodium diet and diuretics as outlined above.|
|Patients with refractory ascites|
|Total paracentesis plus intravenous albumin can be performed as needed. Consider use of TIPS in patients without severely impaired hepatic function, aged < 70 yrs, with no hepatic encephalopathy or severe cardiopulmonary disease who require very frequent paracentesis or in whom ascites cannot be adequately eliminated by paracentesis|
Grade 2 ascites
These patients typically can be managed as outpatients unless other complications of cirrhosis are present. A negative sodium balance with loss of ascites is quickly and easily obtained in most cases with diuretics. Patients with new onset ascites respond to spironolactone 50-100mg /day and the dose may be increased progressively if needed. Patients with prior episodes of ascites should receive the combination of spironolactone 100mg/day with furosemide (20–40mg/day). If there is no response, compliance with diet and medications should be confirmed and diuretics may then be increased in a stepwise fashion every 5–7 days by doubling doses to a maximal dose of spironolactone of 400mg/day and a maximal dose of furosemide of 160mg/day. Diuretic therapy is effective in the elimination of ascites in 80–90% of all patients, a percentage that may increase to 95% when only patients without renal failure are considered. Spironolactone-induced gynecomastia may cause patients to stop the drug; in these cases amiloride (5-10mg/day) may be useful, although its potency is lower than that of spironolactone. Eplerenone, another aldosterone antagonist has fewer endocrine adverse effects compared with spironolactone and could be a good alternative to spironolactone in patients with spironolactone-induced gynecomastia but there is limited data. The goal of diuretic therapy is to achieve an average weight loss of 300–500g per day in patients without edema and 800–1000g per day in those with peripheral edema. A greater degree of weight loss may induce volume depletion and renal failure. After minimizing ascites, sodium restriction should be maintained while the dose of diuretics may be reduced as needed.
Grade 3 ascites
These patients are best managed by therapeutic paracentesis. Complete removal of ascites in one tap (as many liters as possible) with intravenous albumin (8g per liter tapped) has been shown to be quick, effective, and associated with a lower number of complications than conventional diuretic therapy. After a therapeutic tap, postparacentesis circulatory dysfunction may develop; this is a circulatory derangement with marked activation of the renin-angiotensin system that occurs 24–48h after the procedure. This disorder is clinically silent, not spontaneously reversible, and associated with hyponatremia and renal impairment in up to 20% of patients. In addition it is associated with decreased survival. Post-paracentesis circulatory dysfunction may be prevented with the administration of albumin (8 grs/lt tapped). Although the use of albumin after paracentesis is controversial due to the lack of data proving a survival benefit and high cost in some countries, the protective effect of albumin on the circulatory system favors its use and current guidelines recommend the use of albumin after large volume paracentesis. Patients with a known history of cirrhosis and without any complications can be managed as outpatients. However, patients in whom tense ascites is the first manifestation of cirrhosis or those with associated hepatic encephalopathy, gastrointestinal bleeding, or bacterial infections require hospitalization. Most of these patients have marked sodium retention and need to be started or continued on relatively high doses of diuretics after paracentesis.
Up to 10% of patients with ascites can be refractory to treatment with diuretics. In refractory ascites, sodium excretion cannot be achieved either because patients do not respond to high doses of diuretics (spironolactone 400mg/day and furosemide 160mg/day) or because they develop side effects that prohibit their use. These patients in general have features of advanced liver disease, a high recurrence rate of ascites after large-volume paracentesis, an increased risk of hepatorenal syndrome, and a poor prognosis. Current treatment strategies include repeated therapeutic paracentesis plus intravenous albumin, and transjugular intrahepatic portosystemic shunts (TIPS). Therapeutic paracentesis is the accepted initial therapy for refractory ascites. Patients, on average, require a tap every 2–4 weeks and the majority may be treated as outpatients, making this option easy to perform and cost effective. TIPS, a non-surgical method of portal decompression, reduces sinusoidal and portal pressure and decreases ascites and diuretic requirements in these patients. A disadvantage with TIPS is the development of side effects that include hepatic encephalopathy and impairment in liver function. Additionally uncovered TIPS may be complicated by a high rate of stenosis of the prosthesis. Newer polytetrafluoroethylene-covered prostheses seem to improve TIPS patency and decrease the number of clinical relapses and reinterventions without increasing the risk of encephalopathy. Randomized studies comparing TIPS with repeated paracentesis demonstrate that TIPS is associated with a lower rate of ascites recurrence, but hepatic encephalopathy occurred in up to 50% of patients treated with TIPS. The studies report discrepant findings with respect to survival: two studies showed a survival benefit with TIPS and two other studies demonstrated no difference in survival. Meta-analyses of these randomized controlled studies conclude that TIPS is better at controlling ascites but does not improve survival compared to paracentesis and increases the risk of hepatic encephalopathy. Thus, the preferred initial treatment for refractory ascites is large volume paracentesis with albumin replacement. TIPS as initial therapy should be evaluated on a case-by-case basis and reserved for patients aged < 70, with preserved liver function, without hepatic encephalopathy or severe cardiopulmonary disease who require very frequent paracentesis or in whom ascites cannot be adequately eliminated by paracentesis.
Spontaneous bacterial peritonitis
Bacterial infections in patients with cirrhosis occur at admission or during hospitalization in 20-60% of patients. Of these, most are secondary to SBP (30%), other common causes are urinary tract infection, pneumonia and bacteremia secondary to invasive procedures. When considering all types of infections in patients with cirrhosis 54% will have positive cultures and of these 44% are community acquired and 72% are nosocomial. Among all these patients nearly 50% are due to gram negative bacteria and 48% due to aerobic Gram-positive bacteria. The prevalence of SBP in hospitalized cirrhotic patients is approximately 10-30%. The 1-year survival probability after an episode is around 40%. The clinical spectrum of SBP is variable and ranges from no symptoms to fever, chills, abdominal pain, hepatic encephalopathy, severe peritonitis, shock, worsening liver failure and/or the development of hepatorenal syndrome.
Therapy of Sponataneous Bacterial Peritonitis.
Once the diagnosis is secured, empiric antibiotic therapy is started with an intravenous third-generation cephalosporin (cefotaxime 2gm every 8-12 hours; ceftriaxone 1 gm/24 hours) for at least 5-7 days. It is recommended patients have a repeat tap 2 days after to ensure a drop in neutrophil count by at least 25% of the pre-treatment value. If it fails to drop, antibiotic resistance should be suspected and modification in therapy be implemented.Antibiotics are changed depending on results from cultures. Response to therapy should be monitored by clinical signs, white blood count and PMN count in the ascitic fluid. Therapy can be stopped when clinical signs of infection have disappeared and the PMN count in the ascitic fluid has normalized. Given the high prevalence of nosocomial infections in patients with cirrhosis, the current empirical therapeutic approach may need to be altered in such patients as they may have multiresistant bacteria mainly Extended Spectrum Beta-Lactamase bacteria, Pseudomona aeruginiosa and methicillin resistant Staphylococcus aureus. Thus in patients with nosocomial infections and according to every hospital’s data on resistant bacteria, empirical therapy should include antibiotics that cover such microorganisms.
The most important predictor ofsurvival in patients with SBP is the development of renal failure during the infection. Administration of albumin at a dose of 1.5 gm/kg at the diagnosis and 1 gm/kg 48 hours later prevents hepatorenal syndrome and reduces mortality from 30% to 10%. Since recurrence of SBP occurs in 70% of cases and constitutes a major cause of death in these patients, prophylaxis is recommended, particularly for listed patients. Because most cases are caused by gram-negative bacteria from the intestinal flora, long-term use of norfloxacin (400 mg/day) or ciprofloxacin (750 g/ week) or co-trimoxazole (800 mg sulfamethoxazole and 160 mg trimethoprim daily, orally) are recommended as secondary prophylaxis.
There are two conditions associated with an increased risk of the first episode of SBP where primary prophylaxis is recommended. The first is in patients with GI hemorrhage. Multiple studies have shown that short-term (7 days) administration of oral norfloxacin 400 mg twice a day or intravenous ceftriaxone 1gm/day reduces the incidence of SBP, bacteremia and rebleeding. The second is in patients with advanced cirrhosis (serum creatinine > 1.2mg/dL, Child-Pugh score >9, and/or serum sodium < 130mEq/L and ascitic fluid protein levels < 15 gm/L). These patients benefit from norfloxacin (400mg/day) as it not only reduces the probability of developing SBP but also reduces the risk of developing HRS and improves survival. Recommendations for the management of SBP are outlined in
Recommendations for the management of spontaneous bacterial peritonitis
|1||After diagnosis start with third-generation cephalosporins (i.e. cefotaxime 2g/8–12 hourly intravenously or ceftriaxone 1 g/24 hours intravenously). In nosocomial spontaneous bacterial peritonitis, consider the addition of an antibiotic active against Gram-positive cocci and/or multiresistant bacteria|
|2||Give albumin 1.5g/kg intravenously at the time of diagnosis of the infection and 1 g/kg 48 hours later|
|3||A repeat diagnostic tap 2 days after the start of treatment may help guide the antibiotic therapy|
|4||Maintain antibiotic therapy until disappearance of signs of infection and reduction of polymorphonuclear cells in ascitic fluid below 250/mm3|
|5||After resolution of infection, start long-term oral norfloxacin 400 mg/day|
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