Chapter 11 Ascites and spontaneous bacterial peritonitis

Ke-Qin Hu, MD, Armine Avanesyan, MD, Bruce A. Runyon, MD

1 In the United States, 85% of cases of ascites occur in the setting of cirrhosis with portal hypertension; the development of ascites is associated with a 50% 2-year survival.

2 Evaluation of the patient with ascites begins with a thorough history and physical examination focused on identifying clinical clues to the underlying disease process.

3 Abdominal paracentesis with ascitic fluid analysis is a safe and cost-effective strategy in the differential diagnosis of ascites. Routine ascitic fluid tests include cell count, culture in blood culture bottles, albumin, and total protein, with additional testing depending on the clinical setting.

4 Treatment of patients with cirrhosis and ascites involves a stepwise approach including dietary sodium restriction and dual diuretic therapy. Second-line therapies include intermittent large-volume paracentesis (LVP), transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation.

5 Spontaneous bacterial peritonitis (SBP) is the prototype ascitic fluid infection and usually develops in the setting of preexisting ascites in patients with cirrhosis. The morbidity and mortality of ascitic fluid infection and the efficacy of early treatment warrant a high index of suspicion, early diagnosis by paracentesis with appropriate ascitic fluid analysis, and prompt non-nephrotoxic antibiotic treatment.

6 Selective intestinal decontamination with norfloxacin or trimethoprim–sulfamethoxazole has been demonstrated to prevent SBP in high-risk subgroups (i.e., prior SBP, active gastrointestinal hemorrhage, and low-protein ascitic fluid).

Overview of Ascites

Definition

Ascites is defined as pathologic accumulation of fluid within the peritoneal cavity.

Epidemiology and Natural History

1. In the United States, 85% of cases of ascites occur in the setting of cirrhosis. Table 11.1 lists common causes of ascites.

2. Ascites is the most common clinical manifestation of hepatic decompensation.

3. Approximately 50% of patients with cirrhosis will develop ascites within 10 years.

4. Once ascites occurs, the 2-year survival rate is 50%.

5. Ascites becomes unresponsive to diuretic therapy in 10% of patients with cirrhosis.

6. Once ascites becomes refractory, the 1-year survival rate is 25%.

TABLE 11.1 Causes of ascites in the United States

Cause	Percentage (%)
Cirrhosis	85
Miscellaneous portal hypertension-related	8
Cardiac ascites	3
Peritoneal carcinomatosis	2
Miscellaneous non–portal hypertension-related	2

Pathogenesis in the Setting of Cirrhosis

1. Portal hypertension leads to excess formation of fluid within the congested hepatic sinusoids; the fluid overwhelms intrahepatic lymphatics and weeps across the liver.

2. The overflow theory proposes that a stimulus arising from the liver results in a primary increase in plasma volume through increased renal sodium retention.

3. The underfill theory proposes that when ascites formation begins, the intravascular fluid compartment contracts, with an increase in the plasma oncotic pressure and a decrease in portal venous pressure; this results in a secondary increase in renal sodium retention in an attempt to compensate.

4. The peripheral arterial vasodilatation theory is a modification of the underfill theory and proposes that peripheral arterial vasodilatation results in an increase in vascular capacitance and a decrease in effective plasma volume, which results in the secondary increase in renal sodium retention.

Evaluation of the Patient with Ascites

History

1. History often reveals clues to alcoholic liver diseases or chronic viral hepatitis.

2. A thorough history is necessary to rule out a cause other than liver disease, such as heart failure, tuberculosis, or nephrotic syndrome (Table 11.2).

3. History related to ascites

The most common symptom of ascites is an increase in abdominal girth accompanied by weight gain, frequently with lower extremity edema.

Acute onset of uncontrollable ascites can be associated with the Budd–Chiari syndrome.

Ascites associated with fever and/or abdominal pain may indicate ascitic fluid infection or malignancy.

A history of heart failure raises the possibility of cardiac ascites; alcoholic cardiomyopathy can mimic alcoholic cirrhosis superficially.

TABLE 11.2 Clinical clues to causes of ascites other than cirrhosis

Cause	Clinical clues
Cardiac ascites	Setting and examination findings suggestive of heart failure
Malignant ascites	Setting of known malignancy and absence of stigmata of liver disease; often abdominal pain and profound weight loss
Tuberculous ascites	Persistent abdominal pain and fever; often extraperitoneal tuberculosis
Nephrotic syndrome	Anasarca and substantial proteinuria in a diabetic patient
Pancreatic ascites	Follows episode of severe acute pancreatitis or occurs in the setting of chronic pancreatitis

Grade and Type of Ascites

1. Grading ascites

Grade 1: detectable only by careful physical examination

Grade 2: easily detected but relatively small amount

Grade 3: obvious but not tense

Grade 4: tense

3. Bloody ascites

Red blood cell count higher than 10,000/mm³ in ascitic fluid

Most commonly associated with slightly traumatic paracentesis

4. Chylous ascites

Ascitic fluid milky, with triglyceride content greater than 200 mg/dL

Ascitic Fluid Analysis

Diagnostic Paracentesis

Paracentesis is safe despite the coagulopathy that is usually present.

Diagnostic paracentesis is the final confirmation of the presence of ascites.

Careful ascitic fluid analysis is essential for the differential diagnosis of ascites.

1. Indications

New-onset ascites

Routine on hospital admission or readmission of patients with ascites

Symptoms or signs suggestive of ascitic fluid infection (i.e., fever, abdominal pain, elevated white blood cell count, encephalopathy, and renal impairment)

2. Technically, diagnostic paracentesis involves passing a steel 22-gauge needle, by a Z-tract technique, below the level of percussed dullness, either in the left lower quadrant (two fingerbreadths cephalic and two fingerbreadths medial to the anterior superior iliac spine) or in the midline between the symphysis pubis and umbilicus.

3. Complications include fluid leak at the site (if a Z-tract is not used), abdominal wall hematoma, and inadvertent bowel perforation.

4. Routine prophylactic use of fresh frozen plasma or platelets before paracentesis is not recommended because bleeding is very uncommon. Coagulopathy may preclude paracentesis only when clinically evident primary hyperfibrinolysis or disseminated intravascular coagulation (DIC) is present.

Ascitic Fluid Tests

Ascitic fluid tests commonly ordered are shown in Table 11.3.

1. Ascitic fluid cell count is the most important test.

Fluid with 250 or more polymorphonuclear neutrophils (PMNs)/mm³ (and a predominance of PMNs) is presumed infected.

Any inflammatory cause of ascites can lead to neutrocytic ascites (250 or more PMNs/mm³).

For bloody ascites, 1 PMN is subtracted from the cell count for every 250 red blood cells, to correct for PMNs that enter the fluid with the blood.

2. Culture results are optimized by immediate inoculation of aerobic and anaerobic blood culture bottles with 10 mL of ascitic fluid at the bedside (sensitivity is approximately 90%).

3. Ascitic fluid albumin measurement is necessary to calculate the serum–ascites albumin gradient (SAAG).

A SAAG of 1.1 g/dL or more is 97% accurate in detecting portal hypertension; this value narrows the differential diagnosis (Table 11.4).

4. Ascitic fluid total protein measurement assists in determining the cause of ascites (Table 11.5) and the risk of ascitic fluid infection (values lower than 1.0 g/dL indicate a high risk).

TABLE 11.3 Ascitic fluid tests

TABLE 11.4 Differential diagnosis of ascites based on the serum–ascites albumin gradient

High gradient (≥1.1 g/dL)	Low gradient (<1.1 g/dL)
Cirrhosis	Peritoneal carcinomatosis
Alcoholic hepatitis	Tuberculous peritonitis
Cardiac ascites	Pancreatic ascites
Massive liver metastases	Biliary ascites
Fulminant hepatic failure	Nephrotic syndrome
Budd–Chiari syndrome	Connective tissue diseases
Portal vein thrombosis	Intestinal obstruction/infarction
Sinusoidal obstruction syndrome	Postoperative lymphatic leak
Acute fatty liver of pregnancy
Myxedema
“Mixed” ascites

TABLE 11.5 Ascitic fluid clues regarding the cause of ascites

Cause of ascites	Ascitic fluid clues
Cirrhotic ascites	SAAG ≥1.1 g/dL AFTP <2.5 g/dL (usually)
Cardiac ascites	SAAG ≥1.1 g/dL AFTP ≥2.5 g/dL
Peritoneal carcinomatosis	SAAG <1.1 g/dLAFTP ≥2.5 g/dL Cytology generally yields malignant cells
Tuberculous ascites	SAAG <1.1 g/dL (without cirrhosis) AFTP >2.5 g/dL (without cirrhosis) WBC >500/mm³, lymphocyte predominance
Chylous ascites	SAAG <1.1 g/dL AFTP ≥2.5 g/dL Triglycerides in ascites > serum (usually >200 mg/dL)
Nephrotic syndrome	SAAG <1.1 g/dL AFTP <2.5 g/dL
Pancreatic ascites	SAAG <1.1 g/dL AFTP ≥2.5 g/dL Amylase in ascites > amylase in serum (often >1000 U/L)