Ascites Fluid Analysis

Also See Pleural Effusion

Pathophysiology

Diagnosis

Treatment

  1. Indications for paracentesis
  2. Large vol paracentesis (5-10 L, ~100 mL/kg body weight) w/IV albumin replacement (8 g/L fluid removed)
  3. Nonparacentesis ascites reduction
  4. Peritonitis

Disposition

  1. Admit pts w/peritonitis, ascites w/SOB, refractory or tense ascites not responding to ED treatment (w/ GI/surgery consult), or serious underlying condition
  2. May DC after 8hr post-paracentesis observation


WORK-UP DETAIL

Routine tests:

SAAG


Serum-to-Ascites Albumin Gradient

<1.1
  • Infection (Peritoneal TB)
  • Peritoneal Cancer
  • Pancreatic Ascites
  • Biliary Ascites
  • Nephrotic Syndrome
  • Lupus Serositis
  • Bowel Infarction or Obstruction
  • Post-Op Lymphatic leak
  • Hypothyroidism
>1.1 Portal
HTN
Varices (+) Bleed BAND then TIPS
(-) bleed Propanolol 40 mg PO bid or Nadolol 20-40 mg PO qd.
Hepato-Renal syndrome Octreotide 50 mcg x 1, then 50 mcg/hr IV drip x 3-5 d after endoscopic variceal band ligation.
SBP
(WBC > 500,
Neutrophils > 250)
Cefotaxime 2g IV Q8H x 5-7d
Alcoholic Hepatitis
R-sided CHF
Multi. Liver Mets.
Fulminant hepatic failure
Budd-chiari synd.
Veno-occlusive disease
Fatty liver of pregnancy
Portal vein thrombosis
 

Cell Count & differential 

  • The cell count with differential is the single most useful test performed on ascitic fluid to evaluate for infection and should be ordered on every specimen, including therapeutic paracentesis specimens (ie, a paracentesis being performed as part of the treatment of ascites).
  • Ascitic fluid infection is a reversible cause of deterioration and a preventable cause of death in patients with cirrhosis and ascites.
  • The key to survival is early detection and treatment.
  • The cell count should be available within one hour, while the culture takes several hours to days.
  • Antibiotic treatment should be considered in any patient with a corrected neutrophil count  ≥250/mm3.
  • WBC Correction:
    • The white blood cell and neutrophil counts need to be corrected in patients with bloody samples.
    • One white blood cell should be subtracted from the white blood cell count for every 750 red blood cells to yield the "corrected white blood cell count", and
    • One neutrophil should be subtracted from the absolute neutrophil count for every 250 red blood cells to yield the "corrected neutrophil count".
    • In bloody ascites, the corrected neutrophil count is frequently <0 due to remote hemorrhage with lysis of neutrophils.  

Total Protein 

  • Ascitic fluid can be classified as an exudate if the total protein concentration is ≥2.5 or 3 g/dL and a transudate if it is below this cut-off. However, the exudate/transudate system of ascitic fluid classification has been replaced by the SAAG.
  • Despite its problems, the ascitic fluid total protein concentration remains of some value. This parameter does not change with development of spontaneous bacterial peritonitis (SBP), and patients with a value < 1 g/dL have a high risk of SBP.
  • Patients with ascitic fluid that has a corrected neutrophil count ≥250 cells/mm3 and meets two out of the following three criteria are unlikely to have SBP and warrant immediate evaluation to determine if bowel perforation into ascites has occurred:
    • Total protein >1 g/dL
    • Glucose <50 mg/dL (2.8 mmol/L)
    • LDH greater than the upper limit of normal for serum
       
  • The total protein concentration may also help differentiate uncomplicated ascites from cirrhosis from cardiac ascites, both of which have a SAAG ≥1.1 g/dL (≥11 g/L). In the case of ascites from cirrhosis, the total protein is <2.5 g/dL (<25 g/L), whereas in cardiac ascites it is ≥2.5 g/dL (≥25 g/L).
     
  • In patients with nephrotic ascites, the SAAG is <1.1 g/dL (<11 g/L), and the total protein in the ascites of <2.5 g/dL (<25 g/L).

     


Optional tests:

Culture

  • Cultures of ascitic fluid should be obtained on specimens from patients who are being admitted to the hospital with ascites and those who deteriorate with fever, abdominal pain, azotemia, acidosis, or confusion.
  • By comparison, therapeutic paracentesis samples in patients without symptoms of infection do not need to be cultured.
  • An adequate volume of ascitic fluid (generally 10 mL per bottle, but the amount varies according to the manufacturer of the bottle) should be inoculated into aerobic and anaerobic blood culture bottles at the bedside; this method is more sensitive for detecting bacterial growth in ascitic fluid than conventional culture methods.
  • Bedside inoculation of the blood culture bottles is preferable to delayed inoculation of the bottles in the microbiology laboratory 

Glucose

  • The ascitic fluid glucose concentration is similar to that in serum unless glucose is being consumed in the peritoneal cavity by white blood cells or bacteria.
  • Malignant cells also consume glucose; thus, the concentration of glucose may be low in peritoneal carcinomatosis.
  • In the setting of bowel perforation (eg, perforated ulcer or diverticulum) into ascitic fluid, glucose may be undetectable. 

LDH

  • Because lactate dehydrogenase (LDH) is a much larger molecule than glucose, it enters ascitic fluid less readily.
  • The ascitic fluid/serum (AF/S) ratio of LDH is approximately 0.4 in uncomplicated ascites due to cirrhosis.
  • In SBP, the ascitic fluid LDH level rises such that the mean ratio approaches 1.0.
  • If the LDH ratio is > 1.0, LDH is being produced in or released into the peritoneal cavity, usually because of infection, bowel perforation, or tumor.

Gram Stain

  • Approximately 10,000 bacteria/mL are required for detection by Gram stain, while the median concentration of bacteria in SBP is only one organism/mL. Thus, a Gram stain of ascitic fluid is analogous to a Gram stain of blood in bacteremia; it is only positive when there is an enormous colony count.
  • The Gram stain is most helpful in ruling in free perforation of the bowel into ascites, in which case sheets of multiple bacterial forms can be seen.
  • A syringe or tube of fluid must be submitted to the laboratory in addition to the culture bottles when requesting a Gram stain.

Amylase

  • The mean ascitic fluid amylase concentration is about 40 int. unit/L in uncomplicated ascites due to cirrhosis, and the AF/S ratio of amylase is approximately 0.4.
  • The ascitic fluid amylase concentration rises above this level in the setting of pancreatitis or bowel perforation into ascites.
  • In pancreatic ascites, the ascitic fluid amylase concentration is approximately 2000 int. unit/L, and the AF/S ratio is approximately 6.0 

Unusual Tests:

Tuberculosis Smear & Culture

  • Direct smear – The direct smear of ascitic fluid has only 0 to 2 percent sensitivity for detecting Mycobacteria. Studies have not encountered a single true positive ascitic fluid Mycobacterial smear.
  • Culture – When 1 liter of fluid is cultured, sensitivity for Mycobacteria reportedly reaches 62 to 83%. However, most laboratories can only process 50 mL of ascitic fluid for Mycobacterial culture.
  • Peritoneoscopy – Peritoneoscopy with culture of a biopsy specimen has a sensitivity for detecting tuberculous peritonitis that approaches 100%. Fluid and tissue can be sent for PCR for tuberculosis.
  • Cell count – Tuberculous peritonitis can mimic the culture-negative variant of SBP, but mononuclear cells usually predominate in tuberculosis.
  • Adenosine deaminase – Adenosine deaminase is a purine-degrading enzyme that is necessary for the maturation and differentiation of lymphoid cells. Adenosine deaminase activity of ascitic fluid has been proposed as a useful non-culture method of detecting tuberculous peritonitis; however, patients with tuberculous peritonitis who also have cirrhosis usually have falsely low values. This test is useful in countries such as India, but it is of very limited utility in the United States because most patients in the United States with tuberculous peritonitis also have cirrhosis.

Cytology

  • Almost 100% of patients with peritoneal carcinomatosis will have positive ascitic fluid cytology due to the presence of viable malignant cells exfoliating into the ascitic fluid. However, only about 2/3 of patients with malignancy-related ascites have peritoneal carcinomatosis. The remaining patients have massive liver metastases, chylous ascites due to lymphoma, or hepatocellular carcinoma; these patients usually have negative cytology. As a result, the overall sensitivity of cytology smears for the detection of malignant ascites is 58-75 %.
  • Hepatomas rarely metastasize to the peritoneum.

CEA

  • Measurement of carcinoembryonic antigen (CEA) in ascitic fluid has been proposed as a helpful test in detecting malignancy-related ascites. However, the study that validated CEA was small and did not subgroup patients based on the type of cancer.
  • CEA may be of some utility in ascitic fluid analysis, but its precise value remains unclear

Triglyceride

  • A triglyceride concentration should be obtained on ascitic fluid that is milky.
  • Chylous ascites has a triglyceride content > 200 mg/dL (2.26 mmol/L) and usually > 1000 mg/dL (11.3 mmol/L) 
Chylous ascites is the extravasation of milky chyle into the peritoneal cavity. This can occur de novo as a result of trauma or obstruction of the lymphatic system. Moreover, an existing clear ascitic fluid can turn chylous as a secondary event.

True chylous ascites is defined as the presence of ascitic fluid with high fat (triglyceride) content, usually higher than 110 mg/dL

Source: Medscape, Uptodate.

Bilirubin

  • The bilirubin concentration should be measured in patients with brown ascites.
  • As mentioned above, an Ascitic fluid bilirubin value > Serum suggests bowel or biliary perforation into ascites 

Serum Pro-BNP

  • Measurement of pro-brain natriuretic peptide in serum can help distinguish ascitic fluid due to cirrhosis from ascitic fluid due to heart failure.  

Useless Test

  • Some tests of ascitic fluid appear to be useless.
  • These include pH, lactate, and "humoral tests of malignancy" such as fibronectin, cholesterol, and many others 

Algorithm

 

Reference:
- Hepatology 2004;39:1; NEJM 2004;350:1646; South Med J 2006;99:600; and Hepatology 2005;41:1.
- Uptodate.com