Workup for Ascites of Undetermined Origin
Perform diagnostic paracentesis immediately in all patients with new-onset Grade 2 or 3 ascites—this is the single most important diagnostic intervention that should never be delayed. 1, 2
Initial Clinical Assessment
History and Physical Examination
- Check for flank dullness using the shifting dullness test, which requires at least 1,500 mL of fluid to be detectable and has 83% sensitivity 1, 3
- Assess for jugular venous distension, which indicates cardiac ascites rather than cirrhotic ascites 1, 3
- Measure serum BNP or NT-proBNP if heart failure is suspected, as this helps discriminate between cardiac and hepatic causes 1, 4
- Confirm ascites with abdominal ultrasound if physical examination is equivocal, particularly in obese patients (ultrasound detects as little as 100 mL) 1
Diagnostic Paracentesis: Core Laboratory Tests
Every diagnostic paracentesis must include these four essential tests 1, 2:
1. Cell Count with Differential
- Neutrophil count >250 cells/mm³ diagnoses spontaneous bacterial peritonitis (SBP) requiring immediate antibiotics 1, 2, 4
- This must be checked even in asymptomatic patients 2, 4
2. Total Protein
- Values <1.5 g/dL (or 15 g/L) indicate increased risk for SBP and help with differential diagnosis 1, 2, 4
3. Albumin (Ascitic Fluid)
- Required to calculate the serum-ascites albumin gradient (SAAG) 1, 2
- Obtain simultaneous serum albumin to calculate SAAG 2, 4
4. Bacterial Culture
- Inoculate at least 10 mL of ascitic fluid into blood culture bottles at the bedside before starting any antibiotics 1, 2, 4
- This increases culture sensitivity from ~50% to >80-90% 2, 4
- Never start antibiotics before obtaining cultures, as this significantly reduces yield 2, 4
Diagnostic Algorithm
Step 1: Rule Out Infection
Step 2: Calculate SAAG to Determine Etiology
- SAAG = (Serum Albumin) - (Ascitic Fluid Albumin) 1, 5
- SAAG ≥1.1 g/dL indicates portal hypertension with 97% accuracy 1, 2, 3, 5
- Causes include: cirrhosis (60-85% of cases), cardiac ascites, Budd-Chiari syndrome 1
- SAAG <1.1 g/dL indicates non-portal hypertension causes 3, 4
- Causes include: peritoneal carcinomatosis, tuberculous peritonitis, pancreatic ascites, nephrotic syndrome 1
Step 3: Additional Tests Based on Clinical Context
Order these selectively based on your differential diagnosis 1, 4:
- Cytology: If malignancy suspected (sensitivity 96.7% with three samples processed promptly) 2
- Adenosine deaminase (ADA): If tuberculosis suspected
- Glucose and LDH: If secondary bacterial peritonitis from perforated viscus suspected
- Amylase: If pancreatic disease suspected (typically >1,000 mg/dL in pancreatic ascites) 1, 2
When Initial Workup Remains Inconclusive
If the cause remains uncertain after paracentesis and laboratory analysis, proceed to laparoscopy with peritoneal biopsy 1, 6:
- Laparoscopy with biopsy clarifies the diagnosis in 85% of unexplained ascites cases 6
- Most common findings: peritoneal carcinomatosis (56%), tuberculous peritonitis (18%), cirrhosis (11%) 6
Critical Pitfalls to Avoid
- Do not delay paracentesis to correct coagulopathy unless there is clinically evident DIC or hyperfibrinolysis—severe hemorrhage occurs in only 0.2-2.2% of procedures 1, 4
- Do not skip paracentesis in hospitalized cirrhotic patients even if asymptomatic, as SBP can be silent 2, 4
- Do not order CA125 for differential diagnosis—it is elevated in all types of ascites and is nonspecific 1
- Approximately 5% of patients have two or more causes of ascites (e.g., cirrhosis plus heart failure), so consider mixed etiologies 1