For an adult with cirrhosis undergoing large‑volume paracentesis (>5 L), should intravenous albumin be administered and what is the recommended dosing?

Albumin Replacement in Large-Volume Paracentesis

For adults with cirrhosis undergoing large-volume paracentesis (>5 L), intravenous albumin should be administered at a dose of 8 grams per liter of ascitic fluid removed to prevent post-paracentesis circulatory dysfunction. 1

Mandatory Albumin Administration

• Albumin is indicated whenever more than 5 liters of ascites is removed, as recommended by the European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), and the International Collaboration for Transfusion Medicine Guidelines. 1

• The standard dose is 8 grams of albumin per liter of ascitic fluid removed (e.g., 40 grams for 5 L, 80 grams for 10 L). 1, 2

• This represents a conditional recommendation with very low certainty of evidence from the most recent 2024 international guideline, but the recommendation is consistent across all major hepatology societies. 1

Dosing Protocol

• Use 20% or 25% albumin solution to minimize volume load; 5% albumin is inadequate for this indication. 2, 3

• Administer albumin after the paracentesis is completed, not during the procedure, infused over 1-2 hours to avoid circulatory overload. 2, 3

• For a 5-liter paracentesis: Give 40 grams total (200 mL of 20% albumin or 160 mL of 25% albumin). 2

• For a 10-liter paracentesis: Give 80 grams total (400 mL of 20% albumin or 320 mL of 25% albumin). 2

Clinical Rationale and Evidence

Post-paracentesis circulatory dysfunction (PICD) occurs in up to 70-80% of patients when albumin is not administered, compared to only 18.5% when albumin is given at the recommended dose. 1, 4

• Albumin reduces the odds of PICD by 61% (OR 0.39,95% CI 0.27-0.55), reduces mortality by 36% (OR 0.64,95% CI 0.41-0.98), and reduces hyponatremia by 42% (OR 0.58,95% CI 0.39-0.87). 5

• PICD is characterized by activation of the renin-angiotensin-aldosterone system, defined as a >50% increase in plasma renin activity to a level >4 ng/mL/h by day 6 post-paracentesis. 4, 6

• Patients who develop PICD have shorter time to readmission (1.3 vs 3.5 months) and shorter survival (9.3 vs 16.9 months) compared to those who do not develop PICD. 4

Alternative Plasma Expanders Are Inferior

Do not use dextran 70, polygeline, or hydroxyethyl starch as alternatives to albumin. 1

• These synthetic colloids result in higher rates of PICD (34-38% vs 18.5% with albumin), greater activation of the renin-angiotensin system, and worse clinical outcomes. 4

• The 2010 EASL guidelines explicitly state that plasma expanders other than albumin are not recommended for paracentesis >5 L. 1

Paracentesis <5 Liters

For paracentesis volumes less than 5 liters, albumin replacement is not mandatory in most patients, as the risk of PICD is low. 1, 5

• However, consider albumin at 8 g/L even for <5 L volumes in patients with acute-on-chronic liver failure or high risk of post-paracentesis acute kidney injury. 2, 3

• The 2004 AASLD guideline states that albumin "may not be necessary" for single paracentesis <4-5 L, but can be considered. 1

Controversy: Lower-Dose Albumin

Two small studies suggested that 4 grams per liter might be equivalent to 8 grams per liter, but these findings are not endorsed by major guidelines. 7, 8, 9

• A 2011 pilot study (n=70) found no difference in PICD rates between 4 g/L and 8 g/L (14% vs 20%, p=NS), but this was underpowered and unblinded. 7

• A 2020 retrospective study using a standardized order set with lower albumin doses (6.5 g/L vs 8.3 g/L) showed no difference in adverse outcomes, but this was not a randomized trial. 8

• Despite these studies, all current guidelines continue to recommend 8 g/L as the standard dose, and the lower-dose regimens have not been validated in adequately powered randomized trials. 1, 2

Post-Paracentesis Monitoring

Monitor for complications over the 6 days following paracentesis: 2, 4

• Daily serum creatinine: Watch for increases >0.3 mg/dL from baseline, which may signal evolving hepatorenal syndrome. 2

• Daily serum sodium: Hyponatremia develops in approximately 17% of inadequately replaced patients vs 8% with proper albumin dosing. 2

• Mean arterial pressure: Declines >8 mmHg may indicate advancing circulatory dysfunction. 2

Diuretic Management After Paracentesis

Resume diuretics within 1-2 days after paracentesis to prevent rapid re-accumulation of ascites. 1, 2

• Without diuretics, ascites re-accumulates in approximately 93% of cases vs 18% when spironolactone is used. 2

• Recommended regimen: Spironolactone 100 mg daily (titrated up to 400 mg) combined with furosemide 40 mg daily (maintaining a 100:40 mg ratio). 2

• Diuretic re-introduction does not increase PICD risk when adequate albumin has been provided. 2

Common Pitfalls to Avoid

• Do not underdose albumin due to cost concerns; the financial burden of managing PICD-related complications (renal failure, prolonged hospitalization) exceeds the expense of albumin itself. 2

• Do not withhold paracentesis due to coagulopathy or thrombocytopenia; routine correction of INR or platelet count is not recommended before paracentesis, even with INR up to 8.7 or platelets as low as 19×10³/μL. 3

• Do not confuse the paracentesis albumin dose with the spontaneous bacterial peritonitis (SBP) dose; SBP requires weight-based dosing (1.5 g/kg within 6 hours, then 1.0 g/kg on day 3), which is a completely different protocol. 2, 3

Long-Term Management

Patients requiring repeated large-volume paracentesis should be evaluated for definitive therapies: 1, 2

• Liver transplantation evaluation is indicated for patients with refractory ascites, given a 21% six-month mortality risk. 2

• Transjugular intrahepatic portosystemic shunt (TIPS) should be considered when large-volume paracentesis is needed every 2-3 weeks despite maximal diuretic therapy. 1, 2