What are the evidence‑based indications and recommended dosing of albumin in cirrhosis (e.g., large‑volume paracentesis, spontaneous bacterial peritonitis, hepatorenal syndrome, acute variceal hemorrhage)?

Evidence-Based Albumin Use in Cirrhosis

Albumin has four firmly established indications in cirrhosis: large-volume paracentesis (>5 L), spontaneous bacterial peritonitis, hepatorenal syndrome, and prevention of paracentesis-induced circulatory dysfunction—all other uses lack sufficient evidence to recommend routine administration. 1

Established Indications with Strong Evidence

Large-Volume Paracentesis (>5 Liters)

Administer 8 g of albumin per liter of ascites removed when total volume exceeds 5 L. 1

• The dose is calculated solely on ascites volume, not patient weight 2
• Use 20% or 25% hyperoncotic albumin solutions; 5% albumin is inadequate 1, 2
• Infuse after paracentesis completion over 1–2 hours to prevent cardiac overload 1, 2
• For a 5 L tap: give 40 g albumin (200 mL of 20% solution or 160 mL of 25% solution) 2

Clinical rationale: Without albumin, post-paracentesis circulatory dysfunction (PICD) occurs in 70–80% of patients versus only 18% with proper replacement 1, 2. Renal impairment develops in 21% without albumin compared to 0% with albumin 2. The 2024 International Collaboration for Transfusion Medicine Guidelines made this a conditional recommendation based on low-certainty evidence, acknowledging that trials were small and outcomes imprecise 1.

For volumes <5 L: Albumin is optional but should be considered in patients with acute-on-chronic liver failure or high risk of acute kidney injury 1, 3

Spontaneous Bacterial Peritonitis (SBP)

Give 1.5 g/kg albumin within 6 hours of SBP diagnosis, followed by 1.0 g/kg on day 3. 1

• This weight-based regimen differs from the volume-based dosing used for paracentesis 2
• Albumin reduces renal impairment (10% vs 33%) and mortality (22% vs 41%) compared to antibiotics alone 1
• The benefit is most pronounced when baseline bilirubin >4 mg/dL or creatinine >1 mg/dL 4

Evidence strength: A meta-analysis of 6 RCTs (577 patients) showed albumin plus antibiotics improved 3-month survival (OR 0.66,95% CI 0.45–0.96) 1. The landmark Sort et al. trial established this as standard practice 1.

Hepatorenal Syndrome (HRS)

Albumin is recommended in combination with vasoconstrictors (terlipressin preferred) for type 1 HRS. 1, 4

• Typical dosing: 1 g/kg on day 1 (maximum 100 g), then 20–40 g daily 5
• Albumin plus terlipressin appears superior to albumin plus other vasoconstrictors 4
• The FDA label explicitly lists HRS as an approved indication 5

Acute Variceal Hemorrhage

Albumin administration is recommended as part of resuscitation in variceal bleeding, though specific dosing protocols vary. 1

• The 2024 AASLD guidance recommends albumin for select indications including variceal hemorrhage 1
• Balanced crystalloids or albumin are preferred over hydroxyethyl starch and saline in sepsis-related scenarios 1

Indications with Emerging but Insufficient Evidence

Sepsis-Induced Hypotension in Cirrhosis

Two single-center RCTs showed conflicting results 1:

• One trial (308 patients) found 5% albumin improved 1-week survival (43.5% vs 38.3%, p=0.03) compared to saline 1
• Another trial (100 patients) showed higher shock reversal but no survival benefit and increased pulmonary complications with 20% albumin 1

Current recommendation: Albumin may be considered for sepsis-induced hypotension in cirrhosis, but evidence is insufficient for routine use outside established indications 1

Long-Term Albumin Administration

The 2021 ATTIRE trial (777 patients) randomized hospitalized patients with decompensated cirrhosis to daily albumin targeting serum levels ≥3 g/dL versus standard care 1:

• No difference in the composite endpoint (infection, renal failure, or death) 1
• Significantly higher rates of pulmonary edema and fluid overload in the albumin group 1

Current recommendation: Targeting specific albumin levels with daily infusions is not recommended and may cause harm 1, 6. The 2024 guidelines explicitly state albumin should not be used in uncomplicated ascites 6.

Situations Where Albumin is NOT Indicated

Do not use albumin for: 1, 6, 5

• Uncomplicated ascites without large-volume paracentesis 6
• Chronic nephrosis (albumin is promptly excreted) 5
• Protein nutrition in malnutrition, malabsorption, or chronic cirrhosis 5
• Routine correction of hypoalbuminemia 1, 6
• First-line volume replacement in critical illness without cirrhosis 1

Dosing Summary Table

Indication	Dose	Timing	Evidence Level
Large-volume paracentesis (>5 L)	8 g/L ascites removed	After procedure, over 1–2 h	Conditional, low certainty [1]
SBP	1.5 g/kg → 1.0 g/kg	Within 6 h, then day 3	Strong, moderate certainty [1]
HRS	1 g/kg day 1 (max 100 g), then 20–40 g daily	With vasoconstrictors	Guideline-endorsed [1,5]
Paracentesis <5 L (high-risk)	8 g/L (optional)	After procedure	Conditional [1,3]

Critical Monitoring Parameters

After large-volume paracentesis (days 1–6): 1, 2

• Daily serum sodium (hyponatremia occurs in 17% without albumin vs 8% with albumin)
• Daily serum creatinine (rising >0.3 mg/dL suggests evolving HRS)
• Mean arterial pressure (decline >8 mmHg may signal circulatory failure)
• Plasma renin activity (>50% rise indicates PICD)

Red flags requiring escalation: 2

• Worsening hypotension or oliguria despite albumin
• Rising creatinine suggesting HRS (21% six-month mortality)
• Fever or abdominal pain (rule out SBP with diagnostic tap)

Common Pitfalls to Avoid

Underdosing albumin: Giving only 4 g/L instead of 8 g/L markedly increases PICD incidence 1, 2. All major guidelines converge on 8 g/L as the standard 1, 2.

Using synthetic colloids: Dextran-70, polygeline, and hydroxyethyl starch are inferior to albumin and cause greater RAAS activation, worse outcomes, and (for hydroxyethyl starch) potential renal failure 1, 2. The 2010 EASL guidelines explicitly state these should not be used 1.

Rapid infusion: Infusing albumin too quickly can precipitate cardiac overload in patients with cirrhotic cardiomyopathy; always infuse over 1–2 hours 1, 2.

Wrong albumin concentration: 5% albumin is inadequate for paracentesis; use 20% or 25% hyperoncotic solutions 1, 2.

Delaying diuretics: Restart spironolactone 100 mg daily (titrated to 400 mg) plus furosemide 40 mg within 1–2 days after paracentesis to prevent rapid ascites re-accumulation (93% recurrence without diuretics vs 18% with spironolactone) 1, 2.

Nuances in the Evidence

The 2024 International Collaboration guidelines downgraded the certainty of evidence for large-volume paracentesis to "low" because trials were small, outcomes were imprecise, and the primary endpoint (plasma renin rise) is a surrogate marker rather than a patient-important outcome 1. However, the panel still conditionally recommended albumin because the practice is widely accepted and alternative fluids perform worse 1.

For SBP, the two largest RCTs lacked explicit fluid resuscitation protocols in control arms, raising concern for underresuscitation bias 1. Despite this limitation, the mortality benefit was consistent enough to support guideline recommendations 1.

The ATTIRE trial's negative results for long-term albumin administration highlight that targeting serum albumin levels is fundamentally different from using albumin for specific complications 1. The trial's design (daily infusions to maintain albumin ≥3 g/dL) does not reflect guideline-endorsed indications and should not be extrapolated to established uses 1.