Why is albumin given to patients with hepatic encephalopathy and a history of liver cirrhosis?

Albumin Administration in Hepatic Encephalopathy and Cirrhosis

Direct Answer

Albumin is given to patients with hepatic encephalopathy and cirrhosis primarily for four established indications: preventing circulatory dysfunction after large-volume paracentesis (>5L), treating spontaneous bacterial peritonitis, managing hepatorenal syndrome, and as adjunctive therapy in acute hepatic encephalopathy to improve resolution and reduce mortality. 1, 2

Established Indications with Strong Evidence

Large-Volume Paracentesis

• Administer albumin when removing >5L of ascitic fluid to prevent paracentesis-induced circulatory dysfunction 1
• This is recommended by the American Association for the Study of Liver Diseases with moderate certainty of evidence 1

Spontaneous Bacterial Peritonitis

• Give 1.5 g/kg at diagnosis and 1.0 g/kg on day 3 1, 2
• This represents a strong recommendation with moderate certainty of evidence 1
• Albumin reduces mortality and prevents hepatorenal syndrome in these patients 1

Sepsis-Induced Hypotension in Cirrhosis

• Use 5% albumin over normal saline in cirrhotic patients with sepsis-induced hypotension 1
• A 2024 RCT showed higher 1-week survival with albumin (43.5% vs 38.3%, p=0.03) 1

Hepatic Encephalopathy: Emerging but Supported Indication

Evidence for Albumin in Acute Hepatic Encephalopathy

The American Thoracic Society recommends albumin administration in combination with standard therapy to improve resolution of encephalopathy and reduce mortality 2, though the certainty of evidence remains low to very low 1.

Key Supporting Data:

• Complete resolution occurred in 75% of patients receiving albumin plus lactulose versus 53% with lactulose alone (p=0.03) 3, 2
• Mortality at day 10 was significantly lower: 18% in the albumin-lactulose group versus 32% with lactulose alone (p=0.04) 3
• A masked RCT demonstrated improved 90-day mortality (23% vs 47%) and better transplant-free survival (p=0.02) with albumin compared to normal saline 3, 2
• A 2021 meta-analysis showed albumin reduced hepatic encephalopathy (RR 0.60,95% CI 0.38-0.95) and mortality (RR 0.54,95% CI 0.33-0.90) 2, 4

Recommended Dosing for Hepatic Encephalopathy

For acute hepatic encephalopathy: administer 1.5 g/kg on day 1 followed by 1.0 g/kg on day 3 2, always in combination with lactulose and rifaximin 5.

An alternative regimen is 1.5 g/kg/day for up to 10 days combined with lactulose 2.

Mechanistic Rationale in Cirrhosis

Albumin provides benefits beyond simple volume expansion in cirrhotic patients:

• Plasma expansion properties help correct the effective hypovolemia characteristic of decompensated cirrhosis 6
• Antioxidant and anti-inflammatory functions mitigate oxidative stress and bind proinflammatory cytokines (TNFα and IL-6) 6
• Ammonia reduction in hepatic encephalopathy by improving hepatocyte function and ammonia clearance 6
• Binding capacity for endotoxins and other inflammatory mediators that accumulate in cirrhosis 6

Critical Contraindications and Safety Concerns

When NOT to Use Albumin

Do not use albumin as first-line volume replacement in critically ill cirrhotic patients 1 or for correction of hypoalbuminemia alone 1, 7.

• Balanced crystalloids (lactated Ringer's) are preferred for initial resuscitation 1
• The ATTIRE trial (N=149) showed no improvement in the composite endpoint of new infections, kidney dysfunction, or death (adjusted OR 0.91,95% CI 0.44-1.86) when albumin was used broadly in hospitalized cirrhotic patients 3
• Do not use albumin in patients with cirrhosis and uncomplicated ascites, whether hospitalized or outpatient 7

Monitoring for Adverse Effects

Immediately discontinue albumin if pulmonary edema develops 1.

• Patients with cirrhosis have increased capillary permeability, raising the risk of fluid overload 2
• Monitor closely for respiratory distress or declining oxygen saturation 1
• Use echocardiography to guide fluid management in high-risk patients 1
• Up to 45% of patients may experience cardiovascular complications 7

Practical Clinical Algorithm

Step 1: Identify the Specific Indication

• Large-volume paracentesis (>5L removed)? → Give albumin 1
• Spontaneous bacterial peritonitis? → Give 1.5 g/kg at diagnosis, 1.0 g/kg on day 3 1, 2
• Hepatorenal syndrome? → Give albumin 1
• Sepsis-induced hypotension? → Give 5% albumin over saline 1
• Acute hepatic encephalopathy (grade II-IV)? → Consider 1.5 g/kg on day 1.0 g/kg on day 3 plus lactulose 2

Step 2: Assess Contraindications

• Evaluate cardiac and pulmonary function before administration 3
• Check for signs of volume overload or heart failure 1
• Avoid if patient has uncomplicated ascites without other indications 7

Step 3: Monitor During and After Administration

• Watch for respiratory distress, declining oxygen saturation, or signs of pulmonary edema 1, 2
• Consider echocardiography in patients with compromised cardiac function 1

Important Caveats and Pitfalls

The Evidence Remains Mixed for Hepatic Encephalopathy

While two small RCTs showed benefit 3, 2, 4, the larger ATTIRE trial found no improvement in outcomes when albumin was used broadly in hospitalized cirrhotic patients with encephalopathy 3. The International Collaboration for Transfusion Medicine Guidelines panel explicitly abstained from making a recommendation for albumin in hepatic encephalopathy due to this uncertainty 1.

Avoid Common Misuse Patterns

• Never use albumin simply to correct low serum albumin levels 7
• The MACHT trial found no benefit from albumin plus midodrine in patients with advanced cirrhosis awaiting transplantation 7
• Weekly albumin infusions for uncomplicated ascites are not recommended based on the highest quality evidence from the 2024 ATTIRE trial 7

Weighing Risks vs Benefits in Hepatic Encephalopathy

Given the mortality benefit demonstrated in acute hepatic encephalopathy (18% vs 32% at day 10, p=0.04 3 and 23% vs 47% at 90 days 2), albumin should be strongly considered in acute hepatic encephalopathy despite the low certainty of evidence, particularly in patients without significant cardiac or pulmonary dysfunction 2. The potential mortality reduction outweighs the risks when appropriate monitoring is in place.