Side Effects of Intravenous Albumin
Adverse reactions to intravenous albumin are rare, but when they occur, they include allergic reactions (urticaria, chills, fever, respiratory changes, pulse and blood pressure alterations) and complications from excessive administration such as fluid overload, hypotension, pulmonary edema, hemodilution requiring blood transfusion, anaphylaxis, and peripheral gangrene from dilution of natural anticoagulants 1, 2.
Allergic and Hypersensitivity Reactions
The most commonly recognized adverse effects are allergic in nature, manifesting as:
- Urticaria (hives)
- Chills and fever
- Changes in respiration
- Pulse alterations
- Blood pressure changes 1
These hypersensitivity reactions can range from mild erythema to severe anaphylaxis and even cardiac arrest, though such severe reactions have become less frequent with modern purification techniques 3. The incidence of these allergic reactions is low but requires vigilance during administration 4.
Volume-Related Complications
Complications from high plasma protein levels due to excessive albumin administration are particularly important and affect multiple organ systems 1:
Cardiovascular and Pulmonary Effects
- Fluid overload and circulatory embarrassment - especially when administered too rapidly (>2 mL/min in hypoproteinemic patients) 1
- Pulmonary edema - the pulmonary system is particularly prone to complications from excessive albumin 4, 5
- Hypotension - paradoxically can occur despite albumin's intended use for volume expansion 2
Hematologic Effects
- Hemodilution requiring RBC transfusion - from excessive volume expansion 2
- Coagulation derangements - including dilution of natural anticoagulants leading to potential peripheral gangrene 2, 6
Renal Effects
- Potential worsening of acute kidney injury - some recent studies suggest hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock, though the overall evidence is weak 7
- Renal complications may occur more frequently in patients with severe injuries 3
Metabolic and Biochemical Effects
- Trace metal loading, especially aluminum contamination - well-documented and requires appropriate manufacturing procedures and user awareness of residual aluminum concentrations 3
- Serum amino acid alterations 4
Special Considerations in Liver Disease
In patients with acute-on-chronic liver failure, pathological and dysfunctional albumin forms increase substantially, including oxidized isoforms (human nonmercaptalbumin 1 and 2, and nitrosoalbumin), which are potentially toxic 6. The role of albumin administration in these patients remains unclear.
Important Clinical Caveats
- Transfusion reactions and antibody formation can occur 6
- Many reported adverse effects appear to be extensions of albumin's pharmacologic activities and worsen with large doses 4
- The 2024 International Collaboration for Transfusion Medicine Guidelines emphasize that 12 of 14 recommendations did not suggest albumin use in most clinical situations where it is commonly transfused, partly due to these potential adverse effects 2
- Adverse effects occur more frequently in patients with severe injuries, cardiac, or respiratory compromise 3
The key to minimizing side effects is judicious use with appropriate dosing, slow administration rates (not exceeding 2 mL/min in hypoproteinemic patients), and limiting use to evidence-based indications 1, 6.