Albumina

Albumin Usage in Clinical Medicine: Tradition or Therapeutic?
Albert Farrugia
Plasma protein therapies have been sheltered historically from the scrutiny of evidence-based medicine. Thus, a number of albumin solutions became part of the established therapeutic armamentarium with a very modest evidence base. As evidence-based medicine has turned its focus on plasma protein therapies, albumin'sappropriate use has become increasingly questioned. Concurrently, interest in other colloid plasma expanders has increased as efforts to address their side-effects have resulted in new products. The decadeold meta-analysis from the Cochrane collaboration linking albumin with increased mortality, although currently disproven, has resulted in ongoing scrutiny of albumin's safety and has led to alarge randomized clinical trial which, while demonstrating equivalent safety with saline, has also shown equivalent mortality in the patient population assessed. Albumin's manufacture yields products which vary between different brands, as well as occasionally between batches from the same brand. These changes affect albumin's physiologic properties and may contribute to the different therapeuticeffects observed in clinical practice. More clinical investigations of albumin's therapeutic role are needed before its unique biological features can be shown to result in therapeutically useful drugs. © 2010 Elsevier Inc. All rights reserved.

UMAN ALBUMIN IS a multifunctional, non-glycosylated, negatively charged plasma protein, with a molecular weight of 69 kd. It is composed of a simple aminoacid chain with a quaternary helix-line structure. The center of the molecule is made up of hydrophobic radicals which are binding sites for many ligands, while the outer part of the molecule is composed of hydrophilic ligands. At physiological concentrations of 40 to 50 g/L, albumin is the most abundant protein in human plasma, constituting 50% of the total plasma protein content and accountingfor 70% of plasma's oncotic pressure.a The total body albumin content is 4 to 5 g/kg of which one third is in the intravascular space and two thirds in the extravascular compartment. Half of the extravascular albumin is concentrated close to the skin, explaining the rapid protein losses encountered after burns. Albumin is synthesized primarily in the liver at a rate of 9 to 12 g/d, and has ahalf-life of 2 to 3 weeks before being catabolized by the reticuloendothelial system. Albumin is not stored in the liver and there is no reserve for rapid release if required. Under physiological circumstances, only 20% to 30% of hepatocytes produce albumin; synthesis can be increased on demand by 200% to 300%. Synthesis seems to respond to changes in plasma colloidal osmotic pressure but is alsoregulated by nutritional status and hormones including insulin, glucagon, cortisol, and thyroid

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hormones. In addition to maintaining colloidal osmotic pressure, albumin plays other roles related to its capacity to bind other molecules and ions. These include buffering through binding hydrogen ions; transporting hormones; and neutralizing toxins such as bilirubin as well as contributing to theredox potential of plasma and binding and transporting drugs.1
DEVELOPMENT OF ALBUMIN SOLUTION

Edwin Cohn's development of a stable albumin solution during World War II was based on a fractionation scheme which was rapidly adopted— and adapted—by a number of pharmaceutical companies. Cohn never took a patent on his work. His technology quickly yielded other therapeutics including immunoglobulinsand procoagulants such as fibrinogen. Albumin, however, remained the mainstay product of the plasma protein industry for decades and is claimed to be crucial for its viability.2 That being the case, the level of clinical
From the Plasma Protein Therapeutics Association, Annapolis, MD, and Centre for Orthopaedic Research/ Department of Surgery, Faculty of Medicine and Surgery, University of...