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Human albumin: ICU


"There is a strong physiological rationale to consider human albumin as a crucial molecule, both as a natural colloid, and also as a drug"


assuming a critical role in processes regulating the maintenance and fluid exchanges involving the blood compartment.5


In addition, specific


characteristics of its molecular structure provide human albumin with crucial secondary properties. First, the presence of cysteine residues, especially of the residue in position 34, leading to the exposition of a thiol group (-SH radical), provides human albumin the ability of binding free oxygen radicals and nitric oxide, and therefore the ability to act as antioxidant and anti-inflammatory agent.6,7


Second, the presence of the


specific domains I and II makes human albumin extremely important for the transportation of various molecules, both endogenous (such as electrolytes, hormones, fat acids) and exogenous (such as drugs). Finally, the presence of 16 histidine imidazole residues confers the ability of acting as a buffer molecule within the context of acid–base equilibrium. On the whole, there is a strong physiological rationale to consider human albumin as a crucial molecule, both as a natural colloid, and also as a 'drug', with potential clinically relevant pharmacological properties.1


Clinical evidence: primary functions


Human albumin has a crucial role in


regulating the homeostasis of the intravascular blood compartment. Consequently, it is reasonable to consider this molecule in the haemodynamic management of critically ill patients, especially when dealing with fluid therapy. Being a natural colloid, albumin-containing solutions are generally considered more effective for intravascular volume replacement as compared with crystalloids, and similarly less prone to accumulation within the interstitial space. Although the classical view by Ernest Starling on


compartments' model has recently been questioned,8


the biological rationale for


considering volume replacement with colloids more effective than with crystalloids still stands. This argument becomes even more important when facing the recent evidence on increased risk of acute renal injury, bleeding and ultimately death, which accompanies the administration of hydroxyethyl starches, one of the most employed categories of synthetic colloids.9,10 Despite a clear rationale, no robust clinical advantages seem to justify their costs in a general population of critically ill patients, as recently concluded by the updated edition of the Cochrane meta-analysis on the use of crystalloid and colloid solutions.11


Nevertheless, these findings do not reject the


hypothesis that the oncotic properties of human albumin may have beneficial effects in specific categories of critically ill patients. In a post hoc analysis performed on patients with severe sepsis included in the SAFE trial, the use of 4% albumin solution was associated with an increased central venous pressure and a reduced heart rate over the first seven days as compared with crystalloids, suggesting a greater intravascular blood compartment.12


As a consequence, and in


the absence of a detrimental effect, the last edition of the Surviving Sepsis Campaign guidelines for the management of severe sepsis and septic shock included the suggestion (graded as grade 2C) of using albumin during the first phase of fluid resuscitation, especially when large amounts of crystalloids are required.13


Clinical evidence: secondary functions


The current evidence investigating the clinical benefits of the secondary functions of human albumin is scarce. Certainly, the molecular specificity and complexity of some of these properties make this a difficult task. Nonetheless, indirect evidence, together with some preliminary findings, may provide an insight.


On the antioxidant properties of www.hospitalpharmacyeurope.com 15


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