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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
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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
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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
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