ALBUMIN
Benefits in the ICU
To fully understand whether human albumin might be beneficial in ICU , specific categories of patients who may benefit from this treatment need to be determined . Here , the physiological rationale and the available clinical evidence behind this are discussed
Pietro Caironi MD Department of Anesthesia and Critical Care , Azienda Ospedaliero-Universitaria S . Luigi Gonzaga , Orbassano ( TO ); University of Turin , Turin , Italy
The administration of human albumin as a clinical treatment for critically ill patients has been much debated in the past 20 years . 1 Despite the undeniable importance of this molecule in human physiology , the publication in 1998 of a large meta-analysis by the Cochrane Injuries Group Albumin Reviewers 2 highlighted a possible increased risk of death , even in categories of patients historically considered as ‘ therapeutic targets ’ of this treatment . Unfortunately , subsequent research on this topic did not yield full clarification , and scarcely led to evidence-based recommendations , with the exception of very few . . 3 , 4 There are two likely reasons for such uncertainty : first , the excessive emphasis on meta-analyses as a tool to achieve high-quality evidence , in association with the lack of well-designed randomised , controlled trials ( RCTs ); and second , the great heterogeneity characterising critically ill patients . 5 Therefore , to fully understand whether human albumin may be beneficial in ICU , the appropriate strategy could be to determine specific categories of patient who may benefit from this treatment , based upon a robust physiological rationale and solid clinical evidence , and individualise its application . In parallel , because the efficacy of albumin may rely on still-unveiled relevant secondary functions , further research is warranted to pinpoint specific effects which might be clinically relevant , as it has been shown in the last few years . This approach is crucial , in terms of efficacy ( favourable balance between beneficial and detrimental effects ), as well as in terms of costs ( favourable balance between benefits and costs ). It is therefore worthwhile summarising the physiological rationale and the available clinical evidence supporting the potential benefit or harm of using human albumin in critically ill patients .
Physiological role In humans , albumin is a protein presenting many crucial functions . 1 In healthy conditions , the liver , under the stimulation of the neuroendocrine system and the intravascular oncotic pressure , employs about 50 % of its energy expenditure for the synthesis and the secretion of 10 – 12g / day of albumin . Moreover , although mainly located within the intravascular compartment , albumin may pass at various degrees into the interstitial space , through a partially receptor-mediated process termed ‘ transcapillary escape rate ’. Indeed , albumin is generally distributed in the entire extra-cellular space .
As a primary function , human albumin is responsible for about 80 % of the intravascular oncotic pressure , thereby assuming a key role in processes regulating micro-circulatory fluid dynamics . 6 In addition , specific characteristics of its molecular structure provide human albumin with important ancillary properties , with undoubtedly clinically relevant effects . Among others , the presence of cysteine residues , especially of 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 an antioxidant and anti-inflammatory agent . 7 , 8 The presence of the specific domains I and II makes human albumin extremely important for the transportation of several molecules , both endogenous ( such as electrolytes , hormones , fatty acids ) and exogenous ( such as antibiotics and other drugs ). Moreover , the presence of 16 histidine imidazole residues confers the ability of acting as a buffer molecule within the context of acid – base equilibrium . Lately , recent evidence has suggested the potential role of albumin as a stabilising agent both for the immune system , 9 and for the endothelial functions . 10 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 as relevant for 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 . 5 Although the classical view by Ernest Starling on the compartments ' model has recently been questioned , 11 the biological rationale for considering volume replacement with colloids more effective than with crystalloids still stands . This argument becomes even more relevant 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
12 , 13 synthetic colloids .
Despite a clear rationale , no robust clinical advantages seem to justify its costs in a general un-characterised population of critically ill patients , as recently concluded by the updated edition of the Cochrane meta-analysis on the use of crystalloid and
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