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Human albumin: benefits

Box 1: The main physiological functions of albumin

• regulation of oncotic pressure of the plasma • regulation of the acid-base • binding, transport and metabolism of organic compounds, metabolic degradation products, drugs and protection from exogenous toxins

• effects on hemostasis • integrity of the microcirculation and capillary permeability

• antioxidant reserves and extracellular sulfhydryl groups

macromolecules and solutes and restricts the increase in the course of inflammation. This function is due to the presence of albumin within the capillary wall and may be directly derived both from its high negative charge, resulting in electrostatic repulsion of negatively charged molecules, and from space-occupying effects.6 Indirect action on the microcirculation could be mediated by binding with arachidonic acid, a molecule that increases capillary permeability. Furthermore, albumin inhibits the adhesion of human neutrophils to endothelial cells.7

Fluid therapy

In general, fluid therapy is used for replenishing fluid losses, to restore effective circulation as well as to correct acid-base and electrolyte disturbances. This is accomplished with two categories of substance: crystalloid and colloids (see pp xx–xx). The crystalloid solutions distribute easily into the extracellular space, are used for maintenance as well as replacement of blood volume and serve as a vehicle for drug delivery. Crystalloids should have a composition similar to extracellular fluid. Their disadvantage is that they have a short duration of action (see pp xx–xx). Colloids are solutions that contain larger and heavier molecules, which procure an increase in COP and are able to increase the volume of plasma by attracting water from the extracellular spaces. Colloids in clinical use are classified into natural (plasma and human albumin) and artificial or semi-synthetic solutions. The individual colloids differ in their ability to expand plasma volume depending on the COP of each fluid. Human albumin solutions are available both at low (4%, 5%) and high

concentrations (20%, 25%) and exert a COP of about 20 and 70mmHg, respectively, the latter being the highest COP solution available. Synthetic colloids have been proposed as an alternative to crystalloids but they may have serious side effects (see

pp xx–xx). Human albumin may therefore be preferentially used in cases where a sustained action on the blood volume is required or when there is a contraindication for non-protein colloids.

Indications and clinical benefits of human albumin

Evidence-based use of albumin solutions in fluid therapy has been shown in acute conditions such as expansion of plasma volume for maintenance of effective circulatory blood volume (volume resuscitation) as well as in some chronic conditions with low serum albumin. Hypoalbuminemia is a known prognostic factor for adverse outcome and administration of albumin solution has been shown to reduce morbidity.8,9

is also considered appropriate in the exchange of large volumes of plasma.10 Regarding volume resuscitation, current consensus and guideline recommendations are controversial (see pp xx–xx). Recent studies confirm that the volume effect of albumin is superior to that of crystalloids.11

Box 2: Clinical use of human albumin solution

• circulatory support in critically ill patients • cirrhosis and some of its complications (ascites and large volume paracentesis, spontaneous bacterial peritonitis, hepato-renal syndrome, ascites)

• severe sepsis or septic shock (volume resuscitation and disturbance of microcirculation)

• burns (after 24 hours) • cardiac surgery • post-surgical (post-hemorrhagic hypovolemia) • acute respiratory distress syndrome • malabsorption syndromes • plasmapheresis • ovarian hyperstimulation syndrome

Its use

different levels of evidence (Box 2). Then, large-scale clinical trials have been performed. Their results are now available, confirming human albumin’s safety, and they also provide high grade level of evidence for its modern therapeutic use.

The exclusive use

of crystalloids is nevertheless proposed by some experts in the field; crystalloids as a first choice followed by colloids as a second choice is recommended by others. The issue of which type of colloid should be used (artificial or natural) is controversial as well, including when (early versus late) and where (emergency, ICU, surgery). However, recent clinical trials have confirmed long-standing safety concerns regarding the widespread use

In cirrhotic patients with ascites, the therapeutic goal of treatment with albumin is not limited to the maintenance of COP but to improve effective circulating blood volume because splanchnic vasodilation reduces blood volume at the central level with activation of the renin-angiotensin system, sodium retention and development of ascites.12 The appearance of refractory ascites, that is, resistant to the administration of diuretics, represents an established indication for the use of albumin, when large volume paracentesis is performed leading to improved morbidity and

"Current guidelines strongly recommend the inclusion of albumin solutions in the circulatory support in certain critically ill patients and in complications of cirrhosis of the liver ”

artificial colloids. In contrast, human albumin solutions have been confirmed to be safe and effective in various clinical indications, in particular some complications in cirrhosis of the liver (see pp xx–xx) and in intensive care medicine, where the subgroup of patients with severe sepsis or septic shock has been shown in the SAFE study and subsequent meta-analyses to derive significant survival benefit (see pp xx–xx). Before having been abandoned because of higher costs and conflicting results of meta-analyses in the late 1990s, albumin solutions had been used in various clinical indications on basis of


In cirrhotic patients, additional indications include spontaneous bacterial peritonitis (1.5g/kg on day 1 and 1g/kg on day 3) and hepato-renal syndrome in association with vasoconstrictors (1g/kg on day 1 then 20–40g/day for 2 weeks) (see pp xx–xx).13

Severe sepsis and septic shock are characterised by micro-vascular leakage into the interstitium due to increased capillary permeability, production of pro-inflammatory cytokines and severe hypovolemia. This results in a reduction in blood pressure and insufficient blood supply to major organs, with the risk of developing multiple organ failure. Volume


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