Wonderful albumin?

Not all it is cracked up to be

Albumin solutions are commonly used to treat low serum albumin concentrations and hypovolaemia. Human albumin effectively replaces volume and supports colloid oncotic pressure. Unlike synthetic colloids, it has transport functions and binds reversibly with anions, cations, and some substances that are active or toxic only in the free form. It is a scavenger of free radicals1 and improves prognosis in the sheep model of the adult respiratory distress syndrome.2 It has anticoagulant properties, inhibiting platelet aggregation and enhancing the inhibition of factor Xa by antithrombin III.3 4 It may also have a role in preserving microvascular integrity, which is possibly mediated by glycoproteins distributed through the capillary membrane.5

Common reasons for using albumin rather than synthetic alternatives are generally clinical associations and beliefs related to the importance of hypoalbuminaemia. Hypoalbuminaemia is associated with a poor surgical outcome and a longer stay in hospital and is a marker of higher risk in critically ill patients. It is associated with oedema and, by implication, with low serum colloid oncotic pressure. Starling's law is commonly invoked to suggest cause and effect. Serum albumin concentration fails rapidly in critically ill patients. This is often blamed on catabolism or failure of synthesis of albumin, which then implies albumin deficiency and that replacement is necessary.

Unsurprisingly, albumin replacement is popular. It has tremendous theoretical advantages while at the same time either preventing or treating the fall in serum albumin concentrations, which carries such fearful connotations.

But let us consider the evidence for such beliefs. Although hypoalbuminaemia may be associated with a poor outcome, there is always an underlying problem. Correcting this problem—not the serum albumin concentration—influences the outcome. A return of serum albumin concentration towards normal usually indicates improvement.

Oedema in critically ill patients has the same pathophysiological basis as hypoalbuminaemia; hypoalbuminaemia is usually an effect rather than a cause.6 Serum albumin concentration correlates poorly with colloid oncotic pressure,7 but Starling stated that, even if the correlation was high, the oncotic gradient—not the absolute plasma value—was important. Albumin distributes across the capillary membrane, thereby minimising the transcapillary gradient, and this process is accelerated in critically ill patients.6 8 Consequently, the absolute serum albumin concentration may fall with minimal change in the transcapillary gradient. The fall in serum albumin concentration seen in sepsis, trauma, and major surgery occurs too rapidly to be due to either catabolism or failed synthesis, which together account for less than a tenth of circulating albumin a day. Redistribution is more likely, which is probably also relevant in conditions such as pre-eclampsia.

Hypoalbuminaemia is associated with poor gut motility, but increasing the serum concentration by giving albumin does not increase gut motility. Conversely, correcting the underlying problem, and incidentally improving the serum albumin concentration, improves gut motility.9

Should we support a particular range of serum albumin concentrations? Undoubtedly, giving albumin will help to maintain the serum albumin concentration, but if this is a marker of rather than a cause of pathophysiology then why treat it? Several studies have failed to show that treatment with albumin improves outcome.10 11 12 One study found more infections in patients whose serum albumin concentrations were not supported13; other studies have failed to confirm this.10 11 12

What of the impressive theoretical arguments for using albumin as the preferred colloid solution? If albumin is effective for binding drugs and toxic substances, is a scavenger of free radicals, and is important for vascular integrity and blood coagulation we would expect it to be better than other agents. As administration of colloid is a substantial component in the management of critically ill patients the long term benefits of albumin should be easily identifiable. Curiously, there is a dearth of studies on this. While many studies have shown the comparative haemodynamic efficacy of albumin and synthetic colloids, few have examined longer term use. One study comparing gelatin and albumin found no difference in outcome, length of stay in an intensive care unit, or requirement for blood products and coagulation factors.10

Should we use albumin for volume replacement? It is expensive. It is a human product. In critically ill patients its impressive array of theoretical advantages over synthetic agents does not translate into overt clinical benefits. If it is unhelpful in this population then whom is it likely to benefit?

What is the role of albumin solutions? There is no convincing evidence that albumin is better than synthetic alternatives for volume replacement; nor is there clear evidence for maintaining the serum albumin value concentration above a certain level. Currently, the widespread use of albumin has more to do with word association and the treatment of items that are marked on the pathology form with an asterisk than with scientific medical management. At a time when molecular biology and genetic engineering are the focus of our research we would do well to review critically some of our beliefs about more basic science.