Science commentary

Why albumin may not work

Starling's principle is often represented as the leakage of fluids from the arterial end of capillaries, where the hydrostatic pressure is greater than the oncotic pressure (derived from the plasma proteins), and the reabsorption of fluid into the venous end, where the oncotic pressure exceeds the hydrostatic pressure. A small excess of fluid in the interstitial spacewhen filtration from the capillaries is greater than reabsorptionis dealt with by lymphatic drainage from the interstitial space. The rationale for giving albumin solutions rather than crystalloid solutions in cases of hypovolaemic shock is that fluid reabsorption from the interstitial space is enhanced, and fluid therefore remains in the vascular system for longer.

But in recent years the assumed reabsorption of fluid at the venous end of capillaries has been challenged. There is now good evidence to show that, except in the gut and the renal circulation, there is no sustained reabsorption of fluid at the venous end of capillaries. Instead, there is a small constant level of filtration from the capillaries, restrained by the osmotic pressure of the plasma proteins. In some rare circumstancesfor example, in hypovolaemic shockthere is a transient reabsorption of fluid, but this lasts for only a few minutes and it amounts to an "internal transfusion" of about 500 ml of fluid over 15 minutes.

The production of life threatening pulmonary oedema begins when the loss of protein and fluid from the blood vessels exceeds the volume of fluid that can be drained from the interstitial space by the lymphatics. In some disease states or when tissue is damaged, as in severe burns, the capillary walls become very much more permeable under the influence of direct cellular damage and from inflammatory mediators. The filtration of fluids, together with proteins, out into the interstitial space is greatly increased and cannot be matched by lymphatic drainage. The filtration rate may be further increased by a fall in the hydrostatic pressure in the interstitial space as a result of tissue damage, so that even more fluid is sucked out of the capillaries.

Conventionally, colloids such as albumin are administered to these patients in an attempt to maintain their intravascular volume, but because of the increased permeability of the vessels, the albumin solution becomes much less effective in maintaining plasma volume than in healthy individuals who have normal vessel permeability. Thus the rationale for administering albumin solutions becomes much less clear. In disease states such as the nephrotic syndrome, for example, there is new evidence to show that protein is lost not only from the renal circulation owing to greater permeability of the renal vessels, but also from the rest of the systemic circulation. This being the case, it is difficult to see how the administration of albumin could ever replace the deficit without causing further problems.

Abi BergerScience editor, BMJ