Crystalloid, colloid, albumin?BMJ 1998; 317 doi: https://doi.org/10.1136/bmj.317.7153.0 (Published 25 July 1998) Cite this as: BMJ 1998;317:0
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Unfortunately, most of the heated debate on albumin therapy seems to ignore some substantial progress made in our basic understanding of albumin distribution in the interstitial space (1,2). Accordingly, too much emphasis is given to the "capillary leak syndrome," which is still largely a hypothesis in search of facts. Facts, however, may be better explained by an alternative, maybe complementary, pathophysiological approach
Sixty percent of the total albumin mass is located in the extravascular interstitial space. The volume of the interstitial space which is available for albumin is regulated by the degree of hydration and the chemical integrity of its glycosaminoglycan gel matrix. Probably the single most relevant component of the interstitial matrix regulating albumin distribution is hyaluronan. This glycosaminoglycan can be washed away by an expanded extracellular fluid resulting from aggressive resuscitation (3. There is some evidence that hyaluronan may also be lost from the interstitium in sepsis. Thus, "interstitial disease" is highly likely in the critically ill patient because both overhydration and sepsis may damage the integrity of the glycosaminoglycan gel matrix. Thus, rather than albumin "leaking from capillaries" the severely ill patient has an increased albumin distribution volume which results in extravascular sequestration of the albumin molecules that passively pass through a basically normal capillary endothelium (convective fluid-dependent transport. Thus, we hypothesize that the extravascular albumin mass (normally 60% of the total albumin mass)is dramatically increased in ill patients because its volume distribution in the interstitium is notably expanded. Administration of albumin in this setting probably leads to a further increase in the extravascular albumin mass with a worsening of the "interstitial disease" due to increased oncotic interstitial pressure, edema organization and failure to respond to diuretics.
We need to know more about the regulation of the extravascular albumin distribution volume in health and, above all, in diseaase, to refine -if there exist- the indications of albumin therapy. Meanwhile, I agree with the main messages of your review and editorials in that administration of albumin has little physiological sense and even less support from published trials.
1. Sitges-Serra A, Franch-Arcas G. Fluid and sodium problems in perioperative feeding: what further studies need to be done. Curr Op Clin Nutr Metabol Care 1998,1:9-14.
2. Bell DR, Watson PD, Renkin EM. Exclusion of plasma proteins in interstitium of tissues from the dog hind paw. Am J Physiol 1980; 239:H532-H538.
2. Townsley MI, Reed RK, Ishibashi M, Parker JC, Laurent TC, Taylor AE. Hyaluronan efflux from canine lung with increased hydrostatic pressure and saline loading. Am J Respir Crit Care Med 1994; 150:1605-11.
Competing interests: No competing interests