Albumin—does the bell toll for thee?
1999; Wiley; Volume: 39; Issue: 2 Linguagem: Inglês
10.1046/j.1537-2995.1999.39299154723.x
ISSN1537-2995
Autores Tópico(s)Acute Kidney Injury Research
ResumoTransfusionVolume 39, Issue 2 p. 120-122 Free Access Albumin—does the bell toll for thee? First published: 19 December 2002 https://doi.org/10.1046/j.1537-2995.1999.39299154723.xCitations: 5AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Faced with major bleeding from blunt or penetrating trauma to the abdomen or chest, most anesthesiologists and surgeons choose an isotonic salt and water solution and red cells as the most suitable replacement therapy. The aim of fluid resuscitation is to restore adequate circulation and cellular perfusion to the critical organs—brain, kidneys, liver, heart, and lungs. The role of colloid, specifically the infusion of albumin in treating patients with critical illness, including those patients who have burns and hypoalbuminemia, has been hotly debated for at least 20 years.1-5 The source of this debate stems from the significant cost and limited supply of the drug, the possible adverse effects that the addition of albumin may have on the function of the critical organs, and the outcome of the patients. Albumin should be considered a drug, just as saline and balanced electrolyte solutions are drugs.6 An infusion of 25 g of 25-percent albumin has been shown to increase the plasma volume by an average of about 400 mL when the plasma volume is measured 2 hours after the infusion. When 5-percent albumin is infused, the increase in plasma volume is equal to the volume infused (less the dispersal of albumin into the extracellular fluid space—which begins immediately with its infusion—at a rate of 5–10%/hour). When isotonic normal saline (or balanced electrolyte) is infused, the increase in plasma volume is approximately one-fourth that achieved by the infusion of an equivalent volume of 5-percent albumin. Equivalent plasma volume expansion can be achieved with approximately 4 volumes of isotonic salt solution to 1 volume of isotonic albumin solution (5% albumin). If one desires to limit the amount of saline used for volume replacement to a specific hemodynamic endpoint, it is possible to do so by adding albumin to the infusate. However, it is not these volume-expansion properties of albumin infusion that have created such controversy. A series of articles3, 7-10 concluded that a salt-and-water resuscitation regimen including albumin was associated with more prolonged pulmonary dysfunction (especially in sepsis where a capillary leak of albumin in the pulmonary alveoli occurs), more renal excretory function abnormalities, and even more coagulation abnormalities than were seen in patients who did not receive albumin. Although the work of some investigators from the 1970s1, 2, 4 to the 1990s11 agreed with this general thesis, others who measured a variety of aspects of cardiopulmonary or renal function showed either improvement with albumin5, 12 or no difference13, 14 between resuscitation therapies that included albumin and those that did not. A different look at the relevance of infusing albumin uses the modern convention of meta-analysis.15 Metaanalysis of randomized controlled trials has become the prescribed method of answering the question of whether a treatment is worthwhile. Because human albumin solutions are expensive and are in limited supply, a meta-analysis of the effect of human albumin or plasma protein fraction on mortality in critically ill patients was undertaken recently by the Cochrane Injuries Group Albumin Reviewers.15 They identified 32 randomized controlled trials that met the study's inclusion criteria. The pooled difference in the risk of death with albumin use was increased by 6 percent (95% CI, 3–9%) over that with regimens that did not use albumin. This group concluded that, for every 17 critically ill patients treated with albumin, there was one additional death. The groups of critically ill patients analyzed were patients with hypovolemia, burns, or hypoalbuminemia. Although it is arguable whether these patients should be grouped together, the authors contend that the fact that the results were consistent across all three categories showed that it was reasonable to do so. The reviewers’final recommendation is that a strong argument could be made for giving albumin to critically ill patients only in the context of a properly blinded and rigorously conducted, randomized, controlled trial. In a comparison of treatments, a series of questions should be asked. 1 Are the patients being studied comparable? For example, patients with major burns are clearly different in a variety of ways from patients who have hypovolemia due to acute blood loss and from patients who have hypoalbuminemia as an isolated marker of severe illness. Patients with major acute burns have hypovolemia due to the loss of plasma volume and albumin into a greatly expanded extravascular space, while patients with hypoalbuminemia may have a normal circulating blood volume and a low serum albumin concentration due to decreased synthesis of albumin. The hemodynamic consequences of an acute major burn and of nutritional hypoalbuminemia are obviously different. Patients with acute burns, especially when sepsis develops, often develop hyperdynamic circulation. These circulatory changes are usually absent with simple hypoalbuminemia. 2 Are the treatments and study endpoints comparable? Treatment regimens employing albumin have varied greatly from study to study in terms of the amount of albumin used, the total volume of crystalloid versus crystalloid plus albumin infused, and the cardiovascular endpoints studied. This makes comparison of physiologic endpoints difficult and the cause (or causes) of the final pathway endpoint of death even more obscure. 3 Are the endpoints meaningful? The endpoint of mortality is clearcut, but many of the studies of albumin usage evaluated pathophysiologic changes rather than death. For example, although deterioration of renal function is an important endpoint, and was more common in the albumin-treated patients in the study by Lucas et al.,10 this complication may contribute to a patient's death, but not necessarily be the proximate cause of death unless the patient develops acute tubular necrosis. 4 Are the side effects of the treatments comparable? Clearly, cardiopulmonary and renal side effects of albumin infusion are important overall negative variables of albumin-rich versus albumin-poor regimens. However, using death as the only significant endpoint may mask valuable short-term benefits of albumin infusion. How then, in the light of the four questions posed and the current conclusions of the meta-analysis of the randomized trials, does the clinician decide whether or not to provide albumin to critically ill patients? Death would appear to be too gross an endpoint for the elimination of a therapy that may or may not have anything to do with death. Stating that the infusion of albumin is the cause of a 6-percent difference in mortality may require a leap of faith that many cannot easily take. Could the relatively small 6-percent difference in mortality be due to some other confounding factor (such as a hidden selection bias) not easily detected in the meta-analysis? I think so. However, prudence argues for a large measure of suspicion as to whether albumin is an essential ingredient of fluid resuscitation regimens. It seems clear that albumin should not be used for simple hypoalbuminemia (an index of the general severity of illness16) because of its cost and lack of benefit. It might be considered a reasonable therapy, however, in the patient who has been resuscitated aggressively with an electrolyte and red cell replacement regimen for blood and third-space fluid losses, and who is grossly edematous from that resuscitation and yet shows continued, measured evidence of hypovolemia or cardiovascular instability. Albumin infusion to maintain the plasma volume in association with diuretic therapy may result in beneficial diuresis in such situations.12 This specific use of albumin may prevent the continued increase in total body salt-and-water accumulation that accompanies the apparent increased need for infusion of salt and water and the resultant exaggerated total body edema (the beached-whale syndrome). Overly aggressive salt-and-water infusion alone can induce pulmonary edema even in relatively young patients.5 That fluid resuscitation of critically ill patients who have hypovolemia, burns, or hypoalbuminemia requires albumin, especially in the resuscitation period, is not supported by the available data. The other extreme, that albumin should never be used in caring for such patients, is unreasonable. The specific volume-expansion properties of albumin may have at least short-term benefits in the critically ill patient. The conclusion of the meta-analysis researchers that albumin should be used only in a properly conducted, blinded, randomized trial—a conclusion based largely on a small difference in mortality rate that may be unrelated to albumin—seems an unjustifiably strong conclusion. Albumin, the bell may be clanging softly somewhere in the distance, but, perhaps, it does not yet toll for thee. John J. Skillman, MD1 1Harvard Medical School Beth Israel Deaconess Medical Center 330 Brookline Avenue Boston, MA 02215 REFERENCES 1 Lowe RJ, Moss GS, Jilek J, Levine HD. Crystalloid vs colloid in the etiology of pulmonary failure after trauma: a randomized trial in man Surgery 1977; 81: 676– 83. PubMedWeb of Science®Google Scholar 2 Virgilio RW, Rice CL, Smith DE, et al. Crystalloid vs. colloid resuscitation: is one better? A randomized clinical study Surgery 1979; 85: 129– 39. CASPubMedWeb of Science®Google Scholar 3 Weaver DW, Ledgerwood AM, Lucas CE, et al. 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