La controversial albúmina

Clin Perinatol 31 (2004) 475 – 488

The albumin controversy
Michael R. Uhing, MD
Division of Neonatology, Medical College of Wisconsin, Neonatal Intensive Care Unit, Children’s Hospital of Wisconsin, 9000 West Wisconsin Avenue Milwaukee, WI 53226, USA

A recent meta-analysis of 90 studies in critically ill patients showed that each 1 g/dL decrease in serum albumin concentration increasesthe odds of morbidity and mortality by 89% and 137%, respectively [1]. Similarly, in the National Veterans Administration Surgical Risk Study of 54,215 major noncardiac surgery cases, preoperative serum albumin concentrations were the strongest predictor of surgical mortality and morbidity [2]. Based on this correlation between hypoalbuminemia and adverse outcome, it would seem prudent to treatpatients who are hypoalbuminemic or at risk for developing hypoalbuminemia with exogenous albumin. A meta-analysis of 30 randomized controlled trials by the Cochrane Injuries Group, however, showed that the risk for death was increased in critically ill patients treated with albumin for hypovolemia, burns, or hypoalbuminemia [3]. Albumin treatment was associated with one additional death for every 17patients treated and the study concluded that albumin should be given only in ‘‘the context of rigorously conducted, randomized controlled trials’’ [3]. Several limitations of the Cochrane analysis have been outlined, however, including (1) the lack of a homogenous patient population, (2) the lack of consistency in disease severity and treatment regimens, (3) the lack of correlation between timeof death and time of albumin administration, and (4) mortality was used as the primary endpoint for the Cochrane analysis but was not the primary endpoint for many of the studies in the analysis [4– 6]. A larger meta-analysis of 55 randomized controlled trials involving trauma, surgery, hypoalbuminemia, neonates, and ascites found that albumin supplementation did not increase mortality [7].Although suggesting that albumin supple-

E-mail address: muhing@mcw.edu 0095-5108/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.clp.2004.03.018

476

M.R. Uhing / Clin Perinatol 31 (2004) 475–488

mentation was safe, this analysis did not show that albumin supplementation improved patient outcome. Considering the above issues, neonatologists often are facedwith the dilemma of whether albumin should be administered to their patients. This dilemma is compounded because most literature regarding albumin supplementation involves adult patients. Indeed, the above meta-analyses included relatively few neonatal patients [3,7]. This article reviews the physiology of albumin and the effects of albumin administration in various disease processes. Because thereare relatively few studies of albumin administration in neonates, many studies of albumin use in adult patients are included. Although not optimal, these studies offer the best evaluation of the effects of albumin use in clinical situations common in sick neonates and adults, such as sepsis and postoperative fluid management.

Albumin physiology Albumin consists of 585 amino acids and has arelatively low molecular weight of 66 kd [8,9]. In comparison, IgG and fibrinogen have molecular weights of 150 kd and 340 kd, respectively [9]. Albumin’s relatively low molecular weight accounts for its 75% to 80% contribution to plasma oncotic pressure despite comprising only 50% of total plasma protein concentration [8]. Albumin is synthesized in the hepatocytes by the polysomes bound to theendoplasmic reticulum as preproalbumin, a precursor protein possessing a 24 amino-acid extension on the N terminus [10,11]. Subsequently, 18 of these amino acids are removed to form proalbumin. Albumin is formed when the remaining 6 amino acids are removed from proalbumin in the golgi apparatus. The primary factor regulating the synthesis of albumin is the osmotic pressure and osmolality of the...