Treating Hypoalbuminemia In Critically Ill Patients

Gregory S. Martin, MD, MSc


August 09, 2004


Are we justified in administering albumin in critically ill patients with hypoalbuminemia? What are the indications for administration of human albumin?

B. Ravinder Reddy, MBBS, Ms, FRCSEd, FRCSGl

Response from Gregory S. Martin, MD, MSc

Your question represents one of the most common clinical questions in the practice of intensive care medicine. Although we know that hypoalbuminemia is a strong predictor of poor clinical outcomes, including death, we have long considered this purely an association reflecting greater severity of disease (either acute or chronic) rather than a true causative effect of hypoalbuminemia on survival.[1] These beliefs have been challenged recently by advanced statistical techniques showing that hypoalbuminemia (or more broadly, hypoproteinemia) predicts poor clinical outcomes even after adjusting for severity of illness and other common clinical predictors.[2,3] Based on these data, is it possible that albumin plays a direct and causative role in ultimate survival? It is clearly possible, although more work is required before that conclusion can be drawn.

In the interim, should albumin be used in treating hypoalbuminemic intensive care patients? There are no clear data to support its use, and meta-analysis of the literature has suggested that colloid use in general may produce more harm than good, although these data are conflicted.[4,5,6] These concerns have been reasonably laid to rest, at least for albumin, with the completion of the Saline vs Albumin Fluid Evaluation (SAFE) trial.[7] This study randomized 7000 critically ill patients to receive albumin or saline for resuscitation and found no difference in important clinical outcomes, such as survival. Thus, it is fair to conclude that general use of albumin in critically ill patients is safe, but does not necessarily improve outcomes. Given the higher pharmacy acquisition cost associated with albumin, its use should be justified against some important clinical benefit. As we understand more about albumin, it may be best used in niche populations for which it is uniquely effective. From the SAFE trial, an important trend towards improved survival with albumin was noted in patients with sepsis (relative risk of death, 0.87; 95% confidence interval, 0.74-1.02; P =.06), thus raising the possibility that albumin may be beneficial in this subset of critically ill patients. For patients with spontaneous bacterial peritonitis, the addition of albumin to antibiotics and other standard therapies reduces the risk of renal dysfunction and improves survival.[8] Albumin may be beneficial in a specialized protocol-driven care system of treating acute ischemic stroke patients.[9] The combination of albumin with furosemide has, at least, physiologic benefits for patients with acute lung injury/adult respiratory distress syndrome,[10] possibly because of its ability to scavenge free radicals and alter systemic antioxidant balance.[11]

The indications for albumin usage vary among different countries, with the primary indication in the United States being for intravascular volume expansion (ie, resuscitation). Although broad utilization in all critically ill patients is unlikely to be effective, the use of albumin in specific niche populations may prove to have important clinical benefits.