Albumin for severe sepsis and septic shock: More confusing findings (ALBIOS Trial)
Albumin: Better Than Crystalloid in Septic Shock?
Human albumin boosts oncotic pressure, and has a number of important biologic functions (protein binding, antioxidant, etc.) that could in theory support the body during critical illness. In the 2004 SAFE study, which tested albumin against crystalloid solutions in ~7,000 critically ill patients of various etiologies, 4% albumin was safe but showed no signal of benefit overall. Among patients with sepsis, there was a nonsignificant trend toward improved survival among those receiving albumin. A small 2006 trial of 100 critically ill patients suggested giving albumin to those with low levels could improve organ function, but a meta-analysis of 30 trials suggested albumin could harm the critically ill.
Albumin's main disadvantage is cost: about $100 per dose, compared with $2 for crystalloids. With 200 million units of normal saline infused each year in the U.S. alone, the expense of choosing albumin over crystalloid as a resuscitation fluid for severe sepsis should be supported by a clear benefit. The ALBIOS study, published in the New England Journal of Medicine in April 2014, helps to answer the question, does albumin administration improve outcomes in severe sepsis and septic shock?
Authors randomized 1,818 people with severe sepsis who had already been resuscitated during early goal directed therapy to receive 20% albumin in crystalloid in order to keep albumin levels > 30 g/L (3 g/dL), or not, in an unblinded open-label design. Both groups got crystalloid as needed for fluid replacement.
Patients in both groups actually received equivalent amounts of total fluids, although the albumin patients' net fluid balance after 7 days was lower (+350 vs +1220 mL). The albumin did seem to have physiologic benefits, producing lower heart rates and higher mean arterial pressure. However, there was no difference in mortality at 28 days (32%) or 90 days (~42%), nor in overall organ failure scores. Patients receiving albumin did have improved organ function scores for heart, coagulation, and liver.
Most interestingly: although the overall trial was negative, the mortality findings split according to disease severity. Among the ~1,100 patients with septic shock, those receiving albumin had a significant 0.87 relative risk for death. Since there was no benefit overall, that meant those with severe sepsis (but not shock) had an equivalent increased risk for death (RR 1.13) with receipt of albumin, although this did not reach statistical significance.
The study did not test albumin as a resuscitation fluid; albumin was given to improve hypoalbuminemia. Patients had already undergone goal directed therapy before receiving albumin, and crystalloids were given to both groups as fluid replacement. Also, because it was an open label and treatment teams knew the randomization assignments, unmeasured difference in care delivered could have affected the results.
Clinical Takeaway: This trial further confirms albumin's role should be limited in management of shock states. Albumin's properties as an oncotic "volume expander" are exaggerated, with only about a 1:1.4 efficacy ratio over crystalloid. The lack of benefit in the SAFE study and the severe sepsis arm of the current trial, along with a Cochrane analysis suggesting harm, argue for restraint in using this expensive resource. However, albumin advocates will find confirmation of their practices in the hemodynamic benefits seen here, and especially the increased survival among the sickest patients with septic shock. Answering the question of albumin's proper role in sepsis treatment more clearly will take another randomized trial, preferably one that is properly blinded. This one in Brazil looks interesting, although it won't be definitive.
Pietro Caironi et al. Albumin Replacement in Patients with Severe Sepsis or Septic Shock. N Engl J Med 2014; 370:1412-1421.