Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials

Abstract

Objective: To determine whether hypoalbuminemia is an independent risk factor for poor outcome in the acutely ill, and to assess the potential of exogenous albumin administration for improving outcomes in hypoalbuminemic patients.

Summary background data: Hypoalbuminemia is associated with poor outcomes in acutely ill patients, but whether this association is causal has remained unclear. Trials investigating albumin therapy to correct hypoalbuminemia have proven inconclusive.

Methods: A meta-analysis was conducted of 90 cohort studies with 291,433 total patients evaluating hypoalbuminemia as an outcome predictor by multivariate analysis and, separately, of nine prospective controlled trials with 535 total patients on correcting hypoalbuminemia.

Results: Hypoalbuminemia was a potent, dose-dependent independent predictor of poor outcome. Each 10-g/L decline in serum albumin concentration significantly raised the odds of mortality by 137%, morbidity by 89%, prolonged intensive care unit and hospital stay respectively by 28% and 71%, and increased resource utilization by 66%. The association between hypoalbuminemia and poor outcome appeared to be independent of both nutritional status and inflammation. Analysis of dose-dependency in controlled trials of albumin therapy suggested that complication rates may be reduced when the serum albumin level attained during albumin administration exceeds 30 g/L.

Conclusions: Hypoalbuminemia is strongly associated with poor clinical outcomes. Further well-designed trials are needed to characterize the effects of albumin therapy in hypoalbuminemic patients. In the interim, there is no compelling basis to withhold albumin therapy if it is judged clinically appropriate.

Figure 1. Effect of serum albumin on mortality. ICU, intensive care unit; CAPD, chronic ambulatory peritoneal dialysis; CRP, C-reactive protein.

Figure 2. Effect of serum albumin on morbidity. ESRD, end-stage renal disease.

Figure 3. Morbidity in controlled trials evaluating the correction of hypoalbuminemia.

Figure 4. Meta-analysis regression assessing the effect of attained serum albumin level on morbidity in controlled trials to evaluate the correction of hypoalbuminemia. Data points are scaled in proportion to precision. Incidence of complications was reported on a per-patient basis in six trials. The average number of complications per patient in these trials was 1.1. For the other three studies complications per patient were estimated from total complication data using 1.1 as the conversion factor. For analytic purposes the attained serum albumin reported in two early trials was adjusted downward by 13 g/L, corresponding to the difference between the mean serum albumin for healthy term infants using contemporary assay methods (35 g/L) and the corresponding mean using older methodology (48 g/L), as documented in one of the two early trials.