Hypoalbuminemia in the acutely ill – risks and rationale for treatment: a meta-analysis

Hypoalbuminemia is associated with poor outcome; however, the causal role of low serum albumin concentration and appropriateness of albumin therapy are controversial. We conducted a meta-analysis focusing on two types of evidence: (1) cohort studies with multivariate analysis capable of more accurately assessing whether serum albumin is a direct contributor to poor outcome rather than merely a marker for other pathological processes; and (2) controlled trials of albumin therapy for hypoalbuminemia reporting data on morbidity, which may afford a comparatively sensitive endpoint. The meta-analysis included 66 cohort studies with 171,654 total patients evaluating hypoalbuminemia as an outcome predictor by multivariate analysis and seven prospective controlled trials with 449 total patients on correcting hypoalbuminemia. The pooled results of the included cohort studies revealed hypoalbuminemia to be a potent, dose-dependent, independent predictor of poor outcome. For each 10 g/l decline in serum albumin concentration the odds of mortality increased by 124% (OR, 2.24; CI, 1.83–2.74), morbidity by 78% (OR, 1.78; CI, 1.45–2.18), prolongations in intensive care unit and hospital stay respectively by 22% (OR, 1.22; CI, 1.06–1.41) and 64% (OR, 1.64; CI, 1.26–2.14), and increased resource utilization by 18% (OR, 1.18; CI, 1.03–1.35). These effects were independent of both nutritional status and inflammation. In controlled trials, albumin therapy reduced complications in hypoalbuminemic patients (OR, 0.79; CI, 0.36–1.72), although the overall effect was not statistically significant. However, there was a strong and significant (P = 0.019) inverse relationship between morbidity and attained serum albumin level during therapy, which suggested that complication rate may be diminished by exogenous albumin sufficient to elevate serum albumin level above 30 g/l. The value of albumin therapy for hypoalbuminemia needs to be investigated further in well-designed trials. At present, the evidence suggesting a causal link between hypoalbuminemia and poor outcome and a dose-dependent effect of exogenous albumin in reducing complications provides a logical basis for albumin therapy, and there appears to be no compelling argument for withholding albumin therapy if deemed clinically appropriate.