A Pilot Study on Continuous Infusion of 4% Albumin in Critically Ill Patients: Impact on Nosocomial Infection via a Reduction Mechanism for Oxidized Substrates

Abstract

Care-related infections affect up to 11% of ICU patients. Running therapeutic albumin is sometimes associated to less infection: whether a specific method of its infusion is of any interest to modulate innate defense is unknown. Our objectives were: 1) to test whether the method for albumin infusion is important to prevent care-related infections and 2) to analyze in vitro the antioxidative role of albumin on host defense proteins during shock (using vasostatin-I as an example).

Design: In a prospective, randomized, open-label trial, shock patients were allocated to receive either continuously 4% albumin or intermittently 20% albumin, as long as they were infused with norepinephrine. A translational study including in vivo and in vitro analyses of albumin-vasostatin-I interactions is reported.

Setting: A tertiary ICU caring for 1,000 patients per year.

Patients: Fifty shock patients with serum albumin less than 20 g/L.

Interventions: In vivo colonization and nosocomial infections were recorded and time-dependent changes in serum albumin, chromogranin A, and vasostatin-I concentrations as well. In vitro, we studied biochemical albumin-vasostatin-I relationship using biochemical methods.

Measurements and main results: Over 18 days, we recorded a decrease in colonization (four vs 12 episodes; p = 0.035) and nosocomial infection frequency (two vs 13 episodes; p = 0.002) in patients infused continuously 4% albumin versus controls. In vitro, albumin interacts with the disulfide loop vasostatin-I (residues 17-40) and continuous 4% albumin infusion restores its oxidative status required for antimicrobial activity.

Conclusions: Continuous 4% albumin is effective in reducing care-related infections in shock patients by increasing the availability of antimicrobial vasostatin-I. This might guide future care of shock patients.

Keywords: antimicrobial peptides; chromogranin A; critical care; nosocomial infections; protein-protein interaction; therapeutic albumin.

Figure 1.

Design of the experimental strategy. HSA = human serum albumin, ThAlb = therapeutic albumin, VS-I = vasostatin-I.

Figure 2.

Influence of ThAlb on HSA concentrations in critically ill patients. Circles and triangles represent medians in patients infused with 20%-ThAlb and 4%-ThAlb, respectively. The lower bounds of the error bars equal the first quartiles and the upper bounds the third quartiles. Sample sizes are n = 26 (20%-ThAlb) and n = 22 (4%-ThAlb; provided that two patients died after inclusion). At 48 hr after inclusion (H48), the Mann-Whitney U test shows a significant difference (p < 0.001) between the HSA concentrations in both arms. H24 = 24 hr after inclusion, H72 = 72 hr after inclusion, H96 = 96 hr after inclusion, HSA = human serum albumin, ThAlb = therapeutic albumin.

Figure 3.

Colonization and nosocomial infection in critically ill patients according to the arm of ThAlb treatment (4%-ThAlb and 20%-ThAlb). Frequency of ThAlb treatment on (A) colonization and (B) nosocomial infection (NI+) or (NI–). ThAlb = therapeutic albumin.