Purified Fibronectin Administration to Patients with Severe Abdominal Infections

Abstract

Subnormal plasma fibronectin (Fn) levels are found in patients with severe abdominal infections (SAI). The repletion of Fn has been postulated to have therapeutic benefit by virtue of its opsonic, reticuloendothelial system (RES) stimulating effects. A controlled, prospective trial of Fn administration was performed in patients with SAI to assess its use as an adjunct to standard procedures of intensive care. Thirty-three SAI patients were given daily doses of 0.8 g of purified Fn on days 1-5 following admission to the ICU, whereas 34 control patients received no Fn. All patients received the clinical care, antibiotics, and pharmacologic agents appropriate to their individual needs. The admission status and laboratory profiles of the two patient groups (+ and -Fn) were comparable on admission to the study. No side effects of the Fn preparation were observed. As judged by subgroup averages, the Fn replacement regimen was effective in elevating Fn levels to within normal range from day 2 onwards, as measured by immunological and functional assays. The estimated intravascular recovery of Fn averaged 82% in those patients who survived, yet only 52% in the nonsurvivors. Ultimate hospital mortality was 9/33 (27.3%) in the +Fn group versus 13/34 (38.2%) in the -Fn group (p = 0.244, Fisher''s exact test). Although ultimate mortality was not significantly changed by the administration of Fn, the Fn treated patients appeared to survive longer than did the control patients. This trend was confirmed through the analysis of expected survival curves (D = 3.12, 0.1 > P > 0.05). When compared to the survivors, the ultimate nonsurvivors entered the study with statistically higher group averages of bilirubin and creatinine concomitant with lower averages of Fn, antithrombin III, C4, C3, C3b-INH, and transferrin. These differences persisted throughout the 11-day monitoring period; differences between survivors and nonsurvivors with respect to platelets, plasminogen, B-1-H, alpha-2-macroglobulin, and prealbumin appeared during the same period. Dramatic differences between the +Fn and -Fn treatment groups were not seen. Other than Fn, the Fn recipients only developed higher levels of the acute phase reactants C4, C3b-INH, B-1-H and alpha-1-antitrypsin (p < 0.05) than did their non-Fn treated counterparts. In the present study, we again found a highly significant pattern of correlations between the absolute levels as well as the changes of Fn and other plasma proteins. Our results suggest that the behavior of Fn in patients with SAI is only one small part of a general plasma protein "depletion and recovery syndrome" that is associated with the clinical course of the disease. It is concluded that further controlled therapeutic trials of purified Fn alone or in combination with other depleted factors would be desirable.