Does Fibronectin Reduce Mortality in Sepsis? A Meta-Analysis

Abstract

AD Does fibroncctin reduce mortality in sepsis? A mera-analysis.] J Intensive Care Med 1989;4:265-271 We examine the effect of fibronectin administration on mortality in sepsis. An English language literature search using MEDLINE, EMBASE, SCISEARCH, and computerized databases of unpublished research in addition to bibliographic review was performed, and duplicate independent review of 41 articles by two observers identified six relevant randomized clinical trials. Study quality and descriptive information concerning the population, intervention, and outcome measurements were assessed. Three of six trials demonstrated favorable mortality trends, but none reached statistical significance. Results of the 282 patients in all six trials yield a common odds ratio of 0.97 and a 95% confidence interval of 0.58 to 1.61. These results do not show a statistically significant effect favoring treatment, but neither do they exclude a clinically important benefit. The benefit of fibronectin in decreasing mortality in sepsis is not supported by these studies. However, methodological heterogeneity and the possibility of a Type II error, as well as our understanding of the role of fibronectin in the pathophysiology of sepsis, do not allow for a firm negative conclusion regarding the therapeutic efficacy of fibronectin in sepsis. A large, rigorously designed trial should be considered once investigators can reach a consensus regarding current methodological and pathophysiological controversies.Plasma, tissue, and cell fibronectins are a family of glycoproteins with a variety of biological properties, some of which suggest key roles for fibronectin in the pathophysiology of sepsis and multiple organ system failure [1-6]. The nonspecific opsonic properties of plasma fibronectin and the adhesive properties of tissue fibronectin imply potential for protection from microembolization of capillary beds as well as maintenance of endothelial barrier integrity. Both microembolism and capillary permeability are integral components of the cascade leading to tissue injury during sepsis and endotoxemia [7]. The association of sepsis and other severe illnesses with low plasma fibronectin concentrations [1,4,6,S], the ability to replenish plasma fibronectin by the administration of various fibronectin concentrates [1,9], and the apparent dynamic equilibrium between plasma fibronectin and tissue fibronectin [10,11] have provoked considerable interest as well as controversy in the area of fibronectin therapy.In early uncontrolled studies, infusion of fibronectin-rich cryoprecipitate into septic and trauma patients raised fibronectin levels and appeared to have favorable effects on cardiovascular, lung, and kidney function [12][13][14]. However, subsequent controlled clinical trials designed to measure an effect on morbidity and mortality have yielded inconsistent results [1>-21; Todd et al, personal communication, 1988]. Although these studies have been recently reviewed [4][5][6], no attempt has been made to synthesize these data in a formal qu...