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Crit Care Med. 2001 Jul;29(7 Suppl):S121-5.

Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned.

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  • 1Department of Anesthesiology and Intensive Care Medicine, University Hospital, Jena, Germany. Konrad.Reinhart@med.uni-jena.de

Abstract

OBJECTIVE:

Tumor necrosis factor (TNF) is an important mediator involved in the pathogenesis of sepsis. We review clinical studies investigating the efficacy of anti-TNF therapy in decreasing mortality rates in septic patients.

DATA SOURCES:

We conducted a computerized bibliographic search of randomized, clinical, multicenter trials studying the effects of anti-TNF therapy in the treatment of sepsis. We included all primary studies, reviewed all published meta-analyses, and contacted primary investigators of multicenter trials where necessary.

DATA SYNTHESIS:

Almost all randomized studies targeting TNF during sepsis show a small, albeit nonsignificant, benefit in decreasing mortality. Strategies using monoclonal antibodies are more effective than are strategies using TNF receptor proteins. Analysis of randomized multicenter trials shows a small but significant benefit with anti-TNF therapeutic strategies. Furthermore, a recent study in 2634 septic patients using a murine anti-TNF antibody shows a 3.6% significant benefit in reducing mortality.

CONCLUSIONS:

Anti-TNF strategies are only partially effective in patients with sepsis. Although individual studies show small, nonsignificant benefits, analysis of all trial data as well as data from a recent trial in a large population of septic patients show that anti-TNF strategies may confer a small survival benefit. Better characterization of patients and a more multimodal approach by concomitantly targeting other mediators involved in sepsis may be helpful in enlarging the clinical benefit of anti-TNF therapy.

PMID:
11445746
[PubMed - indexed for MEDLINE]
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