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Investigational and ineffective therapies for sepsis

Gregory A Schmidt, MD
Peter F Clardy, MD
Section Editors
Polly E Parsons, MD
Daniel J Sexton, MD
Deputy Editor
Geraldine Finlay, MD


A number of potential therapies have been investigated or are being evaluated in an attempt to improve clinical outcomes in sepsis. Therapies that are being investigated are the focus of this review, although none are recommended for use at this time because the ratio of potential benefits and harms has not been adequately studied. Therapies that have proven ineffective are also mentioned briefly. The definition, pathophysiology, and management of sepsis are discussed elsewhere. (See "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Evaluation and management of suspected sepsis and septic shock in adults".)


A number of potential therapies for sepsis appear promising in animal models, but have not yet been adequately studied in humans. Other potential therapies have been studied in humans, but have given conflicting results and require additional investigations to clarify their effects. These therapies are the focus of this section. Often there is no better therapy to offer a patient than enrollment onto a well-designed, scientifically valid, peer-reviewed clinical trial. Additional information and instructions for referring a patient to an appropriate research center can be obtained from the United States National Institutes of Health (www.clinicaltrials.gov).

Inhibition of innate immunity — Infecting microbes display highly conserved macromolecules (eg, lipopolysaccharides, peptidoglycans) on their surface. When these macromolecules are recognized by pattern-recognition receptors (called Toll-like receptors [TLRs]) on the surface of immune cells, the host’s immune response is initiated. This may contribute to the excess systemic inflammatory response that characterizes sepsis. Inhibition of several TLRs is being evaluated as a potential therapy for sepsis:

Inhibition of TLR-4 with the antagonist, E5564 (Eritoran) was tested in humans with severe sepsis in the ACCESS (A Controlled Comparison of Eritoran Tetrasodium and Placebo in Patients with Severe Sepsis) Trial, showing no effect on 28-day mortality [1]. An earlier clinical trial that evaluated the inhibition of TLR-4 with another antagonist, TAK 242 (Resatorvid), found a non-statistically significant reduction in 28-day mortality [2].

Intravenous immune globulin — It has been hypothesized that polyclonal intravenous immune globulin (IVIG) may benefit patients with sepsis by binding endotoxin. However, we and others believe that IVIG should NOT be administered to patients with sepsis [3-10]:

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Literature review current through: Nov 2017. | This topic last updated: Oct 13, 2017.
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