[Adjuvant treatment of sepsis: what is known?]

Abstract

Background: Recent decades have been characterized by a large number of trials for registration of new drugs or indication approvals in the field of sepsis. Modern anti-inflammatory drugs or interventions are intended to correct the overwhelming dysregulation of inflammatory and coagulation pathways seen particularly in the early phase of sepsis. Immunostimulatory therapies are also being studied in order to correct immunoparalysis, which develops later in the course of sepsis as a compensatory mechanism.

Current study results: Recombinant activated protein C, drotrecogin α, was conditionally approved and later withdrawn from the market by the producer because the initially observed beneficial effect could not be confirmed. The efficacy and safety of antithrombin, which, like drotrecogin α, also modulates inflammation and coagulation as an endogenous anticoagulant could not be confirmed when used for treating sepsis. As sepsis leads to disseminated intravascular coagulation which may be counteracted by antithrombin, new guidelines recommend antithrombin as a treatment option in this subgroup of sepsis patients. Intravenous administration of immunoglobulin, enteral administration of immunomodulating substances as immunonutrition, and the substitution of selenium, all showed some effectiveness in small heterogeneous studies, but their efficacy was not confirmed in large high-quality trials. Intensive glycemic control, which was temporarily recommended for acutely ill patients, increased the risk for adverse hypoglycemia in several clinical trials so that blood glucose target levels have been redefined and guidelines now no longer ask for normalization of blood glucose values with insulin.

Conclusion and outlook: None of the new drugs, however, has successfully become established as a new standard of care. In the future, studies of novel sepsis therapies may succeed better if suitable biomarkers allow for patient selection, reflecting key pathophysiologic mechanisms that are targeted by the innovative drugs.