Hypothesis: The therapeutic approach to sepsis is following an evolutionary process of scientific discovery as articulated in the landmark work by Kuhn, The Structure of Scientific Revolutions, first published 50 years ago.
Background: Incremental advances, beginning with the introduction of antimicrobials and most recently highlighted by revised, evidence-based guidelines for the management of sepsis, have been accompanied by episodic paradigm shifts. Although some of these have shown success, there are numerous, noteworthy failures, largely involving immune- and coagulation-based therapeutic strategies.
Conclusion: A sustained paradigm shift in the approach to treating sepsis has yet to emerge, but recent data suggest that an open-minded posture informed by novel pathobiologic findings may eventually bear fruit.
1Department of Medicine, Baystate Health and Tufts University School of Medicine, Springfield, MA.
2Division of Infectious Diseases, Memorial Hospital of Rhode Island and the Alpert Medical School of Brown University, Providence, RI.
Dr. Higgins received support for travel from Glaxo-Welcome (L-NG-monomethyl arginine), Norvartis (polymyxin-622), Knoll (interleukin-6), ICOS (recombinant platelet-activating factor-acetylhydrolase), Centeon (antithrombin III), Chiron (recombinant tissue factor pathway inhibitor), Lilly (activated protein C), Apex (pyridoxylated hemoglobin polyoxethylene conjugate), Esai (eritoran tetrasodium), Tanox (TNX-832), and Agennix (Talactoferrin). Dr. Opal’s institution received grant support from Sirtris, Atox Bio, Asahi Kasei, Agennix, and Astra Zenaca. His institution has pending patents on a vaccine strategy to the core glycolipid of lipopolysaccharide and an interalpha inhibitor as a novel therapy for anthrax (Memorial Hospital of RI). He consulted for Medimmune and Arsanis. He receives textbook royalties from Elsevier publishers. He has had membership with Sangart and Spectral diagnostics (data safety and monitoring board member for their clinical trials). Dr. Artenstein has disclosed that he does not have any potential conflicts of interest.
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