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The Emperor Has No Clothes? Searching for Dysregulation in Sepsis

Department of Emergency Medicine, University of New Mexico, Albuquerque, NM 87131, USA
J. Clin. Med. 2018, 7(9), 247; https://doi.org/10.3390/jcm7090247
Received: 20 July 2018 / Revised: 14 August 2018 / Accepted: 25 August 2018 / Published: 29 August 2018
(This article belongs to the Section Hematology)
The core conception of sepsis—that it is a dysregulated state—is a powerful and durable idea that has inspired decades of research. But is it true that the body’s response to sepsis is dysregulated? To answer that question, this review surveyed the history of trials of experimental sepsis treatments targeting the host response. Sepsis survival is not improved by blocking one or many immune pathways. Similarly, sepsis is resistant to treatment by normalizing one or many physiologic parameters simultaneously. The vast majority of interventions are either ineffective or harmful. With this track record of failure, it is time to consider the alternative hypothesis—regulation instead of dysregulation—and the possibility that sepsis traits are often functional, and that some physiologic alterations in sepsis do more good than harm, while others are neutral. This review discusses the implications of this perspective for the future of sepsis research. View Full-Text
Keywords: sepsis; dysregulation; organ dysfunction; early goal-directed therapy; adaptation; evolution sepsis; dysregulation; organ dysfunction; early goal-directed therapy; adaptation; evolution
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Alcock, J. The Emperor Has No Clothes? Searching for Dysregulation in Sepsis. J. Clin. Med. 2018, 7, 247.

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