The Emperor Has No Clothes? Searching for Dysregulation in Sepsis

Journal of Clinical Medicine
Joe Alcock

Abstract

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.

References

Jul 16, 1976·Science·H A Bernheim, M J Kluger
Sep 14, 1972·The New England Journal of Medicine·L Thomas
Sep 28, 2000·Critical Care Medicine·C J Fisher, S B Yan
Mar 10, 2001·The New England Journal of Medicine·G R BernardUNKNOWN Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group
Oct 26, 2001·JAMA : the Journal of the American Medical Association·B L WarrenUNKNOWN KyberSept Trial Study Group
Jan 17, 2002·The New England Journal of Medicine·G van den BergheR Bouillon
Jan 17, 2002·The New England Journal of Medicine·E RiversUNKNOWN Early Goal-Directed Therapy Collaborative Group
Oct 31, 2002·American Journal of Respiratory and Critical Care Medicine·Peter Q EichackerCharles Natanson
Dec 20, 2002·Nature·Jonathan Cohen
Oct 16, 2004·The American Journal of the Medical Sciences·Michael R Pinsky
Sep 30, 2005·The New England Journal of Medicine·Edward AbrahamUNKNOWN Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group
Oct 20, 2006·The New England Journal of Medicine·Peter Q EichackerRobert L Danner
Jul 20, 2007·American Journal of Human Biology : the Official Journal of the Human Biology Council·Peter T Ellison, Grazyna Jasienska
Jul 21, 2009·Current Opinion in Critical Care·Nicolas MongardonMervyn Singer
Oct 12, 2010·Lancet·Jean-Louis Vincent, Mervyn Singer
Nov 19, 2010·Molecular Medicine·Alex G CuencaLyle L Moldawer
May 28, 2011·The New England Journal of Medicine·Kathryn MaitlandUNKNOWN FEAST Trial Group
Feb 1, 2012·Intensive Care Medicine·Paul Jeffrey YoungKathryn Rowan
Apr 24, 2012·The Quarterly Review of Biology·Edmund Kenwood LeGrand, Joe Alcock
May 24, 2012·The New England Journal of Medicine·V Marco RanieriUNKNOWN PROWESS-SHOCK Study Group
Dec 20, 2012·International Journal of Inflammation·Aline M Bernard, Gordon R Bernard
Mar 21, 2013·JAMA : the Journal of the American Medical Association·Steven M OpalUNKNOWN ACCESS Study Group
Jul 23, 2013·Mayo Clinic Proceedings·Vinay PrasadAdam Cifu
Nov 16, 2013·Nature Reviews. Immunology·Richard S HotchkissDidier Payen
Mar 4, 2014·Trends in Molecular Medicine·John C Marshall
Mar 19, 2014·The New England Journal of Medicine·Donald M YealyDerek C Angus
May 20, 2014·The New England Journal of Medicine·Jonathon D TruwitB Taylor Thompson
Sep 4, 2014·Critical Care : the Official Journal of the Critical Care Forum·Heleen M Oudemans-van StraatenMonique C de Waard
Oct 2, 2014·The New England Journal of Medicine·Sandra L PeakePatricia Williams
Dec 17, 2014·Science·Matthew F Barber, Nels C Elde
May 2, 2015·The Lancet Infectious Diseases·Jonathan CohenEric Pelfrene
Jul 15, 2015·Intensive Care Medicine·Eric A J HosteJohn A Kellum
Oct 29, 2015·British Journal of Anaesthesia·P Marik, R Bellomo
Feb 24, 2016·JAMA : the Journal of the American Medical Association·Mervyn SingerDerek C Angus
Mar 12, 2016·American Journal of Respiratory and Critical Care Medicine·Matthew J MaidenRinaldo Bellomo
Apr 9, 2016·Critical Care Medicine·Junko KosakaRinaldo Bellomo
Jan 19, 2017·Critical Care Medicine·John C Alverdy, Monika A Krezalek
Jan 25, 2017·The New England Journal of Medicine·Michael S D AgusUNKNOWN HALF-PINT Study Investigators and the PALISI Network
Apr 25, 2017·Nature Reviews. Immunology·Tom van der PollMihai G Netea

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Citations

Mar 11, 2021·Evolutionary Anthropology·Jessica F Brinkworth, Negin Valizadegan

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Software Mentioned

ADRENAL
EGDT
ProMISe
Shock
APROCCHSS
PROWESS
ProCESS
ARISE

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