Sepsis and septic shock
Richard S Hotchkiss, Lyle L Moldawer, Steven M Opal, Konrad Reinhart, Isaiah R Turnbull, Jean-Louis Vincent, Richard S Hotchkiss, Lyle L Moldawer, Steven M Opal, Konrad Reinhart, Isaiah R Turnbull, Jean-Louis Vincent
Abstract
For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
Conflict of interest statement
Competing interests
R.S.H. has received no direct financial support, nor does he or his family hold patents or equity interest in any biotech or pharmaceutical company. He has received laboratory research support from Bristol-Myers Squibb, GlaxoSmithKline and Medimmune. He has served as a paid consultant to Bristol-Myers Squibb, GlaxoSmithKline, Medimmune and Merck. R.S.H. and Washington University in St Louis, Missouri, USA, have also received grant support from the US NIH, US Public Health Service for research investigations of sepsis. L.L.M. and the University of Florida College of Medicine, USA, have received financial support from the US National Institute of General Medical Sciences, US Public Health Service. No other financial support, patents or equity interest to him or his family are disclosed. S.M.O. has received no direct financial support, nor does he or his family hold patents or equity interest in any biotech or pharmaceutical company. S.M.O. and Brown University, Rhode Island, USA, have received preclinical grants in the past from the NIH, US Public Health Service, Atoxbio, GlaxoSmithKline and Arsanis, and have received financial support for assistance with clinical trial coordination from Asahi Kasei, Ferring, Cardeas and Biocartis. S.M.O. serves as a member of the Data Safety and Monitoring Board (DSMB) for Paratek (for Omadcycline), Acheogen (for Placomicin) and Bristol-Myers Squibb (anti-PDL1 monoclonal antibody). He also serves on the DSMB for two NIH-funded studies: one examining procalcitonin-guided antibiotic administration and the other investigating early intervention for community- acquired sepsis. S.M.O. serves as a paid consultant for BioAegis, Arsanis, Aridis, Batelle and Cyon on various biodefense and monoclonal antibody projects. He also receives royalty payments from Elsevier publishers for the textbook entitled, Infectious Diseases 4th edition. K.R. holds an equity interest in InflaRx and is a paid consultant for Adrenomed. J.-L.V. and I.R.T. declare no competing interests.
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Source: PubMed