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Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2016

Rhodes, Andrew MB BS, MD(Res) (Co-chair); Evans, Laura E. MD, MSc, FCCM (Co-chair); Alhazzani, Waleed MD, MSc, FRCPC (methodology chair); Levy, Mitchell M. MD, MCCM; Antonelli, Massimo MD; Ferrer, Ricard MD, PhD; Kumar, Anand MD, FCCM; Sevransky, Jonathan E. MD, FCCM; Sprung, Charles L. MD, JD, MCCM; Nunnally, Mark E. MD, FCCM; Rochwerg, Bram MD, MSc (Epi); Rubenfeld, Gordon D. MD (conflict of interest chair); Angus, Derek C. MD, MPH, MCCM; Annane, Djillali MD; Beale, Richard J. MD, MB BS; Bellinghan, Geoffrey J. MRCP; Bernard, Gordon R. MD; Chiche, Jean-Daniel MD; Coopersmith, Craig MD, FACS, FCCM; De Backer, Daniel P. MD, PhD; French, Craig J. MB BS; Fujishima, Seitaro MD; Gerlach, Herwig MBA, MD, PhD; Hidalgo, Jorge Luis MD, MACP, MCCM; Hollenberg, Steven M. MD, FCCM; Jones, Alan E. MD; Karnad, Dilip R. MD, FACP; Kleinpell, Ruth M. PhD, RN-CS, FCCM; Koh, Younsuck MD, PhD, FCCM; Lisboa, Thiago Costa MD; Machado, Flavia R. MD, PhD; Marini, John J. MD; Marshall, John C. MD, FRCSC; Mazuski, John E. MD, PhD, FCCM; McIntyre, Lauralyn A. MD, MSc, FRCPC; McLean, Anthony S. MB ChB, MD, FRACP, FJFICM; Mehta, Sangeeta MD; Moreno, Rui P. MD, PhD; Myburgh, John MB ChB, MD, PhD, FANZCA, FCICM, FAICD; Navalesi, Paolo MD; Nishida, Osamu MD, PhD; Osborn, Tiffany M. MD, MPH, FCCM; Perner, Anders MD; Plunkett, Colleen M.; Ranieri, Marco MD; Schorr, Christa A. MSN, RN, FCCM; Seckel, Maureen A. CCRN, CNS, MSN, FCCM; Seymour, Christopher W. MD; Shieh, Lisa MD, PhD; Shukri, Khalid A. MD; Simpson, Steven Q. MD; Singer, Mervyn MD; Thompson, B. Taylor MD; Townsend, Sean R. MD; Van der Poll, Thomas MD; Vincent, Jean-Louis MD, PhD, FCCM; Wiersinga, W. Joost MD, PhD; Zimmerman, Janice L. MD, MACP, MCCM; Dellinger, R. Phillip MD, MCCM

doi: 10.1097/CCM.0000000000002255
Special Article
Editor's Choice

Objective: To provide an update to “Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012.”

Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development.

Methods: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

Results: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions.

Conclusions: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Supplemental Digital Content is available in the text.

1St. George’s Hospital London, England, United Kingdom.

2New York University School of Medicine New York, NY.

3McMaster University Hamilton, Ontario, Canada.

4Brown University School of Medicine Providence, RI.

5Instituto di Anestesiologia e Rianimazione, Università Cattolica del Sacro Cuore, Rome, Italy.

6Vall d’Hebron University Hospital Barcelona, Spain.

7University of Manitoba Winnipeg, Manitoba, Canada.

8Emory University Hospital Atlanta, GA.

9Hadassah Hebrew University Medical Center Jerusalem, Israel.

10Sunnybrook Health Sciences Centre Toronto, Ontario, Canada.

11University of Pittsburgh Critical Care Medicine CRISMA Laboratory Pittsburgh, PA.

12Hospital Raymond Poincare Garches, France.

13Saint Thomas Hospital London, England, United Kingdom.

14University College London Hospitals London, England, United Kingdom.

15Vanderbilt University Medical Center Nashville, TN.

16Service de Reanimation Medicale Paris, France.

17CHIREC Hospitals Braine L’Alleud, Belgium.

18Western Hospital Victoria, Australia.

19Keio University School of Medicine, Tokyo, Japan.

20Vivantes-Klinikum Neukölln, Berlin, Germany.

21Karl Heusner Memorial Hospital Belize Healthcare Partners Belize City, Belize.

22Cooper Health System Camden, NJ.

23University of Mississippi Medical Center Jackson, MS.

24Jupiter Hospital Thane, India.

25Rush University Medical Center Chicago, IL.

26ASAN Medical Center University of Ulsan College of Medicine Seoul, South Korea.

27Hospital de Clinicas de Porto Alegre Porto Alegre, Brazil.

28Federal University of Sao Paulo Sao Paulo, Brazil.

29Regions Hospital St. Paul, MN.

30Saint Michael’s Hospital Toronto, Ontario, Canada.

31Washington University School of Medicine St. Louis, MO.

32Ottawa Hospital Ottawa, Ontario, Canada.

33Nepean Hospital, University of Sydney Penrith, New South Wales, Australia.

34Mount Sinai Hospital Toronto, Ontario, Canada.

35UCINC, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.

36University of New South Wales, Sydney, New South Wales, Australia.

37Università dellla Magna Graecia Catanzaro, Italy.

38Fujita Health University School of Medicine, Toyoake, Aich, Japan.

39Rigshospitalet Copenhagen, Denmark.

40Università Sapienza, Rome, Italy.

41Christiana Care Health Services Newark, DE.

42University of Pittsburgh School of Medicine Pittsburgh, PA.

43Stanford University School of Medicine Stanford, CA.

44Kaust Medical Services Thuwal, Saudi Arabia.

45University of Kansas Medical Center Kansas City, KS.

46Wolfson Institute of Biomedical Research London, England, United Kingdom.

47Massachusetts General Hospital Boston, MA.

48California Pacific Medical Center San Francisco, CA.

49University of Amsterdam Amsterdam, Netherlands.

50Erasmé University Hospital Brussels, Belgium.

51University of Amsterdam, Amsterdam, Netherlands.

52Houston Methodist Hospital, Houston, TX.

*See also p. 553.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this on the journal’s Web site

This article is being simultaneously published in Critical Care Medicine and Intensive Care Medicine.

The following sponsoring organizations (with formal liaison appointees) endorse this guideline: American Association of Critical-Care Nurses, American College of Chest Physicians, American College of Emergency Physicians, American Thoracic Society, Asia Pacific Association of Critical Care Medicine, Associação de Medicina Intensiva Brasileira, Australian and New Zealand Intensive Care Society, Consorcio Centroamericano y del Caribe de Terapia Intensiva, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, German Sepsis Society, Indian Society of Critical Care Medicine, International Pan Arab Critical Care Medicine Society, Japanese Association for Acute Medicine, Japanese Society of Intensive Care Medicine, Latin American Sepsis Institute, Scandinavian Critical Care Trials Group, Society for Academic Emergency Medicine, Society of Hospital Medicine, Surgical Infection Society, World Federation of Critical Care Nurses, World Federation of Societies of Intensive and Critical Care Medicine.

The following non-sponsoring organizations (without formal liaison appointees) endorse this guideline: Academy of Medical Royal Colleges, Chinese Society of Critical Care Medicine, Asociación Colombiana de Medicina Crítica y Cuidado Intensivo, Emirates Intensive Care Society, European Resuscitation Council, European Society of Paediatric and Neonatal Intensive Care, European Society for Emergency Medicine, Federación Panamericana e Ibérica de Medicina Crítica y Terapia Intensiva, Sociedad Peruana de Medicina Intensiva, Shock Society, Sociedad Argentina de Terapia Intensiva, World Federation of Pediatric Intensive and Critical Care Societies. Dr. Rhodes is a past-president of the European Society of Intensive Care Medicine. Dr. Levy received consulting fees from ImmuneExpress. Dr. Antonelli received funding from Pfizer, MSD, Cubist, Maquet, Drager, Toray, and Baxter; he participates in ESA and SIAARTI. Dr. Kumar received scientific consulting fees from Baxter, Isomark, and Opsonix on diagnostic technologies; he received grant funding from GSK in the area of influenza. Dr. Ferrer Roca received funding from Estor, MSD, Astra-Zeneca, and Grifols and participates in ESICM and SEMICYUC. Dr. Sevransky is an Associate Editor of Critical Care Medicine. Dr. Sprung received funding from Asahi Kasei Pharma America Corporation (consultant, Data Safety and Monitoring Committee) and LeukoDx Ltd. (consultant; PI, research study on biomarkers of sepsis). He participates in International Sepsis Forum (board member). Dr. Angus received funding Ferring Inc (consulting fees for serving on the Trial Steering Committee of a Phase 2/3 trial of selepressin for septic shock), and from Ibis and Genmark (both for consulting fees regarding diagnostic strategies in sepsis). He is a contributing editor for JAMA, has conducted committee membership work for the American Thoracic Society, and has contributed to an IOM workshop on regulatory science. Dr. Angus provided expert testimony in medical malpractice cases. Dr. Beale’s institution received funding from Roche (consulting regarding sepsis diagnostics); he received funding from Quintiles (consulting on routes to license for a potential ARDS therapy); he participates in the UK National Institute for Clinical and Healthcare Excellence Sepsis Guideline Development Group; he has served as an expert witness, disclosing that he is approached from time to time regarding expert witness testimony for ICU cases, which may involve patients who have sepsis and the testimony relates to generally accepted current standards of care, and formal guidance, as it currently pertains within the UK. Dr. Bellingan received funding from Faron (research into interferon in lung injury) and Athersys (stem cells in lung injury). Dr. Chiche received funding for consulting activities and honoraria for lectures from GE Healthcare, monitoring and IT solutions; he received funding from Nestlé Healthsciences (consulting activities and honorarium), and from Abbott diagnostics (consulting activities). Dr. Coopersmith is on the fellowship committee of Surgical Infection Society. Dr. De Backer received funding from Edwards Healthcare, Fresenius Kabi, and Grifols. Dr. Dellinger provided expert testimony for alleged malpractice in critical care. Dr. French participates in Australian and New Zealand Intensive Care Society Clinical Trials Group (chair). Dr. Fujishima participates in the Japanese Association for Acute Medicine (board member, Japanese Guidelines for the management of sepsis) and Japanese Respiratory Society (board member, Japanese Guidelines for the management of ARDS); he received funding from Asahi Kasei Co (lecture). Dr. Hollenberg participates in the ACC/AHA PCI and Heart Failure guidelines, CHEST editorial board, ACCP-SEEK, and CHEST CV Network chair. Dr. Jones participates in ACEP and SAEM, and has served as an expert witness on various cases. Dr. Karnad received funding from Quintiles Cardiac Safety Services (consultant) and from Bharat Serum and Vaccines Ltd (consultant). He participates in the Indian Society of Critical Care Medicine and the Association of Physicians of India. Dr. Kleinpell participates in Critical Care Medicine American Board of Internal Medicine (board member), Institute of Medicine of Chicago (board member), and the Commission on Collegiate Nursing Education (board member). Dr. Koh participates in The Korean Society of Critical Care Medicine, The European Society of Intensive Care Medicine, and The Korean Society of Medical Ethics. Dr. Lisboa participates in ILAS, AMIB, and ESICM. Dr. Machado participates in the Latin America Sepsis Institution (CEO). Dr. Marshall received funding from Member Data Safety Monitoring Committee AKPA Pharma; he participates in International Forum for Acute Care Trialists (Chair) and World Federation of Societies of Intensive and Critical Care Medicine (Secretary-General). Dr. Mazuski received funding from Actavis (Allergan) (consultant), Astra-Zeneca (consultant), Bayer (consultant), and from Cubist (now part of Merck) (consultant); he received research grant funding from Astra-Zeneca, Bayer, and from Merck; and participates in Surgical Infection Society (President-elect and Chair of Task Force on Guidelines for the Management of Intra-abdominal Infection) and in the American College of Surgeons (speaker at Annual Congress, member of Trusted Medical Information Commission). Dr. Mehta participates in ATS activities. Dr. Moreno participates in the Portuguese and Brasilian Societies of Intensive Care Medicine. Dr. Myburgh’s institution received unrestricted grant funding, logistical support and reimbursement from Fresenius Kabi for travel expenses to conduct a randomized controlled trial of fluid resuscitation (CHEST study): 2008–2012: A$7600000 (US$ 5000000); an unrestricted grant for partial funding from Baxter Healthcare of an international observational study of patterns of fluid resuscitation (FLUID TRIPS study) in 2014: A$70,000 (US$ 50,000); honoraria and travel reimbursements from Baxter Healthcare for participation in Advisory Board meetings in Sydney (2013), Paris (2014) and China (2014); and an unrestricted grant for partial funding from CSL Bioplasma for an international observational study of patterns of fluid resuscitation (FLUID TRIPS study) in 2014: A$10,000 (US$ 7,500); he also participates as a council member in the World Federation of Societies of Intensive and Critical Care Medicine. Dr. Navalesi participates in the European Respiratory Society (Head of Assembly Respiratory Intensive Care), is a member of ESICM (European Society of Intensive Care Medicine) and ESA (European Society of Anaesthesiology), and is in the Scientific Committee of SIAARTI (the Italian Association of Anesthesia and Intensive Care). Dr. Nishida participates in The Japanese Society of Intensive Care Medicine (vice chairman of the executive boards), the Japanese Guidelines for the Management of Sepsis and Septic Shock 2016 (chairman), The Japanese Guidelines for Nutrition Support Therapy in the Adult and Pediatric Critically Ill Patients (board), The Japanese Guidelines for the Management of Acute Kidney Injury 2016 (board), The Expert Consensus of the Early Rehabilitation in Critical Care (board), The sepsis registry organization in Japan (member). Dr. Osborn received funding from Cheetah (speaker related to fluid resuscitation and use of NICOM); she participates in American College of Emergency Physicians (Representative to SCC), consultant for national database development, CDC sepsis task force, IHI consultant. Dr. Perner is the editor of ICM; his department received research funding from CSL Behring and Fresenius Kabi. Dr. Ranieri participates in ESICM. Dr. Seckel received funding from American Association of Critical-Care Nurses (AACN) (honorarium for speaker at 2016 annual conference; AACN Online Web based Essentials of Critical Care Orientation); she participates as a volunteer for AACN, and served as AACN liaison to the ATS/ESICM/SCCM CPG: Mechanical Ventilation in Adult Patients with ARDS. Dr. Shieh participates in Society of Hospital Medicine Faculty for Sepsis Workshop, SHM-SCCM Moore Foundation collaborative faculty. Dr. Shukri participates in the International Pan Arab Critical Care Society educational activities. Dr. Simpson participates in CHEST Regent at Large (board of directors), and is an ATS member. Dr. Singer received funding from Deltex Medical, Bayer, Biotest, and MSD; he participates in the UK Intensive Care Society research and Meeting committees; he has provided expert testimony, disclosing: I do medicolegal work (6 cases/year) as an independent expert, 80% on behalf of the defendant. Dr. Thompson received funding from serving on DSMBs trials sponsored by Ferring Pharmaceuticals, Farron Labs, and Roche Genentec; also received funding from Asahi Kasei Pharma America (consulting), UpToDate (wrote two chapters on pulmonary embolism diagnosis), and was a pro bono consultant for BioAegis; participates as a member of the American Thoracic Society committee to develop the ATS/ESICM/SCCM Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Dr. Vincent participates in World Federation of Societies of Intensive and Critical Care Societies (president) and Critical Care Foundation (president). Dr. Wiersinga is treasurer of both the ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS) and the Dutch Working Party on Antibiotic Policy (SWAB), Academic Medical Center, University of Amsterdam (all non-profit). Dr. Zimmerman participates in ACCP, ACP, WFSICCM, and PAIF; she has provided expert testimony on loss of digits due to DIC, mesenteric ischemia. Dr. Nunnally participates in SOCCA (board), ASA (committee), NYSSA, IARS, and AUA. Dr. Rochwerg participates as a methodologist for ATS, ESCIM, and Canadian Blood services. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Governance of Surviving Sepsis Campaign Guidelines Committee

SSC Executive and Steering Committees

SSC Guidelines Committee Oversight Group

Andrew Rhodes, Laura Evans, Mitchell M. Levy

SSC Guidelines Committee Group Heads

Massimo Antonelli (Hemodynamics), Ricard Ferrer (Adjunctive therapies), Anand Kumar (Infection), Jonathan E. Sevransky (Ventilation), Charles L. Sprung (Metabolic)

GRADE Methodology Group

Waleed Alhazzani (chair), Mark E. Nunnally, Bram Rochwerg

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