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The intensive care medicine research agenda on septic shock

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Abstract

Septic shock remains a global health challenge with millions of cases every year, high rates of mortality and morbidity, impaired quality of life among survivors and relatives, and high resource use both in developed and developing nations. Care and outcomes are improving through organisational initiatives and updated clinical practice guidelines based on clinical research mainly carried out by large collaborative networks. This progress is likely to continue through the collaborative work of the established and merging trials groups in many parts of the world and through refined trial methodology and translational work. In this review, international experts summarize the current position of clinical research in septic shock and propose a research agenda to advance this field.

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Authors and Affiliations

  1. Department of Intensive Care, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Anders Perner

  2. Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, United Kingdom

    Anthony C. Gordon

  3. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, USA

    Derek C. Angus

  4. Department of Medicine, Faculté de médecine et des sciences de la santé, Centre de recherche du CHU de Sherbrooke, Université de Sherbrooke, Sherbrooke, Canada

    Francois Lamontagne

  5. Federal University of São Paulo, São Paulo, Brazil

    Flavia Machado

  6. Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada

    James A. Russell

  7. APHP Medical and Infectious Diseases ICU Bichat University Hospital, UMR 1137 IAME, Inserm/University Paris-Diderot, Paris, France

    Jean-Francois Timsit

  8. Departments of Surgery and Critical Care Medicine, The Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, University of Toronto, Toronto, Canada

    John C. Marshall

  9. The George Institute for Global Health, Sydney, St George Clinical School, University of New South Wales, Sydney, Australia

    John Myburgh

  10. Guys and St Thomas’ Hospital NHS Foundation Trust, London, Department of Immunobiology, Kings College London, London, United Kingdom

    Manu Shankar-Hari

  11. Division of Medicine, Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom

    Mervyn Singer

Authors
  1. Anders Perner
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  2. Anthony C. Gordon
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  3. Derek C. Angus
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  4. Francois Lamontagne
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  5. Flavia Machado
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  6. James A. Russell
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  7. Jean-Francois Timsit
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  8. John C. Marshall
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  9. John Myburgh
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  10. Manu Shankar-Hari
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  11. Mervyn Singer
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Corresponding author

Correspondence to Anders Perner.

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Conflicts of interest

AP is member of the steering committee and national investigator of a vasopressin trial in septic shock sponsored by Ferring Pharmaceuticals; his department is reimbursed for his time. The department also receives research funding from Fresenius Kabi and CSL Behring. ACG has received speaker fees from Orion Pharmaceuticals and Amomed. He has consulted for Ferring Pharmaceuticals, Tenax Therapeutics, GlaxoSmithKline and received grant support from Orion Pharmaceuticals, Tenax Therapeutics and HCA International with funds paid to his institution. He is the Chief Investigator for two NIHR funded trials in septic shock: VANISH—examining vasopressin and LeoPARDS—examining levosimendan. He is supported by an NIHR Research Professorship award. DCA has received consulting fees from Abbott, Bayer, Beckman-Coulter, Biocartis, GenMark, GlaxoSmithKline, and Sobi for advice on sepsis trial design and is paid by Ferring for his participation on the Trial Steering Committee of the Sepsis-ACT multicenter trial of selepressin for septic shock. JMa is the chair of InFACT, a DSMB member for AK Pharma and a consultant for Regeneron Therapeutics and Bristol-Myers Squibb. JMy was the principal investigator of the CHEST trial; his institution, the George Institute for Global Health, has received unrestricted grant funding from Fresenius Kabi and Baxter Healthcare in relation to fluid resuscitation research; he is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia. JR reports patents owned by the University of British Columbia (UBC) that are related to PCSK9 inhibitor(s) and sepsis and related to the use of vasopressin in septic shock. JR is an inventor on these patents. JR is a founder, Director and shareholder in Cyon Therapeutics Inc. (developing a sepsis therapy). Dr. Russell has share options in Leading Biosciences Inc. JR is a shareholder in Molecular You Corp. JR reports receiving consulting fees from Cubist Pharmaceuticals (now owned by Merck; formerly Trius Pharmaceuticals; developing antibiotics), Ferring Pharmaceuticals (manufactures vasopressin and is developing selepressin), Grifols (sells albumin), La Jolla Pharmaceuticals (developing angiotensin II; JR chairs the DSMB of a trial of angiotensin II), CytoVale Inc. (developing a sepsis diagnostic), and Asahi Kesai Pharmaceuticals of America (AKPA) (developing recombinant thrombomodulin). JR reports having received grant support from Ferring Pharmaceuticals that was provided to and administered by UBC. MSH acknowledges the support from National Institute for Health Research Clinician Scientist Award (CS-2016-16-011). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. MS is a co-investigator of the UK Department of Health-funded LeoPARDs trial (levosimendan in septic shock), the ADAPT trial (comparing biomarkers) and the STRESS-L trial (beta-blockade in septic shock). He is Clinical PI of a multicenter sepsis biomarker study conducted by the UK Ministry of Defence (DSTL), and a multiplex biomarker panel study with Mologic UK. He has grants from MedCity to develop an antibiotic monitoring with Probe Scientific, and the Wellcome Trust/UK Department of Health to investigate a novel tissue perfusion monitor with Oxford Optronix. He is also Co-PI of a sub-study of the EU Innovative Medicines Initiative Combacte-Magnet Program. He sits on advisory boards for Biotest, Bayer, Bristol Myers Squibb, Deltex and La Jolla Pharmaceuticals. He chaired the Data Safety and Monitoring Committee for InflaRx’s Phase II trial of a novel C5a inhibitor.

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Perner, A., Gordon, A.C., Angus, D.C. et al. The intensive care medicine research agenda on septic shock. Intensive Care Med 43, 1294–1305 (2017). https://doi.org/10.1007/s00134-017-4821-1

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