Redefining critical illness

David M Maslove^#^{1

2}, Benjamin Tang^#³, Manu Shankar-Hari^{4

5}, Patrick R Lawler^{6

7}, Derek C Angus^{8

9}, J Kenneth Baillie^{5

10

11}, Rebecca M Baron^{12

13}, Michael Bauer^{14

15}, Timothy G Buchman^{16

17}, Carolyn S Calfee¹⁸, Claudia C Dos Santos^{7

19}, Evangelos J Giamarellos-Bourboulis²⁰, Anthony C Gordon²¹, John A Kellum⁸, Julian C Knight²², Aleksandra Leligdowicz^{23

24}, Daniel F McAuley^{25

26}, Anthony S McLean³, David K Menon²⁷, Nuala J Meyer²⁸, Lyle L Moldawer²⁹, Kiran Reddy^{25

26}, John P Reilly²⁸, James A Russell³⁰, Jonathan E Sevransky^{16

31}, Christopher W Seymour⁸, Nathan I Shapiro^{13

32}, Mervyn Singer³³, Charlotte Summers³⁴, Timothy E Sweeney³⁵, B Taylor Thompson^{13

36}, Tom van der Poll³⁷, Balasubramanian Venkatesh^{38

39}, Keith R Walley³⁰, Timothy S Walsh⁴⁰, Lorraine B Ware⁴¹, Hector R Wong⁴², Zsolt E Zador⁴³, John C Marshall^{7

43

44}

Affiliations

¹ Department of Critical Care Medicine, Queen's University, Kingston, Ontario, Canada. david.maslove@queensu.ca.
² Kingston Health Sciences Center, Kingston, Ontario, Canada. david.maslove@queensu.ca.
³ Department of Intensive Care Medicine, Nepean Hospital, Sydney, New South Wales, Australia.
⁴ The Queen's Medical Research Institute, Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh, UK.
⁵ Intensive Care Medicine, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK.
⁶ Cardiac Intensive Care Unit, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
⁷ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁰ Roslin Institute, University of Edinburgh, Edinburgh, UK.
¹¹ Pandemic Science Hub, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
¹² Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹³ Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
¹⁵ Center for Sepsis Care & Control, Jena University Hospital, Jena, Germany.
¹⁶ Emory Critical Care Center, Emory University, Atlanta, GA, USA.
¹⁷ Santa Fe Institute, Santa Fe, NM, USA.
¹⁸ Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
¹⁹ Keenan Centre for Biomedical Research of Saint Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
²⁰ 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
²¹ Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
²² Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
²³ Department of Medicine, Division of Critical Care, University of Western Ontario, London, Ontario, Canada.
²⁴ Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
²⁵ Regional Intensive Care Unit, Royal Victoria Hospital, Belfast, UK.
²⁶ Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
²⁷ Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
²⁸ Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA.
²⁹ Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
³⁰ Centre for Heart Lung Innovation and Critical Care Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³¹ Division of Pulmonary, Allergy, Critical Care and Sleep, School of Medicine, Emory University, Atlanta, GA, USA.
³² Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
³³ Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, UK.
³⁴ Department of Medicine, University of Cambridge School of Medicine, Cambridge, UK.
³⁵ Inflammatix, Inc, Burlingame, CA, USA.
³⁶ Divisions of Biostatistics and Pulmonary/Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA.
³⁷ Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
³⁸ Department of Intensive Care, Wesley and Princess Alexandra Hospitals, Brisbane, Queensland, Australia.
³⁹ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁴⁰ Usher Institute for Population Health Sciences, Deanery of Molecular, Genetics, and Population Health Sciences, University of Edinburgh, Edinburgh, UK.
⁴¹ Departments of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
⁴² Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁴³ Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
⁴⁴ Departments of Surgery and Critical Care Medicine, Unity Health Toronto, Toronto, Ontario, Canada.

^# Contributed equally.

PMID: 35715504
DOI: 10.1038/s41591-022-01843-x

Review

Redefining critical illness

David M Maslove et al. Nat Med. 2022 Jun.

. 2022 Jun;28(6):1141-1148.

doi: 10.1038/s41591-022-01843-x. Epub 2022 Jun 17.

Authors

Affiliations

¹ Department of Critical Care Medicine, Queen's University, Kingston, Ontario, Canada. david.maslove@queensu.ca.
² Kingston Health Sciences Center, Kingston, Ontario, Canada. david.maslove@queensu.ca.
³ Department of Intensive Care Medicine, Nepean Hospital, Sydney, New South Wales, Australia.
⁴ The Queen's Medical Research Institute, Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh, UK.
⁵ Intensive Care Medicine, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, UK.
⁶ Cardiac Intensive Care Unit, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada.
⁷ Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada.
⁸ Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁰ Roslin Institute, University of Edinburgh, Edinburgh, UK.
¹¹ Pandemic Science Hub, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
¹² Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹³ Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany.
¹⁵ Center for Sepsis Care & Control, Jena University Hospital, Jena, Germany.
¹⁶ Emory Critical Care Center, Emory University, Atlanta, GA, USA.
¹⁷ Santa Fe Institute, Santa Fe, NM, USA.
¹⁸ Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
¹⁹ Keenan Centre for Biomedical Research of Saint Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
²⁰ 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
²¹ Division of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
²² Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
²³ Department of Medicine, Division of Critical Care, University of Western Ontario, London, Ontario, Canada.
²⁴ Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
²⁵ Regional Intensive Care Unit, Royal Victoria Hospital, Belfast, UK.
²⁶ Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.
²⁷ Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
²⁸ Department of Medicine, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania, Philadelphia, PA, USA.
²⁹ Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, USA.
³⁰ Centre for Heart Lung Innovation and Critical Care Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
³¹ Division of Pulmonary, Allergy, Critical Care and Sleep, School of Medicine, Emory University, Atlanta, GA, USA.
³² Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
³³ Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London, UK.
³⁴ Department of Medicine, University of Cambridge School of Medicine, Cambridge, UK.
³⁵ Inflammatix, Inc, Burlingame, CA, USA.
³⁶ Divisions of Biostatistics and Pulmonary/Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA.
³⁷ Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
³⁸ Department of Intensive Care, Wesley and Princess Alexandra Hospitals, Brisbane, Queensland, Australia.
³⁹ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
⁴⁰ Usher Institute for Population Health Sciences, Deanery of Molecular, Genetics, and Population Health Sciences, University of Edinburgh, Edinburgh, UK.
⁴¹ Departments of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
⁴² Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁴³ Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
⁴⁴ Departments of Surgery and Critical Care Medicine, Unity Health Toronto, Toronto, Ontario, Canada.

^# Contributed equally.

PMID: 35715504
DOI: 10.1038/s41591-022-01843-x

Abstract

Research and practice in critical care medicine have long been defined by syndromes, which, despite being clinically recognizable entities, are, in fact, loose amalgams of heterogeneous states that may respond differently to therapy. Mounting translational evidence-supported by research on respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-suggests that the current syndrome-based framework of critical illness should be reconsidered. Here we discuss recent findings from basic science and clinical research in critical care and explore how these might inform a new conceptual model of critical illness. De-emphasizing syndromes, we focus on the underlying biological changes that underpin critical illness states and that may be amenable to treatment. We hypothesize that such an approach will accelerate critical care research, leading to a richer understanding of the pathobiology of critical illness and of the key determinants of patient outcomes. This, in turn, will support the design of more effective clinical trials and inform a more precise and more effective practice at the bedside.

PubMed Disclaimer

References

1. Marshall, J. C. Why have clinical trials in sepsis failed? Trends Mol. Med. 20, 195–203 (2014). - PubMed - DOI
1. Writing Group for the PReVENT Investigators. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: a randomized clinical trial. JAMA 320, 1872–1880 (2018).
1. The Recovery Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N. Engl. J. Med. 384, 693–704 (2021). - DOI
1. REMAP-CAP Investigators et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N. Engl. J. Med. 384, 1491–1502 (2021).
1. WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA 326, 499–518 (2021).

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Medical
- ClinicalTrials.gov
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Redefining critical illness

Affiliations

Redefining critical illness

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous