Mortality Risk Profiles for Sepsis: A Novel Longitudinal and Multivariable Approach

Patricia C. Liaw, PhD; Alison E. Fox-Robichaud, MSc, MD, FRCPC; Kao-Lee Liaw, PhD; Ellen McDonald, RN; Dhruva J. Dwivedi, PhD; Nasim M. Zamir, MD; Laura Pepler, PhD; Travis J. Gould, PhD; Michael Xu, MSc; Nicole Zytaruk, RN; Sarah K. Medeiros, BSc; Lauralyn McIntyre, MD, FRCPC; Jennifer Tsang, MD, PhD, FRCPC; Peter M. Dodek, MD, MHSc; Brent W. Winston, MD, FRCPC; Claudio Martin, MSc, MD, FRCPC; Douglas D. Fraser, MD, PhD, FRCPC; Jeffrey I. Weitz, MD, FRCPC; Francois Lellouche, MD, PhD; Deborah J. Cook, MD, FRCPC; John Marshall, MD, FRCPC; for the Canadian Critical Care Translational Biology Group (CCCTBG) and the Canadian Critical Care Trials Group (CCCTG); Jamie Hutchison; Jane Batt; Emmanuel Charbonney; Jean-Francois Cailhier; Rob Fowler; Paul Hebert; Kusum Menon; Karen Burns; Shane English; John Drover; Bram Rochwerg; Dominique Piquette; Margaret Herridge; Sylvie Debigare; Srinivas Murthy; Michelle Kho; Danae Tassy

doi:10.1097/CCE.0000000000000032

Critical Care Explorations (Aug 2019)

Mortality Risk Profiles for Sepsis: A Novel Longitudinal and Multivariable Approach

Patricia C. Liaw, PhD,
Alison E. Fox-Robichaud, MSc, MD, FRCPC,
Kao-Lee Liaw, PhD,
Ellen McDonald, RN,
Dhruva J. Dwivedi, PhD,
Nasim M. Zamir, MD,
Laura Pepler, PhD,
Travis J. Gould, PhD,
Michael Xu, MSc,
Nicole Zytaruk, RN,
Sarah K. Medeiros, BSc,
Lauralyn McIntyre, MD, FRCPC,
Jennifer Tsang, MD, PhD, FRCPC,
Peter M. Dodek, MD, MHSc,
Brent W. Winston, MD, FRCPC,
Claudio Martin, MSc, MD, FRCPC,
Douglas D. Fraser, MD, PhD, FRCPC,
Jeffrey I. Weitz, MD, FRCPC,
Francois Lellouche, MD, PhD,
Deborah J. Cook, MD, FRCPC,
John Marshall, MD, FRCPC,
for the Canadian Critical Care Translational Biology Group (CCCTBG) and the Canadian Critical Care Trials Group (CCCTG),
Jamie Hutchison,
Jane Batt,
Emmanuel Charbonney,
Jean-Francois Cailhier,
Rob Fowler,
Paul Hebert,
Kusum Menon,
Karen Burns,
Shane English,
John Drover,
Bram Rochwerg,
Dominique Piquette,
Margaret Herridge,
Sylvie Debigare,
Srinivas Murthy,
Michelle Kho,
Danae Tassy

Affiliations

Patricia C. Liaw, PhD: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Alison E. Fox-Robichaud, MSc, MD, FRCPC: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Kao-Lee Liaw, PhD: 3 School of Geography and Earth Sciences, McMaster University, Hamilton, ON, Canada.
Ellen McDonald, RN: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Dhruva J. Dwivedi, PhD: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Nasim M. Zamir, MD: 2 Department of Medicine, McMaster University, Hamilton, ON, Canada.
Laura Pepler, PhD: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Travis J. Gould, PhD: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Michael Xu, MSc: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Nicole Zytaruk, RN: 2 Department of Medicine, McMaster University, Hamilton, ON, Canada.
Sarah K. Medeiros, BSc: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Lauralyn McIntyre, MD, FRCPC: 4 Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
Jennifer Tsang, MD, PhD, FRCPC: 5 Department of Surgery, University of Toronto, ON, Canada.
Peter M. Dodek, MD, MHSc: 6 Centre for Health Evaluation and Outcomes Sciences, University of British Columbia, Vancouver, BC, Canada.
Brent W. Winston, MD, FRCPC: 7 Department of Critical Care Medicine, University of Calgary, Calgary, AB, Canada.
Claudio Martin, MSc, MD, FRCPC: 8 Department of Medicine, University of Western Ontario, London, ON, Canada.
Douglas D. Fraser, MD, PhD, FRCPC: 8 Department of Medicine, University of Western Ontario, London, ON, Canada.
Jeffrey I. Weitz, MD, FRCPC: 1 Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada.
Francois Lellouche, MD, PhD: 9 Department of Medicine, Laval University, Quebec City, QC, Canada.
Deborah J. Cook, MD, FRCPC: 2 Department of Medicine, McMaster University, Hamilton, ON, Canada.
John Marshall, MD, FRCPC: 5 Department of Surgery, University of Toronto, ON, Canada.
for the Canadian Critical Care Translational Biology Group (CCCTBG) and the Canadian Critical Care Trials Group (CCCTG)
Jamie Hutchison
Jane Batt
Emmanuel Charbonney
Jean-Francois Cailhier
Rob Fowler
Paul Hebert
Kusum Menon
Karen Burns
Shane English
John Drover
Bram Rochwerg
Dominique Piquette
Margaret Herridge
Sylvie Debigare
Srinivas Murthy
Michelle Kho
Danae Tassy

DOI: https://doi.org/10.1097/CCE.0000000000000032
Journal volume & issue: Vol. 1, no. 8
p. e0032

Abstract

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Objectives:. To determine if a set of time-varying biological indicators can be used to: 1) predict the sepsis mortality risk over time and 2) generate mortality risk profiles. Design:. Prospective observational study. Setting:. Nine Canadian ICUs. Subjects:. Three-hundred fifty-six septic patients. Interventions:. None. Measurements and Main Results:. Clinical data and plasma levels of biomarkers were collected longitudinally. We used a complementary log-log model to account for the daily mortality risk of each patient until death in ICU/hospital, discharge, or 28 days after admission. The model, which is a versatile version of the Cox model for gaining longitudinal insights, created a composite indicator (the daily hazard of dying) from the “day 1” and “change” variables of six time-varying biological indicators (cell-free DNA, protein C, platelet count, creatinine, Glasgow Coma Scale score, and lactate) and a set of contextual variables (age, presence of chronic lung disease or previous brain injury, and duration of stay), achieving a high predictive power (conventional area under the curve, 0.90; 95% CI, 0.86–0.94). Including change variables avoided misleading inferences about the effects of day 1 variables, signifying the importance of the longitudinal approach. We then generated mortality risk profiles that highlight the relative contributions among the time-varying biological indicators to overall mortality risk. The tool was validated in 28 nonseptic patients from the same ICUs who became septic later and was subject to 10-fold cross-validation, achieving similarly high area under the curve. Conclusions:. Using a novel version of the Cox model, we created a prognostic tool for septic patients that yields not only a predicted probability of dying but also a mortality risk profile that reveals how six time-varying biological indicators differentially and longitudinally account for the patient’s overall daily mortality risk.

Published in Critical Care Explorations

ISSN: 2639-8028 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Medical emergencies. Critical care. Intensive care. First aid
Website: https://journals.lww.com/ccejournal/pages/default.aspx

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