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Heart Rate Variability, Clinical and Laboratory Measures to Predict Future Deterioration in Patients Presenting With Sepsis

Barnaby, Douglas P.*; Fernando, Shannon M.†,‡; Herry, Christophe L.§; Scales, Nathan B.§; Gallagher, Edward John*; Seely, Andrew J. E.‡,§,||

doi: 10.1097/SHK.0000000000001192
Clinical Science Aspects
Editor's Choice

Background: Risk stratification of patients presenting to the emergency department (ED) with sepsis can be challenging. We derived and evaluated performance of a predictive model containing clinical, laboratory, and heart rate variability (HRV) measures to quantify risk of deterioration in this population.

Methods: ED patients aged 21 and older satisfying the 1992 consensus conference criteria for sepsis and able to consent (directly or through a surrogate) were enrolled (n = 1,247). Patients had clinical, laboratory, and HRV data recorded within 1 h of ED presentation, and were followed to identify deterioration within 72 h.

Results: Eight hundred thirty-two patients had complete data, of whom 68 (8%) reached at least one endpoint. Optimal predictive performance was derived from a combination of laboratory values and HRV metrics with an area under the receiver-operating curve (AUROC) of 0.80 (95% CI, 0.65–0.92). This combination of variables was superior to clinical (AUROC = 0.69, 95% CI, 0.54–0.83), laboratory (AUROC = 0.77, 95% CI, 0.63–0.90), and HRV measures (AUROC = 0.76, 95% CI, 0.61–0.90) alone. The HRV+LAB model identified a high-risk cohort of patients (14% of all patients) with a 4.3-fold (95% CI, 3.2–5.4) increased risk of deterioration (incidence of deterioration: 35%), as well as a low-risk group (61% of all patients) with 0.2-fold (95% CI 0.1–0.4) risk of deterioration (incidence of deterioration: 2%).

Conclusions: A model that combines HRV and laboratory values may help ED physicians evaluate risk of deterioration in patients with sepsis and merits validation and further evaluation.

*Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, New York

Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada

Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada

§Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

||Department of Surgery, University of Ottawa, Ottawa, ON, Canada

Address reprint requests to Douglas P. Barnaby, MD, MS, Department of Emergency Medicine, Montefiore Medical Center, 3411 Wayne Ave., #651, Bronx, NY 10467. E-mail:

Received 13 February, 2018

Revised 20 March, 2018

Accepted 18 May, 2018

Authors’ contributions: DPB, SMF, CLH, AJES, and EJG conceived and designed the study. DPB supervised data collection and managed its retrieval and storage. DPB, CLH, AJES, NBS, and EJG provided statistical advice on study design and analyzed the data. DPB had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the analysis. DPB, SMF, NBS, AJES, and CLH drafted the manuscript, and all authors contributed substantially to its revision.

The research described was supported by NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA Grant Number UL1TR001073.

Prior Presentation: Preliminary results from this study were presented at the Critical Care Canada Forum annual meeting in Toronto, ON (November 2016).

AJES founded Therapeutic Monitoring Systems in order to commercialize patented Continuous Individualized Multiorgan Variability Analysis (CIMVA) technology, with the objective of delivering variability-directed clinical decision support to improve quality and efficiency of care. CLH is a patent holder related to waveform quality assessment necessary for variability analysis.

The remaining authors report no conflicts of interest.

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