Altered Heart Rate Variability Early in ICU Admission Differentiates Critically Ill Coronavirus Disease 2019 and All-Cause Sepsis Patients

  1. Rishikesan Kamaleswaran
  2. Ofer Sadan
  3. Prem Kandiah
  4. Qiao Li
  5. Craig M. Coopersmith
  6. Timothy G. Buchman

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Abstract

Altered heart rate variability has been associated with autonomic dysfunction in a number of disease profiles, in this work we elucidate differences in the biomarker among patients with all-cause sepsis and coronavirus disease 2019.

OBJECTIVES:

To measure heart rate variability metrics in critically ill coronavirus disease 2019 patients with comparison to all-cause critically ill sepsis patients.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective analysis of coronavirus disease 2019 patients admitted to an ICU for at least 24 hours at any of Emory Healthcare ICUs between March 2020 and April 2020 up to 5 days of ICU stay. The comparison group was a cohort of all-cause sepsis patients prior to coronavirus disease 2019 pandemic.

MAIN OUTCOMES AND MEASURES:

Continuous waveforms were captured from the patient monitor. The electrocardiogram was then analyzed for each patient over a 300 seconds observational window that was shifted by 30 seconds in each iteration from admission till discharge. A total of 23 heart rate variability metrics were extracted in each iteration. We use the Kruskal-Wallis and Steel-Dwass tests ( p < 0.05) for statistical analysis and interpretations of heart rate variability multiple measures.

RESULTS:

A total of 141 critically ill coronavirus disease 2019 patients met inclusion criteria, who were compared with 208 patients with all-cause sepsis. Three nonlinear markers, including the ratio of standard deviation derived from the Poincaré plot, sample entropy, and approximate entropy and four linear features, including mode of beat-to-beat interval, acceleration capacity, deceleration capacity, and the proportion of consecutive RR intervals that differ by more than 50 ms, were all statistically significant ( p < 0.05) between the coronavirus disease 2019 and all-cause sepsis cohorts. The three nonlinear features and acceleration capacity, deceleration capacity, and beat-to-beat interval (mode) were statistically significant ( p < 0.05) when comparing pairwise analysis among the combinations of survivors and nonsurvivors between the coronavirus disease 2019 and sepsis cohorts. Temporal analysis of the main markers showed low variability across the 5 days of analysis compared with sepsis patients.

CONCLUSIONS AND RELEVANCE:

In this descriptive statistical study, heart rate variability measures were found to be statistically different across critically ill patients infected with severe acute respiratory syndrome coronavirus 2 and distinct from bacterial sepsis.

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  1. Version published to 10.1097/cce.0000000000000570
  2. ScreenIT

    SciScore for 10.1101/2020.06.05.20123752: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Emory University Institutional Review Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All medical, surgical. neurocritical, transplant and cardiac ICU admissions with COVID-19 between March 1 through April 31st, 2020 within Emory Healthcare system were screened.
    Emory Healthcare
    suggested: (One Mind Biospecimen Bank Listing, RRID:SCR_004193)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.06.05.20123752v1 on medRxiv