Evaluation of the ROX index in SARS-CoV-2 Acute Respiratory failure treated with both High-Flow Nasal Oxygen (HFNO) and Continuous Positive Airway Pressure (CPAP)

  1. Hakim Ghani
  2. Michael Shaw
  3. Phyoe Pyae
  4. Rigers Cama
  5. Meghna Prabhakar
  6. Alessio Navarra
  7. Rahul Mogal
  8. Andrew Barlow
  9. Nazril Nordin
  10. Rama Vancheeswaran
  11. Janice Yu Ji Lee
  12. Felix Chua

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Abstract

Background

Non-invasive respiratory support including high-flow nasal oxygen (HFNO), and continuous positive airway pressure (CPAP) have been used to provide therapy in selected SARS-CoV-2 patients with acute respiratory failure (ARF). The value of the ROX index, a validated benchmark for outcomes in HFNO is unknown in CPAP.

Objective

Can the ROX, a validated benchmark in HFNO be used for measuring treatment outcomes of CPAP in SARS-COV-2 ARF?

Study Design and Methods

A non-randomised prospective protocol driven observational non-intensive care unit study in 130 SARS-COV-2 patients with ARF treated with non-invasive therapy from March 2020 to January 2021. The primary end point was failure of therapy (death or escalation). Secondary outcomes included time to failure including invasive mechanical ventilation (IMV) or death, the effect of escalation to CPAP from HFNO and the utility of ROX in ARF.

Results

HFNO was better than CPAP in treating SARS-COV-2 ARF: 17/35 (48.5%) with successful HFNO therapy versus 24/95 (25.2%) with CPAP. The ROX index was more sensitive to outcomes with CPAP compared to HFNO and distinguished treatment failure early at 1, 4, 6, 12, and 24 hours with the highest sensitivity at 24 hours (ROX-24h). The AUC for the ROX-24h was 0.77 for HFNO (P<0.0001), and 0.84 for CPAP (P<0.0001). The ROX-24h cut-points predicted failure with HFNO when < 3.9 (PPV 71%, NPV 75%) and CPAP < 4.3 (PPV 75%, NPV 91%). For success, ROX-24h cut-points of 7.6 for HFNO (PPV 85%, NPV 48%) and 6.1 for CPAP (PPV 88%, NPV 62%) were observed. Escalation from HFNO to CPAP was mostly not successful.

Conclusion

ARF in SARS-COV-2 can be successfully managed by non-invasive support. The ROX index, validated for HFNO, provides a timely, low resource measure for both HFNO and CPAP avoiding delayed intubation.

Trial registration

Study approved by NHS HRAREC (20/HRA/2344;ethics 283888)

KEY MESSAGE

What is the key question?

Can the ROX, a validated benchmark in high-flow nasal oxygen (HFNO) be used for measuring treatment outcomes of continuous positive airway pressure (CPAP) in SARS-COV-2 ARF?

What is the bottom line?

The ROX index, validated for HFNO, provides a timely, low resource measure for both HFNO and CPAP support avoiding delayed intubation.

Why read on?

The present study compares the efficacy of HFNO and CPAP, two common globally used modalities of treatment for SARS-CoV-2 and notes the superior utility of the ROX-24h in CPAP to predict outcome, enabling timely escalation decisions.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.03.23.21254203: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis: Descriptive statistics and comparisons between parametric and non-parametric samples were calculated using the GraphPad PRISM statistics software (GraphPad, San Diego, USA).
    PRISM
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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: We detected the following sentences addressing limitations in the study:
    This limitation has been reported to be mitigated by the addition of the respiratory rate: the ROX index23. We document improved mortality with HFNO compared with face mask CPAP like numerous others10,13,14,21,26,27. The ranges of measurements for the ROX were similar for HFNO and CPAP in SARS-CoV-2 ARF. For HFNO, we note a similar ROX at 4 hours to the French investigators (>5.37 for success) 10,14 and UK reports at 12 hours (ROX-12h <4.88 for failure)11. We note different results to a South African study (<3.7 for failure versus <4.46)13 which may be explained by the younger age of the population (52y vs 60y), a lower presenting PF ratio (68 vs 106) and differing treatment regimens (70% corticosteroid use) and comorbidities particularly HIV. The increased sensitivity of the ROX with time is well reported particularly at or before 24 hours aiming to maximise decisions about escalation early11,13. While our HFNO data is not significant at 4 and 6 hours, the trend with time is clearly significant with divergence at 4 hours and may reflect the smaller HFNO patient numbers in our study, a limitation due to the late UK adoption of HFNO. We provide an early positive report of the value of the ROX in CPAP, unlike the small studies in the past with 20 and 18 patients who report mixed results11,25. The ROX discriminates outcomes early from 1 hour onwards with the most sensitivity at 24 hours. This should enable timely decision making, particularly in the ‘golden window’ between 24 ho...

    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.

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  2. Version published to 10.1101/2021.03.23.21254203 on medRxiv