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      ROX index and SpO 2/FiO 2 ratio for predicting high-flow nasal cannula failure in hypoxemic COVID-19 patients: A multicenter retrospective study

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          Abstract

          Background

          The ratio of oxygen saturation (ROX) index, defined as the ratio of oxygen saturation (SpO 2)/fraction of inspired oxygen (FiO 2) to respiratory rate, can help identify patients with hypoxemic respiratory failure at high risk for intubation following high-flow nasal cannula (HFNC) initiation; however, whether it is effective for predicting intubation in coronavirus disease 2019 (COVID-19) patients receiving HFNC remains unknown. Moreover, the SpO 2/FiO 2 ratio has been assessed as a prognostic marker for acute hypoxemic respiratory failure. This study aimed to determine the utility of the ROX index and the SpO 2/FiO 2 ratio as predictors of failure in COVID-19 patients who received HFNC.

          Methods

          This multicenter study was conducted in seven university-affiliated hospitals in Korea. Data of consecutive hospitalized patients diagnosed with COVID-19 between February 10, 2020 and February 28, 2021 were retrospectively reviewed. We calculated the ROX index and the SpO 2/FiO 2 ratio at 1 h, 4 h, and 12 h after HFNC initiation. The primary outcome was HFNC failure defined as the need for subsequent intubation despite HFNC application. The receiver operating characteristic curve analysis was used to evaluate discrimination of prediction models for HFNC failure.

          Results

          Of 1,565 hospitalized COVID-19 patients, 133 who received HFNC were analyzed. Among them, 63 patients (47.4%) were successfully weaned from HFNC, and 70 (52.6%) were intubated. Among patients with HFNC failure, 32 (45.7%) died. The SpO 2/FiO 2 ratio at 1 h after HFNC initiation was an important predictor of HFNC failure (AUC 0.762 [0.679–0.846]). The AUCs of SpO 2/FiO 2 ratio at 4 h and ROX indices at 1 h and 4 h were 0.733 (0.640–0.826), 0.697 (0.597–0.798), and 0.682 (0.583–0.781), respectively. Multivariable analysis showed that the patients aged ≥70 years are 3.4 times more likely to experience HFNC failure than those aged <70 years (HR 3.367 [1.358–8.349], p = 0.009). The SpO 2/FiO 2 ratio (HR 0.983 [0.972–0.994], p = 0.003) at 1 h was significantly associated with HFNC failure.

          Conclusions

          The SpO 2/FiO 2 ratio following HFNC initiation was an acceptable predictor of HFNC failure. The SpO 2/FiO 2 ratio may be a good prognostic marker for predicting intubation in COVID-9 patients receiving HFNC.

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          Most cited references25

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          Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

          Background The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. Methods We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. Results The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. Conclusion The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines. Electronic supplementary material The online version of this article (10.1007/s00134-020-06022-5) contains supplementary material, which is available to authorized users.
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            An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy

            Rationale: One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation. Objectives: To validate the diagnostic accuracy of an index (termed ROX and defined as the ratio of oxygen saturation as measured by pulse oximetry/FiO2 to respiratory rate) for determining HFNC outcome (need or not for intubation). Methods: This was a 2-year multicenter prospective observational cohort study including patients with pneumonia treated with HFNC. Identification was through Cox proportional hazards modeling of ROX association with HFNC outcome. The most specific cutoff of the ROX index to predict HFNC failure and success was assessed. Measurements and Main Results: Among the 191 patients treated with HFNC in the validation cohort, 68 (35.6%) required intubation. The prediction accuracy of the ROX index increased over time (area under the receiver operating characteristic curve: 2 h, 0.679; 6 h, 0.703; 12 h, 0.759). ROX greater than or equal to 4.88 measured at 2 (hazard ratio, 0.434; 95% confidence interval, 0.264-0.715; P = 0.001), 6 (hazard ratio, 0.304; 95% confidence interval, 0.182-0.509; P < 0.001), or 12 hours (hazard ratio, 0.291; 95% confidence interval, 0.161-0.524; P < 0.001) after HFNC initiation was consistently associated with a lower risk for intubation. A ROX less than 2.85, less than 3.47, and less than 3.85 at 2, 6, and 12 hours of HFNC initiation, respectively, were predictors of HFNC failure. Patients who failed presented a lower increase in the values of the ROX index over the 12 hours. Among components of the index, oxygen saturation as measured by pulse oximetry/FiO2 had a greater weight than respiratory rate. Conclusions: In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation. Clinical trial registered with www.clinicaltrials.gov (NCT02845128).
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              Failure of high-flow nasal cannula therapy may delay intubation and increase mortality.

              Intubation in patients with respiratory failure can be avoided by high-flow nasal cannula (HFNC) use. However, it is unclear whether waiting until HFNC fails, which would delay intubation, has adverse effects. The present retrospective observational study assessed overall ICU mortality and other hospital outcomes of patients who received HFNC therapy that failed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – original draft
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 May 2022
                2022
                12 May 2022
                : 17
                : 5
                : e0268431
                Affiliations
                [1 ] Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
                [2 ] Division of Allergy and Pulmonology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea
                [3 ] Department of Pulmonary and Critical Care Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
                [4 ] Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
                [5 ] Department of Pulmonology and Critical Care Medicine, Chosun University Hospital, Gwangju, Republic of Korea
                [6 ] Division of Allergy and Respiratory Diseases Soonchunhyang University Hospital, Seoul, Republic of Korea
                [7 ] Department of Internal Medicine, Jeju National University College of Medicine, Jeju, Republic of Korea
                AIIMS: All India Institute of Medical Sciences, INDIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-8372-4511
                https://orcid.org/0000-0001-6455-0376
                Article
                PONE-D-21-37464
                10.1371/journal.pone.0268431
                9098056
                35551328
                a0dfbbd6-c26d-40b4-a165-c6993e717ccc
                © 2022 Kim et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 25 November 2021
                : 29 April 2022
                Page count
                Figures: 2, Tables: 4, Pages: 13
                Funding
                The author(s) received no specific funding for this work.
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