key: cord-0711476-cxcv4eya authors: Bhasin, A.; Bregger, M.; Kluk, M.; Park, P.; Feinglass, J.; Barsuk, J. title: The Presence of Ambulatory Hypoxia as an Early Predictor of Moderate to Severe COVID-19 Disease date: 2020-12-16 journal: nan DOI: 10.1101/2020.12.14.20248209 sha: 89127ef0ed88bf270ff4ac0795d1d494871ca485 doc_id: 711476 cord_uid: cxcv4eya Importance: The development and importance of ambulatory hypoxia in COVID-19 is unknown. The presence of ambulatory hypoxia may help risk-stratify hospitalized patients with COVID-19. If sufficient lead-time exists between development of ambulatory hypoxia and other outcome measures, interventions might be initiated earlier. Objective: To determine the association of ambulatory hypoxia with the eventual need for nasal cannula or advanced oxygenation therapies (defined as use of high flow nasal cannula, Bi-PAP, ventilator, or extracorporeal membrane oxygenation). Design: Retrospective, observational study of patients hospitalized with COVID-19 from March 1, 2020 to October 30, 2020. Setting: Ten hospitals in an integrated academic medical system (Northwestern Medicine) in the Chicagoland area. Participants: Adult patients (age > 18) hospitalized for COVID-19 who had ambulatory oximetry measured. Intervention(s) / Exposure(s): Ambulatory oximetry measurement. Main outcomes and measures: The association of ambulatory hypoxia with subsequent use of nasal cannula and advanced oxygen therapies and the time between ambulatory hypoxia and need for these oxygen therapies. Patients who had ambulatory oximetry measurements after use of nasal cannula or advanced oxygen therapies were excluded. Results: Of 531 patients with ambulatory oximetry measured, 132 (24.9%) had ambulatory hypoxia. Presence of ambulatory hypoxia was strongly associated with subsequent use of nasal cannula (OR 4.8, 95% CI 2.8 - 8.4) and advanced oxygen therapy (IRR 7.7, 95% CI 3.4 - 17.5). Ambulatory hypoxia measurement preceded nasal cannula use by a median 12.5 hours [IQR 3.25, 29.25] and advanced oxygenation therapies by 54 hours [IQR 25, 82]. Conclusion and Relevance: Ambulatory hypoxia is associated with moderate to severe COVID-19. It may serve as an early, non-invasive physiologic marker for the likelihood of developing moderate to severe disease and help clinicians triage patients and initiate earlier interventions. 4 cannula (OR 4.8, 95% CI 2.8 -8. 4 ) and advanced oxygen therapy (IRR 7.7, 95% CI 3.4 -17.5). 45 Ambulatory hypoxia measurement preceded nasal cannula use by a median 12.5 hours [IQR 46 3.25, 29.25] and advanced oxygenation therapies by 54 hours [IQR 25, 82] . 47 Conclusion and Relevance: Ambulatory hypoxia is associated with moderate to severe COVID- 48 19. It may serve as an early, non-invasive physiologic marker for the likelihood of developing 49 moderate to severe disease and help clinicians triage patients and initiate earlier interventions. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. Coronavirus-induced-disease-2019 (COVID-19) has caused a pandemic with 56,178,674 52 cases and 1,348,348 deaths worldwide. 1 In our experience, we noted many inpatients with 53 COVID-19 first exhibit hypoxia with exertion, then subsequently develop moderate to severe 54 disease requiring nasal cannula or more advanced oxygen therapies. Early COVID-19 induces 55 occult lung damage, noted by peripheral ground-glass opacities on imaging. 2 We suspect patients 56 at this stage exhibit ambulatory but not resting hypoxia. Several studies have characterized risk 57 factors for severe COVID-19 based on patient-specific comorbidities and laboratory data. To our 58 knowledge, no study has evaluated ambulatory hypoxia as a risk factor for development of 59 moderate to severe disease. Therefore, we aimed to evaluate if ambulatory hypoxia is associated 60 with COVID-19 progression. We performed a retrospective observational study of adults (age >18 years) hospitalized 63 with COVID-19 who had ambulatory oxygen measurements (without first developing resting 64 hypoxia) at Northwestern Medicine (NM) between March 1, 2020 and October 30, 2020. NM is 65 an integrated academic medical system in the Chicagoland area with 10 affiliated hospitals. We is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint Our study shows that the presence of ambulatory hypoxia is strongly associated with the 120 subsequent development of moderate to severe COVID-19. In our patient population, 121 ambulatory hypoxia occurred several hours before the need for NC and advanced oxygen 122 therapies. This is important because it may enable clinicians to start therapeutic treatments such 123 as remdesivir 5 and/or dexamethasone 6 earlier. It may also help health systems effectively identify 124 patients most likely to require ICU-level care, which may improve hospital throughput especially 125 when hospitals are near or at capacity. 126 Ambulatory oximetry has been used to help determine severity of cardiopulmonary 127 diseases including heart failure, 7 pulmonary hypertension, 8 chronic obstructive pulmonary 128 disease, 9 and interstitial lung disease. 10 To our knowledge, the presence of ambulatory hypoxia 129 has never been shown to acutely predict cardiopulmonary disease progression. Recently, some 130 authors have advocated for ambulatory oximetry measurements to evaluate patients for discharge 131 readiness after resolution of COVID-19 symptoms, 11 a strategy already adopted in our hospital. 132 We present the first study showing that ambulatory hypoxia predicts worsening pulmonary 133 disease in patients with COVID-19. Our study has several limitations. First our study was performed at one health network 135 with a relatively small number of patients potentially limiting generalizability. However, the 136 associations between ambulatory hypoxia and worsening oxygenation were statistically very 137 strong. Second, we excluded patients who did not have ambulatory oximetry measurements. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint Ambulatory oxygen measurement is part of the admission order protocols in our health system, 139 so patients without measurements likely represented a sicker cohort unable to ambulate or those 140 discharged quickly. Patients without measurement may also have been cared for by clinicians 141 who did not order ambulatory oximetry, given lacking evidence. Third, we did not directly is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint a scientific statement from the acute heart failure committee of the heart failure association of 176 the CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint The copyright holder for this this version posted December 16, 2020. ; https://doi.org/10.1101/2020.12.14.20248209 doi: medRxiv preprint An interactive web-based dashboard to track COVID-19 in real time Temporal Changes of CT Findings in 90 Patients with COVID-19 162 Pneumonia: A Longitudinal Study What's the relative risk? 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