Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19.

OBJECTIVES: To describe hospital variation in use of "guideline-based care" for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Retrospective, observational study. SETTING: The Society of Critical Care Medicine's Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS: Hospital-level use of "guideline-based care" for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in "guideline-based care." A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1-3.4) for receipt of "guideline-based care" compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47-62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use "guideline-based care" quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7; 95% CI, 0.3-1.9; p = 0.49). CONCLUSIONS: During the first year of the COVID-19 pandemic, only half of patients received "guideline-based care" for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Variation in Use of High-Flow Nasal Cannula and Noninvasive Ventilation Among Patients With COVID-19.

BACKGROUND: The use of high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) for hypoxemic respiratory failure secondary to COVID-19 are recommended by critical-care guidelines; however, apprehension about viral particle aerosolization and patient self-inflicted lung injury may have limited use. We aimed to describe hospital variation in the use and clinical outcomes of HFNC and NIV for the management of COVID-19. METHODS: This was a retrospective observational study of adults hospitalized with COVID-19 who received supplemental oxygen between February 15, 2020, and April 12, 2021, across 102 international and United States hospitals by using the COVID-19 Registry. Associations of HFNC and NIV use with clinical outcomes were evaluated by using multivariable adjusted hierarchical random-effects logistic regression models. Hospital variation was characterized by using intraclass correlation and the median odds ratio. RESULTS: Among 13,454 adults with COVID-19 who received supplemental oxygen, 8,143 (60%) received nasal cannula/face mask only, 2,859 (21%) received HFNC, 878 (7%) received NIV, 1,574 (12%) received both HFNC and NIV, with 3,640 subjects (27%) progressing to invasive ventilation. The hospital of admission contributed to 24% of the risk-adjusted variation in HFNC and 30% of the risk-adjusted variation in NIV. The median odds ratio for hospital variation of HFNC was 2.6 (95% CI 1.4-4.9) and of NIV was 3.1 (95% CI 1.2-8.1). Among 5,311 subjects who received HFNC and/or NIV, 2,772 (52%) did not receive invasive ventilation and survived to hospital discharge. Hospital-level use of HFNC or NIV were not associated with the rates of invasive ventilation or mortality. CONCLUSIONS: Hospital variation in the use of HFNC and NIV for acute respiratory failure secondary to COVID-19 was great but was not associated with intubation or mortality. The wide variation and relatively low use of HFNC/NIV observed within our study signaled that implementation of increased HFNC/NIV use in patients with COVID-19 will require changes to current care delivery practices. (ClinicalTrials.gov registration NCT04323787.).

Hospital Variation in Management and Outcomes of Acute Respiratory Distress Syndrome Due to COVID-19

OBJECTIVES: To describe hospital variation in use of “guideline-based care” for acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN: Retrospective, observational study. SETTING: The Society of Critical Care Medicine’s Discovery Viral Infection and RESPIRATORY ILLNESS UNIVERSAL STUDY COVID-19 REGISTRY. PATIENTS: Adult patients with ARDS due to COVID-19 between February 15, 2020, and April 12, 2021. INTERVENTIONS: Hospital-level use of “guideline-based care” for ARDS including low-tidal-volume ventilation, plateau pressure less than 30 cm H2O, and prone ventilation for a Pao2/Fio2 ratio less than 100. MEASUREMENTS AND MAIN RESULTS: Among 1,495 adults with COVID-19 ARDS receiving care across 42 hospitals, 50.4% ever received care consistent with ARDS clinical practice guidelines. After adjusting for patient demographics and severity of illness, hospital characteristics, and pandemic timing, hospital of admission contributed to 14% of the risk-adjusted variation in “guideline-based care.” A patient treated at a randomly selected hospital with higher use of guideline-based care had a median odds ratio of 2.0 (95% CI, 1.1–3.4) for receipt of “guideline-based care” compared with a patient receiving treatment at a randomly selected hospital with low use of recommended therapies. Median-adjusted inhospital mortality was 53% (interquartile range, 47–62%), with a nonsignificantly decreased risk of mortality for patients admitted to hospitals in the highest use “guideline-based care” quartile (49%) compared with the lowest use quartile (60%) (odds ratio, 0.7;95% CI, 0.3–1.9;p = 0.49). CONCLUSIONS: During the first year of the COVID-19 pandemic, only half of patients received “guideline-based care” for ARDS management, with wide practice variation across hospitals. Strategies that improve adherence to recommended ARDS management strategies are needed.

Variation in Use of Repurposed Medications Among Patients With Coronavirus Disease 2019. From The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 Registry Investigator Group.

IMPORTANCE: At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES: To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN SETTING AND PARTICIPANTS: Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine's Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES: Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS: Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40-4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23-6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01-0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34-0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01-1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE: Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

Variation in use of anti-viral and anti-inflammatory medications in patients hospitalized with COVID-19: Results from the international viral infection and respiratory illness universal study (virus)

RATIONALE: In the absence of effective therapies at the start of the Coronavirus disease of 2019 (COVID-19) pandemic, anti-viral and antiinflammatory medications were used for management of COVID-19 without robust evidence of their benefit. The patterns of use, implementation, and de-implementation of these medications is unclear. METHODS: We performed a retrospective, observational study on an international cohort of adult patients hospitalized from March 2020 to November 2020 with laboratory confirmed COVID-19 infection, receiving supplemental oxygen, and enrolled in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. The primary outcome of interest was to describe the hospital-level variation in the most commonly used medications repurposed for empiric management of patients hospitalized with COVID-19 (hydroxychloroquine, remdesivir, corticosteroids, and anti-IL-6 therapies). Secondary outcomes included geographic and temporal variation in medication use. RESULTS: Among 6,621 patients with COVID-19 across 86 hospitals (predominantly USbased [88%]), 1,373 (20.7%, hospital usage rates range 0%-96.4%) received corticosteroids, 1,302 (19.7%, range 0%-100%) received hydroxychloroquine, 602 (9.1%, range: 0%-65.7%) received remdesivir, and 405 (6.1%, range 0%-87.5%) received an anti-IL6 medication. USbased hospitals vs non-US hospitals showed differences in medication use with 9.9% vs. 0.8% use of remdesivir, 19.5% vs 33.2% use of corticosteroids, 18.7% vs 29.6% use of hydroxychloroquine and 6.3% vs. 3.9% use of anti-IL6 medications. Comparing use prior to July 2020 with use after July 2020, prescription of remdesivir increased from 6.5% to 20.5%, corticosteroid use increased from 17.5% to 35.0%, hydroxychloroquine use decreased from 23.9% to 1.1% and anti-IL6 use decreased from 7.0% to 2.4%. CONCLUSIONS: Hospital-level variation and geographic variation in use of repurposed anti-viral and anti-inflammatory medications for the management of COVID-19 infection was large. Coinciding with accrual of scientific evidence, the use of remdesivir and corticosteroids increased over time, while the use of hydroxychloroquine and anti-IL6 medications decreased over time. Further studies are needed to evaluate the drivers of hospital variation and impact on clinical outcomes.

Variation in high-flow nasal cannula and non-invasive ventilation practice patterns during the COVID-19 pandemic: Results from the international viral infection and respiratory illness universal study (virus)

RATIONALE: Critical care guidelines have supported use of non-invasive respiratory support modalities in patients with acute respiratory failure from COVID-19 since the beginning of the pandemic. However, concerns surrounding viral particle aerosolization, nosocomial spread, and patient self-induced lung injury have likely influenced choice of respiratory support strategies. To date, high flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) practice patterns have not been characterized for patients with COVID-19. METHODS: We enrolled hospitalized patients aged 18 years or older with laboratory confirmed COVID-19 infection who received supplemental oxygen, using the Society of Critical Care Medicine Discovery VIRUS Registry. The primary outcome was hospital-level variation in use of HFNC and NIPPV, summarized using the intraclass correlation coefficient and median odds ratio. Hierarchical random effects models were used to estimate patient and hospital factors associated with HFNC and NIPPV use. Risk-adjusted estimation of the association between hospital HFNC/NIPPV use and patient risk of receiving invasive mechanical ventilation (IMV) was assessed as a secondary outcome. RESULTS: Among 8,532 patients with COVID-19 receiving oxygen support across 73 hospitals, the majority were treated in the US (92.3%) and were older (median age 63 years, IQR 52-74), white (49.1%), men (56.8%) with median SOFA score of 4 (IQR 1-6) and admission PaO2:FiO2 below 300 (49.4%). Of these, 5,298 (62.1%) received low flow oxygen (nasal cannula or face mask), while 1,768 (20.7%) received HFNC, 773 (9.1%) received NIPPV and 693 (8.1%) received both HFNC/NIPPV. Patient SOFA score (OR 0.92, 95% CI 0.90, 0.95), treatment for COVID-19 after July versus March-June (OR 1.3, 95% CI 1.0, 1.6) and ICU versus floor admission (OR 10.3, 95% CI 8.2, 12.8) were associated with HFNC/NIPPV use. After adjusting for patient and hospital characteristics, the hospital of admission contributed to 27% of the variation in use of HFNC and/or NIPPV. Odds of receiving either modality at a randomly selected high vs. low HFNC/NIPPV utilization hospital was 2.9. Hospital rates of HFNC/NIPPV use were not associated with patient receipt of IMV (OR 0.87, 95% CI 0.7, 1.1). CONCLUSION: Throughout the course of the COVID-19 pandemic, use of HFNC and NIPPV varied widely across hospitals, though use of non-invasive respiratory support modalities was not associated with patient risk for invasive mechanical ventilation. Further evaluation of HFNC and NIPPV exposure, progression to IMV and subsequent mortality within these subgroups may provide additional insights regarding optimal oxygenation and ventilation strategies of patients with COVID-19.