key: cord-0836924-6tqy8t65 authors: Loureiro-Amigo, Jose; Suárez-Carantoña, Cecilia; Oriol-Bermúdez, Isabel; Sánchez-Díaz, Cristina; Coloma-Conde, Ana; Manzano-Espinosa, Luis; Rubio-Rivas, Manuel; Otero-Perpiñá, Barbara; Jenaro, María Mercedes Ferreiro-Mazón; Coduras-Erdozain, Ainara; Luis Garcia-Klepzig, José; Vargas-Parra, Derly; Pesqueira-Fontán, Paula M.; Fiteni-Mera, Isabel; García-García, Gema María; Jiménez-Torres, José; Rodríguez-Cortés, Pablo; Costo-Muriel, Clara; Arnalich-Fernández, Francisco; Artero, Arturo; Carrasco-Sánchez, Francisco Javier; Escobar-Sevilla, Joaquín; Nicolás Alcalá-Pedrajas, José; Gómez-Huelgas, Ricardo; Ramos-Rincón, José-Manuel title: La posición prona en los pacientes con covid-19 y síndrome de distrés respiratorio agudo que recibieron oxigenoterapia convencional: un estudio retrospectivo date: 2021-06-06 journal: Arch Bronconeumol DOI: 10.1016/j.arbres.2021.05.018 sha: 0098f37b681a10c05b706cf369321990d37b1387 doc_id: 836924 cord_uid: 6tqy8t65 nan . Although most cases are mild, nearly 20% of patients require hospitalization (2) . Despite supportive care, one third of hospitalized patients meet the Berlin criteria for acute respiratory distress syndrome (ARDS) (3, 4) , and may need admission to intensive care unit (ICU). Overall mortality ranged 21-26% with 4 advanced age, male sex and comorbidities being the strongest predictors of inhospital mortality (5, 6) . Apart from dexamethasone (7) , to date the mainstay of treatment if COVID-19 are supplemental oxygen therapy and best supportive care, including invasive mechanical ventilation (IMV) in severe ARDS (8) . Prone position (PP) is the only technique that has demonstrated to increase survival in patients with severe ARDS receiving IMV(9). However, due to a sudden increase in hospitalizations, exceeding ICU capacity, PP has been attempted in non-intubated awake patients with COVID-19 and severe ARDS in conventional medical wards (10) (11) (12) , despite inconsistent results on the impact of this intervention on mortality (13) . In this study, we evaluated the impact on in-hospital mortality of PP in spontaneously breathing patients with COVID-19 and severe ARDS. This study is based on the data from the SEMI-COVID-19 Registry. This Registry is an ongoing nationwide, multicenter, observational retrospective cohort of adult patients admitted to Spanish hospitals from March 1 st , 2020 because of microbiologically confirmed COVID-19. Characteristics of the Registry are detailed elsewhere (6) . In this study we included patients aged 18-75 years old who presented pneumonia and severe ARDS (PaO2/FiO2 ≤ 100 mmHg)(4) during hospitalization. Exclusion criteria were: a) ICU admission, b) use of non-invasive mechanical ventilation (NIMV), c) use of high-flow nasal cannula (HFNC) oxygen therapy, d) moderate or severe dependence for activities of daily living e) solid or hematologic cancer, f) chronic dialysis, g) neurodegenerative disease or hemiplegia. The primary outcome was death during hospitalization. Patients in whom PP during spontaneous breathing was used for at least one day were compared to those who did not receive this treatment. PP indication and duration registry. Baseline characteristics between groups were compared using Mann-Whitney U test and Fisher's exact test. Univariate logistic regression was used to estimate the crude effect of prone position on mortality, as well as the effect of those baseline variables that were different between both groups (p value < 0.10) or considered as clinically relevant. Afterwards, a multivariate logistic regression model was elaborated, including as confounders the variables that showed a univariate effect on mortality or those a priori (outcome-blinded) considered as relevant according to literature review (14) Baseline characteristics, treatment received and outcomes in both groups are detailed in Table 1 . Patients who receive PP were younger, had less comorbidity, presented higher C-reactive protein and D-dimer levels at admission, and received more corticosteroids and tocilizumab. Besides, although the proportion J o u r n a l P r e -p r o o f 6 of patients with altered mental status at presentation did not meet our prespecified criteria of p value < 0.10 to be considered different between the two groups, we considered the difference clinically relevant ( corticosteroids and tocilizumab as confounders in the adjusted analysis, the exclusion of these variables did not modify the protective effect of PP on mortality, and the accuracy of our adjusted model to predict in-hospital death was very good. Despite PP is a well-established evidence-based practice in patients with typical ARDS undergoing IMV, there is very limited evidence of its use in non-ventilated awake patients and derived mostly from case reports and uncontrolled cohorts using a wide variety of PP protocols (13, 15) . Besides, in most reports the use of respiratory support is inconsistent, with patients receiving NIMV or HFNC oxygen therapy, thus making very difficult to know the true effect of PP (13) . Despite most studies reported an improvement in oxygenation while patients were in PP and even after PP(10), its impact on hard outcomes such as intubation or death remains unclear. In fact, it has been pointed out that improvement in oxygenation during PP may result in delayed intubation and IMV with eventually poor outcomes (16) . However, in a recent retrospective cohort with 166 patients, Padrão et al studied the impact of PP in patients who required supplemental 7 oxygen (but did not receive NIMV or HFNC oxygen) and found no differences on the need of intubation at 15 days (17) . A possible explanation could be that the benefits of PP are related to a reduction in ventilator-induced lung injury rather than with better oxygenation (18) . In our study, we excluded older patients because they could have greater comorbidities and most of them would not benefit from ICU admission in a context of pandemic crisis. This scenario happened in the first weeks of COVID-19 pandemic in Spain and other developed countries and is still ongoing in resourcelimited settings. The main strength of our study is the use of a hard endpoint as mortality as the primary outcome, and the large number of patients included in comparison to previous studies on this topic. Besides, contrary to previous reports, our cohort is homogeneous regarding respiratory support, as we only include patients with spontaneous breathing receiving oxygen supply through a conventional oxygen mask (either Venturi masks or rebreathing masks). This study also has several limitations. The main one is the lack of detailed information on indication, timing, or duration of PP, and as a result, it is probable that PP was heterogeneous across the cohort. Secondly, we do not have information on the reasons why our patients with severe ARDS were not admitted to the ICU, and given the multicenter nature of the cohort, these reasons could be different between hospitals, potentially resulting in a selection bias. To minimize the risk of selection bias we decided to analyze only COVID-19 patients ≤ 75 years and severe ARDS, as we believe that the main reason these patients remained in conventional wards was the unavailability of ICU resources. In summary, the use of prone position in non-intubated COVID-19 patients ≤ 75 years with severe ARDS and without additional respiratory support, may be Infectious Diseases Unit -Internal Medicine Department Ramón y Cajal Hospital Cajal de Investigación Sanitaria (IRYCIS) Internal Medicine Department, La Princesa Hospital Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Acute respiratory distress syndrome: the Berlin Definition Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Registry Dexamethasone in Hospitalized Patients with Covid-19 Acute Respiratory Distress Syndrome Treatment of ARDS With Prone Positioning Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study Use of Prone Positioning in Nonintubated Patients With COVID-19 and Hypoxemic Acute Respiratory Failure Respiratory Parameters in Patients With COVID-19 After Using Noninvasive Ventilation in the Prone Position Outside the Intensive Care Unit Awake prone positioning for COVID-19 hypoxemic respiratory failure: A rapid review Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis Is the Prone Position Helpful during Spontaneous Breathing in Patients with COVID-19? Awake Prone Positioning in COVID-19 Hypoxemic Respiratory Failure: Exploratory Findings in a Single-center Retrospective Cohort Study Prone positioninduced improvement in gas exchange does not predict improved survival in the acute respiratory distress syndrome We want to thank Martín Fabregate Fuente for providing statistical support. We also want to gratefully acknowledge all the investigators who participate in the SEMI-COVID-19 Registry. We also thank the SEMI-COVID-19 Registry Coordinating Center, S&H Medical Science Service, for their quality control data, logistic and administrative support. The authors declare that there is no conflict of interest to report. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.