key: cord-0764963-8ajom8yc authors: Barbeta, Enric; Motos, Ana; Torres, Antoni; Ceccato, Adrian; Ferrer, Miquel; Cilloniz, Catia; Bueno, Leticia; Badia, Joan Ramon; Castro, Pedro; Ferrando, Carlos; Andrea, Rut; Castellà, Manuel; Fernández, Javier; Soriano, Alex; Mellado, Ricard; López-Aladid, Rubén; Yang, Hua; Yang, Minlan; Fernandez-Barat, Laia; Catalina Palomeque, Andrea; Vollmer, Ivan title: SARS-CoV-2–induced Acute Respiratory Distress Syndrome: Pulmonary Mechanics and Gas-Exchange Abnormalities date: 2020-09-03 journal: Ann Am Thorac Soc DOI: 10.1513/annalsats.202005-462rl sha: b5fcd7fff62d8aa7717e7ccf4d90e1f61b3c9b90 doc_id: 764963 cord_uid: 8ajom8yc nan In January 2020, the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were reported in Europe. Multiple outbreaks have since then led to a global pandemic, as well as to massive medical, economic, and social repercussions (1, 2). SARS-CoV-2 pneumonia can develop into acute respiratory distress syndrome (ARDS) when mechanical ventilation (MV) is needed (3, 4) . ARDS produces abnormalities in gas exchange with a variable degree of shunt (5) , high dead space ventilation (dead space volume [VD]/tidal volume [VT] ratio) (6) , diminished pulmonary compliance (7) , and alterations to the pulmonary circulation (8) . The cornerstone of ARDS management is to provide adequate gas exchange without further lung injury as a result of MV. To date, information regarding the characteristics of SARS-CoV-2-induced ARDS is not completely known. However, this information is crucial to better apply MV and facilitate organ support strategies. We therefore present the characteristics of gas exchange, pulmonary mechanics, and ventilatory management of 50 patients with laboratory-confirmed SARS-CoV-2 infection, who developed ARDS and underwent invasive MV (IMV). Descriptive analysis included 50 consecutive patients with laboratory-confirmed SARS-CoV-2 infection who developed ARDS (9) and underwent IMV. These patients were admitted to the SARS-CoV-2-dedicated intensive care units (ICUs) at Hospital Clinic of Barcelona, Spain, between March 7 and March 25, 2020. Upon ICU admission, epidemiological characteristics, the severity of SARS-CoV-2 infection with the Acute Physiology and Chronic Health Evaluation II score, prognostic biomarkers of SARS-CoV-2 infection (described in Reference 4), time from hospital to ICU admission, time from ICU admission to intubation, oxygen therapy or noninvasive ventilation (NIV) use, and microbiology were investigated. On the day that criteria for ARDS diagnosis were met (9) and IMV was needed, the following assessments were performed: impairment in oxygenation was analyzed with the partial pressure of oxygen (Pa O 2 )/fraction of inspired oxygen (FI O 2 ) ratio, and abnormalities of CO 2 metabolism were studied with the ventilatory ratio (VR), a surrogate parameter of VD/VT (10) . In addition, adjunctive therapies and MV parameters related with ventilation-induced lung injury (VILI) described elsewhere (11) (12) (13) (14) (15) were investigated. This letter has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org. Correlations of SARS-CoV-2 prognostic biomarkers (4), pulmonary mechanics, and gas-exchange data were performed. Twenty-eight-day and hospital mortality, ventilator-and ICU-free days at Day 28, hospital and ICU lengths of stay, and need for tracheostomy were also evaluated (16) . Finally, a subanalysis assessing differences before and after prone positioning was performed. For additional detail on the method, see the online supplement. By March 25th, 2020, 50 patients with laboratory-confirmed SARS-CoV-2 infection and ARDS had been admitted to our hospital. Table 1 shows the demographic and clinical characteristics of these patients. The median (interquartile range [IQR]) age was 66 (57-74) years. Thirty-six patients (72%) were men. Upon ARDS diagnosis, 44% of patients were initially classified as having moderate ARDS, whereas 24% were classified as having mild ARDS and 32% were classified as having severe ARDS. The outcomes of these patients are shown in Table 1 . ICU and hospital lengths of stay were prolonged, and tracheostomy was performed in 30 (60%) patients. Hospital mortality was 34%. Table 2 shows the results for gas exchange, pulmonary mechanics, and variables associated with VILI upon ARDS diagnosis. Excluding baseline mechanical power, other MV parameters associated with VILI were within normal range. There was no correlation between Pa O 2 /FI O 2 and the static compliance of the respiratory system (Crs) ( Figure 1A) . Notwithstanding, a weak yet significant correlation was found between VR and both positive end-expiratory pressure and endinspiratory plateau pressure (Figures 1C and 1D) .However, D-dimer was not significantly correlated with VR ( Figure 1B) . Eleven patients underwent prone positioning on the day of ARDS diagnosis (see Table E1 in the online supplement). On average, Pa O 2 /FI O 2 increased from the supine to the prone position by 159 (IQR, 32-143; P = 0.002). Significant differences were also found in Crs between supine to prone position with an increase of 15.45 (IQR, 4.32-18.25; P = 0.015). SARS-CoV-2-induced ARDS produced an impairment in gas exchange and pulmonary mechanics comparable with those of prior cohorts with non-SARS-CoV-2 ARDS (10, 13, 17, 18) . As in other studies, VR was high, and the most frequent presentation was moderate ARDS (10, 17, 19) . On average, Crs in the cohort with SARS-CoV-2-induced ARDS was also found to be comparable, but with remarkable heterogeneity (13, 18) . Other studies have reported similar (20) , higher (21), or lower Crs (19, 22, 23) in SARS-CoV-2-induced ARDS. As Crs decreases alongside the collapse of alveolar units due to lung edema, several factors may provide explanations for such reported differences, including treatments, intubation strategies, and the stage of the disease. In our cohort with early SARS-CoV-2-induced ARDS, the time from ICU admission to intubation was only 24 hours, despite the use of high-flow nasal cannula or NIV in some cases. Mechanical power was calculated following previously published formulas (11) . x Crs is the ratio of tidal volume to driving pressure. Definition of abbreviations: APACHE II = Acute Physiology and Chronic Health Evaluation II; ARDS = acute respiratory distress syndrome; BMI = body mass index; ICU = intensive care unit; IQR = interquartile range; NIV = noninvasive ventilation; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SOFA = sequential organ failure assessment. *Missing data from nine patients. † Missing data from four patients. ‡ Laboratory findings upon ARDS diagnosis. x Six patients were still in the hospital after follow-up ending. We found no correlation between Crs and Pa O 2 /FI O 2 . Crs estimates the amount of aerated lung volume in ARDS (7) . These results might therefore suggest that the proportion of nonaerated or poorly aerated to well-aerated lung volume is not the only determinant for such a degree of hypoxemia. This may not be specific to SARS-CoV-2-induced ARDS, as other factors apart from the amount of aerated lung tissue (i.e., lung perfusion) are largely known to influence pulmonary shunt (24) . However, some authors have reported that lung perfusion in SARS-CoV-2-induced ARDS is more impaired than ARDS by other causes (21) . We identified remarkable abnormal lung perfusion in computed tomographic scans performed in these patients ( Figure E1 ). We found no correlation between D-dimer and VR, suggesting that high VD/VT might not be related to a coagulation disorder (i.e., pulmonary microthrombosis). Nonetheless, as suggested by its association with VR, high end-inspiratory and end-expiratory pressures (i.e., mean airway pressures) could increase VD/VT if the lung is overdistended and perfusion is decreased. Although driving pressure and end-inspiratory plateau pressure were within the protective range, mechanical power was found to be slightly high and might have promoted lung injury (25) . In patients undergoing prone positioning, Pa O 2 /FI O 2 improvement was followed by an increase in Crs, suggesting recruitment and aeration of previously collapsed alveoli. In our study, mortality was similar to that reported in other studies of critically ill patients with SARS-CoV-2 pneumonia (3, 19) . This study presents some limitations. Four manual endinspiratory and end-expiratory pauses could not be performed in all patients because of protective equipment shortages. However, all patients included had at least one end-inspiratory and end-expiratory pause done on the first day. These results cannot be extrapolated to late SARS-CoV-2-induced ARDS. In summary, SARS-CoV-2-induced ARDS presents with an impairment in gas exchange and pulmonary mechanics comparable with those of prior ARDS cohorts. 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Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts Urban-rural disparities in life expectancy in the United States have been widely documented, and this gap appears to be widening (1, 2). Published studies have shown that rural Americans are more likely to die of a range of cardiopulmonary diseases because of poor access to specialty care (2, 3) . To date, there remains a paucity of similar data in the populations of patients with pulmonary hypertension (PH)-an often overlooked cause of morbidity and mortality in many cardiopulmonary disorders. Here, we examined urban-rural disparities in all-cause mortality in a nationally representative cohort of patients with PH in the United States. We performed a retrospective cohort study of nonelderly adults with PH (18-64 yr old) drawn from a commercial health insurance/ Medicare Advantage database (years 2000-2011), including enrollees across all 50 states of the United States. The database comprises