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      Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome

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          Abstract

          Background

          In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)–almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients.

          Methods

          We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 μg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO–almitrine combination. The primary endpoint was the variation of oxygenation (PaO 2/FiO 2 ratio).

          Results

          Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52–72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO 2/FiO 2 ratio varied from 102 [89–134] mmHg at baseline, to 124 [108–146] mmHg after iNO ( p = 0.13) and 180 [132–206] mmHg after iNO and almitrine ( p < 0.01). We found no correlation between the increase in oxygenation caused by iNO–almitrine combination and that caused by proning.

          Conclusion

          In this pilot study of severe C-ARDS patients, iNO–almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.

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          Most cited references22

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.

            To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert the score to a probability of hospital mortality. The SAPS II and the probability of hospital mortality were developed and validated using data from consecutive admissions to 137 adult medical and/or surgical intensive care units in 12 countries. The 13,152 patients were randomly divided into developmental (65%) and validation (35%) samples. Patients younger than 18 years, burn patients, coronary care patients, and cardiac surgery patients were excluded. Vital status at hospital discharge. The SAPS II includes only 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated that the model performed well in the developmental sample and validated well in an independent sample of patients (P = .883 and P = .104 in the developmental and validation samples, respectively). The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample. The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis. This is a starting point for future evaluation of the efficiency of intensive care units.
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              Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

              Summary Background Over 40 000 patients with COVID-19 have been hospitalised in New York City (NY, USA) as of April 28, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. Methods This prospective observational cohort study took place at two NewYork-Presbyterian hospitals affiliated with Columbia University Irving Medical Center in northern Manhattan. We prospectively identified adult patients (aged ≥18 years) admitted to both hospitals from March 2 to April 1, 2020, who were diagnosed with laboratory-confirmed COVID-19 and were critically ill with acute hypoxaemic respiratory failure, and collected clinical, biomarker, and treatment data. The primary outcome was the rate of in-hospital death. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal replacement therapy, and time to in-hospital clinical deterioration following admission. The relation between clinical risk factors, biomarkers, and in-hospital mortality was modelled using Cox proportional hazards regression. Follow-up time was right-censored on April 28, 2020 so that each patient had at least 28 days of observation. Findings Between March 2 and April 1, 2020, 1150 adults were admitted to both hospitals with laboratory-confirmed COVID-19, of which 257 (22%) were critically ill. The median age of patients was 62 years (IQR 51–72), 171 (67%) were men. 212 (82%) patients had at least one chronic illness, the most common of which were hypertension (162 [63%]) and diabetes (92 [36%]). 119 (46%) patients had obesity. As of April 28, 2020, 101 (39%) patients had died and 94 (37%) remained hospitalised. 203 (79%) patients received invasive mechanical ventilation for a median of 18 days (IQR 9–28), 170 (66%) of 257 patients received vasopressors and 79 (31%) received renal replacement therapy. The median time to in-hospital deterioration was 3 days (IQR 1–6). In the multivariable Cox model, older age (adjusted hazard ratio [aHR] 1·31 [1·09–1·57] per 10-year increase), chronic cardiac disease (aHR 1·76 [1·08–2·86]), chronic pulmonary disease (aHR 2·94 [1·48–5·84]), higher concentrations of interleukin-6 (aHR 1·11 [95%CI 1·02–1·20] per decile increase), and higher concentrations of D-dimer (aHR 1·10 [1·01–1·19] per decile increase) were independently associated with in-hospital mortality. Interpretation Critical illness among patients hospitalised with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extrapulmonary organ dysfunction, and substantial in-hospital mortality. Funding National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health, and the Columbia University Irving Institute for Clinical and Translational Research.
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                Author and article information

                Contributors
                armand.dessap@aphp.fr
                Journal
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                2110-5820
                4 November 2020
                4 November 2020
                2020
                : 10
                : 151
                Affiliations
                [1 ]GRID grid.412116.1, ISNI 0000 0001 2292 1474, AP-HP, Hôpitaux Universitaires Henri-Mondor, Service de Médecine Intensive Réanimation, ; 51, avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France
                [2 ]Univ Paris Est Créteil, CARMAS, 94010 Créteil, France
                [3 ]UFR de Médecine Villemin, Université Paris 7 Paris Cité Sorbonne, Paris, France
                [4 ]GRID grid.462410.5, ISNI 0000 0004 0386 3258, Univ Paris Est Créteil, INSERM, IMRB, ; 94 010 Créteil, France
                Author information
                http://orcid.org/0000-0002-3391-0807
                Article
                769
                10.1186/s13613-020-00769-2
                7641257
                33150525
                b4ebc6b9-ad10-4b91-8a53-f2a1d9c7a58d
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 June 2020
                : 24 October 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Emergency medicine & Trauma
                ino,almitrine,covid-19,ards
                Emergency medicine & Trauma
                ino, almitrine, covid-19, ards

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