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      Treatment for severe acute respiratory distress syndrome from COVID-19

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          Abstract

          In The Lancet Respiratory Medicine, Kollengode Ramanathan and colleagues 1 provide excellent recommendations for the use of extracorporeal membrane oxygenation (ECMO) for patients with respiratory failure from acute respiratory distress syndrome (ARDS) secondary to coronavirus disease 2019 (COVID-19). The authors describe pragmatic approaches to the challenges of delivering ECMO to patients with COVID-19, including training health-care personnel, resolving equipment and facilities issues, implementing systems for infection control and personal protection, providing overall support for health-care staff, and mitigating ethical issues. They also address some of the anticipated challenges with local and regional surges in COVID-19 ARDS cases; although there has been an increase in hospitals with the capacity to provide ECMO, the potential demand might exceed the available resources. Furthermore, some health-care systems offer advanced therapies such as ECMO but lack a coordinated local, regional, or national referral protocol. Given the practical constraints on substantially increasing the global availability of ECMO services in the next few months, it is important to emphasise the other evidence-based treatment options that can be provided for patients with severe ARDS from COVID-19 (figure ). 2 Before endotracheal intubation, it is important to consider a trial of high-flow nasal oxygen for patients with moderately severe hypoxaemia. This procedure might avoid the need for intubation and mechanical ventilation because it provides high concentrations of humidified oxygen, low levels of positive end-expiratory pressure, and can facilitate the elimination of carbon dioxide. 4 WHO guidelines support the use of high-flow nasal oxygen in some patients, but they urge close monitoring for clinical deterioration that could result in the need for emergent intubations because such procedures might increase the risk of infection to health-care workers. 5 Figure Therapeutic options for severe acute respiratory distress syndrome related to coronavirus disease 2019 ppm=parts per million. For patients with COVID-19 who require endotracheal intubation, use of low tidal volume (6 mL/kg per predicted bodyweight) with a plateau airway pressure of less than 30 cm H2O, and increasing the respiratory rate to 35 breaths per min as needed, is the mainstay of lung-protective ventilation. If the hypoxaemia progresses to a PaO2:FiO2 ratio of less than 100–150 mm Hg, there are several therapeutic options. The level of positive end-expiratory pressure can be increased by 2–3 cm H2O every 15–30 min to improve oxygen saturation to 88–90%, with the goal of maintaining a plateau airway pressure of less than 30 cm H2O. Lower driving pressures (plateau airway pressure minus positive end-expiratory pressure) with a target of 13–15 cm H2O can also be used. If the patient is not responding to adjustment of the level of positive end-expiratory pressure, additional strategies might stabilise them. Recruitment manoeuvres probably have little value, 6 but moderate pressures of approximately 30 cm H2O for 20–30 s can be applied in the presence of a physician to monitor haemodynamics. If there is no improvement in oxygenation or driving pressure, or if the patient develops hypotension or barotrauma, the recruitment manoeuvres should be discontinued. If there is considerable dyssynchrony with positive pressure ventilation, accompanied by increased plateau airway pressures and refractory hypoxaemia, then deep sedation should be used followed by prompt institution of neuromuscular blockade with cisatracurium. Additionally, prone positioning should be instituted, unless there is a specific contraindication, and can be initiated along with the interventions already described. For persistent refractory hypoxaemia even with prone positioning, neuromuscular blockade, and efforts to optimise positive end-expiratory pressure therapy, there are additional options. Inhaled 5–20 ppm NO might improve oxygenation. Insertion of an oesophageal balloon to measure transpulmonary pressures to set an optimal positive end-expiratory pressure can be considered in patients with moderate-to-severe obesity, although a 2019 trial in patients with ARDS did not show the benefit of this procedure in most patients. 7 Fluid management is important to consider as a measure to reduce pulmonary oedema. 8 In the absence of shock, fluid conservative therapy is recommended to achieve a negative fluid balance of 0·5 to 1·0 L per day. In the presence of shock, fluid balance might be achieved with renal replacement therapy, especially if there is associated acute kidney injury and oliguria. Antibiotics should be considered since secondary bacterial infections have been reported in patients with COVID-19. 9 Glucocorticoids should be avoided in view of the evidence that they can be harmful in cases of viral pneumonia and ARDS from influenza. 10 Rescue therapy with high-dose vitamin C can also be considered. 11 Finally, ECMO should be considered using the inclusion and exclusion criteria of the EOLIA trial. 3 Since treatment of severe ARDS from COVID-19 is an ongoing challenge, it is important to learn from the patients who have been treated to gain an understanding of the disease's epidemiology, biological mechanisms, and the effects of new pharmacological interventions. Currently, there are some research groups working to coordinate and disseminate key information, including information on patients who have been treated with ECMO for COVID-19, although an accurate estimate of the number of such patients is not currently available. The Extracorporeal Life Support Organization is an international non-profit consortium that plans to maintain a registry of patients to facilitate an improved understanding of how ECMO is being used for patients with COVID-19.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases

            Summary WHO interim guidelines recommend offering extracorporeal membrane oxygenation (ECMO) to eligible patients with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The number of patients with COVID-19 infection who might develop severe ARDS that is refractory to maximal medical management and require this level of support is currently unknown. Available evidence from similar patient populations suggests that carefully selected patients with severe ARDS who do not benefit from conventional treatment might be successfully supported with venovenous ECMO. The need for ECMO is relatively low and its use is mostly restricted to specialised centres globally. Providing complex therapies such as ECMO during outbreaks of emerging infectious diseases has unique challenges. Careful planning, judicious resource allocation, and training of personnel to provide complex therapeutic interventions while adhering to strict infection control measures are all crucial components of an ECMO action plan. ECMO can be initiated in specialist centres, or patients can receive ECMO during transportation from a centre that is not specialised for this procedure to an expert ECMO centre. Ensuring that systems enable safe and coordinated movement of critically ill patients, staff, and equipment is important to improve ECMO access. ECMO preparedness for the COVID-19 pandemic is important in view of the high transmission rate of the virus and respiratory-related mortality.
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              Lung Recruitment and Titrated PEEP in Moderate to Severe ARDS

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                Author and article information

                Contributors
                Journal
                Lancet Respir Med
                Lancet Respir Med
                The Lancet. Respiratory Medicine
                Elsevier Ltd.
                2213-2600
                2213-2619
                20 March 2020
                20 March 2020
                :
                Affiliations
                [a ]Department of Medicine, Department of Anesthesia, The University of California, San Francisco, CA 94158, USA
                [b ]Cardiovascular Research Institute, The University of California, San Francisco, CA 94158, USA
                Article
                S2213-2600(20)30127-2
                10.1016/S2213-2600(20)30127-2
                7118607
                32203709
                22238177-8be0-46a5-88fb-a8aaad7b6fe1
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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