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      German recommendations for critically ill patients with COVID‑19 Translated title: Empfehlungen zur intensivmedizinischen Therapie von Patienten mit COVID‑19


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          Since December 2019, a novel coronavirus (severe acute respiratory syndrome—coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The majority of patients presents with mild symptoms of coronavirus disease 2019 (COVID-19). However, about 5% become critically ill and require intensive care treatment. Acute hypoxemic failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to ICU admission. At that point, bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS). To date there is no specific treatment available—the main goal of supportive therapy is to ascertain adequate oxygenation. Early intubation and repeated prone positioning are key elements in treating hypoxemic COVID-19 patients. Strict adherence to basic infection control measures (including hand hygiene) and use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be avoided where possible and carried out with utmost precaution.

          Translated abstract

          Seit Dezember 2019 verbreitet sich das neuartige Coronavirus SARS-CoV‑2 (Severe Acute Respiratory Syndrome – Corona Virus-2) rasch im Sinne einer weltweiten Pandemie. Dies stellt Kliniker und Krankenhäuser vor große Herausforderungen und belastet die Gesundheitssysteme vieler Länder in einem nie dagewesenen Maß.

          Die Mehrheit der Patienten zeigt lediglich milde Symptome der sogenannten Coronavirus Disease 2019 (COVID-19). Dennoch benötigen etwa 5 % eine intensivmedizinische Behandlung. Die akute hypoxämische respiratorische Insuffizienz mit Dyspnoe und hoher Atemfrequenz (>30/min) führt in der Regel zur Aufnahme auf die Intensivstation. Oft finden sich dann bereits bilaterale pulmonale Infiltrate in der Bildgebung und im Verlauf entwickeln viele Patienten ein Acute Respiratory Distress Syndrome (ARDS).

          Bisher gibt es noch keine zugelassene spezifische Therapieoption. Das Hauptziel der supportiven Therapie ist, eine ausreichende Oxygenierung sicherzustellen. Die frühe Intubation und wiederholte Bauchlagerung sind dabei wichtige Elemente in der Behandlung von hypoxämischen COVID-19 Patienten.

          Die strikte Einhaltung der Basishygiene, einschließlich der Händehygiene, sowie das korrekte Tragen von adäquater persönlicher Schutzausrüstung ist im Umgang mit den Patienten unabdingbar. Prozeduren, die zur Aerosolbildung führen könnten, sollten, soweit möglich, vermieden, und, falls nötig, mit äußerster Sorgfalt und Vorbereitung durchgeführt werden.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Critical care crisis and some recommendations during the COVID-19 epidemic in China

            Since December 2019, a severe acute respiratory infection (SARI) caused by 2019 novel coronavirus (SARS-CoV-2), began to spread from Wuhan to all of China [1, 2], and indeed the world. As of Feb 10, 2020, there are more than 40,000 confirmed cases and > 1000 deaths in China. Lack of critical care resource in face of COVID-19 epidemics Based on data reported by the National Health Commission of China, there have been about 2000 new confirmed cases and > 4000 suspected cases daily over the past week in Wuhan [3]. About 15% of the patients have developed severe pneumonia, and about 6% need noninvasive or invasive ventilatory support. Currently, there are about 1000 patients who need ventilatory support and another 120 new patients daily who require noninvasive or invasive ventilation support in Wuhan city; however, there are only about 600 ICU beds [4]. To address this shortfall, 70 ICU beds were created from general beds and the government quickly transformed three general hospitals to critical care hospitals with a total of about 2500 beds that specialize in patients with severe SARS-CoV-2 pneumonia (equipped with monitors and high-flow nasal cannula, noninvasive ventilator or invasive ventilators). An equally great (or potentially greater) problem is the shortage of trained personnel to treat these critically ill patients. Until the crisis, there were about 300 ICU physicians and 1000 ICU nurses in Wuhan city. By the end of January, more than 600 additional ICU doctors and 1500 ICU nurses were transferred to Wuhan from the rest of China. As well, an additional 3000 staff including infectious disease, respiratory, internal medicine physicians and nurses were transferred to Wuhan by the government. There are logistical issues which make care of the patients difficult. These include donning of personal protective equipment (e.g., gloves, gowns, respiratory and eye protection), lack of instruments and disposables, and shortages of supplemental oxygen. Many severe hypoxemic patients only receive high-flow nasal oxygen (HFNO) or noninvasive mechanical ventilation rather than invasive mechanical ventilation because of intubation delay or lack of mechanical ventilators (especially at early phase). Our preliminary data show that only about 25% of patients who died were intubated and received mechanical ventilation. Recommendations It’s not possible at this stage to create new equipment or personnel. However, it would be very helpful to have mathematical models developed which predict the expected number of patients, and the necessary resources (equipment and personnel) required to treat these patients. This would aid in determining what resources might be moved to Wuhan to help local health care personnel. Challenge of early recognition and treatment of critical SARI patients Several previous reports have described the characteristics of SARS-CoV-2 infected patients [2, 5, 6]. Most patients are > 50 years of age; the mean age is much older than patients infected with H1N1 or with Middle East respiratory syndrome (MERS) [7–9]. About 30 to 50% of COVID-19 patients have chronic comorbidities. The duration from the initial symptom to respiratory failure in most patients is > 7 days, which is longer than H1N1 [7, 8]. Additionally, many patients that go on to develop respiratory failure had hypoxemia but without signs of respiratory distress, especially in the elderly patients (“silent hypoxemia”). Moreover, only a very small proportion of patients have other organ dysfunction (e.g., shock, acute kidney injury) prior to developing respiratory failure. These characteristics suggest that traditional methods such as quick sequential organ failure assessment (qSOFA) score and the new early warning score (NEWS) may not help predict those patients who will go on to develop respiratory failure. Therefore, it is urgent to establish a prediction or early recognition model of patients likely to fail. Although the novel coronavirus was quickly isolated and sequenced [10], there are no proven, effective drugs to treat COVID-19. Based on in vitro screening studies, several drugs were found to inhibit the virus [11]. One case report demonstrated a surprising effect of remdesivir for SARS-CoV-2 infection [12]; however, the clinical impact remains unclear. Encouragingly, several clinical trials are undergoing (ChiCTR2000029308, NCT04252664 and NCT04257656) to determine the effect of lopinavir/ritonavir or remdesivir. We have also tried Traditional Chinese Medicine such as Xuebijing, and several clinical trials are ongoing in this regard. Recommendations Identifying a biomarker(s) that predicts severity and outcome in COVID-19 patients early in the presentation would be extremely helpful. Our data (unpublished) demonstrate that severe lymphopenia and high levels of C-reactive protein correlated with the severity of hypoxemia and predicted hospital mortality. In addition, the change of lymphocyte counts during the first 4 days after hospital admission was highly associated with mortality. Crisis in management of SARI in the ICU The mortality rate of SARI is highest (4%) in Wuhan city, followed by other cities in Hubei province (1.4%) and other provinces (0.25%) [3]. The higher morality in Wuhan may due to the limited resources, but we are uncertain whether patients are sicker in Wuhan than in other cities. Understanding the characteristics of the dead patients would help in triaging patients and allocating resources. We analyzed data of 135 patients who died before Jan 30, 2019, in Wuhan city. Older age and male were common in non-surviving patients. More than 70% patients had one or more comorbidities. Hypertension (48.2%) was the most common comorbidity in non-surviving patients, followed by diabetes (26.7%) and ischemic heart disease (17.0%), similar to data reported by others [5, 6]. Importantly, as stated above, of the patients who died only ~ 25% received invasive mechanical ventilation or ECMO. The median duration of HFNO and/or NIV was 6(4–8) days before intubation or death. The mortality of patients who received ECMO is high: of 28 patients who received ECMO up to the present, 14 died, 5 weaned successfully, and 9 are still on ECMO. Lack of ventilators, fear of becoming infected during the intubation procedure, and unclear need for intubation were the main reasons for delaying invasive ventilation. Compliance with lung protective ventilation strategy is also low in some centers, with some patients receiving tidal volumes > 8 ml/kg PBW and with high driving pressures. Sedation and paralysis strategies are also not standardized. Lack of intensivists may be a potential cause. Fortunately, we found a significant benefit of prone position in most severe ARDS patients. Recommendations There should be a focus on high-risk patients, e.g., male, > 60 years old, and patients with comorbidities. Additionally, a standard protocol for SARS-CoV-2 infection recommended by World Health Organization should be widely implemented [13]. It is crucial that our staff is trained to employ standard protocols for management, which may help implement evidence-based ventilatory and general ICU care in the face of an overwhelming workload. More importantly, in the context of a multidisciplinary team, intensivists should act as leaders, ensuring that severe patients receive standardized treatment (Fig. 1). Fig. 1 Some recommendations to face the critical care crisis due to the COVID-19 epidemic In summary, the COVID-19 epidemic has placed a huge burden on the Chinese health care system. This crisis has dramatically affected the delivery of critical care due to a lack of resources, lack of prediction models and of course the lack of effective pharmacotherapies. Front line critical care clinicians desperately require these tools.
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              Severe SARS-CoV-2 infections: practical considerations and management strategy for intensivists

              On December 31, 2019, China reported cases of respiratory illness in humans appearing first in Wuhan, Hubei Province, that involved a novel coronavirus SARS-CoV-2 (aka 2019-nCoV). This new emergency is a zoonotic disease with unknown animal reservoir and with evidence of person-to-person transmission [1]. The basic reproductive number of this infection is estimated to be 2.2 (95% CI, 1.4–3.9) [2]. Etiological agent and epidemiology The new agent causing this pneumonia, a coronavirus (SARS-CoV-2), was identified and sequenced [3] and diagnostic tests were developed [4]. On January 30, 2020, the World Health Organization issued a worldwide public health alert on the emergence of a new epidemic viral disease. On February 3, 2020, 17,391 confirmed cases (153 cases outside of China) have been reported (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/). The overall mortality rate of affected patients is difficult to assess at this time, because of the lack of a reliable denominator. Severe forms represent 14% of the reported cases, and the overall mortality is around 2% of the confirmed cases. To date, 153 cases have been reported in 23 countries outside China (overall, 24 cases in Europe), most of them being imported cases: tourists coming from China, or China-originating persons returning to their country of residence after traveling to visit family in Wuhan or other Chinese regions. In Europe, at least three cases in Germany and one case in France involved patients with no history of travel to China. The German case occurred after exposure to an asymptomatic contact coming from China [5]. Clinical features To date, the ECDC criteria to require diagnostic testing for suspected cases are patients with acute respiratory infection (requiring hospitalization or not) in the 14 days prior to the onset of symptoms with at least one of the following epidemiological criteria being present: close contact with a confirmed or probable case of SARS-CoV-2 infection (COrona VIrus Disease 2019, COVID-19) (or) history of travel to China (or) having worked in or having attended a health care facility where patients with SARS-CoV-2 infections were being treated (https://www.ecdc.europa.eu/en/case-definition-and-european-surveillance-human-infection-novel-coronavirus-2019-ncov). Incubation period and clinical description The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1–7.0), with the 95th percentile of the distribution at 12.5 days [2]. Early signs included non-specific influenza-like symptoms [6]. Data from a series of 99 Chinese patients with COVID-19 pneumonia, diagnosed in all patients by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), have already been published. Three patients out of four received oxygen therapy, 13% had non-invasive ventilation and 4% invasive ventilation, 9% required renal replacement therapy and 3% extracorporeal membrane oxygenation. According to the authors, 11% of these hospitalized patients worsened within a short period of time and died of multiple organ failure [6]. Although these preliminary data are insufficient to draw a clinical overview of the patients affected with this viral respiratory illness novel to humans, it is obvious that COVID-19 could cause severe respiratory failure requiring ICU admission. The first experiences of our Chinese colleagues are described in this journal [7]. Four cases have already been admitted in Bichat-Claude Bernard reference hospital in Paris, including 2 cases in the medical ICU. Clinical presentation based on our experience and available data are depicted on Fig. 1. Fig. 1 Global picture of severe cases Management There are several challenges that intensivists have to face when caring for a patient suspected of infection with an emerging pathogen such as SARS-CoV-2, both in terms of management of the patient, particularly regarding laboratory tests and diagnostic radiologic procedures, and of healthcare workers’ protection and unit organization. Based on previous outbreaks due to emerging coronavirus, MERS and SARS, droplets are likely the major mode of transmission. Transmission from contaminated fomites close to the infected patient is also possible. Airborne transmission has been suspected, especially during invasive respiratory procedures. Personal protective equipment should, therefore, protect from droplets, contact and airborne transmission (see supplemental dress and undress procedures associated with photos and videos). The survival time of coronavirus on dry surfaces is no longer than 4 h, requiring regular environmental cleaning. A coordinated and multidisciplinary management between ICU, infectious diseases (ID) and infection control specialists, and also the institution, is of paramount importance. A trained supervisor is critical to ensure safe practices and reassure the ICU team. Patient management Decision of ICU admission and discharge should be discussed daily in closed collaboration with ID physicians. If COVID-19 is suspected, the patient must be placed in a single room and all principles of infection prevention and control (IPC) should be taken as for confirmed cases (eSupplement Table 1). Diagnostic testing, if not already performed at patient admission, is the first task for intensivists. Etiologic diagnosis relies on rRT-PCR assays. Specimens from upper and if possible lower respiratory tracts should be collected (lower respiratory specimens likely have a higher diagnostic value). Upper respiratory tract specimens are obtained through nasopharyngeal swab, oropharyngeal swab, or nasopharyngeal aspirate or nasal wash. As per the lower respiratory tract samples, a bronchoalveolar lavage (BAL) fluid specimen is possible but it is not recommended due to the high risk that bronchoscopy poses to ICU staff. Plugged telescopic catheter specimen with or without mini-BAL, endotracheal aspirate, or expectorated sputum should be preferred. Additional specimens of blood, urine and feces and any other site if appropriate could be considered for delayed testing. Based on the previous experiences on MERS, if the initial testing is negative in a patient who is strongly suspected to have SARS-CoV-2 infection, it is recommended to perform a repeated test (multiple respiratory tract sites including nose, sputum, and endotracheal aspirate) (https://www.ecdc.europa.eu/sites/default/files/documents/nove-coronavirus-infection-prevention-control-patients-healthcare-settings.pdf). Viral shedding may vary with time; therefore, repeated sampling is recommended for confirmed cases. The prognostic value of the evolution of viral shedding is still unknown. The initial diagnosis testing should include a search for other respiratory pathogens, including blood cultures, sputum culture, providing that specimens are handled according to biosafety practices. Point-of-care testing is useful to quicken biological surveillance, but a limited number of tests are available. When cultures can not be performed because of biosafety issues, multiplex PCR is instrumental for bacterial infections identification. Bronchoscopy is acceptable, but it should be discussed when concerns regarding other diagnoses are high. There are no reasons to limit care intensity for patients infected with SARS-CoV-2. However, procedures ranging from bronchoscopy to extracorporeal membrane oxygenation, to transporting patient outside the ICU or to surgery, should be discussed collectively on a case-by-case basis. Apart from the vital emergency, these procedures should be anticipated. Infection prevention and control (IPC) An important component of IPC is staff education and preparation. IPC strategies have been adapted from IPC for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV), and they are likely to evolve rapidly as new information is collected. Patient should be ideally placed in a negative pressure isolation room. Healthcare staff should use contact, airborne and droplet precautions (see ESM). In the event of a massive influx of patients, the preventive measures will have to be degraded. Without a doubt, the most important component of personal protective equipment is wearing a fit-tested FFP2 (or equivalent) face mask (see ESM). Treatment If the diagnosis is uncertain or if a co-infection is suspected, empirical therapy for community-acquired pneumonia should be considered, using antibiotics with activity against both typical and atypical respiratory pathogens. In ARDS patients, superinfection is often associated with shock and multiple organ failure. Etiologic agents vary with the patients’ country of origin but uncommon pathogens such as Acinetobacter baumannii and Aspergillus fumigatus have been collected [6]. There is no effective disease-specific treatment or vaccine. However, experimental drugs and drug combinations such as remdesivir, lopinavir–ritonavir, or lopinavir–ritonavir and interferon Beta-1b are under investigation and may be considered for compassionate use in severely ill patients [8]. It has been shown that remdesivir and interferon Beta-1b have superior antiviral activity to LPV and RTV in vitro [8]. In view of the high amount of cytokines induced by SARS-CoV, MERS-CoV and SARS-CoV-2 infections [9], corticosteroids were frequently used for the treatment of patients with severe illness, the reduction of the inflammatory-induced lung injury being the expected benefit. However, current evidence suggests that corticosteroids did not have an effect on mortality, but rather delayed viral clearance [10]. Moreover, the increase in the viral load and viremia argue against their use. Therefore, systemic corticosteroids should not be given routinely, according to WHO interim guidance. Discharge to the isolation room Discharge from the ICU to an isolation room in the ward has no specificity compared to another patient admitted to the ICU. According to the World Health Organization, more comprehensive information about the mode of transmission of the SARS-CoV-2 infection is required to define the duration of the precautions set-up. Electronic supplementary material Below is the link to the electronic supplementary material. Supplementary material 1 (DOCX 1659 kb) Supplementary material 2 (MOV 458965 kb)

                Author and article information

                Med Klin Intensivmed Notfmed
                Med Klin Intensivmed Notfmed
                Medizinische Klinik, Intensivmedizin Und Notfallmedizin
                Springer Medizin (Heidelberg )
                14 April 2020
                : 1-4
                [1 ]German Society of Medical Intensive Care and Emergency Medicine (Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin [DGIIN]), Berlin, Germany
                [2 ]GRID grid.491773.f, German Interdisciplinary Association of Critical Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin [DIVI]), ; Berlin, Germany
                [3 ]GRID grid.489525.7, ISNI 0000 0000 9320 5144, German Respiratory Society (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin [DGP]), ; Berlin, Germany
                [4 ]GRID grid.491767.a, ISNI 0000 0001 1091 8411, German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin [DGAI]), ; Nürnberg, Germany
                [5 ]ARDS Network Germany, Berlin, Germany
                [6 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Department of Intensive Care, , University Medical Center Hamburg-Eppendorf, ; Martinistr. 52, 20246 Hamburg, Germany
                © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                covid-19,coronavirus,acute respiratory failure,ards,high-flow nasal cannula,akute respiratorische insuffizienz,high-flow-sauerstofftherapie


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