key: cord-254287-8q2gdy5n
authors: Azoulay, Elie; de Waele, Jan; Ferrer, Ricard; Staudinger, Thomas; Borkowska, Marta; Povoa, Pedro; Iliopoulou, Katerina; Artigas, Antonio; Schaller, Stefan J.; Shankar-Hari, Manu; Pellegrini, Mariangela; Darmon, Michael; Kesecioglu, Jozef; Cecconi, Maurizio
title: International variation in the management of severe COVID-19 patients
date: 2020-08-05
journal: Crit Care
DOI: 10.1186/s13054-020-03194-w
sha: 
doc_id: 254287
cord_uid: 8q2gdy5n

BACKGROUND: There is little evidence to support the management of severe COVID-19 patients. METHODS: To document this variation in practices, we performed an online survey (April 30–May 25, 2020) on behalf of the European Society of Intensive Care Medicine (ESICM). A case vignette was sent to ESICM members. Questions investigated practices for a previously healthy 39-year-old patient presenting with severe hypoxemia from COVID-19 infection. RESULTS: A total of 1132 ICU specialists (response rate 20%) from 85 countries (12 regions) responded to the survey. The survey provides information on the heterogeneity in patient’s management, more particularly regarding the timing of ICU admission, the first line oxygenation strategy, optimization of management, and ventilatory settings in case of refractory hypoxemia. Practices related to antibacterial, antiviral, and anti-inflammatory therapies are also investigated. CONCLUSIONS: There are important practice variations in the management of severe COVID-19 patients, including differences at regional and individual levels. Large outcome studies based on multinational registries are warranted.

There is little evidence to support the optimal management of severe COVID-19 patients [1, 2] . To document whether there is a variation in practices, we performed an online survey (April 30-May 25, 2020) on behalf of ESICM.

In this online survey, a case vignette (https://www.surveymonkey.com/r/F2FFC6S) was sent to ICU specialists who are members of ESICM. Questions investigated practices for a previously healthy 39-year-old patient presenting with severe hypoxemia from COVID-19 infection ( Table 1 ). The 85 participating countries were grouped into 12 different regions [3] : continuous variables are described as median (interquartile range [IQR] ) and are compared between groups using the non-parametric Wilcoxon rank-sum test. Categorical variables are described as frequency (percentages) and are compared between groups using Fisher's exact test. Statistical analyses were performed with R statistical software, version 3.4.3 (available online at http://www.rproject.org/). A p value < 0.05 was considered significant.

Response rate was 20% (N = 1132 intensive care (ICU) specialists from 85 countries, including 1001 complete answers). Respondents (median 45 years [IQR, 39-53], 34% women) were from Middle Europe (25%), South Europe (23%), the United Kingdom (UK) (12%), South America (9%), North Europe (8.1%), Eastern Europe (5.3%), Middle-East (5%), North America (4.7%), Asia (3.3%), India (2.7%), Australia-New Zealand (1.3%), or Africa (0.6%); 54% were living in a large city (> 1 million inhabitants), and 55% were working in university-affiliated hospitals. The median (IQR) number of ICU beds was increased from 20 (11-36) to 35 (20-60) during the pandemic surge. As the patient had 88 (peripheral oxygen saturation) SpO 2 on 9 l/min of oxygen, direct ICU admission was reported in 56% (30-90%) of the respondents, with significant variation across regions ( Fig. 1, P < 0 Respondents were then asked about the first-line oxygenation strategy, which varied significantly across regions (Fig. 2, P < 0.0001) . First-line high flow nasal cannula (HFNC) was used by 22.9% of the respondents (0% in Australia-New Zealand, 38% in Eastern Europe). Noninvasive ventilation was used by 25.5% of the respondents (5.4% in North America, 43.6% in the UK). Interestingly, 8% of the respondents were using first-line intubation (0% in Australia-New Zealand, 23% in Asia). Women less frequently initiated HFNC (32% vs. 42%, P = 0.02). The availability of an intermediate care unit influenced the use of HFNC or non-invasive ventilation (NIV) (32.8% vs. 21.7%, P = 0.03). Along this line, a higher number of ICU beds (24 (12-40) vs. 18 (10-30) beds, P = 0.0009) was associated with the use of HFNC and NIV. Interestingly, 37.5% were using prone positioning in awake nonventilated patients. To assess whether HFNC or NIV should be continued, ICU specialists relied on SpO 2 (85.7%), respiratory rate (71.4%), followed by dyspnea (47.1%), and comfort (45.4%). Criteria for intubation included clinical signs of respiratory distress (94%), high oxygen flow to maintain a SpO 2 of 95% (33.5%), or low SpO 2 only (25.6%). Following intubation, the patient had a partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio of 84 mmHg. Although prone positioning (71.2%) and neuromuscular blockade (59.7%) were often used to optimize oxygenation, the practice varied significantly across countries. For instance, prone positioning was performed in 70-85% of the cases in Asia, India, Eastern Europe, Middle Europe, South America, South Europe, and the UK, whereas Africa, Australia-New Zealand, Middle East, North America, and Scandinavia were in the 50-70% range (Fig. 3, P < 0 Antibiotic prescribing was routine for all patients in 44.2% of the respondents and biomarker-guided in 36.5%, without significant variation across regions. Routine antibiotics were more frequently used by respondents working in university-affiliated hospitals (48.3% vs. 40.9%, P = 0.03) and those living in large cities (49.3% vs. 40.2%, P = 0.01). Biomarker-guided antibiotic therapy was less frequent in large cities (47.3% vs. 57.4%, P = 0.007). Regarding antiviral therapy, 48.9% reported not prescribing antivirals, 42.6% were giving hydroxychloroquine, 17% lopinavir-ritonavir, and 15% remdesivir. Figure 4 displays significant variation in antiviral prescriptions across regions (P < 0.0001 women (41.7% vs. 28.2%, P < 0.0001). There was significant variation in the use of interleukin-6 (IL-6)/IL-1 blockade or of corticosteroids across countries (P < 0.0001 for both tests). Other collected variables were not associated with the use of antiinflammatory drugs.

This survey highlights important practice variations in the management of severe COVID-19 patients, including differences at regional and individual levels. This illustrates that neither IDSA nor Surviving Sepsis Guidelines did recommend any of these treatments, but instead encouraged inclusion of patients into trials [1, 4, 5] . Since the publication of these guidelines, no more evidence has been made available to ascertain that these specific COVID-19 therapies should be included in the standard of care. Learning from this heterogeneity will not only raise hypothesis on optimal patient's management, but also serves as a tool to suggest personalized management for each clinical phenotype [6, 7] . This study has several limitations. First, the study suffers from a nonresponse bias of 80%. Second, even though only physicians have responded, we cannot ascertain that all of them had the clinical expertise and the experience of managing COVID-19 patients. Last, questions about specific treatments did not take into account the fact that the level of evidence has changed over time.

As no management guidelines have allowed to guide practices for the COVID-19 pandemic, heterogeneous behaviors are reported. Large 

Charité -Universitätsmedizin Berlin, corporate member of Freie References

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19)

Randomized clinical trials and COVID-19: managing expectations

Changes in end-of-life practices in European intensive care units from 1999 to 2016

Infectious diseases Society of America guidelines on the treatment and management of patients with COVID-19

Managing ICU surge during the COVID-19 crisis: rapid guidelines

Prothrombotic phenotype in COVID-19 severe patients

Clinical phenotypes of critically ill COVID-19 patients

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

We are indebted to Dominique de Boom, Nicolas Vander Elst, and Guy Francois from the ESICM office for their fast and high-quality support to prepare this survey and its diffusion.

All authors contributed to the design, the development of the instrument, and interpretation of data. All authors have approved the submitted manuscript.

Availability of data and materials Fully available upon request.Ethics approval and consent to participate All participants agreed online to complete the survey.

All participants consented.

The authors declare no conflict of interest in relation to this survey.