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Epidemiology, Ventilation Management, and Outcomes in Invasively Ventilated Coronavirus Disease 2019 Patients: An Analysis of Four Observational Studies in Four Countries on Two Continents
Siebe G. Blok
s.blok@amsterdamumc.nl
Siebe G. Blok
Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands;
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Luigi Pisani
Luigi Pisani
Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands;
Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand;
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Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand;
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Elisa Estenssoro
Elisa Estenssoro
Department of Intensive Care, Hospital Interzonal de Agudos General San Martin La Plata, Buenos Aires, Argentina;
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Juliana Carvalho Ferreira
Juliana Carvalho Ferreira
Department of Pulmonology, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil;
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Michela Botta
Michela Botta
Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands;
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Ana Motos
Ana Motos
Departement of Pulmonology, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain;
Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Institute of Health Carlos III, Madrid, Spain;
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Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Institute of Health Carlos III, Madrid, Spain;
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Ignacio Martin-Loeches
Ignacio Martin-Loeches
Department of Intensive Care, Multidisciplinary Intensive Care Research Organization (MICRO), St. James’ Hospital, Dublin, Ireland;
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Antoni Torres
Antoni Torres
Departement of Pulmonology, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain;
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Marcus J. Schultz
Marcus J. Schultz
Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands;
Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand;
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;
Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria;
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Frederique Paulus
Frederique Paulus
Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands;
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David M. P. van Meenen
David M. P. van Meenen
Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands;
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ABSTRACT.
Epidemiology, ventilator management, and outcomes in patients with acute respiratory distress syndrome (ARDS) because of coronavirus disease 2019 (COVID-19) have been described extensively but have never been compared between countries. We performed an individual patient data analysis of four observational studies to compare epidemiology, ventilator management, and outcomes. We used propensity score weighting to control for confounding factors. The analysis included 6,702 patients: 1,500 from Argentina, 844 from Brazil, 975 from the Netherlands, and 3,383 from Spain. There were substantial differences in baseline characteristics between countries. There were small differences in ventilation management. Intensive care unit mortality was higher in Argentina and Brazil compared with the Netherlands and Spain (59.6% and 56.6% versus 32.1% and 34.7%; P <0.001). The median number of days free from ventilation and alive at day 28 was equally low (0 [0–7], 0 [0–18], 1 [0–16], and 0 [0–16] days, respectively; P = 0.03), and the median number of days free from ventilation and alive at day 60 was higher in the Netherlands and Spain (0 [0–37], 0 [0–50], 33 [0–48], and 26 [0–48] days, respectively; P <0.001). Propensity score matching confirmed the outcome differences. Thus, the outcome of COVID-19 ARDS patients in Argentina and Brazil was substantially worse compared with that of patients in the Netherlands and Spain. It is unlikely that this results from differences in case mix or ventilation management.
- Supplemental Materials (PDF 671.36 KB)
Author Notes
Financial support: The authors report they did not obtain additional funding for this individual patient data meta-analysis.
Disclosures: The original studies were registered at clinicaltrials.gov (NCT04611269, NCT04378582, NCT04346342, and NCT04457505). The pooled dataset, named Practice of Ventilation in Patients with ARDS Due to COVID-19 versus Pneumonia, was also registered at clinicaltrials.gov (NCT05650957). The authors declare no conflicts of interest.
Current contact information: Siebe G. Blok and Michela Botta, Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands, E-mails: siebeblok@gmail.com and m.botta@amsterdamumc.nl. Luigi Pisani, Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands, and Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand, E-mail: luigipisani@gmail.com. Elisa Estenssoro, Department of Intensive Care, Hospital Interzonal de Agudos General San Martin La Plata, Buenos Aires, Argentina, E-mail: estenssoro.elisa@gmail.com. Juliana Carvalho Ferreira, Department of Pulmonology, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil, E-mail: juliana.ferreira@hc.fm.usp.br. Ana Motos and Antoni Torres, Departement of Pulmonology, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Barcelona, Spain, and Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CIBERES), Institute of Health Carlos III, Madrid, Spain, E-mails: amotos@recerca.clinic.cat and atorres@clinic.cat. Ignacio Martin-Loeches, Department of Intensive Care, Multidisciplinary Intensive Care Research Organization (MICRO), St. James’ Hospital, Dublin, Ireland, E-mail: imartinl@tcd.ie. Marcus J. Schultz, Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands, Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, and Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria, E-mail: marcus.j.schultz@gmail.com. Frederique Paulus, Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands, and Faculty of Health, ACHIEVE, Center of Applied Research, University of Applied Research, Amsterdam, The Netherlands, E-mail: f.paulus@amsterdamumc.nl. David M. P. van Meenen, Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, The Netherlands, and Department of Anesthesiology, Amsterdam University Medical Center, Amsterdam, The Netherlands, E-mail: d.m.vanmeenen@amsterdamumc.nl.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Sachs JD et al., 2022. The Lancet Commission on lessons for the future from the COVID-19 pandemic. Lancet 400: 1224–1280.
-
2.
Grasselli G, Pesenti A, Cecconi M, 2020. Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: Early experience and forecast during an emergency response. JAMA 323: 1545–1546.
-
3.
Phua J et al.; Asian Critical Care Clinical Trials Group, 2020. Intensive care management of coronavirus disease 2019 (COVID-19): Challenges and recommendations.Lancet Respir Med 8: 506–517.
-
4.
Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS; ARDS Definition Task Force, 2012. Acute respiratory distress syndrome: The Berlin definition. JAMA 307: 2526–2533.
-
5.
Botta M et al.; PRoVENT-COVID Collaborative Group, 2021. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): A national, multicentre, observational cohort study. Lancet Respir Med 9: 139–148.
-
6.
Torres A et al., 2021. CIBERESUCICOVID: A strategic project for a better understanding and clinical management of COVID-19 in critical patients. Arch Bronconeumol 57: 1–2.
-
7.
Estenssoro E et al.; SATI-COVID-19 Study Group, 2022. Clinical characteristics, respiratory management, and determinants of oxygenation in COVID-19 ARDS: A prospective cohort study. J Crit Care 71: 154021.
-
8.
Ferreira JC et al.; EPICCoV Study Group, 2021. Protective ventilation and outcomes of critically ill patients with COVID-19: A cohort study. Ann Intensive Care 11: 92.
-
9.
Pisani L et al.; PRoVENT-iMiC study investigators, 2022. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: A pooled analysis of four observational studies.Lancet Glob Health 10: e227–e235.
-
10.
Laffey JG et al.; ESICM Trials Group, 2017. Geo-economic variations in epidemiology, patterns of care, and outcomes in patients with acute respiratory distress syndrome: Insights from the LUNG SAFE prospective cohort study. Lancet Respir Med 5: 627–638.
-
11.
Ferreira JC et al.; EPICCoV Study Group, 2020. Characteristics and outcomes of patients with COVID-19 admitted to the ICU in a university hospital in São Paulo, Brazil—Study protocol. Clinics (Sao Paulo) 75: e2294.
-
12.
Torres A et al.; CIBERESUCICOVID Project Investigators, 2022. Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study. Intensive Care Med 48: 850–864.
-
13.
Schoenfeld DA, Bernard GR; ARDS Network, 2002. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome.Crit Care Med 30: 1772–1777.
-
14.
Imai K, Ratkovic M, 2014. Covariate balancing propensity score. J R Stat Soc Ser B 76: 243–263.
-
15.
Schuijt MTU, van Meenen DMP, Martin-Loeches I, Mazzinari G, Schultz MJ, Paulus F, Serpa Neto A, 2021. Association of time-varying intensity of ventilation with mortality in patients with COVID-19 ARDS: Secondary analysis of the PRoVENT-COVID study. Front Med (Lausanne) 8: 725265.
-
16.
van Buuren S, Groothuis-Oudshoorn K, 2011. mice: Multivariate imputation by chained equations in R.J Stat Soft 45: 1–67.
-
17.
Mathur MB, Ding P, Riddell CA, VanderWeele TJ, 2018. Web site and R package for computing e-values. Epidemiology 29: e45–e47.
-
18.
VanderWeele TJ, Ding P, 2017. Sensitivity analysis in observational research: Introducing the e-value. Ann Intern Med 167: 268–274.
-
19.
Teixeira C, Cabral CdR, Hass JS, Oliveira RP, Vargas MA, Freitas AP, Fleig AH, Treptow EC, Rizzotto MI, 2011. Patients admitted to the ICU for acute exacerbation of COPD: Two-year mortality and functional status. J Bras Pneumol 37: 334–340.
-
20.
Warwick M et al.; Resource Optimization Network, 2021. Outcomes and resource utilization among patients admitted to the intensive care unit following acute exacerbation of chronic obstructive pulmonary disease.J Intensive Care Med 36: 1091–1097.
-
21.
Machado FR et al.; SPDM against sepsis project, 2017. Implementation of sepsis bundles in public hospitals in Brazil: A prospective study with heterogeneous results. Crit Care 21: 268.
-
22.
Kaukonen K-M, Bailey M, Suzuki S, Pilcher D, Bellomo R, 2014. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 311: 1308–1316.
-
23.
Mulatu HA, Bayisa T, Worku Y, Lazarus JJ, Woldeyes E, Bacha D, Taye B, Nigussie M, Gebeyehu H, Kebede A, 2021. Prevalence and outcome of sepsis and septic shock in intensive care units in Addis Ababa, Ethiopia: A prospective observational study. Afr J Emerg Med 11: 188–195.
-
24.
Vincent J-L, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators, 2006. Sepsis in European intensive care units: Results of the SOAP study.Crit Care Med 34: 344–353.
-
25.
Tanriover MD, Guven GS, Sen D, Unal S, Uzun O, 2006. Epidemiology and outcome of sepsis in a tertiary-care hospital in a developing country. Epidemiol Infect 134: 315–322.
-
26.
Arshad A, Ayaz A, Haroon MA, Jamil B, Hussain E, 2020. Frequency and cause of readmissions in sepsis patients presenting to a tertiary care hospital in a low middle income country. Crit Care Explor 2: e0080.
-
27.
Estenssoro E et al.; SATISEPSIS Investigators, 2018. Predictive validity of sepsis-3 definitions and sepsis outcomes in critically ill patients: A cohort study in 49 ICUs in Argentina.Crit Care Med 46: 1276–1283.
-
28.
Wang M et al.; China Critical Care Sepsis Trial (CCCST) workgroup, 2020. The prevalence, risk factors, and outcomes of sepsis in critically ill patients in China: A multicenter prospective cohort study. Front Med (Lausanne) 7: 593808.
-
29.
Khan MR, Maheshwari PK, Masood K, Qamar FN, Haque AU, 2012. Epidemiology and outcome of sepsis in a tertiary care PICU of Pakistan. Indian J Pediatr 79: 1454–1458.
-
30.
Phua J et al.; MOSAICS Study Group, 2011. Management of severe sepsis in patients admitted to Asian intensive care units: Prospective cohort study. BMJ 342: d3245.
-
31.
Dünser MW, Bataar O, Tsenddorj G, Lundeg G, Torgersen C, Romand JA, Hasibeder WR; Helfen Berührt Study Team, 2008. Differences in critical care practice between an industrialized and a developing country. Wien Klin Wochenschr 120: 600–607.
-
32.
Frikha N, Mebazaa M, Mnif L, El Euch N, Abassi M, Ben Ammar MS, 2005. Septic shock in a Tunisian intensive care unit: Mortality and predictive factors. 100 cases. Tunis Med 83: 320–325.
-
33.
van der Ven F-SLIM et al.; ERICC-, LUNG SAFE-, PRoVENT-COVID-, EPICCoV-, CIBERESUCICOVID-, SATI-COVID-19-investigators, 2024. Epidemiology, ventilation management and outcomes of COVID–19 ARDS patients versus patients with ARDS due to pneumonia in the pre-COVID era.Respir Res 25: 312.
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