Extracorporeal Membrane Oxygenation in COVID-19 Treatment: a Systematic Literature Review

Tatiana Farias de Oliveira Carlos Alberto de Oliveira Rocha Aisla Graciele Galdino dos Santos Luiz Carlos Francelino Silva Junior Saulo Henrique Salgueiro de Aquino Euclides José Oliveira da Cunha Rafaela Campos Alcântara Rodrigo da Rosa Mesquita Gabriel Monteiro Arnozo Fernanda Mayara Santos Santana Etvaldo Rodrigues da Silva Filho Carlos Dornels Freire de Souza About the authors

Abstract

Introduction:

The present study intends to systematically review the literature on the use of extracorporeal membrane oxygenation (ECMO) in patients with coronavirus disease 2019 (COVID-19).

Methods:

The research was carried out according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). Studies were selected from PubMed/MEDLINE and LILACS databases between December 2019 and May 17 2020, using the descriptors "ECMO AND COVID-19", "Extracorporeal Membrane Oxygenation AND COVID-19", "ECLS AND COVID-19", and "Extracorporeal Life Support AND COVID-19". Exclusion criteria were government epidemiological bulletins, comments, literature reviews, and articles without full access to content.

Results:

Two hundred and thirty-three scientific productions were found, however only 18 did not met the exclusion criteria and could be included in this study, amouting to a total of 911 patients - 624 (68.5%) men, 261 (28.6%) women, and 26 (2.8%) without sex information. The mean age of the patients was 53.7 years. ECMO was necessary in 274 (30.1%) people (200 [73%] submitted to veno-venous ECMO, nine [3.3%] to veno-arterial ECMO, and seven [2.5%] moved between these two types or needed a more specific ECMO according to the disease prognosis). Five studies did not specify the type of ECMO used, amounting 57 (20.8%) patients. Five patients (1.8%) were discharged, 77 (28.1%) died, 125 (45.6%) remained hospitalized until publication time of their respective studies, and 67 patients (24.4%) had no outcome information.

Conclusion:

It is evident that more research, covering larger populations, must be carried out in order to clearly elucidate the role of ECMO in the treatment of COVID-19.

Keywords:
Extracorporeal Membrane Oxygenation; Coronavirus Infections; COVID-19; Patient Discharge

INTRODUCTION

Coronavirus disease 2019 (COVID-19), a disease caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is being considered cause of the most important health crisis of the last hundred years[11 Hartman ME, Hernandez RA, Patel K, Wagner TE, Trinh T, Lipke AB, et al. COVID-19 respiratory failure: targeting inflammation on VV-ECMO support. ASAIO J. 2020;66(6):603-6. doi:10.1097/MAT.0000000000001177.
https://doi.org/10.1097/MAT.000000000000...
]. Originating in the People's Republic of China, the disease quickly spread to all continents. On March 11 2020, the World Health Organization (WHO) declared a pandemic status [22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
].

In June 12 2020, more than 7.4 million people were infected and 400,000 deaths had occurred from the disease worldwide. Behind the United States of America (USA) alone, with two million cases, Brazil occupied, on that date, the second position in the ranking of countries with more cases of COVID-19, with about 850 thousand cases. In terms of number of deaths, USA remains in the lead, accounting for 115,000 deaths[33 World Health Organization. Coronavirus disease (COVID-19). Situation Report; 147. Geneva: WHO; 2020 Jun 15 [cited 2020 Jun 15]. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200615-covid-19-sitrep-147.pdf?sfvrsn=2497a605_2
https://www.who.int/docs/default-source/...
].

SARS-CoV-2 infection can lead to the development of acute respiratory distress syndrome (ARDS)[44 Marullo AG, Cavarretta E, Biondi-Zoccai G, Mancone M, Peruzzi M, Piscioneri F, et al. Extracorporeal membrane oxygenation for critically ill patients with coronavirus-associated disease 2019: an updated perspective of the European experience. Minerva Cardioangiol. 2020. doi:10.23736/S0026-4725.20.05328-1.
https://doi.org/10.23736/S0026-4725.20.0...
]. Approximately 14% of COVID-19 cases are serious and 5% are critical[55 Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323(13):1239-42. doi:10.1001/jama.2020.2648.
https://doi.org/10.1001/jama.2020.2648...
]. In such cases, therapy includes protective pulmonary mechanical ventilation, neuromuscular blockade, higher positive end-expiratory pressure, pulmonary recruitment techniques, and prone positioning. When conventional therapy fails, extracorporeal membrane oxygenation (ECMO) can be considered as an alternative in certain patients[66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
].

In ECMO treatment, there are two basic methods that can be used: veno-venous (VV-ECMO) or veno-arterial (VA-ECMO)[77 Smereka J, Puslecki M, Ruetzler K, Filipiak KJ, Jaguszewski M, Ladny JR, et al. Extracorporeal membrane oxygenation in COVID-19. Cardiol J. 2020;27(2):216-7. doi:10.5603/CJ.a2020.0053.
https://doi.org/10.5603/CJ.a2020.0053...
]. Regarding to COVID-19 respiratory complications, VV-ECMO is the recommended form[66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
]. Thus, this study aims to review the literature on the use of this therapeutic strategy in patients with COVID-19.

METHODS

Data Sources and Search Strategies

This is a systematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes, or PRISMA[88 Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097.
https://doi.org/10.1371/journal.pmed.100...
], recommendations.

For this review, studies involving patients with COVID-19 were used. Studies published in the PubMed/MEDLINE and LILACS databases were screened between December 2019 and May 17 2020, using the descriptors "ECMO AND COVID-19", "Extracorporeal Membrane Oxygenation AND COVID-19", "ECLS AND COVID-19", and "Extracorporeal Life Support AND COVID-19". In addition, a manual search was carried out for references cited in the articles.

Research Variables

The following variables were researched: country of study, study population, sex (male and female), use of ECMO, type of ECMO used in the treatment of patients with COVID-19, main outcomes, and conclusions/recommendations.

Eligibility criteria

We included letters to the editor, clinical trials, cohorts, cross-sectional studies, clinical cases, and case series studies (published and pre-print). Government epidemiological bulletins, comments, literature reviews, articles without full access to content, and studies in animals were excluded.

Selection of Studies

The search was carried out by four independent researchers. After this stage, three researchers independently performed the following steps: 1) reading the title and summary to identify potential eligible studies; 2) reading the full text; 3) collecting ECMO data and setting up the database. The analysis was independently conducted by two other researchers. The divergences were analyzed and resolved by consensus.

The included studies were submitted to a qualitative analysis using the Risk Of Bias In Non-randomized Studies of Interventions, or ROBINS-I[99 Sterne JA, Hernán MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi: 10.1136/bmj.i4919.
https://doi.org/10.1136/bmj.i4919...
], which is a recommended tool to assess the risk of bias in non-randomized studies included in systematic reviews.

Data Extraction

For data extraction, the researchers created a database. At this stage, the database was mounted. The data was entered by a first investigator and subsequently checked by a second investigator on the team. The systematization/analysis of the data was conducted by two other independent researchers.

RESULTS

Initially, 233 scientific productions were found in the researched databases. After the successive stages of analysis, only 18 articles fit the objective of this study, pointing to ECMO as one of the resources in the treatment of COVID-19 (Figure 1): Europe[44 Marullo AG, Cavarretta E, Biondi-Zoccai G, Mancone M, Peruzzi M, Piscioneri F, et al. Extracorporeal membrane oxygenation for critically ill patients with coronavirus-associated disease 2019: an updated perspective of the European experience. Minerva Cardioangiol. 2020. doi:10.23736/S0026-4725.20.05328-1.
https://doi.org/10.23736/S0026-4725.20.0...
] (1 study, 333 patients), People's Republic of China[22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
,66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
,1010 Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. doi:10.1001/jama.2020.1585.
https://doi.org/10.1001/jama.2020.1585...
,1111 Zhan WQ, Li MD, Xu M, Lu YB. Successful treatment of COVID-19 using extracorporeal membrane oxygenation, a case report. Eur Rev Med Pharmacol Sci. 2020;24(6):3385-9. doi:10.26355/eurrev_202003_20705.
https://doi.org/10.26355/eurrev_202003_2...
,1212 Yu Y, Xu D, Fu S, Zhang J, Yang X, Xu L, et al. Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study. Crit Care. 2020;24(1):219. doi:10.1186/s13054-020-02939-x.
https://doi.org/10.1186/s13054-020-02939...
] (5 studies, 385 patients), Japan[1313 Taniguchi H, Ogawa F, Honzawa H, Yamaguchi K, Niida S, Shinohara M, et al. Veno-venous extracorporeal membrane oxygenation for severe pneumonia: COVID-19 case in Japan. Acute Med Surg. 2020;7(1):e509. doi:10.1002/ams2.509.
https://doi.org/10.1002/ams2.509...
,1414 Nakamura K, Hikone M, Shimizu H, Kuwahara Y, Tanabe M, Kobayashi M, et al. A sporadic COVID-19 pneumonia treated with extracorporeal membrane oxygenation in Tokyo, Japan: a case report. J Infect Chemother. 2020;26(7):756-61. doi:10.1016/j.jiac.2020.03.018.
https://doi.org/10.1016/j.jiac.2020.03.0...
,1515 Japan ECMOnet for COVID-19. Nationwide system to centralize decisions around ECMO use for severe COVID-19 pneumonia in Japan (special correspondence). J Intensive Care. 2020;8:29. Erratum in: J Intensive Care. 2020;8:38. doi:10.1186/s40560-020-00445-4.
https://doi.org/10.1186/s40560-020-00445...
,1616 Kato H, Shimizu H, Shibue Y, Hosoda T, Iwabuchi K, Nagamine K, et al. Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship. J Infect Chemother. 2020;26(8):865-9. doi:10.1016/j.jiac.2020.05.005.
https://doi.org/10.1016/j.jiac.2020.05.0...
] (4 studies, 98 patients), USA[1717 Jacobs JP, Stammers AH, St Louis J, Hayanga JWA, Firstenberg MS, Mongero LB, et al. Extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in Coronavirus disease 2019: experience with 32 patients. ASAIO J. 2020;66(7):722-30. doi:10.1097/MAT.0000000000001185.
https://doi.org/10.1097/MAT.000000000000...
,1818 Sultan I, Habertheuer A, Usman AA, Kilic A, Gnall E, Friscia ME, et al. The role of extracorporeal life support for patients with COVID-19: preliminary results from a statewide experience. J Card Surg. 2020;35(7):1410-3. doi:10.1111/jocs.14583.
https://doi.org/10.1111/jocs.14583...
,1919 Firstenberg MS, Stahel PF, Hanna J, Kotaru C, Crossno J Jr, Forrester J. Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report. Patient Saf Surg. 2020;14:20. doi:10.1186/s13037-020-00245-7.
https://doi.org/10.1186/s13037-020-00245...
] (3 studies, 43 patients), Spain[2020 Barrasa H, Rello J, Tejada S, Martín A, Balziskueta G, Vinuesa C, et al. SARS-CoV-2 in Spanish intensive care units: early experience with 15-day survival in Vitoria. Anaesth Crit Care Pain Med. 2020;39(5):553-61. doi:10.1016/j.accpm.2020.04.001.
https://doi.org/10.1016/j.accpm.2020.04....
] (1 study, 48 patients), Italy[2121 Giani M, Seminati D, Lucchini A, Foti G, Pagni F. Exuberant plasmocytosis in bronchoalveolar lavage specimen of the first patient requiring extracorporeal membrane oxygenation for SARS-CoV-2 in Europe. J Thorac Oncol. 2020;15(5):e65-6. doi:10.1016/j.jtho.2020.03.008.
https://doi.org/10.1016/j.jtho.2020.03.0...
] (1 study, 1591 patients), and Switzerland[2222 Schmiady MO, Sromicki J, Kucher N, Ouda A. Successful percutaneous thrombectomy in a patient with COVID-19 pneumonia and acute pulmonary embolism supported by extracorporeal membrane oxygenation. Eur Heart J. 2020;41(32):3107. doi:10.1093/eurheartj/ehaa403.
https://doi.org/10.1093/eurheartj/ehaa40...
] (1 study, 1 patient).

Fig. 1
Flowchart of studies selection, 2020.

The surveys total 911 patients confirmed with COVID-19, 68.5% (n=624) males and 28.6% (n=261) females; there was no sex information about 2.8% (n=26) of the patients. The mean age of patients in studies [11 Hartman ME, Hernandez RA, Patel K, Wagner TE, Trinh T, Lipke AB, et al. COVID-19 respiratory failure: targeting inflammation on VV-ECMO support. ASAIO J. 2020;66(6):603-6. doi:10.1097/MAT.0000000000001177.
https://doi.org/10.1097/MAT.000000000000...
,22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
,44 Marullo AG, Cavarretta E, Biondi-Zoccai G, Mancone M, Peruzzi M, Piscioneri F, et al. Extracorporeal membrane oxygenation for critically ill patients with coronavirus-associated disease 2019: an updated perspective of the European experience. Minerva Cardioangiol. 2020. doi:10.23736/S0026-4725.20.05328-1.
https://doi.org/10.23736/S0026-4725.20.0...
,66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
,1010 Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. doi:10.1001/jama.2020.1585.
https://doi.org/10.1001/jama.2020.1585...
,1111 Zhan WQ, Li MD, Xu M, Lu YB. Successful treatment of COVID-19 using extracorporeal membrane oxygenation, a case report. Eur Rev Med Pharmacol Sci. 2020;24(6):3385-9. doi:10.26355/eurrev_202003_20705.
https://doi.org/10.26355/eurrev_202003_2...
,1212 Yu Y, Xu D, Fu S, Zhang J, Yang X, Xu L, et al. Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study. Crit Care. 2020;24(1):219. doi:10.1186/s13054-020-02939-x.
https://doi.org/10.1186/s13054-020-02939...
,1313 Taniguchi H, Ogawa F, Honzawa H, Yamaguchi K, Niida S, Shinohara M, et al. Veno-venous extracorporeal membrane oxygenation for severe pneumonia: COVID-19 case in Japan. Acute Med Surg. 2020;7(1):e509. doi:10.1002/ams2.509.
https://doi.org/10.1002/ams2.509...
,1414 Nakamura K, Hikone M, Shimizu H, Kuwahara Y, Tanabe M, Kobayashi M, et al. A sporadic COVID-19 pneumonia treated with extracorporeal membrane oxygenation in Tokyo, Japan: a case report. J Infect Chemother. 2020;26(7):756-61. doi:10.1016/j.jiac.2020.03.018.
https://doi.org/10.1016/j.jiac.2020.03.0...
,1515 Japan ECMOnet for COVID-19. Nationwide system to centralize decisions around ECMO use for severe COVID-19 pneumonia in Japan (special correspondence). J Intensive Care. 2020;8:29. Erratum in: J Intensive Care. 2020;8:38. doi:10.1186/s40560-020-00445-4.
https://doi.org/10.1186/s40560-020-00445...
,1616 Kato H, Shimizu H, Shibue Y, Hosoda T, Iwabuchi K, Nagamine K, et al. Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship. J Infect Chemother. 2020;26(8):865-9. doi:10.1016/j.jiac.2020.05.005.
https://doi.org/10.1016/j.jiac.2020.05.0...
,1717 Jacobs JP, Stammers AH, St Louis J, Hayanga JWA, Firstenberg MS, Mongero LB, et al. Extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in Coronavirus disease 2019: experience with 32 patients. ASAIO J. 2020;66(7):722-30. doi:10.1097/MAT.0000000000001185.
https://doi.org/10.1097/MAT.000000000000...
,1919 Firstenberg MS, Stahel PF, Hanna J, Kotaru C, Crossno J Jr, Forrester J. Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report. Patient Saf Surg. 2020;14:20. doi:10.1186/s13037-020-00245-7.
https://doi.org/10.1186/s13037-020-00245...
,2121 Giani M, Seminati D, Lucchini A, Foti G, Pagni F. Exuberant plasmocytosis in bronchoalveolar lavage specimen of the first patient requiring extracorporeal membrane oxygenation for SARS-CoV-2 in Europe. J Thorac Oncol. 2020;15(5):e65-6. doi:10.1016/j.jtho.2020.03.008.
https://doi.org/10.1016/j.jtho.2020.03.0...
,2222 Schmiady MO, Sromicki J, Kucher N, Ouda A. Successful percutaneous thrombectomy in a patient with COVID-19 pneumonia and acute pulmonary embolism supported by extracorporeal membrane oxygenation. Eur Heart J. 2020;41(32):3107. doi:10.1093/eurheartj/ehaa403.
https://doi.org/10.1093/eurheartj/ehaa40...
,2626 Bemtgen X, Krüger K, Supady A, Duerschmied D, Schibilsky D, Bamberg F, et al. First successful treatment of Coronavirus disease 2019 induced refractory cardiogenic plus vasoplegic shock by combination of percutaneous ventricular assist device and extracorporeal membrane oxygenation: a case report. ASAIO J. 2020;66(6):607-9. doi:10.1097/MAT.0000000000001178.
https://doi.org/10.1097/MAT.000000000000...
]that reported this data was 53,7 years. and Japan was the country with the oldest patients, with the highest reported age being 81 years and the lowest, 16 years.

ECMO was necessary as a resource in those patients whose health status was severe/critical, totaling 274 (30.1%) people (Table 1). Regarding the type of ECMO, 73% (n=200) of the patients underwent VV-ECMO. Among the others, nine individuals (3.3%) required VA-ECMO and seven patients (2.5%) moved from one type to another according to the disease prognosis, or needed a more specific type of ECMO such as veno-veno-venous ECMO, veno-arterio-venous ECMO, or veno-veno-arterial ECMO. Five studies[22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
,88 Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. doi:10.1371/journal.pmed.1000097.
https://doi.org/10.1371/journal.pmed.100...
,1212 Yu Y, Xu D, Fu S, Zhang J, Yang X, Xu L, et al. Patients with COVID-19 in 19 ICUs in Wuhan, China: a cross-sectional study. Crit Care. 2020;24(1):219. doi:10.1186/s13054-020-02939-x.
https://doi.org/10.1186/s13054-020-02939...
,1313 Taniguchi H, Ogawa F, Honzawa H, Yamaguchi K, Niida S, Shinohara M, et al. Veno-venous extracorporeal membrane oxygenation for severe pneumonia: COVID-19 case in Japan. Acute Med Surg. 2020;7(1):e509. doi:10.1002/ams2.509.
https://doi.org/10.1002/ams2.509...
,1010 Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. doi:10.1001/jama.2020.1585.
https://doi.org/10.1001/jama.2020.1585...
] did not specify the type of ECMO used to treat their patients (57 [20.8%] patients) (Table 1).

Table 1
Characterization of the articles included in the study (n=18), 2020.

Regarding the outcome related to the use of ECMO, concerning the 274 patients who used the therapeutic resource, five (n=1.8%) were discharged, 125 (45.6%) remained hospitalized until the publication date of the respective study, and there was no outcome information about 67 patients (n=24.4%) (Table 1). Five studies[22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
,44 Marullo AG, Cavarretta E, Biondi-Zoccai G, Mancone M, Peruzzi M, Piscioneri F, et al. Extracorporeal membrane oxygenation for critically ill patients with coronavirus-associated disease 2019: an updated perspective of the European experience. Minerva Cardioangiol. 2020. doi:10.23736/S0026-4725.20.05328-1.
https://doi.org/10.23736/S0026-4725.20.0...
,66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
,1515 Japan ECMOnet for COVID-19. Nationwide system to centralize decisions around ECMO use for severe COVID-19 pneumonia in Japan (special correspondence). J Intensive Care. 2020;8:29. Erratum in: J Intensive Care. 2020;8:38. doi:10.1186/s40560-020-00445-4.
https://doi.org/10.1186/s40560-020-00445...
,1818 Sultan I, Habertheuer A, Usman AA, Kilic A, Gnall E, Friscia ME, et al. The role of extracorporeal life support for patients with COVID-19: preliminary results from a statewide experience. J Card Surg. 2020;35(7):1410-3. doi:10.1111/jocs.14583.
https://doi.org/10.1111/jocs.14583...
] (n=219) reported deaths during treatment, totaling 77 patients (35.2%), among which, two studies[22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
,66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
] developed in the People's Republic of China had the highest mortality rate.

When analyzing the risk of bias in different domains studies, it is noticed that there is a predominance of serious risk of bias due to confounding, to selection of participants, and in measurement of outcomes, however, the studies presented low risk of bias due to deviations from the intended interventios and moderate risk on what concerns to bias in classification of interventions and selection of the reported result. Bias due to missing data presented moderate, low, and no information risk proportional between selected papers. The overall risk of bias of all selected articles was classified as serious (Figure 2).

Fig. 2
Risk of bias in studies.

DISCUSSION

Most patients with COVID-19 have mild symptoms and evolve to cure of the disease. However, some of them progress to a severe state of the disease, developing dyspnoea and hypoxemia about a week after onset. Such patients can rapidly progress to ARDS and, later, to multiple organ failure or even death[1010 Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel Coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. doi:10.1001/jama.2020.1585.
https://doi.org/10.1001/jama.2020.1585...
].

WHO and the Centers for Disease Control and Prevention, or CDC, through the publication of guidelines, indicate the possibility of treatment by ECMO in patients in severe/critical condition, with respiratory failure and cardiac involvement, whose conventional treatment is not being promising[1717 Jacobs JP, Stammers AH, St Louis J, Hayanga JWA, Firstenberg MS, Mongero LB, et al. Extracorporeal membrane oxygenation in the treatment of severe pulmonary and cardiac compromise in Coronavirus disease 2019: experience with 32 patients. ASAIO J. 2020;66(7):722-30. doi:10.1097/MAT.0000000000001185.
https://doi.org/10.1097/MAT.000000000000...
].

ECMO is indicated in patients with refractory hypoxemia with a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) < 50 mmHg for three hours or a PaO2/FiO2 < 80 mmHg for > 6 hours[2323 World Health Organization. Clinical management of severe acute respiratory infection when COVID-19 is suspected 2020. Geneva: WHO; 2020. Available from: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected.
https://www.who.int/publications-detail/...
]. Severe and refractory hypoxemia is an event associated with mortality in over 95% of patients. In this scenario, conventional mechanical ventilation is not able to promote minimal blood oxygenation compatible with life. At this time, the extracorporeal oxygenation technique (ECMO) can be used until the lungs recover and regain their basic function[2222 Schmiady MO, Sromicki J, Kucher N, Ouda A. Successful percutaneous thrombectomy in a patient with COVID-19 pneumonia and acute pulmonary embolism supported by extracorporeal membrane oxygenation. Eur Heart J. 2020;41(32):3107. doi:10.1093/eurheartj/ehaa403.
https://doi.org/10.1093/eurheartj/ehaa40...
].

In this review, less than half of the analyzed patients used ECMO. In fact, it is an intensive therapy whose priority is given to a specific group of patients: younger patients with a relatively low prevalence of comorbidities and with an acceptable probability of reversing the pulmonary failure typical of these patients[2525 World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance. Geneva: WHO; 2020. Available from: https://apps.who.int/iris/bitstream/handle/10665/330854/WHO-nCoV-Clinical-2020.2-eng.pdf?sequence=1&isAllowed=yWHO/nCoV/Clinical/2020.2
https://apps.who.int/iris/bitstream/hand...
]. Thus, an adequate clinical judgment and an understanding of the risk-benefit relationship are important to identify when ECMO may be effective[1313 Taniguchi H, Ogawa F, Honzawa H, Yamaguchi K, Niida S, Shinohara M, et al. Veno-venous extracorporeal membrane oxygenation for severe pneumonia: COVID-19 case in Japan. Acute Med Surg. 2020;7(1):e509. doi:10.1002/ams2.509.
https://doi.org/10.1002/ams2.509...
].

In addition, some factors must be observed, such as old age, comorbidities that portend a poor prognosis (diabetes, heart disease, obesity, among others), and, especially, if patients have hemorrhage in the central nervous system, underlying terminal diseases, or evidence of multisystem organ failure[55 Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323(13):1239-42. doi:10.1001/jama.2020.2648.
https://doi.org/10.1001/jama.2020.2648...
].

A fact verified in this study was that the majority of patients who needed ECMO were submitted to the venous type. In fact, except for VA-ECMO cannulation in emergency situations, as in the case of cardiopulmonary resuscitation, patients are placed on VV-ECMO, in order to correct the hypoxia resulting from the lung failure caused by the virus, having considered that the low oxygen content could progress quickly, leading to multiple organ failure[66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
].

Some patients, during ECMO, may receive antivirals, antibacterial agents, steroids, immunoglobulins, chloroquine, vasoconstrictor agents, or even other medications as complementary treatment. Other concomitant therapies are also possible, such as renal replacement[2020 Barrasa H, Rello J, Tejada S, Martín A, Balziskueta G, Vinuesa C, et al. SARS-CoV-2 in Spanish intensive care units: early experience with 15-day survival in Vitoria. Anaesth Crit Care Pain Med. 2020;39(5):553-61. doi:10.1016/j.accpm.2020.04.001.
https://doi.org/10.1016/j.accpm.2020.04....
,1818 Sultan I, Habertheuer A, Usman AA, Kilic A, Gnall E, Friscia ME, et al. The role of extracorporeal life support for patients with COVID-19: preliminary results from a statewide experience. J Card Surg. 2020;35(7):1410-3. doi:10.1111/jocs.14583.
https://doi.org/10.1111/jocs.14583...
]. Everything will depend on what problems the patient may present as well as the choice of which other treatment will be ideal to help in the recovery of the patient.

It is noteworthy that the role of ECMO in the treatment of the disease caused by this new virus remains uncertain and, in the meantime, new research by several authors is always suggested[22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
,55 Wu Z, McGoogan JM. Characteristics of and important lessons from the Coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA. 2020;323(13):1239-42. doi:10.1001/jama.2020.2648.
https://doi.org/10.1001/jama.2020.2648...
,1313 Taniguchi H, Ogawa F, Honzawa H, Yamaguchi K, Niida S, Shinohara M, et al. Veno-venous extracorporeal membrane oxygenation for severe pneumonia: COVID-19 case in Japan. Acute Med Surg. 2020;7(1):e509. doi:10.1002/ams2.509.
https://doi.org/10.1002/ams2.509...
,1818 Sultan I, Habertheuer A, Usman AA, Kilic A, Gnall E, Friscia ME, et al. The role of extracorporeal life support for patients with COVID-19: preliminary results from a statewide experience. J Card Surg. 2020;35(7):1410-3. doi:10.1111/jocs.14583.
https://doi.org/10.1111/jocs.14583...
,1919 Firstenberg MS, Stahel PF, Hanna J, Kotaru C, Crossno J Jr, Forrester J. Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report. Patient Saf Surg. 2020;14:20. doi:10.1186/s13037-020-00245-7.
https://doi.org/10.1186/s13037-020-00245...
]. From this perspective, the position among researchers may be controversial, because while some authors tend to be more pessimistic when observing high mortality rates with this type of treatment[22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
,1919 Firstenberg MS, Stahel PF, Hanna J, Kotaru C, Crossno J Jr, Forrester J. Successful COVID-19 rescue therapy by extra-corporeal membrane oxygenation (ECMO) for respiratory failure: a case report. Patient Saf Surg. 2020;14:20. doi:10.1186/s13037-020-00245-7.
https://doi.org/10.1186/s13037-020-00245...
], including reporting septic shock and multiple organ failure[22 Zeng Y, Cai Z, Xianyu Y, Yang BX, Song T, Yan Q. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Crit Care. 2020;24(1):148. doi:10.1186/s13054-020-2840-8.
https://doi.org/10.1186/s13054-020-2840-...
], others suggest that it may play an important role and aid to those in the critical state of ARDS due to COVID-19[44 Marullo AG, Cavarretta E, Biondi-Zoccai G, Mancone M, Peruzzi M, Piscioneri F, et al. Extracorporeal membrane oxygenation for critically ill patients with coronavirus-associated disease 2019: an updated perspective of the European experience. Minerva Cardioangiol. 2020. doi:10.23736/S0026-4725.20.05328-1.
https://doi.org/10.23736/S0026-4725.20.0...
,66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
,1111 Zhan WQ, Li MD, Xu M, Lu YB. Successful treatment of COVID-19 using extracorporeal membrane oxygenation, a case report. Eur Rev Med Pharmacol Sci. 2020;24(6):3385-9. doi:10.26355/eurrev_202003_20705.
https://doi.org/10.26355/eurrev_202003_2...
]. Such facts become more evident when assessing the risk of bias in studies.

It should also be noted that the therapeutic modality of extracorporeal ventilation is still not widespread. This scenario may be due to the fact that ECMO is an expensive technology that consumes many resources, which may make it impossible for several countries affected by COVID-19 to pay for it[66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
]. Another important point is that it must be carried out in experienced centers, with qualified professionals, and a multidisciplinary approach[66 Li X, Guo Z, Li B, Zhang X, Tian R, Wu W, et al. Extracorporeal membrane oxygenation for Coronavirus disease 2019 in Shanghai, China. ASAIO J. 2020;66(5):475-81. doi:10.1097/MAT.0000000000001172.
https://doi.org/10.1097/MAT.000000000000...
,2525 World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance. Geneva: WHO; 2020. Available from: https://apps.who.int/iris/bitstream/handle/10665/330854/WHO-nCoV-Clinical-2020.2-eng.pdf?sequence=1&isAllowed=yWHO/nCoV/Clinical/2020.2
https://apps.who.int/iris/bitstream/hand...
].

Limitations

The main limitation of this study was the small number of papers that addressed the use of ECMO treatment in the current pandemic.

CONCLUSION

Based on the above, it is evident that more studies, covering larger populations, should be carried out with regard to the use of ECMO in COVID-19 patients, mainly because it is an alternative to the conventional failed treatment of some critical patients. It can also be seen that with new studies, the mechanisms that involve the disease and death of patients due to COVID-19 could be better evidenced, mainly in critical condition, in order to elucidate the role of ECMO in the treatment of patients affected by COVID-19.

  • This study was carried out at the Department of Medicine, Universidade Federal de Alagoas, Arapiraca, Alagoas, Brazil.
  • No financial support.

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Publication Dates

  • Publication in this collection
    25 Jan 2021
  • Date of issue
    May-Jun 2021

History

  • Received
    25 July 2020
  • Accepted
    04 Sept 2020
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