Dear Editor,
In the earliest phases of the pandemic, the use of extracorporeal life support in patients with severe coronavirus disease 2019 (COVID-19) was associated with disastrous outcomes. However, later series have shown better results, with hospital mortality ranging from 30 to 60% [1–3]. These series included patients receiving support during the first wave of the pandemic. Whilst a trend towards lower mortality in the overall COVID-19 population has been observed over time [4], preliminary data from the EuroECMO registry of the EuroELSO organization suggest that outcomes after extracorporeal membrane oxygenation (ECMO) in the second wave of the pandemic have worsened [5]. The present subanalysis examines this situation.
The ECMOVIBER (use of ECMO during the coVid-19 pandemic in the IBERian peninsula) retrospective observational cohort study included data from 24 ECMO centers, 22 in Spain and 2 in Portugal. We established a cut-off date of June 30, 2020 to define the first and second waves. For more information on the study, including the statistical methodology, see the online material. A total of 319 patients received extracorporeal respiratory support due to acute respiratory distress syndrome (ARDS): 151 (47.3%) during the first wave and 168 (52.6%) during the second. Hospital mortality was significantly higher during the second wave (60.1% vs. 41.1%, p = 0.001; Figure E3, online material). Patients supported during the second wave were older, had more comorbidities and were less likely to be treated at a high-volume center (Table 1). Time between admission to the intensive care unit (ICU) and ECMO start was longer, but not time since intubation. At ECMO indication, the PaO2/FiO2 was significantly higher and levels of COVID-19-associated inflammatory biomarkers were lower. Coinfection, together with new onset pneumonia during ECMO support, was more frequent in patients during the second wave (microbiological profile in table E3, online material).
Table 1.
Patient pre-ECMO characteristics, ECMO management, complications and outcomes according to the wave of the pandemic in which the support was initiated
| Variable* | All (n = 319) | First wave¥ (n = 151) | Second wave¥ (n = 168) | p value |
|---|---|---|---|---|
| Age (years) | 53 ± 10.3 | 51.2 ± 10.5 | 54.6 ± 9.9 | 0.004 |
| Older than 65 | 30 (9.4) | 8 (5.3) | 22 (13.1) | 0.016 |
| Gender (male) | 258 (80.9) | 117 (77.5) | 141 (83.9) | 0.187 |
| Active smoker | 21 (6.6) | 5 (3.3) | 16 (9.5) | 0.045 |
| Hypertension | 121 (37.9) | 49 (32.4) | 72 (42.8) | 0.072 |
| Diabetes mellitus | 62 (19.4) | 30 (19.9) | 32 (19) | 0.966 |
| Chronic kidney disease | 12 (3.8) | 2 (1.3) | 10 (5.9) | 0.061 |
| COPD | 21 (6.6) | 4 (2.6) | 17 (10.1) | 0.014 |
| ICU admission to ECMO (days) | 7 [4–12.8] | 6 [3–10] | 8 [5.5–13.5] | < 0.001 |
| MV days prior to ECMO | 5 [3–9] | 5 [3–9] | 6 [3–9.2] | 0.646 |
| Distribution of cases according to center volume | 0.049 | |||
| ≥ 30 | 96 (30.1) | 54 (35.8) | 42 (25) | |
| < 30 | 223 (69.9) | 97 (64.2) | 126 (75) | |
| Variables before cannulation | ||||
| Coinfection at ECMO initiation | 95 (29.8) | 36 (23.8) | 59 (35.1) | 0.041 |
| PaO2/FiO2 ratio (mmHg) | 76 [63–90] | 72 [62–86] | 80 [68–93] | 0.010 |
| PEEP (cmH2O) | 12 [9–14] | 12 [10–14] | 10 [9–14] | 0.035 |
| Respiratory rate (bpm) | 25 [22–30] | 26 [22–30] | 25 [21–30] | 0.321 |
| Driving pressure (cmH2O) | 18 [15–21] | 18 [15–22] | 17 [15–20] | 0.253 |
| Prone-positioning | 305 (95.6) | 146 (96.6) | 168 (100) | 0.179 |
| Neuromuscular blockade | 314 (98.4) | 146 (96.7) | 168 (100) | 0.048 |
| Corticosteroids | < 0.001 | |||
| No treatment | 54 (16.9) | 45 (39.8) | 9 (5.3) | |
| Dexamethasone | 217 (68) | 70 (46.3) | 147 (87.5) | |
| Methylprednisolone | 45 (14.1) | 35 (23.2) | 10 (5.9) | |
| Tocilizumab | 95 (29.8) | 64 (42.4) | 31 (18.4) | < 0.001 |
| Anticoagulation therapy | 131 (41.1) | 55 (36.4) | 76 (45.2) | 0.138 |
| Arterial pH | 7.3 [7.2–7.4] | 7.3 [7.2–7.4] | 7.3 [7.2–7.4] | 0.192 |
| Arterial PaCO2 (mmHg) | 61 [51–73] | 61 [50–71] | 61 [51–73] | 0.221 |
| Arterial lactate (mmol/L) | 1.6 [1.1–2.2] | 1.6 [1.1–2.2] | 1.6 [1.2–2.2] | 0.96 |
| Leukocyte count (× 109/L) | 12.8 [9.2–16.7] | 11.4 [8.1–16.4] | 13.2 [9.9–17.1] | 0.026 |
| Lymphocyte count (× 109/L) | 0.8 [0.5–1.2] | 0.8 [0.5–1.2] | 0.8 [0.5–1.2] | 0.526 |
| D-dimer (ng/mL) | 2211.5 [1093–3752.5] | 2275 [1087–3947] | 2080 [1100–3500] | 0.836 |
| Ferritin (ng/mL) | 1153 [716–1766] | 1318 [833.5–2024.5] | 1024 [671–1538] | 0.031 |
| IL-6 (pg/mL) | 125.9 [37.5–564.5] | 160 [53.5–1026.8] | 100 [37.4–435] | 0.062 |
| Complications and outcomes | ||||
| New onset pneumonia on ECMO | 161 (50.4) | 62 (41) | 99 (58.9) | 0.003 |
| Acute kidney injury | 83 (26) | 40 (26.5) | 43 (25.6) | 0.538 |
| Vascular thrombosis | 56 (15.6) | 19 (12.6) | 37 (22) | 0.028 |
| Circuit clotting | 119 (37.3) | 55 (36.4) | 61 (36.3) | 0.493 |
| Hemorrhagic shock | 44 (13.8) | 21 (13.9) | 23 (13.7) | 1 |
| ECMO days | 17 [9–32] | 16 [8–28] | 18 [9–37] | 0.107 |
| MV days | 36 [20–57] | 35 [20–55] | 36 [20–58] | 0.710 |
| ICU LOS (days) | 41 [25–62] | 42 [24–61] | 41 [24–67] | 0.829 |
| Hospital LOS (days) | 51 [32–78] | 52 [36–76] | 48 [29–79] | 0.414 |
| ECMO survival | 180 (56.4) | 100 (66.2) | 80 (47.6) | 0.001 |
| Hospital survival | 156 (48.9) | 89 (58.9) | 67 (39.9) | 0.001 |
| 6 months follow up | 0.001 | |||
| Home with no oxygen | 140 (43.8) | 82 (54.3) | 58 (34.5) | |
| Home with oxygen support | 15 (4.7) | 7 (4.6) | 8 (4.8) | |
| Dead | 157 (49.2) | 59 (39.1) | 98 (58.3) | |
| Still admitted | 7 (0.2) | 3 (0.1) | 4 (0.2) | |
Continuous variables are expressed as means ± standard deviation or median [IQ25–IQ75] and categorical variables as absolute value (percentage)
BMI body mass index (weight in kilograms divided by the square of the height in meters), bpm breaths per minute, COPD chronic obstructive pulmonary disease or asthma, IL-6 interleukin 6, MV mechanical ventilation, PEEP positive end expiratory pressure
*The definition of the different variables is detailed in the Supplement
¥First wave cases are those in which ECMO support was started before June 30 and second wave cases are those in which ECMO support was started after June 30 and before December 1, 2020
Although the conclusions derived from an observational study should be treated with caution, these results could be interpreted as follows. The data suggest a certain relaxation of ECMO indication criteria during the second wave, due perhaps to the less demanding context and with the wider acceptance of the use of ECMO in COVID-19 in view of the positive results of early first analyses of large international databases (https://www.euroelso.net/covid-19/covid-19-survey/ and https://www.elso.org/Registry/FullCOVID19RegistryDashboard.aspx). Thus, in the second wave, low-volume centers treated more patients and this tendency for dispersion of ECMO cases may also have negatively affected the results [3]. Another possible influence on the survival difference is the change in the COVID-19 care protocol during the pandemic: for example, the use of corticosteroids and the criteria for intubation. Patients supported during the second wave suffered more coinfections, both at initiation and during extracorporeal support, and this multi-cause lung insult may have had a significant impact on the evolution of cases. Data suggest that in these patients intubation was delayed, and this is known to have potential deleterious effects in ventilated patients.
Our results confirm a higher mortality rate in COVID-19 patients supported with ECMO during the second wave than during the first. Here, we propose possible explanations for this phenomenon, which we feel should be considered in decisions regarding the technique's indication in future patients.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
ECMOVIBER study group: Hospital Universitari Vall d'Hebron, Jordi Riera, Camilo Bonilla, Department of Intensive Care, Barcelona; São João University Hospital Center, Roberto Roncon-Albuquerque Jr, Ana Vaz, Department of Intensive Care, Porto; Hospital Universitari Bellvitge, María Paz Fuset, Department of Intensive Care, Stephani María Luna, Department of Cardiac Surgery, Barcelona; Centro Hospitalar Universitário de Lisboa Central, Philip Fortuna, Pedro Eduardo Silva, Medical Emergency Unit, Lisboa; Hospital Clínico Universitario Virgen de la Arrixaca, Carlos Luis Albacete, Daniel Pérez, Department of Intensive Care, Murcia; Hospital Universitario Rio Hortega, Pablo Blanco-Schweizer, Marta García, Department of Intensive Care, Valladolid; Hospital Universitario La Paz, Pablo Millán, Department of Intensive Care, Javier Veganzones, Department of Anesthesiology, Madrid; Hospital Universitari Germans Trias i Pujol, Pilar Ricart, Sergi Martínez, Department of Intensive Care, Badalona—Barcelona; Hospital Universitario Cruces, María Victoria Boado, Department of Intensive Care, Roberto Voces, Department of Cardiac Surgery, Barakaldo—Bilbo; Hospital Universitario Puerta de Hierro, Sara Alcántara, Héctor Villanueva-Fernández, Department of Intensive Care, Majadahonda—Madrid; Hospital Universitario Ramón y Cajal, Aaron Blandino, Department of Intensive Care and Emergency Medicine, Madrid; Hospital Universitario Gregorio Marañón, Patricia Santa-Teresa, Department of Intensive Care, Madrid; Hospital Universitari Clinic, Elena Sandoval, Department of Cardiovascular Surgery, Barcelona; Hospital Universitario Miguel Servet, Pablo Ruiz de Gopegui, Department of Intensive Care, Zaragoza; Hospital Universitario Central de Asturias, Alfredo González-Pérez, Department of Cardiac Intensive Care, Oviedo; Hospital Clínico San Carlos, Jorge Duerto, Department of Intensive Care, Madrid; Hospital Universitari i Politècnic La Fe, Ricardo Gimeno, Department of Intensive Care, València; Hospital Universitari Son Espases, Joaquín Colomina, Department of Intensive Care, Palma de Mallorca; Hospital Álvaro Cunqueiro, Vanesa Gómez, Department of Intensive Care, Vigo; Hospital Universitario Virgen de Macarena, Helena Pérez-Chomón, Department of Intensive Care, Sevilla; Hospital Clínico Universitario, Gloria Renedo, Department of Intensive Care, Valladolid; Hospital Universitario del Vinalopó, Manuel Alfonso García, Department of Intensive Care, Elx; Hospital Universitario Reina Sofía, José Ricardo Naranjo, Department of Intensive Care, Córdoba; Hospital Clínico Universitario de Santiago de Compostela, Emilio Rodríguez-Ruiz, Department of Intensive Care, Santiago de Compostela.
Compliance with ethical standards
Conflicts of interest
The authors have no conflicts of interest to declare.
Footnotes
The members of “ECMOVIBER Study Group” are presented in the Acknowledgements section.
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Contributor Information
Jordi Riera, Email: jorriera@vhebron.net.
on behalf of ECMOVIBER Study Group:
Jordi Riera, Camilo Bonilla, Roberto Roncon-Albuquerque, Jr, Ana Vaz, María Paz Fuset, Stephani María Luna, Philip Fortuna, Pedro Eduardo Silva, Carlos Luis Albacete, Daniel Pérez, Pablo Blanco-Schweizer, Marta García, Pablo Millán, Javier Veganzones, Pilar Ricart, Sergi Martínez, María Victoria Boado, Roberto Voces, Sara Alcántara, Héctor Villanueva-Fernández, Aaron Blandino, Patricia Santa-Teresa, Elena Sandoval, Pablo Ruiz de Gopegui, Alfredo González-Pérez, Jorge Duerto, Ricardo Gimeno, Joaquín Colomina, Vanesa Gómez, Helena Pérez-Chomón, Gloria Renedo, Manuel Alfonso García, José Ricardo Naranjo, and Emilio Rodríguez-Ruiz
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