Abstract
Introduction
ExtraCorporeal Membrane Oxygenation (ECMO) in pediatric patients with COVID-19 has a survival rate similar to adults. Occasionally, patients may need to be cannulated by an ECMO team in a referring hospital and transported to an ECMO center. The ECMO transport of a COVID-19 patient has additional risks than normal pediatric ECMO transport for the possible COVID-19 transmissibility to the ECMO team and the reduction of the ECMO team performance due to the need of wearing full personal protective equipment. Since pediatric data on ECMO transport of COVID-19 patients are lacking, we explored the outcomes of the pediatric COVID-19 ECMO transports collected in the EuroECMO COVID_Neo/Ped Survey.
Methods
We reported five European consecutive ECMO transports of COVID-19 pediatric patients collected in the EuroECMO COVID_Neo/Ped Survey including 52 European neonatal and/or pediatric ECMO centers and endorsed by the EuroELSO from March 2020 till September 2021.
Results
The ECMO transports were performed for two indications, pediatric ARDS and myocarditis associated to the multisystem inflammatory syndrome related to COVID-19. Cannulation strategies differed among patients according to the age of the patients, transport distance varied between 8 and 390 km with a total transport duration between 5 to 15 h. In all five cases, the ECMO transports were successfully performed without major adverse events. One patient reported a harlequin syndrome and another patient a cannula displacement both without major clinical consequences. Hospital survival was 60% with one patient reporting neurological sequelae. No ECMO team member developed COVID-19 symptoms after the transport.
Conclusion
Five transports of pediatric patients with COVID-19 supported with ECMO were reported in the EuroECMO COVID_Neo/Ped Survey. All transports were performed by an experienced multidisciplinary ECMO team and were feasible and safe for both the patient and the ECMO team. Further experiences are needed to better characterize these transports and draw insightful conclusions.
Keywords: SARS-CoV-2, extracorporeal membrane oxygenation, COVID-19, pediatric intensive care unit, respiratory failure
Introduction
ExtraCorporeal Membrane Oxygenation (ECMO) is an advanced technique to support adults, children and neonates with a high risk of mortality secondary to respiratory and/or circulatory failure refractory to conventional treatment.1,2 Unfortunately, this technology is often not available in many hospitals, therefore the hub and spoke model is generally used to support critically ill patients admitted in hospitals without ECMO facilities and presenting the indications for ECMO. In these circumstances, patients are usually cannulated at the referring hospital by an external ECMO team and subsequently transported to the nearest ECMO center. The inter-hospital ECMO transport requires an experienced team to overcome technical difficulties and reduce the risks of complications. Several studies have shown the feasibility and safety of ECMO transports when performed by highly specialized personnel.3–5
The transport of COVID-19 patients adds special risks, due to the possibility of the spread of virus through the patient’s droplets and subsequent exposure of the transport team. Adult ECMO teams have been used to transport COVID-19 patients without complications, but proving to be particularly demanding both from the clinical and logistical standpoint.6,7
ECMO has been rarely used in pediatric patients with COVID-19. The main indications for ECMO in this group have been severe pediatric ARDS, myocarditis or multisystem inflammatory syndrome related to COVID-19 (MIS-C).8,9
So far, data on inter-hospital transport of pediatric COVID-19 patients supported with ECMO are lacking. Therefore, we aimed to report the outcomes of the first European ECMO transports of pediatric COVID-19 cases reported in the EuroECMO COVID_Neo/Ped Survey endorsed by the EuroELSO from March 2020 till September 2021 (12,13).
Methodology and general data of the five cases
The EuroECMO COVID_Neo/Ped Survey is the largest ECMO dataset of pediatric COVID-19 cases reported in Europe during the pandemic (12,13). After a careful analysis of this survey, we reported a total of five COVID-19 cases transported on ECMO from the beginning of the pandemic till September 2021 (Tables 1 and 2).
Table 1.
ECMO and patients details of children transported.
| Demographics/Diagnosis | ECMO information | PRE-ECMO status/support | COVID-19 information | Outcome | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case | City (country) | Age (months) sex | Reason for ECMO support | Comorbidities | Weight (kg) | ECMO type a | Cannulation strategy | ECMO length (hours) | Oxygenator (O), pump (p), cannulas (C) and heater (H) brands/names | Ventilation mode and duration (days) | Worst OI/iNO | Highest VIS | Other treatments | Onset of symptoms to ECMO (days) | Therapy | Hospital survival/sequelae |
| 1 | Madrid (Spain) | 103 Male | pARDS and recurrent air-leak | STAT3 Immunodeficiency, Allogenic stem cell transplant | 40 | V-A | LFV: 19 Fr LFA: 17 Fr changed to V-V with RIJV: 15 Fr |
720 | O: Quadrox iR P: Cardiohelp C: Bio-medicus Medtronic H: HICO-variotherm 550 |
CV 25 | OI: 49 iNO: No |
20 | Proning Chest tube for air leak (pneumothorax, pneumomediastinum and subcutaneous emphysema) |
31 (+37 days after stem cell transplant) | Steroids; Azithromycin; Hydroxychloroquine; Lopinavir/Ritonavir; Immunoglobulin; Tocilizumab; Anakinra; Mesenquimal cells; Hyperimmune plasma; T-CD8 cells |
No (cardiac arrest for massive pulmonary thromboe-mbolism) |
| 2 | Barcelona (Spain) | 144 Female | Myocarditis MIS-C with cardiogenic shock |
Graves-Basedow disease | 47 | V-A | RIJV: 25 Fr RCCA: 19 Fr |
159 | O: Maquet HLS MODULE ADVANCED 7.0 P: Cardiohelp C: Medtronic-Biomedicus H: Maquet HU-35 |
CV | iNO: No | 270 | Pre-ECMO cardiac arrest (CPR 2 min) | 7 | Steroids Immunoglobulin Anakinra |
Yes (no neurologic sequelae) |
| 3 | Madrid (Spain) | 132 Male | Myocarditis MIS-C MOF 2 episodes cardiac arrest |
/ | 52 | V-A | LFV: 19 Fr LFA: 19 Fr |
96 | O: Quadrox iR P: Cardiohelp C: Avalon elite, Getinge H: HICO-variotherm 550 |
CV 1 | OI: 20 iNO: No |
122 | No | 5 | Steroids Immunoglobulin |
Yes (hypoxic ischemic encephalopathy) |
| 4 | Madrid (Spain) | 104 Male | pARDS | Severe combined immunodeficiency, Allogenic stem cell transplant | 26 | V-V | RIJV: 19 Fr double lumen |
1104 | O: EurosetsEU5045 P: Levitronix Centromag C: : Bio-medicus Medtronic H: HICO-variotherm 550 |
CV 1 | OI: 26 iNO: No |
13 | / | 36 (+143 days after stem cell transplant) | Steroids Remdesivir Tocilizumab Ruxoltinib Hyperimmune plasma T cells (mother) Beta-Interferon T-cells anti SARS CoV2 |
No (ECMO withdrawal for hyperinflammation state, pulmonary hypertension and MOF) |
| 5 | Padova (Italy) | 42 Male | pARDS | VACTERL syndrome | 13.5 | V-V-A | RIJV: 14 Fr LFV: 12 Fr RCCA: 14 Fr |
69 | O: Eurosets 4000 EU5045 P: Livanova SCPC (lifebox during transport) C: Medtronic-Biomedicus H: Maquet HU35 |
CV 5 | OI: 23 iNO:20 ppm |
0 | Proning | 5 | Hyperimmune plasma, Steroids Anakinra | Yes (no neurologic sequelae) |
aV = venous, A = arterial.
ECMO: extracorporeal membrane oxygenation; OI: oxygenation index; iNO: inhaled nitric oxide; VIS: vasoactive-inotropic score; RIJV: right internal jugular vein; LFV: left femoral vein, RCCA: right common carotid artery; LFA: left femoral artery; PICU: pediatric intensive care unit; MIS-C: multisystem inflammatory syndrome in children associated with COVID; pARDS: pediatric acute respiratory distress; CV: conventional controlled mechanical ventilation; MOF: multiorgan failure.
Table 2.
Transport details of children transported.
| Case | Country (city) | Date | Location of referring hospital (country) | Transport distance (Km) | Mode of transport | Time from call to ECMO (hours) | Transportation time hospital to hospital (hours) | Total duration of retrieval (hours) | Ventilation during transport | Complications during retrieval | Team composition and team members COVID status a | Type of anticoagulation |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Madrid (Spain) | April 2020 | Madrid (Spain) | 8 | Road | 2 | 0.3 | 7 | CV: PIP 20, PEEP 10, VR 15, FiO2 0.6 | Harlequin syndrome. In PICU switch to V-V ECMO | 2 Pediatric intensivist (N, N) | Unfractionated heparin Not during transport |
| 2 Pediatric cardiac surgeons (N, N) | ||||||||||||
| 1 PICU nurse (N) | ||||||||||||
| 1 Perfusionist (R) | ||||||||||||
| 2 | Barcelona (Spain) | September 2020 | Mallorca (Spain) | 205 | Air (fixed-wing) | 6 | 4 | 15 | CV: PIP 25, PEEP 10, VR 20, FiO2 0.6 | ECMO heater failure | 2 Pediatric intensivist (N, N) | Unfractionated heparin Not during transport |
| 1 Pediatric cardiac Surgeon (N) | ||||||||||||
| 2 PICU nurses (N, N) | ||||||||||||
| Military personnel | ||||||||||||
| 3 | Madrid (Spain) | November 2020 | Toledo (Spain) | 70 | Road | 3 | 1 | 8 | CV: PIP 20, PEEP 10, RV 15, FiO2 0.6 | None. In PICU atrio-septostomy for left ventricular decompression |
2 Pediatric intensivist (N, N) | Unfractionated heparin Not during transport |
| 2 Pediatric cardiac Surgeons (N, N) | ||||||||||||
| 2 PICU nurses (N, N) | ||||||||||||
| 1 Perfusionists (N) | ||||||||||||
| 4 | Madrid (Spain) | November 2020 | Madrid (Spain) | 8 | Road | 6 | 0.3 | 5 | CV: PIP 20, PEEP 10, VR 18, FiO2 0.6 | Cannula displacement, reposition under echography in PICU | 2 Pediatric intensivist (N, N) | Unfractionated heparin Not during transport |
| 2 Pediatric cardiac surgeons (N, N) | ||||||||||||
| 2 PICU nurses (R, N) | ||||||||||||
| 1 Perfusionist (N) | ||||||||||||
| 5 | Padova (Italy) | September 2021 | Trieste (Italy) | 390 | Road | 8 | 2.5 | 10 | CV: PIP 24, PEEP 10, VR 20, FiO2 0.7 | Difficult cannulation, low ECMO flows | 1 Pediatric intensivist (V) | Unfractionated heparin not during transport |
| 2 Pediatric cardiac surgeons (V and V) | ||||||||||||
| 1 PICU nurse (V) | ||||||||||||
| 2 Perfusionists (V and V) |
CV: conventional ventilation; PIP: peak inspiratory pressure; PEEP: positive end-expiratory pressure; VR: ventilator rate, FiO2: fraction inspired of oxygen, V-V: veno-venous, PICU: pediatric intensive care unit, ECMO: extracorporeal membrane oxygenation.
aCOVID-19 status of the team members: V = vaccinated, R = recovered from COVID-19 infection [date of positivity] N = No COVID-19 infection no COVID-19 vaccination (not available at that time).
COVID-19 transported children had a wide range of age (42–144 months) and weight (13.5–52 kgs). Four patients had comorbidities. Three patients underwent ECMO for pediatric ARDS, while two for hemodynamic instability secondary to MIS-C and myocarditis. V-A ECMO was used to manage four patients despite the indication of ECMO support, while V-V ECMO was used only in one case of respiratory failure. Cannulation using the femoral vessels was used in three patients, while neck cannulation was used in the other patients. The duration of the ECMO run varied from a minimum of 69 h to a maximum of 1,104 h; one patient needed nitric oxide during ECMO for severe pulmonary hypertension despite ECMO. Most of the patients received adjunctive therapies during ECMO such as steroids, immunoglobulin, anakinra, tocilizumab and hyperimmune plasma.
Regarding the transport, the distance between ECMO centers and the referral centers ranged between 8 to 390 km, and time from the call to the ECMO deployment ranged between 2 to 8 h with a total duration of retrieval between 5 to 15 h. One transport was performed by air. Team composition was similar in all cases, with 6–7 members mixing pediatric intensivists, pediatric cardiac surgeons and at least a PICU nurse always present with a perfusionist available in four cases. The entire ECMO procedure was undertaken with PPE for all the teams. Cannulations and transports were reported as extremely challenging from all the ECMO teams due to the use of full PPE for the excessive sweating and the reduced visibility secondary to goggles fogging during the procedures. Nevertheless, the cost of a transport with PPE is higher than a normal ECMO transport for the need of PPE kits changing every few hours.
In all five cases, the transport on ECMO was successfully performed without major adverse events. We observed only the occurrence of a harlequin syndrome in one case and of a cannula displacement in another. Harlequin syndrome was first treated with esmolol infusion, and the next day the ECMO strategy was changed from a femoro-femoral V-A ECMO to a peripheral femoro-jugular V-V ECMO. Regarding the patient with cannula displacement towards the tricuspid annulus, the cannula was then correctly repositioned by echocardiography guidance. Hospital survival was 60% and one patient reported neurological sequelae with hypoxic-ischemic lesions at the brain magnetic resonance imaging and several seizures episodes which were controlled by antiepileptic drugs.
None of the health-care personnel developed any sign of COVID-19 in the following weeks even though vaccination was not available at the time of the transport for four out of five patients.
Discussion
This study reported five European inter-hospital ECMO transports of pediatric patients with COVID-19 and MIS-C collected by the EuroECMO COVID_Neo/Ped Survey from March 2020 till September 2021. In all cases, the ECMO transport was successful without transport-related major adverse events. Furthermore, no ECMO team member contracted COVID-19 following the transport.
Currently, several data support the use of ECMO to manage pediatric COVID-19 patients and patients with MIS-C refractory to maximal medical treatments.8,10–12 ECMO survival in these children was 60%, close to the one reported in adults. 13 However, since ECMO runs are relatively infrequent for pediatric COVID-19, outcomes may be affected by center experience and the relatively small sample size included in our report. Recent guidelines suggest to manage these patients only in experienced centers or transport them to the closest ECMO facility.14,15 The ECMO team members may vary across countries and centers, usually based on local expertise. These teams may include one or more cardiac or cardio-thoracic surgeons, intensivists, nurses and ECMO specialists or perfusionists. Several data showed that ECMO transport is generally safe in both adults and children, however data on ECMO transport of COVID-19 patients are lacking and do not include pediatric patients.
The transport of COVID-19 patients in ECMO is challenging and may increase the risk of patients’ complications and team members’ COVID-19 infection. The ECMO team needs to strictly adhere to airborne contact precautions and wear full PPE to protect themselves from SARS-CoV-2 infection during the whole ECMO procedure. Nevertheless, all these precautions may undermine the team performance (e g. fog on the visor, uncomfortable masks, non-breathable fabrics, increased fatigue due to the reduced possibility of taking pauses/rest, etc.) and increase the risk of patient adverse events. In addition, several factors may increase the risk of ECMO team exposure to SARS-CoV-2 during inter-hospital transport: a) the contact with the COVID-19 patient during the ECMO deployment, b) the time spent in the ambulance with an infectious patient and c) the absence of an effective air exchange or negative pressure airflow in the transport vehicle.
Our data shows that pediatric ECMO transport with ambulance was feasible and safe and that these positive results were not limited to transport related to metropolitan areas, but also to inter-regional transports. Hospital survival was 60% in our cohort and was consistent with the hospital survival of other pediatric ECMO COVID-19 patients not requiring transport.8,10,11
Our case series has several limitations and must be interpreted with caution. First, despite the inclusion of 52 neonatal/pediatric European ECMO centers, there is a possibility that we may have missed other pediatric cases of COVID-19 ECMO transports. Second, the retrospective nature of the study and the small sample size do not allow to reach any robust and generalizable conclusions. Third, all the centers included in the study have an extensive experience with ECMO and ECMO transports, thus, caution should be used when translating these results into the clinical practice of newer ECMO centers. However, complex patients on ECMO should always be managed in tertiary level hospitals in order to reduce their risk of morbidity and increase the likelihood of survival. Third, this study does not include a control group of non-COVID-related transports, thus definitive conclusions regarding safety of ECMO transport for both the patient and the team members cannot be achieved.
Conclusions
This study reports five pediatric COVID-19 patients in Europe in whom ECMO support was instituted at a referring hospital with subsequent transport to an ECMO center. All ECMO transports were challenging secondary to the use of full PPE equipment but no ECMO team member reported COVID-19 following the transports. Despite the limited number of patients treated, this study suggests that the ECMO transport of COVID-19 patients may be feasible and safe when performed by an experienced multidisciplinary team and following established protocols which include a strict adherence to airborne contact precautions.
Footnotes
Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Marco Daverio and Angela Amigoni. The first draft of the manuscript was written by Marco Daverio, Angela Amigoni, Belda Hofheinz Sylvia, Joan Balcells and Matteo Di Nardo. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Informed consent: All listed authors have approved the manuscript before submission, including the names and order of authors.
Statement: Reprints will not be ordered.
ORCID iDs
Marco Daverio https://orcid.org/0000-0002-3127-8836
Sylvia Belda Hofheinz https://orcid.org/0000-0002-4898-1413
Matteo Di Nardo https://orcid.org/0000-0003-0051-8080
References
- 1.Bartlett RH, Gazzaniga AB, Fong SW, et al. Extracorporeal membrane oxygenator support for cardiopulmonary failure. Experience in 28 cases. J Thorac Cardiovasc Surg 1977; 73: 375–386. [PubMed] [Google Scholar]
- 2.Anderson HL, Delius RE, Sinard JM, et al. Early experience with adult extracorporeal membrane oxygenation in the modern era. Ann Thorac Surg 1992; 53: 553–563. [DOI] [PubMed] [Google Scholar]
- 3.Broman LM. Inter-hospital transports on extracorporeal membrane oxygenation in different health-care systems. J Thorac Dis 2017; 9: 3425–3429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Bryner B, Cooley E, Copenhaver W, et al. Two decades’ experience with interfacility transport on extracorporeal membrane oxygenation. Ann Thorac Surg 2014; 98: 1363–1370. [DOI] [PubMed] [Google Scholar]
- 5.Erell Y, Dagan O, Shostak E, et al. Pediatric extracorporeal membrane oxygenation reach-out program: successes and insights. ASAIO J Am Soc Artif Intern Organs 1992 2020; 66: 1036–1041. [DOI] [PubMed] [Google Scholar]
- 6.Odish MF, Yi C, Chicotka S, et al. Implementation and outcomes of a mobile extracorporeal membrane oxygenation program in the United States during the coronavirus disease 2019 pandemic. J Cardiothorac Vasc Anesth 2021; 35: 2869–2874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Widmeier E, Duerschmied D, Benk C, et al. Mobile ECMO retrieval of patients during the COVID-19 pandemic. Artif Organs 2021; 45: 1168–1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Di Nardo M, Hoskote A, Thiruchelvam T, et al. Extracorporeal membrane oxygenation in children with coronavirus disease 2019: preliminary report from the collaborative European chapter of the extracorporeal life support organization prospective survey. ASAIO J Am Soc Artif Intern Organs 1992 2021; 67: 121–124. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Schwartz SP, Walker TC, Kihlstrom M, et al. Extracorporeal membrane oxygenation for COVID-19-associated multisystem inflammatory syndrome in a 5-year-old. Am Surg 2020; 88: 3134820983198. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Schneider J, Tilford B, Safa R, et al. Extracorporeal membrane oxygenation for multisystem inflammatory syndrome in children. Perfusion 2021; 37: 2676591211020904. [DOI] [PubMed] [Google Scholar]
- 11.Ebach F, Hainmann I, Eis-Hübinger AM, et al. Successful ECMO therapy in a child with COVID-19-associated ARDS and acute lymphoblastic leukemia. Pediatr Blood Cancer 2021; 68: e29100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Di Nardo M, De Piero ME, Hoskote A, et al. Extracorporeal membrane oxygenation in children with COVID-19 and PIMS-TS during the second and third wave. Lancet Child Adolesc Health 2022; 6: e14–e15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Ramanathan K, Shekar K, Ling RR, et al. Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis. Crit Care 2021; 25: 211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Badulak J, Antonini MV, Stead CM, et al. Extracorporeal membrane oxygenation for COVID-19: updated 2021 guidelines from the extracorporeal life support organization. ASAIO J 2021; 67: 485–495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Labib A, August E, Agerstrand C, et al. Extracorporeal life support organization guideline for transport and retrieval of adult and pediatric patients with ECMO support. ASAIO J Am Soc Artif Intern Organs 1992 2022; 68: 447–455. DOI: 10.1097/MAT.0000000000001653. Epub ahead of print 15 February 2022. [DOI] [PubMed] [Google Scholar]