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Use of Berlin EXCOR cannulas in both venovenous and venoarterial central extracorporeal membrane oxygenation configurations overcomes the problem of cannula instability while bridging infants and young children to lung transplant
Infants and young children awaiting lung transplantation present challenges that often preclude successful extracorporeal membrane oxygenation support as a bridge to transplantation. Instability of neck cannulas often results in the need for intubation, mechanical ventilation, and muscle relaxation creating a worse transplant candidate. With the use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) in both venoarterial and venovenous central cannulation configurations, 5 pediatric patients were successfully bridged to lung transplant.
We performed a single-center retrospective case review of central extracorporeal membrane oxygenation cannulation used as a bridge to lung transplantation cases performed at Texas Children's Hospital between 2019 and 2021.
Six patients, 2 with pulmonary veno-occlusive disease (15-month-old male and 8-month-old male), 1 with ABCA3 mutation (2-month-old female), 1 with surfactant protein B deficiency (2-month-old female), 1 with pulmonary arterial hypertension in the setting of D-transposition of the great arteries after repair as a neonate (13-year-old male), and 1 with cystic fibrosis and end-stage lung disease, were supported for a median of 56.3 days on extracorporeal membrane oxygenation while awaiting transplantation. All patients were extubated after initiation of extracorporeal membrane oxygenation, participating in rehabilitation until transplant. No complications due to central cannulation and use of the Berlin Heart EXCOR cannulas were observed. One patient with cystic fibrosis developed fungal mediastinitis and osteomyelitis resulting in discontinuation of mechanical support and death.
Novel use of Berlin Heart EXCOR cannulas for central cannulation eliminates the problem of cannula instability allowing extubation, rehabilitation, and bridge to lung transplant for infants and young children.
Use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) in VV and VA configurations overcomes the problem of cannula instability during lengthy wait times while bridging infants and young children to lung transplantation.
The primary difficulty in bridging infants and young children to lung transplant with ECMO is cannula instability. Because of their size, the neck is often the only appropriate access for both VV and VA configurations. The patient's inability to cooperate and the hypermobility of the neck often lead to the need for intubation, mechanical ventilation, and muscle relaxation creating a worse transplant candidate. Use of the Berlin EXCOR cannulas (Berlin Heart, Inc) in VV or VA central configurations allows successful bridging of infants and young children during prolonged waiting times for lung transplant.
Lung transplantation remains a well-recognized, lifesaving procedure for selected pediatric patients with end-stage lung and cardiopulmonary disease. The most recent data available from the International Society for Pediatric Heart and Lung Transplantation show that a total of 914 pediatric lung transplants were performed between January 2010 and June 2018, with infants (age <1 year) and young children (age 1-5 years) making up only 109 (11.9%) of those undergoing transplantation.
Because of the prolonged wait times, extracorporeal membrane oxygenation (ECMO) has become an important tool in providing pediatric patients with the extra time they need for suitable organs to become available.
Neck cannulation for venoarterial (VA) or venovenous (VV) ECMO, which is standard for infants and toddlers, is inherently unstable and therefore imposes activity restrictions that prevent rehabilitation, may prevent airway extubation, and often require significant sedation with or without neuromuscular blockade. Conversely, active rehabilitation while on mechanical circulatory support with the Berlin Heart EXCOR pediatric ventricular assist device (Berlin Heart AG), even in very young children, has been well described.
This is possible because of the unique characteristics of the Berlin Heart EXCOR cannulas (Berlin Heart, Inc) and their surgical insertion and stabilization techniques.
We describe the novel, off-label use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) to eliminate the problem of cannula instability and provide ECMO support in both VA and VV configurations to bridge infants and young children to lung transplantation.
Materials and Methods
A single-center retrospective review was performed of all patients undergoing novel central ECMO cannulation as a bridge to lung transplantation at Texas Children's Hospital between August 1, 2019, and July 1, 2021. Approval was obtained from the Baylor College of Medicine Institutional Review Board (H46310, May 5, 2021) and (H51074, February 9, 2022). Informed consent was waived because of the retrospective nature of the study and risk was less than minimal for the participants. During this time period, 20 bilateral lung transplants were performed. Seven of these patients required ECMO as a bridge to transplant.
Only patients deemed suitable lung transplant candidates and either actively listed or pending final medical review board evaluation were considered for ECMO support. Dependence on mechanical ventilation, inotrope and vasopressor requirements, and clinical decline were factors in consideration for mechanical support. VA versus VV support was determined on the basis of right ventricle (RV) function and hemodynamic stability as determined by vasoactive and inotropic support requirements at the time of cannulation. Table 1 provides patient demographics.
Table 1Patient demographics
Pulmonary veno-occlusive disease
Pulmonary veno-occlusive disease
Surfactant protein B deficiency
ABCA3 mutation surfactant dysfunction syndrome
Pulmonary arterial hypertension
Peripheral to central VA
Peripheral to central VV
Total time on ECMO support (d)
Berlin cannula size (inflow/outflow)
6 mm/6 mm
6 mm/6 mm
6 mm/6 mm
6 mm/6 mm
9 mm/9 mm
9 mm/9 mm
Specific location of cannulae (inflow/outflow)
MPA - AO
MPA - AO
RA - MPA
RA - MPA
RPA - AO
RA - MPA
Patient demographics of Berlin EXCOR central cannulation as bridge to lung transplant. ECMO, Extracorporeal membrane oxygenation; VA, venoarterial; VV, venovenous; MPA, main pulmonary artery; AO, aorta; RA, right atrium; RPA, right pulmonary artery.
Median sternotomy was performed. Cardiopulmonary bypass was not necessary for any of the patients. On the basis of patient size and weight, 6-mm Berlin EXCOR cannulas were used in the 4 infants weighing less than 10 kg and 9-mm Berlin EXCOR cannulas were used for the 2 larger teenage patients (Table 1). Adequate anticoagulation was confirmed before cannula placement. Abdominal skin cannula exit sites were selected and created before heparin administration in 2 of the 4 infants.
For patients undergoing VA ECMO support, a 6-mm or 9-mm cannula, dependent on patient size, was placed directly in the main pulmonary artery (MPA) via purse-string suture and connected to the venous limb. The ascending aorta was cannulated indirectly via a 10-mm polytetrafluoroethylene graft and connected to the arterial limb (Figure 1). To avoid recirculation, for patients undergoing VV ECMO support, a 6-mm or 9-mm cannula was placed directly in the right atrium and connected to the venous limb. The MPA was cannulated indirectly via a 10-mm polytetrafluoroethylene graft and connected to the arterial limb (Figure 2 and Video 1). We routinely use bivalirudin for anticoagulation while on ECMO with an initial partial thromboplastic time hepzyme goal of 55 to 65 that is slowly increased to 65 to 70. Mechanical support flow rate is titrated to provide and achieve optimal systemic cardiac output, appropriate oxygenation, and low intracardiac filling pressures on an individual basis. Although we have no absolute flow range criteria, in this cohort flow rates were 100 to 150 mL/kg/min.
When clinically ready after cannulation, patients were extubated and allowed to participate in developmentally appropriate rehabilitation activities with occupational and physical therapists in the intensive care units under the close supervision of the medical teams and extracorporeal life support specialists.
At the time of lung transplant, reoperative sternotomy was used in all except 1 patient who had pulmonary veno-occlusive disease (PVOD) and massive cardiomegaly. In that patient, a clamshell incision combined with inferior midline sternotomy was used. Both patients on VV ECMO initiated bypass using the Berlin cannulas for venous drainage and transitioned over to standard aorta-bicaval cannulation after exposure was adequate. Standard aorta-bicaval cannulation was used for patients on VA ECMO. Pulmonary artery decompression was accomplished in all patients via the transected Berlin MPA cannula. Three patients underwent bilateral sequential lung transplantation, and 2 patients underwent en bloc double lung transplantation with bronchial artery revascularization according to surgeon preference (Video 1).
Patient 1 was a 15-month-old male transferred from an outside institution for lung transplant evaluation and listing with a diagnosis of PVOD based on findings from chest computed tomography imaging and cardiac catheterization. Within 12 hours of arrival, he demonstrated hemodynamic and echocardiographic evidence of RV failure despite escalating inotropic and vasopressor support with progressive hypoxemia and evidence of end-organ injury. He underwent central VA cannulation as described earlier. He was extubated on postoperative day 5 to nasal cannula versus nasal bilevel positive pressure dependent on his clinical appearance. He participated in increasing therapy periods with both physical and occupational therapy, taking food by mouth, weaned off sedation, and was able to be active while awaiting transplant. He successfully underwent transplantation after 61 days of support.
Patient 2 was an 8-month-old male transferred from an outside institution for evaluation of pulmonary hypertension (PH) and further medical management. His underlying diagnosis was unknown at the time of transfer. He underwent cardiac catheterization on hospital day 2, which revealed a pulmonary vascular resistance (PVR) index of 19.4 Woods units/m2 with a normal wedge pressure of 10 mm Hg and a transpulmonary gradient of 46 mm Hg. However, with the addition of pulmonary vasodilator therapy, he developed significant pulmonary edema and worsening respiratory status. Computed tomography scans of the lungs were suggestive of PVOD. While undergoing lung transplant evaluation, he developed worsening hemodynamic and respiratory status. He was cannulated for peripheral VA ECMO on hospital day 19 via the right internal jugular vein and carotid artery. He was supported for 57 days using this configuration, but because of his age and activity, cannula malposition was a frequent and serious problem, requiring formal surgical repositioning on 5 occasions. This sedation requirement, which prevented meaningful rehabilitation, as well as the progression of his RV dysfunction, ultimately prompted conversion to central VA cannulation. After conversion, he was extubated and participated in age-appropriate rehabilitation before undergoing lung transplantation on hospital day 87, with a total of 71 days of ECMO support.
Patient 3 was a 2-month-old female with surfactant protein B deficiency transferred to our institution for lung transplant evaluation and listing. Initially managed with noninvasive positive pressure ventilation, progressive respiratory failure necessitated intubation, sedation, and neuromuscular blockade on day of life 35. After transfer to our hospital, she was placed on central VV ECMO on hospital day 32 and supported for 60 additional days before undergoing lung transplantation. While on central VV ECMO, she was extubated and managed on high-flow nasal cannula during the day and continuous positive airway pressure at night to help maintain lung recruitment and mitigate potential RV strain. Sedation was weaned before transplant, and she participated with physical therapy and occupational therapy in developmentally appropriate rehabilitation.
Patient 4 was a 2-month-old female with ABCA3 mutation resulting in surfactant dysfunction and severe respiratory failure who was transferred to our institution for lung transplant evaluation and listing. She arrived intubated, and on hospital day 13 was placed on central VV ECMO and supported for 31 days before undergoing transplantation. Once on ECMO, sedation and neuromuscular blockade were stopped and she was extubated and received similar care to patient 3. Echocardiogram 11 days after cannulation demonstrated moderately depressed RV function. Milrinone therapy was initiated with improvement in function before transplantation.
Patient 5 was a 13-year-old male with newly diagnosed pulmonary arterial hypertension and a remote history of D-transposition of the great arteries who underwent arterial switch operation as an infant. Echocardiogram demonstrated evidence of severe PH with RV dysfunction. Cardiac catheterization demonstrated mean pulmonary artery pressures of 90 mm Hg with a pulmonary capillary wedge pressure of 10 mm Hg and a calculated PVR of 34.2 Woods units × m2. Aggressive pulmonary vasodilator therapy was initiated; however, marginal hemodynamics did not allow for significant up-titration of intravenous prostacyclins. He was evaluated and listed for lung transplantation and underwent central VA ECMO cannulation via a modified technique given the previous arterial switch operation and anterior translocated MPA.
He was extubated and participated in daily physical and occupational therapy while on central VA ECMO support for 18 days before lung transplantation. His postoperative course was complicated by bleeding requiring reoperation.
Patient 6 was a 17-year-old female with end-stage lung disease and portal hypertension related to her underlying diagnosis of cystic fibrosis. Failed attempts with noninvasive and invasive mechanical ventilation to manage progressive hypercapnia and hypoxemia prompted peripheral VV ECMO with subsequent transition to central VV ECMO in the described configuration 4 days later. Like the other patients, while on this support she was successfully extubated and participated in meaningful rehabilitation activities to improve her overall candidacy for dual lung-liver transplantation. Unfortunately, she developed Candida fungemia, with mediastinitis, sternal osteomyelitis, which led to removal of active transplant listing. Candida was a known organism this patient routinely grew from respiratory cultures, yielding concern for translocation from her lungs to thoracic cavity and eventual disseminated infection. Because she was no longer a transplant candidate, the family elected for comfort measures. ECMO support was discontinued, and she died peacefully with her family surrounding her. Figure 3 provides a graphical display of patient demographics, central VA and VV cannulation configurations, stages of targeted rehabilitation for patients on ECMO, outcomes after ECMO cannulation, and implications for clinical significance in this patient population.
Infants and young children requiring lung transplantation present a unique challenge. The insidious, progressive nature of the diseases that require lung transplantation in this population can result in an unrelenting hypoxemic, hypercapnic respiratory failure that often requires prolonged mechanical ventilation and heavy sedation to survive. Coupled with the gas exchange associated with these diseases is the detrimental effect on the functional architecture of the pulmonary vasculature, often causing substantial increases in PVR that, over time, can induce RV dysfunction. In such a difficult setting, the medical teams are faced with managing cardiopulmonary failure while also attempting to ensure good physical and nutritional status optimizing the patient's overall condition and potential for a successful recovery from transplant surgery once suitable donor organs have been procured.
More centers are using ECMO as a bridge to transplant.
However, since that time, ECMO techniques have evolved and more recent data show that patients bridged with ECMO support have equivalent outcomes to those not requiring mechanical support before transplant.
Rehabilitation using an “awake” ECMO strategy in nonintubated patients while on mechanical support awaiting lung transplantation has also become more commonplace, not only for both pediatric and adult patients on VV ECMO but also for adult patients on VA ECMO as well.
However, the use of this type of “awake” ECMO has been traditionally limited to older children and adult patients with the developmental capabilities to understand what is happening to them and the danger posed if they displace the ECMO cannulas. Larger body size often lends larger vessels and more surface area to safely secure cannulas. Additionally, larger cannulas also provide more safety simply due to the cannula length and the longer distance between skin and inflow/outflow ports should a cannula be inadvertently displaced. Pediatric patients receiving single-site VV ECMO support, in particular, need frequent cannula repositioning and often require reintubation, sedation, and resuturing, which, over time, leads to skin erosion and loss of rehabilitation time and gains, and may ultimately negate the initial benefits sought with ECMO support.
On the basis of our experience, patients were able to tolerate sedation weaning and participate in age-appropriate rehabilitation activities with certain modifications made to accommodate the Berlin Heart EXCOR cannulas (Berlin Heart, Inc) and ECMO circuit. All patients had a dedicated ECMO specialist at the bedside who, during therapy activities, was responsible for monitoring the circuit and cannula stability. Depending on the type of activity, either 1 or 2 bedside nurses were present along with 2 to 3 senior physical or occupational therapists with expertise in ECMO for patient ambulation. Table 2 and Figure 4 outline our institutional ECMO rehabilitation approach for patients on ECMO. No ECMO or cannula-specific complications occurred during rehabilitation activities or during parent interactions with the patients. Specified times were scheduled to ensure adequate staffing to maintain patient safety because of the significant amount of manpower required for intensive therapy activities.
Table 2Components of therapy evaluation
Assessment of neurodevelopmental state
Tolerance to handling/tactile stimulation
Ability to maintain vital signs stable with basic cares/diaper changes, removal of boundaries, containment/swaddle
States of arousal/state regulation
Ability to maintain quiet alert or active alert state
Hands to mouth, pacifier
Tolerance to positional changes
Ability to maintain vital signs stable in supine, side lying, sitting, prone, standing
Range of motion
Assessment of joint mobility
Passive range of motion
Active range of motion
Cause of limitations
Assessment for abnormal muscle tone
Assessment of active movement of extremities
Head and trunk control
Hands to midline
Head in midline
Assessment of age-appropriate gross motor function
Patients with progressive lung disease requiring transplant often have elevated PVR, resulting in increased workload for the RV, which, over time, begins to fail. These patients face an increased risk of mortality secondary to lung disease and rising risk of morbidity and mortality from RV failure as a result of worsening PH. Mechanical RV unloading can help preserve function and may decrease morbidity and intensive care unit length of stay after lung transplantation because the resuscitated RV should recover more quickly. This form of mechanical unloading typically requires VA ECMO cannulation. Traditionally, in small pediatric patients, this has been via the neck vessels, which may or may not be repairable at the time of decannulation. This method comes with the need for moderate to deep sedation at times with intubation to maintain cannula position and patient safety.
Central VA ECMO cannulation with the venous drainage cannula placed in the MPA allows for pressure unloading of the failing RV, because it no longer has to pump against an elevated PVR and is instead able to easily send cardiac output to the ECMO circuit actively siphoning blood. This decrease in RV afterload allows for potential and beneficial RV remodeling before transplantation, possibly improving outcomes as pretransplant PH in patients awaiting lung transplant for diseases such as cystic fibrosis has been associated with worse outcomes.
Because blood is then returned to the aorta, RV afterload reduction is provided for the duration of ECMO support with this method. The RV is not, however, volume unloaded. Despite volume unloading of the left ventricle, we did not observe left ventricular dysfunction after transplant in these patients. Inotropic and vasoactive agents often can be immediately discontinued after initiation of support, allowing for institution of full enteral nutrition. As the Berlin Heart EXCOR cannulas (Berlin Heart, Inc) were used and secured in their usual fashion, ECMO support was provided with cannulas that were extremely durable and secure, located away from the head and neck. This provided more ability for physical activity compared with traditional ECMO cannulas in this age population. Given these benefits, early consideration for this form of support may be prudent in this patient population. Some centers have described a similar central technique using Berlin Heart EXCOR cannulas (Berlin Heart, Inc) within a paracorporeal lung assist device framework. Because of the potential for significant thrombotic events with this technique and the lack of pumping mechanism should cardiovascular collapse occur, we chose to use traditional ECMO support.
In patients who do not demonstrate echocardiographic or clinical evidence of RV dysfunction and do not need hemodynamic support, arterial cannulation and its associated risks may be avoided with adequate support provided via VV ECMO. To overcome the challenges associated with traditional single-site VV ECMO, the central VV ECMO technique with the Berlin Heart EXCOR cannulas (Berlin Heart, Inc) was used. The frequent need for repositioning, potential for recirculation, and limitations of neck mobility and cannula insecurity were all obviated. Patients could be extubated and awake while receiving developmentally appropriate targeted therapy and interactions with both the medical teams and their families while awaiting transplant. For the youngest infants, this may simply consist of appropriate oral intake, breathing spontaneously, and interacting with their surroundings, whereas for older patients, this will include more involved exercise regimens. Recirculation and its attendant dangers were not a concern because of the central configuration.
Unique challenges associated with this approach involved difficulty assessing clinical conditions. Because the patients' innate respiratory drive was minimal due to the ECMO circuit providing gas exchange, profound atelectasis can potentially ensue with “white-out” of the chest radiograph, which we did see in 1 patient on VV ECMO. Additionally, at times they appeared dyspneic with erratic breathing patterns, namely, after initial extubation. This breathing pattern also created challenges for patients when trying to take food orally, while sleeping or communicating with others, and often caused concerns for the medical staff related to the potential discomfort of the patients. Although this perception of discomfort improved to some degree overall with time, patients, families, and medical team members learned to adapt. The white-out appearance of the lung fields on routine imaging proved to be a paramount learning point. It prevented teams from being able to as readily identify usual thoracic pathology. Patient 1 was found to have a large pulmonary abscess at time of transplant. This was not identified on routine imaging and the patient never became febrile, likely in part due to the active temperature management of the ECMO circuit. Patient 3 had an unexpected cardiac arrest related to large pleural effusions undiagnosed on daily routine imaging prompting emergency bilateral chest tube placement. Therefore, we instituted routine weekly chest ultrasounds as part of our management algorithm for these patients. One patient on VA ECMO needed multiple oxygenator changes, thought in part to be due to the hypertensive MPA being used as the inflow to the VA ECMO circuit, thus lowering the transmembrane gradient, potentially increasing the propensity for thrombosis.
One patient with cystic fibrosis who developed fungal mediastinitis required withdrawal of support before transplant. Although we do not typically consider fungal colonization of the lungs a contraindication to lung transplant, perhaps caution should be exercised when considering extracorporeal support as a bridge to transplant in patients with known colonization/infection. After our experience with this patient, we now consider disseminated fungemia or bacteremia a contraindication to using central ECMO.
Central ECMO cannulation using Berlin Heart EXCOR cannulas (Berlin Heart, Inc) appears to be a safe and effective strategy for bridging awake, actively rehabilitating infants and young children, who otherwise would have limited mechanical support options, to successful lung transplantation. This approach allows for inotropic and vasoactive support weaning or discontinuation while mitigating potential end-organ injury by preventing episodes of profound hypoxemia or low cardiac output state. Consequently, for the sickest patients this strategy may decrease risk of death on the wait-list and improve their physiologic state entering the transplant procedure and potential for a successful postoperative recovery.
Conflict of Interest Statement
The authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.