Bridge to Transplantation
One of the major limitations to lung transplantation in infants prior to the actual operation itself is the lack of suitable donors. Waitlist time for these patients can be unpredictable, with reported times ranging between 27 and 48 days; therefore, physicians must be ready to support infants for an extended period of time.[1,6] In addition, infants have the highest waitlist mortality rates compared to older pediatric patients, indicating that listed infants tend to be sicker. Early referral for transplant evaluation prior to the onset of respiratory failure may thus be beneficial in this age group, as it would possibly shorten the time to transplant, thereby halting the progression of the underlying pathology and reducing waitlist mortality, Despite their increased waitlist mortality, infants who survive to transplant have promising long-term outcomes. Thus selection of the appropriate bridge-to-transplant approach is crucial for ensuring survival of these patients successful transplantation and beyond.
In older children and adolescents, extracorporeal membrane oxygenation (ECMO) support has shown favorable results as a bridge to transplantation.[8,9] The benefits of this modality are particularly pronounced when paired with a cannulation strategy compatible with physical rehabilitation, such as veno-venous (VV) ECMO. In infants, however, ECMO support has relied mainly on veno-arterial (VA) cannulation and has been associated with lower rates of survival to discharge. Given these results, some institutions, including St. Louis Children's Hospital (SLCH), have contraindicated lung transplantation in infants placed on VA ECMO. Available data on infants bridged to lung transplantation on awake VV ECMO are scarce. Given the positive results in older children, at SLCH we attempted to bridge two infants on central VV ECMO, cannulating the right atrium and pulmonary artery, and then tunneling out the Berlin H
Heart cannulas through the abdominal wall and closing the sternum (undergoing peer review). This strategy allows for reduced sedation and improved physical rehabilitation; although both patients improved initially, they eventually had redirection of care and died 67 and 27 days after VV ECMO placement. We believe this approach may yield promising results in the future, although more experience is needed to establish its utility as a bridge to lung transplantation.
Conversely, the use of paracorporeal lung assist device (PLAD) as a bridge to lung transplant has shown promising results in this age group. This technique, consisting of the placement of an extracorporeal oxygenator with cannulation of the pulmonary artery and left atrium without an interposed pump, has been described in three infants and one 14-month-old child. Some advantages of PLAD over ECMO include extubation and the reduction of sedatives and right ventricular afterload, which improve ventricular function and facilitate physical rehabilitation. Moreover, the PLAD circuit is more stable, allowing for longer support times. Experience with this bridging strategy in pediatric patients is limited; of the three infants on PLAD, one was successfully bridged to lung transplant and two died while awaiting transplant 54 and 72 days after cannulation.[13,15] The 14-month-old placed on PLAD support significantly improved and was discharged home. Currently this technique is limited to infants with suprasystemic primary pulmonary hypertension; by offering a low-resistance circuit, PLAD allows for blood to be shunted to the oxygenator, thereby reducing right ventricular stress and remodeling. Modifications to this strategy, such as the use of Berlin Heart cannulas in both the left atrium and the pulmonary artery, and changes to the anticoagulation therapy, have been made over the years, resulting in improved outcomes.[12,14] However, these studies have been limited to a small number of patients at a single institution, and PLAD use in infants with other indications for lung transplantation has yet to be explored.
In addition to circulatory support, the need for mechanical ventilation in the preoperative period plays an important role in infants awaiting lung transplant. Given the diagnostic composition of this age group, infants are significantly more likely to require intubation prior to transplant.[1,17] In contrast to older patients, an analysis of the United Network for Organ Sharing (UNOS) database showed that infants ventilated mechanically prior to lung transplant had improved long-term survival. This finding is possibly due to the different underlying disease processes, as older children are overwhelmingly more likely to be transplanted for cystic fibrosis compared to infants, and preoperative ventilation before lung transplantation in pediatric cystic fibrosis patients is associated with higher rates of early graft dysfunction and 1-year mortality. As with PLAD and awake VV ECMO, the use of tracheostomy for mechanical ventilation allows for physical rehabilitation while awaiting transplant. In a single-center study on pediatric patients bridged to lung transplant with tracheostomy or endotracheal intubation for respiratory failure, 12 of 16 patients were alive 1 year after transplant, although it is unclear whether any of these patients were infants. However, the hemodynamic advantages of both PLAD and awake VV ECMO potentially make these better bridging options than tracheostomy.
American Journal of Transplantation. 2021;21(1):15-20. © 2021 Blackwell Publishing