Columbus, OH - July 2016
While common practice in lung transplantation is to limit graft ischemic time as much as possible, some evidence in adults suggests that times even longer than six hours do not necessarily result in worse outcomes. It has been unclear, though, how ischemia times affect survival in children with cystic fibrosis (CF) who require a lung transplant.
A recent study from physician-scientists at Nationwide Children’s Hospital shows that an ischemia time of four to six hours is actually associated with better long-term survival than either a shorter or longer ischemic period.
“The lung itself is a low-metabolic organ, so it didn’t surprise me that the lung could tolerate a longer period of ischemia and still do well after lung transplantation,” says Don Hayes Jr., MD, medical director of the Lung and Heart-Lung Transplant Program at Nationwide Children’s and lead author of the study. “What was surprising was the fact that we found a sweet spot in which children with cystic fibrosis seem to do better.”
The study, published in Pediatric Pulmonology, retrospectively evaluated data on 199 pediatric patients with cystic fibrosis who were first-time recipients of a lung transplant from a cadaveric donor between May 2005 and September 2013. The data was drawn from the United Network for Organ Sharing (UNOS) registry.
The mean distance between donor and recipient hospitals was 446 km. Donors and recipients were located at the same hospital only nine times. A total of 106 cases were in the four to six hour ischemia window, while 28 cases had ischemia times of less than four hours and 65 cases had times longer than six hours. Transplant recipients had a wide range of supplemental oxygen requirements.
Using univariate and multivariate analysis, the groups with graft ischemic times of less than four hours and greater than six hours were comparable -- both had significantly worse survival after lung transplantation compared to the group with graft ischemic times between four and six hours. Of covariates, only higher supplemental oxygen was also associated with increased mortality hazard.
The data from UNOS registry does not differentiate between warm ischemic time and cold ischemic time, so definitive conclusions about the role each plays aren’t possible, says Dr. Hayes, who is also a professor of Pediatrics, Internal Medicine and Surgery at The Ohio State College of Medicine and professor of Epidemiology at The Ohio State College of Public Health.
“Further research is needed to identify the mechanisms involved in this process, but the inferior outcomes associated with shorter ischemic times suggest that a certain level of hypothermia, as organs are placed in ice during this time of ischemia, suppresses certain cellular metabolisms and biomolecular pathways involved in the ischemia-reperfusion process that occurs in solid organ transplantation,” Dr. Hayes says.
The study has potential implications for transplant centers, as it suggests that they may lengthen the distance that acceptable lungs can travel from a donor to a pediatric recipient with cystic fibrosis.
“Transplant centers may be limiting themselves with ischemic time more than they need to,” Dr. Hayes says. “When a donor is located in the same hospital or in close proximity to a pediatric recipient with cystic fibrosis, transplant centers may want to even consider extending ischemic time to four to six hours based on the findings of our study.”
He continues: “This is counterintuitive to how we commonly think, but this is an area of lung transplant that has had limited research. There needs to be more to confirm what we found.”
Hayes D Jr, Tumin D, Kopp BT, Tobias JD, Sheikh SI, Kirkby SE. Influence of graft ischemic time on survival in children with cystic fibrosis after lung transplantation. Pediatric Pulmonology. 2016 Apr 29. [Epub ahead of print]