Medical Professional Publications

Is Less Ischemic Time Always Better for Pediatric Lung Transplants?

Columbus, OH — January 2017

Three studies by researchers at Nationwide Children's Hospital lead them to one conclusion: graft ischemic time is important in lung transplantation, but too complicated to set a threshold. It's not even clear that less ischemia is always better.

"Depending on the strategies used to control for confounding factors, we have found that the relationship between prolonged ischemic time and worse clinical outcomes can be more or less apparent," says Dmitry Tumin, PhD, statistical director of the Center for Epidemiology of Organ Failure and Transplantation at Nationwide Children's and an author of the studies.

"The patient, the transplant center, the experience of the transplant center, and the diagnosis are all variables influencing outcomes," says Dr. Tumin, who is also an adjunct assistant professor of Pediatrics at The Ohio State College of Medicine.

Contrary to the widely-held belief that shorter ischemic times benefit the patient, two studies of pediatric patients showed that ischemic times of less than four hours were associated with lower rates of survival. Among all children undergoing lung transplantation, ischemia time of four to six hours was associated with the highest survival rates.

In the third study, of 12,447 adults, the researchers found that patient survival in high-volume transplant centers, despite longer ischemic times, was better than in low-volume hospitals where transplants tended to involve shorter ischemic times.  As in the pediatric cohort, the distance the organ was transported from donor to recipient had no effect on outcomes. 

"We don't have any scientific evidence of what the ideal ischemic time is, but we're seeing that some level of ischemia is associated with better outcomes for kids," says Don Hayes Jr., MD, medical director of the Lung and Heart-Lung Transplant Program at Nationwide Children's and lead author of the studies.

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 Health, referred to a 2013 study that suggested the upper limit for ischemic time in adults is up to 12 hours in some cases. "There's probably something innate involved between pediatric and adult organs," he says.

All three studies are retrospective, using data supplied by the United Network for Organ Sharing. 

The first pediatric study focused on 199 patients with cystic fibrosis who received their initial transplant between 2005 and 2013. The second is based on 930 children and adolescents who received their initial transplants due to a variety of diseases and disorders, between 1987 and 2013.

The researchers found increased donor age and greater BMI were associated with increased mortality risk among the second group. More recent transplants were associated with better survival.

In the adult study, a multivariable survival analysis found that longer ischemic times at centers that performed between 50 and 150 transplants from 2005 to 2015 were associated with increased mortality rates. No such association was found at centers that performed 350 or more transplants in that time.

Lung transplants at the high-volume centers were more likely to be single lung transplants, involve older recipients and involve recipients with a greater priority score for donor organs, the study found.

The researchers hope their findings may assist doctors in the management of donor lung grafts for children but concede the studies strongly point to the need for more research.  

"There should probably be some consideration of these findings in how donor organs are allocated, to optimize the use of pediatric organs, of which there are far fewer available than adult organs," Dr. Hayes says.

In the meantime, Hayes and his colleagues are working to develop animal models of lung injury and ischemia and are investigating a potential therapy to ameliorate the extent of this injury. 

References:

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 Sep; 51(9): 908-13.

Hayes D Jr, Hartwig MG, Tobias JD, Tumin D. Lung transplant center volume ameliorates adverse influence of prolonged ischemic time on mortality. American Journal of Transplantation. 2016 Jun 9. [Epub ahead of print]

Hayes D, Joy BF, Reynolds SD, Tobias JD, Tumin D. Influence of graft ischemic time and geographic distance between donor and recipient on survival in children after lung transplantation. The Journal of Heart and Lung Transplantation. 2016 Oct; 35(10):1220-1226.

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