By Ramsey Hachem, M.D.
Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care
November, 2009
The number of lung transplants performed annually has increased significantly in recent years. In fact, over 1,400 procedures were performed in the United States in 2007 compared to less than 1,000 procedures in 2000. However, the number of lung transplants performed remains substantially smaller than most other solid organs. For example, over 16,000 kidney transplants were performed in 2007 and over 10,000 of these were from deceased donors. This is in part because two kidneys are usually retrieved from one deceased donor for two recipients, whereas two lungs are often retrieved for a single recipient. Indeed, bilateral lung transplants are performed for approximately 60% of recipients in the United States. Nonetheless, even after accounting for the number of bilateral procedures, the disparity between the number of lung and kidney transplants performed is still striking. Furthermore, in liver transplantation where a single organ is retrievable from each donor, over 5,500 liver transplants were performed from deceased donors in 2007. The difference in the number of lung, liver, and kidney transplants performed is driven primarily by differences in donor organ utilization rates. Approximately 75% of potentially recoverable kidneys and livers were transplanted in 2007 compared to less than 20% of lungs. In other words, kidneys and livers can be retrieved and transplanted from approximately 75% of donors whereas lungs can only be transplanted from less than 20% of donors. Lungs are most susceptible to injury after brain death, such as neurogenic pulmonary edema, aspiration, pneumonia, or ventilator induced lung injury, and this renders most organ unsuitable for transplantation. Yet, the death rate on the waiting list is significantly higher for patients awaiting a lung transplant (125 deaths per 1,000 patient-years at risk) than for those awaiting a kidney transplant (65 deaths per 1,000 patient-years at risk). Clearly, retrieving lungs from a greater proportion of deceased donors would increase the number of transplants performed and reduce the death rate on the waiting list. Ideally however, this should not compromise donor organ quality.
Over the past several years, there has been growing research in the field of ex vivo lung perfusion, or perfusing the lungs outside of the body. After retrieving lungs from the donor, a standard ventilator is used to inflate them using relatively low pressures and oxygen concentrations to avoid overdistention and further lung injury. The lungs are then perfused with a mixture of a special preservation solution and red blood cells. Using this system, lungs can be maintained for up to 12 hours, and this allows additional time to assess their suitability for transplantation. More importantly, some interventions can be implemented to improve lung function and convert unsuitable organs into lungs suitable for transplantation. For example, the tonicity of the preservation solution can be altered to remove edema fluid from the lungs via diffusion into the perfusion solution. This would be beneficial in cases where lungs have been injured by neurogenic pulmonary edema, a common complication after brain death. Furthermore, maintaining donor lungs at normal body temperatures would preserve the necessary cellular metabolism for endogenous reparative processes that are inhibited by hypothermic storage. Theoretically, this would allow an injured lung to partially repair itself. Most of this encouraging research has been performed in animal models. However, a Swedish group reported their early clinical experience using this technique. The group was able to successfully recondition six of nine pairs of lungs initially deemed unsuitable for transplantation, and these six pairs of lungs were transplanted into six patients. All recipients survived three months after transplantation indicating adequate early pulmonary function, but two recipients died in the first year after transplantation of apparently unrelated causes. This early experience with this technique is encouraging, and a multi-center clinical trial is planned in the United States.
The real impact of ex vivo lung perfusion on donor organ utilization, the number of transplants performed, and long-term outcomes after transplantation remains to be seen. However, this technique offers the possibility of addressing the donor organ shortage that has limited a more wide spread use of lung transplantation.