Ex Vivo Lung Perfusion Yields Good Donor Lungs

The use of normothermic ex vivo lung perfusion (EVLP) to make suboptimal donor lungs more viable for transplant yields clinical outcomes similar to those obtained with conventionally selected lungs, according to a new study.

Researchers at the University of Toronto (Canada) conducted a prospective, nonrandomized clinical trial, subjecting lungs considered to be high risk for transplantation to four hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen (PO(2)) to the fraction of inspired oxygen (FIO(2)) of less than 300 mmHg. Lungs with acceptable function were subsequently transplanted; lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was graft dysfunction 72 hours post-transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit (ICU) and hospital. A total of 136 lungs were transplanted.

The results showed that during the study period, lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mmHg in the donor lung to 414 and 443 mmHg at one hour and four hours of perfusion, respectively; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group compared to 30% in the control group. No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. The study was published in April 14, 2011, issue of the New England Journal of Medicine (NEJM).

"Extracorporeal resuscitation of lungs is likely to be useful for expanding access to donor lungs. The future, I think, is that the device can be used to treat the lungs with medications to reverse the causes of lung dysfunction, and perhaps to treat infections that currently prevent us from using some donor lungs,” said lead author Marcelo Cypel, MD, of the Toronto Lung Transplant Program at the University of Toronto. "In principle, EVLP could also be used to administer gene therapy or other treatments to improve long-term outcomes after transplant. It's exciting to see this turning into something we can use for patient care.”

An EVLP system involves perfusion of the lungs outside of the body with a dilute blood supply containing a solution that can potentially recondition and improve their function; the apparatus also includes a ventilator to inflate the lungs. The system permits the re-expansion of collapsed lung regions; removal of secretions; removal of clots from the lung circulation; improved lung ventilation; and a better and more complete assessment of lung function.

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