Prolonged Lung Allograft Ischemia and Posttransplant Outcome
Authors: Ankit Bharat
Journal: JAMA Surgery (2015)

Mammalian cells do not possess intrinsic tolerance to hypoxiaor ischemia.Hypothermia cansuppress cellularmetabolism and the chemical reactions that drive the detrimental effectsofhypoxiaandischemia. However, hypothermia also nonspecifically inhibits vital enzymatic processes required formaintaining cellular integrity and tissuehomeostasis. Therefore, reducing ischemia time and exposure to hypothermia during organ transplantation is desirable. The traditionally acceptedupper limit for total ischemia in lungallografts is about 6 hours.1 Longer ischemia has been shown to decrease lungallograft function.2Contrastingly,other studies,3 including thearticlebyGrimmandcolleagues,4 argue thatprolonged ischemia more than 6 hours might not impact shortor long-term outcomes. Ischemia time isoneamongamultitudeof risk factors that impact lung allograft function (or dysfunction).While still important, itmight spuriously appear to have decreased significance, if other risks are disproportionately increased. Because risk factor–specific contribution inallograft dysfunction remainsunclear andhighlyvariabledependingon thedata set used, risk-adjustmentmodels inmultivariate analysesmight not accurately account for such biases. For instance, keeping all other variables constant, a 35-year-old recipient with cystic fibrosis is likely to do better with lungs exposed to 3-hour ischemiawhencomparedwith8-hour ischemia.However,even with 8-hour ischemia, a 35-year-old patient with cystic fibrosis will perhaps have better outcome than a 65-year-old ventilated patient with scleroderma and secondary hypertension receiving lungs with 5-hour ischemia. While the study by Grimm and colleagues4 includes a large cohort from a reliable source, there are certain caveats. Warm allograft ischemia is worse than cold5; however, owing to limitations of the database used, distinction between warm and cold ischemia could not be made. Variables, such as center volume and preservative solution, are also important but could not be included owing to unavailability of data. Further, for bilateral transplants, the study used ischemia time after reperfusion of the second lung. Because transplant outcome is dependent on the function of both lungs, the detrimental effects of prolonged ischemia in the second lung might be mitigated by the timely perfusion of the first. Additionally, double-lung transplants are expected to have longer total ischemia, but better outcomes, than single-lung transplants. It is hard to make the argument that prolonged ischemia is not worse than shorter ischemia when there is considerable discrepancy in the proportion of double and single transplants between the 2 groups. Finally, it is more valuable to study ischemia time as a continuous variable. With the introductionof strategies for normothermicperfusion of lungs, prolonged ischemia might not remain an issue in the future. However, in the contemporary lung transplantpractice, unforeseencircumstancesormedical necessity might sometimes preclude completion of lung transplantationwithin the accepted limits of allograft ischemia. Thepresent studybyGrimmandcolleagues4does lendreassurance that satisfactory allograft function can still be achieved.Nevertheless, efforts should be made to ameliorate all potential risks to the allograft, including ischemia time, to achieve the best possible outcomes.