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University of Rome "La Sapienza", Department of Thoracic Surgery, Policlinico Umberto I, V.le del Policlinico, Rome, 00100 Italy
(Email: federico.venuta{at}uniroma1.it).
A number of different techniques for lung preservation have been tested in experimental models; many of them were successfully transferred to the clinical practice. However, none of these techniques is ideal because the early function of the transplanted lungs may still be deranged by primary graft dysfunction. High-volume antegrade pulmonary artery flushing with extracellular solutions is currently the most widely used method of lung preservation. However, it still presents some drawbacks (ie, pulmonary arterial vasoconstriction requires bolus injection of prostaglandin E; the bronchial circulation is not perfused; clots and fat emboli may jeopardize the uniformity of flushing and graft reperfusion). Retrograde pneumoplegia delivered through the pulmonary veins may help to eliminate the residual blood, clots, and fat emboli; it is uniformly distributed and also flushes the bronchial circulation [1–5]. This technique has been validated experimentally; it has been found useful in the clinical setting, and it is now adopted by many transplant centers; it has been proposed for living related lung transplantation [6] and nonheart beating donors [7]. Timing of the retrograde flush is still debated. Most of the authors use it at the time of harvesting as a completion of the antegrade flush; only one study has proposed to deliver it at the time of implantation [8]; this study was proposed on the base of an experimental observation demonstrating functional improvement with late additional flushing [9]. That is the only prospective, randomized clinical study available [8], although with very small groups; it clearly demonstrated as the benefit of pre-implantation retrograde pneumoplegia with significantly better chest roentgenogram score, shorter intubation time, and lower extravascular lung water index after the completion of implantation, and afterward the differences were not statistically significant due to the intense diuretic therapy and fluid depletion usually used after transplantation. In addition, the indexed alveolar—arterial oxygen gradient, intrapulmonary shunt fraction, and mean airway pressure were improved. Lung biopsy performed after reperfusion showed a reduction of alveolar edema. These are probably the only improvements that can be observed with an ischemia time within the 6 hours; this ischemia time is not critical for the lungs and probably fails to show the potential impact of a better preservation solution or a different delivery route; differences may be amplified with a longer ischemia time, as in most of the experimental studies.
The study by Ferraro and colleagues [10] is a retrospective analysis reporting on three subsequent groups of patients transplanted during a period of 6 years; these groups include re-transplantation and double lung–kidney transplants. The authors should be commended for the results obtained (less than 10% mortality). The three groups look homogeneous from the statistical point of view, even if there are some differences in terms of number of single/double transplants, ischemia time, and characteristics of the donors (ie, smoking habit and percentage of trauma patients). This retrospective study does not confirm many points that are nowadays fully agreed to by most of the transplant centers (ie, the advantages of pneumoplegia with an extracellular solution of fluid restriction, and also of the use of a retrograde flush, in that series, that was administered before implantation). The ischemic time in those groups was very short (ie, approximately 3 and 5 hours for the first and second lung, respectively); this is the potential reason why those variables did not show any significant difference. The potential advantage of preimplantation retrograde flushing is not confirmed in this retrospective study; however, unfortunately, it lacks of a control group with immediate retrograde flushing delivered at the time of harvesting, which could have helped to evaluate if the problem with retrograde perfusion concerns only timing. At least it was confirmed that preimplantation retrograde pneumoplegia is not harmful.
These are the problems that may be encountered with a retrospective study; only prospective randomized studies should be designed to evaluate variables that need clear differences to be validated and widely accepted. This would take a little more time, but results will be much more consistent and interesting.
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