172: Ex Vivo Lung Perfusion

Introduction

Lung transplantation is a life-saving therapy for patients suffering from end-stage lung diseases. The number of patients waiting for lung transplantation, however, greatly exceeds the number of donor lungs available. Moreover, only about 15% of lungs from multiorgan donors are deemed usable for transplantation.¹ Most potential lungs are considered unsuitable as the result of injury that occurs with brain death and ICU-related complications (i.e., barotrauma or lung edema associated with fluid resuscitation). Since primary graft dysfunction leads to severe early and long-term consequences for lung transplant recipients, transplant teams tend to be very conservative in their selection of donor lungs. As a result, fewer organs are selected and the wait list mortality may climb as high as 30% to 40%.^2,3 While the current cornerstone of clinical lung preservation is to limit the metabolic rate of the donor lung by hypothermia, this strategy best serves lungs meeting ideal acceptance criteria. The current donor organ shortage has prompted most donor programs to use increasing numbers of extended criteria organs, where lung function is not as assured as with an ideal lung. The ex vivo phase of organ preservation, prior transplantation into the recipient, provides a window of opportunity for further evaluation and even resuscitation of these compromised lungs. To take advantage of this opportunity, however, it is necessary to preserve the donor organs under normothermic or near-normothermic conditions. One strategy, termed ex vivo lung perfusion (EVLP), attempts to simulate in vivo conditions through ventilation and perfusion of the donor lung graft. One important advantage of normothermic perfusion is that it maintains the active metabolic functions of the lung, providing an opportunity for continued assessment of the organ during the ex vivo phase of organ preservation, active treatments, and restoration of normal function. This chapter focuses on the resurgence of EVLP, important technical aspects, clinical outcomes, and future perspectives.

Normothermic EVLP—Historical Perspectives

Originally proposed in 1938 by Carrel for organs in general and then in 1970 by Jirsch et al. for the evaluation and preservation of lungs in cases of distant procurement, attempts at EVLP in those eras failed because of an inability to maintain the air/fluid barrier integrity within the lung, which led to the development of edema and increased pulmonary vascular resistance in the donor lung.^4,5 For most of the past century, EVLP systems were used in small animal studies of lung physiology. More recently, normothermic perfusion became a research focus as a preservation alternative in experimental models of lung, liver, and kidney transplantation.^6–11

Experimental Work

The resurgence of EVLP as a potential tool in lung transplantation started with the work of Steen et al.¹² This group described EVLP as a method to reassess lungs after uncontrolled donation from cardiac death donors (DCD),¹³ since these organs cannot be evaluated in vivo. A lung perfusion specific solution (Steen^...