Ann Thorac Surg 2007;84:e4-e5
© 2007 The Society of Thoracic Surgeons
Case Reports
Donor Fat Embolism and Primary Graft Dysfunction After Lung Transplantation
José Padilla, MDa,*,
Carlos Jordá, MDa,
Juan Carlos Peñalver, MDa,
José Cerón, MDa,
Juan Escrivá, MDa,
Francisco Vera-Sempere, MDb
a Department of Thoracic Surgery, Lung Transplant—Cystic Fibrosis Unit, La Fe University Hospital, Valencia, Spain
b Department of Pathology, La Fe University Hospital, Valencia, Spain
Accepted for publication April 11, 2007.
* Address correspondence to Dr Padilla, Servicio de Cirugía Torácica, Unidad de Trasplante Pulmonar—Fibrosis Quística, Hospital Universitario La Fe, Avenida de Campanar 21, Valencia, 46009, Spain (Email: jpadilla{at}comv.es).
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Abstract
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Primary lung graft dysfunction is one of the major causes of perioperative morbidity and mortality in lung transplantation. Primary lung graft dysfunction is a clinical syndrome occurring in the immediate postoperative period after lung transplantation and is characterized by severe hypoxemia, pulmonary edema, and pulmonary infiltrates on chest x-ray film, requiring that the patient remain intubated and thus favoring pulmonary infection, sepsis, and subsequent multiple organ failure in the transplanted patient. It has recently been shown that unexpected pulmonary embolism is relatively common in the donor and is associated with primary lung graft dysfunction. However, we believe that only one case of primary lung graft dysfunction due to pulmonary fat embolism has been documented histologically in patients undergoing lung transplantation. The objective of this study is to report our experience with a case of primary lung graft dysfunction due to fat embolism in the donor lung detected in the morphologic study.
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Introduction
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Primary lung graft dysfunction (PLGD) remains one of the major causes of perioperative morbidity and mortality in lung transplantation [1]. Primary lung graft dysfunction is a clinical syndrome occurring in the immediate postoperative period after lung transplantation and is characterized by severe hypoxemia, pulmonary edema, and pulmonary infiltrates on chest x-ray films, requiring that the patient remain intubated and ventilated with high concentrations of oxygen and nitric oxide. This favors pulmonary infection, sepsis, and subsequent multiple organ failure in the transplanted patient. Oto and colleagues [2] have recently shown that unexpected pulmonary embolism (clot or fat) is relatively common in the donor and is associated with PLGF. However, we believe that only one case of PLGD due to pulmonary fat embolism [3] has been documented histologically by lung biopsy after lung transplantation.
The objective of this study is to report our experience with a case of PLGD due to fat embolism in the donor lung detected in the morphologic study.
The transplant recipient was an 18-year-old man diagnosed with cystic fibrosis who was on the waiting list for lung transplantation due to respiratory insufficiency with a forced vital capacity of 30% and forced expiratory volume in 1 second of 18%.
The donor was a 31-year-old woman who was a nonsmoker with an otherwise unremarkable medical history, with brain death due to head injury after a road traffic accident and fractures of the sternum, pelvis, and right femur. The duration of her intensive care unit stay was 24 hours. Her chest x-ray film was within normal limits. Her PaO
2 was 528 mm Hg under ventilation with a PIO
2 of 1 and a positive end-expiratory pressure of 5 mm H2O. The macroscopic appearance of her lungs was normal. Both lungs were perfused through the main pulmonary artery with modified Euro-Collins solution at 4°C. A second retrograde lung flush performed before implantation did not find evidence of blood clots or fat emboli, although fat droplets were noted in the supernatant of the reperfusion fluid. No germ was isolated in the analysis of the bronchoalveolar lavage fluid.
Sequential bilateral lung transplantation was performed. Ischemia time was 90 and 150 minutes for the first and second lung, respectively. Extracorporeal circulation was required during implantation of the second lung because of hemodynamic instability. An atypical lingular and middle lobe segmentectomy was also performed to adapt the size of the donor’s lungs to the recipient.
The chest x-ray film performed in the immediate postoperative period revealed a significant pattern of pulmonary edema (Fig 1). The PaO
2/PIO
2 ratio was 151, 167, 350, and 297 at 6, 24, 48, and 72 hours, respectively, thus requiring ventilation with high concentrations of oxygen and nitric oxide and a negative water balance. After excluding infection and hemodynamic alteration as the cause of the patient’s clinical condition, a diagnosis of PLGD was established. The patient was extubated at 96 hours from admission and discharged from the recovery unit and hospital at 6 and 34 days post-transplantation, respectively.
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Fig 1. Chest x-ray film performed in the immediate postoperative period revealed a significant pattern of pulmonary edema.
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The morphologic study of the segmentectomies performed on both donor lungs revealed the presence of intravascular embologenic material in the middle-sized arterial vessels consisting of islands of adipose cells intermixed with hematopoietic bone marrow elements (Fig 2).
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Fig 2. Panoramic view showing lung parenchyma with a bifurcated middle-sized arterial structure and partial embolic occlusion of its lumen. (Larger inset: hematoxylin and eosin; x150.) Detail of microscopic image of intravascular embolic filling showing adipose cell islands and hematopoietic bone marrow elements. (Smaller inset: hematoxylin and eosin; x250.)
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The patient died 28 months after transplantation from chronic rejection.
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Comment
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Primary lung graft dysfunction continues to be a significant cause of perioperative and early mortality in lung transplantation, requiring that acute rejection, pneumonia, heart failure, or thrombosis of the venous suture is previously excluded for its diagnosis [1]. The mechanism leading to the development of PLGD is not well understood, although ischemia-reperfusion injury has been identified as a major component. Other factors have also been noted, although reports of unsuspected donor pulmonary embolism as the cause of this clinical syndrome have been anecdotal [3–5]. However, Oto and colleagues [2] found that unsuspected pulmonary embolism was relatively common, with an incidence of 38% in a series of 78 lung donors, and it was significantly related to PLGD and 1-year survival. Death due to head trauma associated with long bone fracture and a smoking history of more than 20 pack-years were significant donor risk factors for pulmonary embolism.
One of the problems posed by PLGD it that it is very difficult to establish the diagnosis during donor maintenance. On the other hand, as occurred in our case, the chest roentgenogram is usually normal and the PaO
2/PIO
2 ratio remains with the limits defining a donor as optimal. This fact could be explained by reflex bronchoconstriction of nonperfused pulmonary areas; however, after transplantation the denervated lungs might not be able to correct a ventilation/perfusion mismatch; this would result in impaired oxygenation in the implanted lung [2]. Also, the endothelium is more than a simple barrier and the presence of any stimulus can activate the inflammatory cascade that will be implemented by ischemia and especially pulmonary reperfusion. In our case, the presence of fat embolism favored the formation of blood thrombi, which conditioned a maldistribution of preservation solution. The diagnosis was established during retrograde donor lung flush before implantation, which underscores the importance of performing this second flush of the pulmonary vascular bed.
Unlike the donor lung with known pulmonary embolism in whom certain therapeutic strategies can be adopted to obtain a viable graft [6], there is no treatment when the diagnosis is made during retrograde flush of the donor lung. Anticoagulation with warfarin has been successfully used in a case of donor cerebral tissue pulmonary embolus [5]. Retrograde flush at the time of procurement might have a protective effect on damage endothelium. Further therapeutic strategies, such as complement inhibitor [7] or antagonist of platelet-activating factor [8], must be considered.
In conclusion, unsuspected pulmonary embolism shows that the presence of subclinical lesions in the lung donor is not uncommon, which could explain the considerable number of lung transplant recipients who have PLGD develop for which the cause was previously unknown.
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References
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- Christie JD, Carby M, Bag R, Corris PA, Hertz M, Weill D. Report of the ISHLT working group on primary lung graft dysfunction part II: definitionA consensus statement on the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2005;24:1454-1459.[Medline]
- Oto T, Rabinov M, Griffiths AP, et al. Unexpected donor pulmonary embolism affects early outcomes after lung transplantation: a major mechanism of primary graft failure? J Thorac Cardiovasc Surg 2005;130:1446-1452.[Abstract/Free Full Text]
- Waller DA, Bennett MK, Corris PA, Dark JH. Donor-acquired fat embolism causing primary organ failure after lung transplantation Ann Thorac Surg 1995;59:1565-1566.[Abstract/Free Full Text]
- Rosendale BE, Keenan RJ, Duncan SR, et al. Donor cerebral embolism as a cause of acute graft dysfunction in lung transplantation J Heart Lung Transplant 1992;11:72-76.[Medline]
- Simonetti VA, Basha MA, Allenspach L, Klosterman KG, Nakhleh R, Higgins RS. Donor cerebral tissue pulmonary emboli in a functioning transplanted lung Clin Transplant 1998;12:504-507.[Medline]
- Fischer S, Gohrbandt B, Meyer A, Simon AR, Haverich A, Struber M. Should lungs from donors with severe acute pulmonary embolism be accepted for transplantationThe Hannover experience. J Thoracic Cardiovasc Surg 2003;126:1641-1643.[Free Full Text]
- Keshavjee S, Davis RD, Zamora MR, de Perrot M, Patterson GA. A randomized, placebo controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings J Thoracic Cardiovasc Surg 2005;129:423-428.[Abstract/Free Full Text]
- Wittwer T, Grote M, Oppelt P, Franke U, Schaefers HJ, Wahler T. Impact of PAF antagonist BN5201 (Ginklolide B) on post-ischemic graft function in clinical lung transplantation J Heart Lung Trasnplant 2001;20:358-363.
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Abstract
Introduction
