Subtherapeutic ganciclovir (GCV) levels and GCV-resistant cytomegalovirus in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5-10% of CMV-infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown. METHODS: A retrospective review was conducted in all 51 patients who underwent lung transplantation between March 2007 and June 2008 at Loyola University Medical Center. GCV resistance and outcome data of CMV-infected patients were analyzed to identify variables that may contribute to suboptimal response to CMV infection. RESULTS: During the 16-month period, CMV infection was identified in 21 of 51 lung transplant recipients. Ten of 21 patients (47.6%) had CMV infection with early response to GCV, and 11 patients (52.4%) had CMV infection with suboptimal response to GCV. GCV levels were obtained in the 11 CMV-infected patients with suboptimal response. In 6 patients, GCV levels were therapeutic; all 6 had delayed response to GCV. In 5 patients, GCV levels were subtherapeutic; each had persistent suboptimal response to GCV. Genotyping documented GCV-resistant (GCV-R) CMV in all 5 patients. Cystic fibrosis as the diagnosis requiring lung transplantation was associated with GCV-R CMV infection (P = 0.01). CONCLUSION: In our lung transplant recipient cohort, GCV levels were subtherapeutic in all patients with persistent suboptimal response to GCV, each of whom had GCV-R CMV infection. In contrast, GCV levels were therapeutic in CMV-infected patients with delayed GCV response.

Successful emergent lung transplantation after remote ex vivo perfusion optimization and transportation of donor lungs.

A recent clinical trial provided evidence that ex vivo lung perfusion (EVLP) results in optimized human donor lungs for transplantation. Excellent recipient outcomes were documented after 4 h of normothermic perfusion. We report a clinical case utilizing remote EVLP to assess and improve function of initially otherwise unacceptable injured donor lungs followed by transportation and subsequent bilateral lung transplantation in a patient with virally induced refractory respiratory failure supported with extracorporeal membrane oxygenation. This is the first lung transplantation with the application of remote EVLP, wherein the donor lungs were transported from the donor hospital to a center for EVLP and then transported to another hospital for transplantation. It is also the first case of lung transplantation in the United States utilizing EVLP for functional optimization leading to successful transplantation. Organ procurement data, EVLP assessment, and the pre- and postoperative course of the recipient are presented. The available evidence supporting EVLP, the humanitarian and cooperative utilization of lungs otherwise discarded, are discussed.

Morgagni hernia presenting with bowel obstruction in a lung transplant recipient: case report.

Morgagni hernias are uncommon congenital diaphragmatic deficiencies that may remain asymptomatic till adulthood. We report a case of Morgagni hernia presenting with subacute bowel obstruction in a bilateral lung transplant recipient. This diaphragmatic deficiency was not evident during bilateral lung transplantation surgery via clamshell incision. To our knowledge this is the first report of a congenital defect evident after lung transplantation.

Mitral valve dysfunction and repair following orthotopic heart transplantation: a case report.

Mitral valve dysfunction after orthotopic heart transplantation may cause symptoms refractory to medical therapy. In this report, we present a patient who underwent mitral annuloplasty for severe symptomatic mitral valve insufficiency 9 years after heart transplantation, and we critically appraise the literature available for mitral valve dysfunction in this setting. Mitral valve repair, when feasible, should be considered for mitral insufficiency after transplantation to improve functional status and reduce the risk of retransplantation--this is particularly prudent in view of chronic donor shortage.

Early hemodynamic injury during donor brain death determines the severity of primary graft dysfunction after lung transplantation.

Sympathetic discharge and hypertensive crisis often accompany brain death, causing neurogenic pulmonary edema. Progressive systemic inflammatory response develops, which can injure the lung further. We investigated whether (a) early hemodynamic injury during donor brain death increases reperfusion injury after lung transplantation and (b) delaying lung recovery would augment reperfusion injury further, because of the progressive systemic inflammatory response in the donor. Brain death was induced by intracranial balloon inflation in rats, with or without alpha-adrenergic blockade pretreatment to prevent the hypertensive crisis. Another group of rats had a sham procedure. Lungs were retrieved 15 min after brain death or sham procedure and reperfused using recipient rats. In a fourth group, brain death was induced and the lungs were retrieved 5 h after brain death and reperfused. Postreperfusion, lungs retrieved early from untreated brain-dead donors developed more severe reperfusion injury, as assessed by functional parameters and inflammatory markers, than those from sham or alpha-blockade-treated donors. Lungs retrieved late from brain-dead donors had similar inflammatory markers after reperfusion to those retrieved early, but significantly lower pulmonary vascular resistance. Early hemodynamic damage during donor brain death increases reperfusion injury after lung transplantation. Delaying retrieval may allow the lung to recover from the hemodynamic injury.

Impact of donor and recipient factors on allograft survival in lung transplantation: A single-center analysis.

BACKGROUND: It remains unclear which donor and recipient factors influence long-term allograft function in lung transplantation (LTx). METHODS: From October 1988 to February 2005, a total of 280 recipients underwent LTx at our center. Donor data and cause of death (CoD) were analyzed. The CoD was categorized according to rate of increase in intracranial pressure at the time of death. Each donor and recipient factor was correlated with long-term graft function. Recipient details, type of transplant, indication for transplant, and time on waiting list were analyzed. Recipients were stratified based on allograft ischemia time (AIT): 0 to 6, 6 to 8, 8 to 10, and >10 hours. RESULTS: Mean donor age was 30.9 years (36.7% male); 49.8% were cytomegalovirus (CMV) positive. Donor CoD was characterized by a slow rise in intracranial pressure (ICP) in 34.4%, rapid ICP in 18.7%, an intermediate ICP in 44.3%, and with no rise in 2.6%. A graft survival benefit was seen with female donors (P = .048); 34.4% of recipients ultimately developed graft failure at long term follow-up. Mean recipient age was 48 years; 63% were male and mean body-mass index (BMI) was 23.6; 60.2% had single lung transplantation, and mean wait list time was 323 days. Mean AIT totaled 421 minutes. Graft survival was longer with AIT of 8 to 10 hours compared to 6 to 8 hours (P = .03). CONCLUSIONS: Donor factor analysis implied only female donor status conferred a long-term graft survival advantage. Intracranial pressure rise differences appear clinically unimportant. Prolonged cold ischemic time (>10 hours) or low recipient BMI did not adversely affect allograft function in our review.