Reversible posterior leukoencephalopathy syndrome: diagnosis and management in the setting of lung transplantation.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a potentially devastating early complication of calcineurin inhibitor (CNI) therapy in solid organ transplantation. Management centres on cessation of CNI therapy; however, this strategy is complicated in lung transplantation because of the threat of allograft rejection, or, if CNI is replaced with mammalian target of rapamycin-based immunosuppression, poor wound healing and bronchial dehiscence. We describe four cases of RPLS after lung transplantation, emphasizing the diagnostic and management approach required to maintain a healthy allograft and ensure that RPLS is, as the name suggests, reversible.

Endothelin receptor antagonists are an effective long term treatment option in pulmonary arterial hypertension associated with congenital heart disease with or without trisomy 21.

INTRODUCTION: Traditionally, treatment options for patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) are limited. Bosentan has been shown to improve pulmonary haemodynamics and exercise tolerance short term but long term clinical studies are lacking. AIM: To report long term efficacy and safety data with endothelin receptor antagonists (ERA) in patients with PAH associated CHD. METHODS: Prospective, open label, uncontrolled, single centre study of 53 patients (33 females, 17 Trisomy 21, mean age 34 ± 12 years) prescribed ERA (48 bosentan, 5 sitaxentan) from 2003 to August 2009. Outcome measurements of oxygen saturation (SaO2), WHO functional class, 6-minute walk test distance (6MWD) and adverse events were analysed. RESULTS: Mean duration of therapy was 15 ± 13 months in 53 patients with CHD. Four patients failed ERA, seven died (five progressive RHF) and one delisted from transplantation. No abnormal liver transaminases occurred on bosentan, with one case on sitaxentan. After 3, 6, 12, 18 and 24 months of treatment a significant improvement was seen in WHO functional class (mean 3.15 vs 2.8 vs 2.5 vs 2.5 vs 2.4 vs 2.4; p<0.01) and 6MWD (344 ± 18 vs 392 ± 17 vs 411 ± 17 vs 420 ± 17 vs 442 ± 18 vs 417 ± 23: p<0.0005, p<0.01) compared with baseline. The Trisomy 21 and PAH-CHD showed a significant improvement in 6MWD at 6 and 12 months (263 ± 24 vs 348 ± 29 vs 360 ± 32, p<0.01, p<0.05) respectively. No changes in SaO2, BNP, RV or LV function were demonstrated during follow-up. CONCLUSION: This large single centre study demonstrates that endothelin receptor antagonism is an effective and safe treatment in PAH associated CHD with or without Trisomy 21. The improvements in exercise tolerance are similar to reported benefits in other forms of PAH.

Resolution of severe ischemia-reperfusion injury post-lung transplantation after administration of endobronchial surfactant.

BACKGROUND: Ischemia-reperfusion injury (IRI) is a prominent cause of primary graft failure after lung transplantation and is associated with an altered surfactant profile. Experimental animal studies have found that replacement with exogenous surfactant administered via fiber-optic bronchoscopy (FOB) enhanced recovery from IRI with improved pulmonary compliance and gas exchange after lung transplantation. We report our clinical experience with FOB instillation of surfactant in severe IRI after human lung transplantation. METHODS: This study is a retrospective review of 106 consecutive lung or heart-lung transplants performed at a single institution. Severe IRI was defined as diffuse roentgenographic alveolar infiltrates, worsening hypoxemia and decreased lung compliance within 72 hours of lung transplantation. One vial of surfactant (20 mg/ml phospholipid) was instilled into each segmental bronchus upon diagnosis of IRI. RESULTS: Six patients (5 bilateral sequential and 1 re-do heart-lung transplant), mean age 46 years, were diagnosed with IRI and surfactant was administered at a mean of 37 hours (range 2.3 to 98) post-transplant. Mean graft ischemia time was 376 minutes (range 187 to 625) and cardiopulmonary bypass time 174 minutes (range 0 to 210). Mean Pao(2) [mm Hg]/Fio(2) ratio before and 48 hours after surfactant instillation was 70 and 223, respectively. Significant resolution of radiologic infiltrates was evident in all cases within 24 hours. Successful extubation occurred at a mean of 13.5 days and survival is presently 100% at 19 months (range 3 to 54). CONCLUSIONS: Bronchoscopic instillation of surfactant improves oxygenation and prognosis after severe IRI in lung transplant recipients. It represents a cost-effective, relatively non-invasive therapeutic alternative to extracorporeal membrane oxygenation.