A pharmacokinetic analysis of posaconazole oral suspension in the serum and alveolar compartment of lung transplant recipients.

Invasive fungal infections cause significant morbidity and mortality after lung transplantation. Fungal prophylaxis following lung transplantation is not standardised, with transplant centres utilising a variety of regimens. Posaconazole is a broad-spectrum antifungal triazole that requires further investigation within the setting of lung transplantation. This prospective, single-centre, observational study explored the pharmacokinetics of posaconazole oral suspension (POS) in the early perioperative period following lung transplantation in 26 patients. Organ recipients were scheduled to receive 400mg POS twice daily for 6 weeks as primary antifungal prophylaxis. Therapeutic drug monitoring (TDM) of serum posaconazole levels was performed in accordance with local clinical protocols. Bronchoalveolar lavage fluid (BALF) was sampled during routine bronchoscopies. Posaconazole levels were measured both in serum and BALF using mass spectrometry. Posaconazole levels were highly variable within lung transplant recipients during the perioperative period and did not achieve 'steady-state'. Serum posaconazole concentrations positively correlated with levels within the BALF (r=0.5527; P=0.0105). Of the 26 patients, 10 failed to complete the study for multiple reasons and so the trial was terminated early. Unlike study findings in stable recipients, serum posaconazole levels rarely achieved steady-state in the perioperative period; however, they do reflect the concentrations within the airways of newly transplanted lungs. The role of POS as primary prophylaxis in the perioperative period is uncertain, but if used TDM may be helpful for determining attainment of therapeutic levels.

"Hanging donors": are we still skeptical about the lungs?

BACKGROUND: Suicidal hanging may cause compression of the neck blood vessels and the airway leading, to hypoxic brain damage caused by cerebral ischemia and respiratory distress. Hanging engenders global tissue hypoxia, particularly affecting the lungs as the result of pulmonary edema and barotrauma. There is scant evidence about outcomes of transplantation with the use of lungs from "hanging donors." This study evaluates the outcomes of lung transplantations (LTx) that use organs from this group. METHODS: We retrospectively analyzed lung "organ offers" and LTx at our center between January 2007 and November 2013. The outcomes of LTx with lungs from donors with hanging as the cause of death ("hanging group") were compared with those with donors having other causes of death (control group), with the use of an unadjusted model as well as propensity score matching. RESULTS: LTx (n = 302) were performed during this period and were grouped on the basis of the cause of death in donors: the hanging group (n = 8) and the control group (n = 294). No statistically significant difference was found in the donor characteristics except for the incidence of cardiac arrest, which was significantly higher in hanging donors. Preoperative characteristics in recipients in both groups were comparable. Intra-operative and post-LTx variables including PaO2/FiO2 ratios, duration of mechanical ventilation, and intensive care unit and hospital stays were comparable. One-year and 3-year survival rates were also comparable in both groups. Two recipients in the hanging group required extracorporeal life support after LTx and could not survive. CONCLUSIONS: Suicidal hanging is a relatively rare cause of death for potential organ donors. Because it does not appear to negatively affect outcomes after LTx, it should not be considered per se a contraindication for lung donation. A word of caution is necessary until we gather larger experience with lungs from hanging donors.

Utilization of the Organ Care System Lung for the assessment of lungs from a donor after cardiac death (DCD) before bilateral transplantation.

In this manuscript, we present the first experience of evaluating donation after circulatory death (DCD) lungs, using the normothermic preservation Organ Care System (OCS) and subsequent successful transplantation. The OCS could be a useful tool for the evaluation of marginal lungs from DCD donors as it allows a proper recruitment and bronchoscopy in such donations in addition to continuous ex-vivo perfusion and assessment and treatment during transport. The OCS could potentially be a standard of care in the evaluation of marginal lungs from DCD.