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 as ex-vivo lung perfusion after cold storage transportation.

The Organ Care System (OCS) allows perfusion and ventilation of the donor lungs under physiological conditions. Ongoing trials to compare preservation with OCS Lung with standard cold storage do not include donor lungs with suboptimal gas exchange and donor lungs treated with OCS following cold storage transportation. We present a case of a 48-yr-old man who received such lungs after cold storage transportation treated with ex-vivo lung perfusion utilizing OCS.

Outcomes in patients receiving HeartMate II versus HVAD left ventricular assist device as a bridge to transplantation.

OBJECTIVE: Ventricular assist devices have become a standard treatment for patients with advanced heart failure. We present data comparing results after implantation of HeartMate II (HM II) versus HVAD (HW) left ventricular assist devices (LVADs) for the past 7 years at our institution. METHODS: From July 2006 to August 2012, 121 consecutive patients underwent LVAD implantation: 70 (57.9%) received HM II and 51 (42.1%) HW. Patient demographics, perioperative characteristics, and laboratory parameters as well as postoperative outcome were compared retrospectively. RESULTS: Patients in the HM II group were significantly younger (P < .01), with more deranged liver function (higher bilirubin [P = .02] and alanine aminotransferase [P = .01] levels), and had a significantly higher rate of preoperative infections requiring antibiotic treatment (P = .02) and a higher body core temperature (P < .01). Other demographic and preoperative parameters did not show statistical differences. Most postoperative characteristics were also similar between the two groups. HM II patients had a significantly higher transfusion rate, but there were no differences in incidence of resternotomy (P = .156). Recovery and VAD explantation were more likely in the HM II group (P = .02). Although there was no significant difference in survival (log rank test: P = .986; Breslow test: P = .827), HM II patients were more likely to develop a percutaneous site infection (P = .01). CONCLUSIONS: Both HM II and HW provide similar early postoperative outcome and good long-term survival. The differences observed between the groups may be related to demographic and preoperative factors rather than the type of the device used.

Ex vivo evaluation of lungs from donation after cardiac death after recent cardiac surgery with cardiopulmonary bypass.

Lack of suitable donor lungs is still a major limitation of lung transplantation. Extended donor acceptance criteria combined with innovative assessment tools can be used to expand the number of suitable organs. We describe a successful transplantation of lungs retrieved from a donor who had undergone aortic root replacement 9 days before donation after cardiac death. The lungs were assessed using ex-vivo lung perfusion.

Pulmonary resection for airway complication after lung transplantation in a patient with cystic fibrosis: a case report.

We report a case of the interdisciplinary management of recurring bronchial stenosis after bilateral sequential single-lung transplantation (BSSLT) in a 35-year-old female with cystic fibrosis. Initial bronchoscopic therapy including balloon dilatation, stenting, and cryotherapy for granulation tissue overgrowth was unsuccessful in maintaining airway patency. In view of the persistent left lower lobe (LLL) atelectasis and fibrosis predisposing to recurrent infections, she was submitted for left lower lobectomy.