Colistin-based Treatment of Multidrug-resistant Gram-negative Bacterial Pulmonary Infections After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is a viable option for a select group of patients with end-stage lung disease. However, infections are a major complication after LT, accounting for significant morbidity and mortality. Several germs may be responsible; multidrug-resistant Gram-negative (MDR-GN) bacteria are emerging. Colistin is widely used in the treatment of these infections and is administered by inhalation and/or parenterally. At our institution, in patients with tracheostomy, colistin is administered by direct instillation in the airway during bronchoscopy. We reviewed a series of patients who underwent LT complicated by postoperative MDR-GN bacterial pulmonary infection. METHODS: From January 2015 to May 2017, 26 lung transplants were performed. In the postoperative course, 14 (54%) developed MDR-GN bacterial infection; respiratory specimen culture, blood tests, and chest X-ray were considered. Colistin was the only antibiotic usable. Thirteen patients received intravenous (IV) colistin; in the subgroup of patients with tracheostomy, colistin was instilled directly in the airway, and 6 patients received inhaled colistin. RESULTS: Seven patients needed tracheostomy. Pseudomonas aeruginosa was the predominant infection (86%), with Acinetobacter baumanii seen in 2 cases (14%). An early clinical-laboratory response was observed in 9 patients (64%). White blood cell count and C-reactive protein values improved (P = .02 and P = .001, respectively). A significant reduction in bacterial load was observed on microbiologic bronchoalveolar lavage specimens. CONCLUSION: Colistin instilled directly in the airway did not show side effects. The combination of IV and inhaled/instilled colistin could be a useful treatment option for MDR-GN infections after LT.

Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is only therapeutic option for patients affected by chronic respiratory failure. Chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is still the main cause of death and the most important factor that influences post-transplantation quality of life. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Extracorporeal photopheresis (ECP) seems to reduce the rate of lung function decline in transplant recipients with progressive BOS. METHODS: From 1991 until now, 239 LTs were performed at our center. Fifty-four patients (22.5%) developed BOS; 15 of these (27.7%) were treated with ECP. At the beginning of the treatment, all patients showed a mean decline of forced expiratory volume in 1 second (FEV1) from baseline values of 45.8% ± 17.2%; 2 patients were in long-term oxygen therapy. RESULTS: Mean follow-up from November 2013 to June 2016 was 11.6 ± 7 months. Twelve patients (80%) showed lung function stabilization with an FEV1 range after treatment between -6% to +8% from the pre-treatment values. We did not report any adverse effects or increase of infections incidence. DISCUSSION: ECP seems to be an effective and well-tolerated therapeutic option for LT patients with BOS in terms of stabilization of lung function and increased survival.

Evaluation of Renal Function in Patients Undergoing Lung Transplantation.

BACKGROUND: Acute kidney injury and chronic kidney failure are serious complications after lung transplantation. Glomerular filtration rate (GFR) is the primary indicator of renal function. Several equations have been proposed to evaluate the estimated GFR (eGFR). We compared three different equations to determine which has the better correlation with the development of acute and chronic renal failure in lung recipients. METHODS: Twenty-two patients with a mean age of 54.4 ± 8.5 years underwent lung transplantation from 2010 to 2015. Thirteen (59%) had pulmonary fibrosis, 7 (32%) emphysema, 1 (4.5%) bronchiectasis, and 1 (4.5%) lymphangioleiomyomatosis. In all patients, eGFR was measured preoperatively using Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Levey's Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. In 20 patients (90%) eGFR was calculated at 1, 3, and 6 months. RESULTS: According to CKD-EPI and MDRD, eight patients (36.3%) had preoperative reduction in eGFR, whereas 6 patients (27.2%) had preoperative reduction according to the CG (P = .04). The mean values were higher for the CG (103.2 vs. 102 vs. 94.4). Five patients (22.7%) developed perioperative acute renal failure requesting a dialysis treatment; four of these showed a preoperative eGFR to the highest CG (P = .05). At 1 and 6 months after lung transplantation, the CG, MDRD and CKD-EPI eGFR values were, respectively, 86.6, 84.1 and 76.6 mL/min/1.73m2 and 75.8, 72.7, and 72.3 mL/min/1.73m2. CKD-EPI eGFR values are more predictable than the other equations of AKI. CONCLUSIONS: Preoperative assessment of eGFR using the MDRD and CKD-EPI seems to correlate better than the CG to the prediction of acute renal failure, whereas for the chronic form the three equations seem equivalent.

Selection of Candidates for Lung Transplantation: The First Italian Consensus Statement.

Lung transplantation is a well-established treatment for selected patients with advanced chronic respiratory insufficiency. Recognizing those patients with end-stage lung disease who might benefit from lung transplantation is a crucial task. Considering the presence of inadequate evidence-based practice, international and national scientific societies provided consensus opinions regarding the appropriate timing of listing. The Study Group for Thoracic Organs Transplantation (branch of the Italian Society for Organs Transplantation) promoted and realized a Delphi conference among the Italian lung transplantation centers to provide guidance to clinical practice based on international recommendations. The experts from the nine Italian centers completed two rounds of standardized questionnaires (answer rate, 100%): 42 statements received a consensus ≥80%. The selected statements presented in this article are intended to assist Italian clinicians in selecting patients for lung transplantation.

A combined therapeutic approach in progressive idiopathic pulmonary fibrosis-pirfenidone as bridge therapy for ex vivo lung transplantation: a case report.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial pneumonia of unknown etiology, which is associated with the histopathologic pattern of usual interstitial pneumonia (UIP) and leads to a progressive decrease of respiratory function. The present article describes a case of a 62-year-old ex-smoker referred to our hospital because of IPF. After 2 years of follow-up, the subject experienced a significant worsening of pulmonary function and was enrolled in a lung transplantation program. Afterward, a pharmacological treatment with pirfenidone was started, achieving a stabilization of respiratory function. The patient underwent a single lung transplantation by means of a normothermic ex vivo lung perfusion (EVLP) approach according to the Toronto model. At 20-month evaluation the subject's respiratory function was significantly improved, and quality of life was considerably ameliorated. We believe that an integrated multidisciplinary approach should be considered a key option for the treatment of individuals with IPF.

Independent lung ventilation in the postoperative management of single lung transplantation: case report.

Independent lung ventilation (ILV) is a ventilation strategy used in patients with significant differences in respiratory mechanics between the 2 lungs owing to asymmetric or unilateral lung diseases. We report the case of a 66-year-old patient treated with ILV for a primary graft dysfunction occurred early after single lung transplantation. On intensive care unit admission, the patient was ventilated with pressure-controlled mechanical ventilation. Despite efforts to optimize ventilation and medical therapy, his clinical condition progressively worsened, manifesting hypoxemia, hypercapnia, and radiologic evidence of hyperinflation of the native lung, collapse of the graft, and mediastinal shift. The ventilation was therefore switched to ILV. A constant improvement in clinical conditions, arterial blood gas parameters, and radiologic findings was then obtained. The patients was weaned from mechanical ventilation and finally successfully extubated.

Extracorporeal membrane oxygenation as bridge to lung transplantation.

Lung transplantation (OLT) is a viable option for end-stage pulmonary diseases in selected patients with satisfactory long-term results. However, the paucity of available donors engenders a prolonged stay on the waiting list with progressive decline of lung function. In cases of sudden respiratory failure, admission to an intensive care unit with institution of extracorporeal membrane oxygenation (ECMO) may be an option while a waiting an emergency OLT. In 12 OLT candidates we started ECMO because of acute decline of lung function. Eleven patients had cystic fibrosis and the other subject, histiocytosis X. In 7 patients bilateral OLT was performed after a mean waiting time of 6 days from ECMO institution; 5 patients died on ECMO at a mean time of 11.6 days. After OLT 2 patients required reoperation for hemothorax; renal failure and acute leg ischemia occurred in 2 patients. The mean weaning time from ECMO after OLT was 2.14 days. No patient died in the perioperative period and 1-year survival was 85.7%. ECMO represents a valid option as a bridge to urgent OLT for selected candidates.

Low-flow venovenous CO2 removal in association with lung protective ventilation strategy in patients who develop severe progressive respiratory acidosis after lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) might occur after lung transplantation. In some severe cases, conventional therapies like ventilatory support, administration of inhaled nitric oxide (iNO), and intravenous prostacyclins are not sufficient to provide an adequate gas exchange. The aim of our study was to evaluate the use of a lung protective ventilation strategy associated with a low-flow venovenous CO2 removal treatment to reduce ventilator-associated injury in patients that develop severe PGD after lung transplantation. METHODS: From January 2009 to January 2011, 3 patients developed PGD within 24 hours after lung transplantation. In addition to conventional medical treatment, including hemodynamic support, iNO and prostaglandin E1 (PGE1), we initiated a ventilatory protective strategy associated with low-flow venovenous CO2 removal treatment (LFVVECCO2R). Hemodynamic and respiratory parameters were assessed at baseline as well as after 3, 12, 24, and 48 hours. RESULTS: No adverse events were registered. Despite decreased baseline elevated pulmonary positive pressures, application of a protective ventilation strategy with LFVVECCO2R reduced PaCO2 and pulmonary infiltrates as well as increased pH values and PaO2/FiO2 ratios. Every patient showed simultaneous improvement of clinical and hemodynamic conditions. They were weaned from mechanical ventilation and extubated after 24 hours after the use of the low-flow venovenous CO2 removal device. CONCLUSION: The use of LFVVECCO2R together with a protective lung ventilation strategy during the perioperative period of lung transplantation may be a valid clinical strategy for patients with PGD and severe respiratory acidosis occured despite adequate mechanical ventilation.

Lung transplantation for cystic fibrosis: outcome of 101 single-center consecutive patients.

Bilateral sequential lung transplantation (BSLT) is nowadays considered a valid therapeutic option for patients with end stage cystic fibrosis. We report our experience with 104 BSLTs in 101 patients. The overall survivals at 1, 3, 5, 10 years were 79%, 65%, 58%, and 42%, respectively. Perioperative mortality was 14.8% (n = 15). The leading causes of perioperative mortality were primary graft dysfunction and sepsis. Three patients were retransplanted owing to obliterative bronchiolitis. In 70 cases (69%), patients displayed ≥ 1 additional risk factors: previous lung resections, colonization by Burkholderia cepacia, diabetes, pneumothorax, or noninvasive ventilatory support. The mean preoperative 1-second forced expiratory volume of 0.69 ± 0.2 L (22%) increased to 85% at 1 year after the operation. The mean time on the waiting list was 12 ± 5 months. The 5 patients treated with extracorporeal membrane oxygenation before urgent transplantation were operated after 3, 5, 6, 30, and 3 days respectively. During the procedure, cardiopulmonary bypass was required in 33 patients (32%). Lung transplantation represents a unique opportunity to ameliorate the quality and improve the survival of patients affected by cystic fibrosis. Timing of referral and patient selection remain crucial for success.

Pulmonary hypertension is associated with higher mortality in cystic fibrosis patients awaiting lung transplantation.

AIM: Pulmonary hypertension (PH) is frequently found in patients with advanced parenchymal lung diseases. In advanced stages, cystic fibrosis (CF) patients can develop PH and eventually cor pulmonale. Little is known about the prevalence of PH in CF patients and its impact on outcome. METHODS: We retrospectively studied a large cohort of CF patients evaluated for lung transplantation between 1995 and 2010. All the patients underwent right heart catheterization as part of the evaluation. We included 179 unique consecutive adult CF patients. Age was 24±9 years and 45.8% were women. RESULTS: Eighty-seven patients were transplanted (48.6%) and 65 died (36.3%) while waiting for LT. By right heart catheterization, 38.5% of the patients had PH (mean ≥25 mm Hg). PaCO(2) (P=0.045) and forced vital capacity (P=0.023) were independent predictors of PH in CF patients. The median survival (free of lung transplantation) was 13.4 months. After adjusting for several covariates, the presence of PH significantly increased mortality (hazard ratio, HR) (P<0.001). Pulmonary vascular resistance was associated with mortality (P=0.03). When both PH and PVR were included in the model, only PH predicted mortality. CONCLUSION: Pulmonary hypertension of mild degree is frequently found in CF patients with advanced lung disease and its presence significantly worsens survival.