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Concept: Lung transplantation

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BACKGROUND: Preoperative extracorporeal membrane oxygenation (ECMO) is a risk factor for poor outcome and currently considered a contraindication to lung transplantation. The lung allocation score system was introduced in May 2005 and prioritizes lung allocation to those with the greatest respiratory impairment. The purpose of this study is to determine whether ECMO as a bridge to lung transplantation is an acceptable option to support those in respiratory failure until donor lungs become available in the lung allocation score era. METHOD: A retrospective review of 715 consecutive lung transplants performed between May 2005 and September 2011 was conducted using a prospectively collected institutional registry database. Twenty-four lung transplants (3.4%) were performed in the 31 patients with attempted pretransplant ECMO; 7 patients who received ECMO patients did not survive or were deemed unfit for transplantation. These patients were compared with a control group of 691 patients who did not receive pretransplant ECMO. RESULTS: The duration of pretransplant ECMO was 171 ± 242 hours (median, 91 hours). Venovenous ECMO was used for respiratory failure in 15 patients, whereas venoarterial ECMO was used for circulatory collapse due to pulmonary hypertension in 9 patients. Patients in the retransplant ECMO group were younger (46 ± 15 years vs 57 ± 14 years, P < .01) compared with the control group, with no difference in recipient gender (male/female: 10/14 vs 380/311), donor age (33 ± 14 years vs 36 ± 15 years), or donor gender (male/female: 10/14 vs 352/339). Emphysema was less common (1, 4% vs 260, 38%, P < .01), and cystic fibrosis (5, 21% vs 72, 10%, P = .09), redo lung transplant (3, 13% vs 28, 4%, P = .08), and bronchiectasis (2, 8% vs 6, 1%, P = .03) were more common in the pretransplant ECMO group. Patients in the pretransplant ECMO group had a significantly higher lung allocation score (87 ± 9 vs 44 ± 15, P < .01). All patients in the pretransplant ECMO group underwent double lung transplants on pump (cardiopulmonary bypass/ECMO), and single lung transplants were performed in 171 patients (25%) and pump was used in 243 patients (35%) in the control group. The cardiopulmonary bypass time was longer in the pretransplant ECMO group (277 ± 69 minutes vs 225 ± 89 minutes, P = .02), with no difference in ischemic time (343 ± 93 minutes vs 330 ± 98 minutes, P = .54). Cadaveric lobar lung transplants were performed because of the urgency to overcome size mismatch with an oversized donor more frequently in 25% (n = 6, no mortality with the longest follow-up at 6 years) of patients in the pretransplant ECMO group versus 0.3% (n = 2) of patients in the control group (P < .01). Post-transplant ECMO was used for primary graft dysfunction in 13 patients (54%) in the pretransplant ECMO group and 41 patients (6%) in the control group (P < .01). The median hospital stay was 46 days in the pretransplant ECMO group versus 27 days in the control group (P = .16). The actuarial survivals after lung transplants at 1, 3, 6, 12, and 24 months were 96%, 88%, 83%, 74%, and 74%, respectively, in the pretransplant ECMO group, and 97%, 94%, 90%, 83%, and 74%, respectively, in the control group (P = .787). CONCLUSIONS: Although the incidence of primary graft dysfunction requiring post-transplant ECMO is higher and the hospital stay is longer in patients receiving pretransplant ECMO, the graft survival is good (2-year survival, 74%). ECMO is efficacious as a bridge to lung transplantation with good post-lung transplant outcomes.

Concepts: Pulmonology, Cystic fibrosis, Organ transplant, Pulmonary hypertension, Lung transplantation, Extracorporeal, Extracorporeal membrane oxygenation, Lung allocation score

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OBJECTIVESA sternal-sparing approach for bilateral lung transplantation was recently applied to reoperative lung transplant cases and is compared with the traditional clamshell approach.METHODSA retrospective analysis of 15 consecutive reoperative bilateral lung transplants performed from January 2008 to April 2011 was conducted. Outcomes were compared between the first 11 patients who underwent the traditional clamshell and the most recent 4 patients who underwent the sternal-sparing approach.RESULTSThe indication for retransplantation was obliterative bronchiolitis in all patients. Both groups were similar with regard to age, allograft ischaemic time and operative time. Cardiopulmonary bypass was more frequent in the sternal-sparing group although required for a shorter period of time. The need for postoperative extracorporeal membrane oxygenation for primary graft dysfunction was similar in both groups. The length of ICU care and total hospitalization length of stay were similar for the sternal-sparing group compared with the traditional clamshell approach. Operative mortality and overall survival also did not differ.CONCLUSIONSReoperative bilateral lung transplantation with a sternal-sparing approach is feasible and may yield outcomes similar to those in the traditional clamshell approach. Further analysis with larger numbers of patients is warranted to delineate the benefits of this approach for patients requiring reoperative lung transplantation.

Concepts: Time, Pulmonology, Pleural effusion, Organ transplant, Cardiopulmonary bypass, Lung transplantation, Bronchiolitis obliterans, Extracorporeal

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BACKGROUND: In May 2005, the Lung Allocation Score (LAS) became the primary method for determining allocation of lungs for organ transplantation for those at least 12 years of age in the United States. During the pre-LAS period, black patients were more likely than white patients to become too sick or die while awaiting transplant. The association between gender and lung transplant outcomes has not been widely studied. METHODS: Black and white patients aged ≥18 years registered on the United Network of Organ Sharing (UNOS) lung transplantation waiting list from January 1, 2000, to May 3, 2005 (pre-LAS, n = 8,765), and from May 4, 2005, to September 4, 2010 (LAS, n = 8,806), were included. Logistic regression analyses were based on smaller cohorts derived from patients listed in the first 2 years of each era (2,350 pre-LAS, and 2,446 LAS) to allow for follow-up time. Lung transplantation was the primary outcome measure. Multivariable analyses were performed within each interval to determine the odds that a patient would die or receive a lung transplant within 3 years of listing. RESULTS: In the pre-LAS era, black patients were more likely than white patients to become too sick for transplantation or die within 3 years of waiting list registration (43.8% vs 30.8%; odds ratio [OR], 1.84; p < 0.001). Race was not associated with death or becoming too sick while listed for transplantation in the LAS era (14.0% vs 13.3%; OR, 0.93; p = 0.74). Black patients were less likely to undergo transplantation in the pre-LAS era (56.3% vs 69.2%; OR, 0.54; p < 0.001) but not in the LAS era (86.0% vs 86.7%; OR, 1.07; p = 0.74). Women were more likely than men to die or become too sick for transplantation within 3 years of listing in the LAS era (16.1% vs 11.3%; OR, 1.58; p < 0.001) compared with the pre-LAS era (33.4% vs 30.7%; OR, 1.19; p = 0.08). CONCLUSION: Racial disparities in lung transplantation have decreased with the implementation of LAS as the method of organ allocation; however, gender disparities may have actually increased in the LAS era.

Concepts: Regression analysis, Pulmonology, United States, Organ transplant, Race, Transplantation medicine, Lung transplantation, Lung allocation score

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This article summarizes the current literature regarding surgical interventions in pulmonary hypertension, excluding chronic thromboembolic pulmonary hypertension. The article discusses the use of atrial septostomy in patients meeting criteria as well as single, double, and heart-lung transplantation.

Concepts: Pulmonology, Cardiology, Heart, Pulmonary artery, Organ transplant, Pulmonary hypertension, Lung transplantation

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A case is presented on a patient who underwent left single lung transplantation for emphysema type COPD. There was early graft dysfunction gradeiii during the immediate postoperative period, which required the implantation of an extracorporeal membrane oxygenator (ECMO). Respirator ventilatory parameters were adjusted to avoid lung distension, low tidal volume (Vc) (280ml), high respiratory rates (20rpm), and a positive pressure at end expiration (PEEP) level of 8cmH2O. On monitoring the pulmonary tidal volume distribution by bedside electrical impedance tomography (EIT), it was noted that most of the tidal volume was distributed in the native lung emphysema. An alveolar recruitment manoeuvre was performed, under control of the EIT, that enabled the current volume and distribution and the pressures required to ventilate the transplanted lung to be observed.

Concepts: Pulmonology, Lung, Chronic obstructive pulmonary disease, Emphysema, Alpha 1-antitrypsin deficiency, Organ transplant, Pressure, Lung transplantation

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Successful lung transplantation (LTx) depends on multiple components of healthcare delivery and performance. Therefore, we conducted an international registry analysis to compare post-LTx outcomes for cystic fibrosis (CF) patients using the UNOS registry in the United States and the National Health Service (NHS) Transplant Registry in the United Kingdom. Patients with CF who underwent lung or heart-lung transplantation in the United States or United Kingdom between January 1, 2000 and December 31, 2011 were included. The primary outcome was all-cause mortality. Kaplan-Meier analysis and Cox proportional hazards regression evaluated the effect of healthcare system and insurance on mortality after LTx. 2,307 US LTx recipients and 451 individuals in the United Kingdom were included. 894 (38.8%) US LTx recipients had publically funded Medicare/Medicaid insurance. US private insurance and UK patients had improved median predicted survival compared with US Medicare/Medicaid recipients (p < 0.001). In multivariable Cox regression, US Medicare/Medicaid insurance was associated with worse survival after LTx (US private: HR0.78,0.68-0.90,p = 0.001 and UK: HR0.63,0.41-0.97, p = 0.03). This study in CF patients is the largest comparison of LTx in two unique health systems. Both the United States and United Kingdom have similar early survival outcomes, suggesting important dissemination of best practices internationally. However, the performance of US public insurance is significantly worse and may put patients at risk.

Concepts: Health care, Medicine, Universal health care, Cystic fibrosis, United Kingdom, Organ transplant, Massachusetts, Lung transplantation

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A higher predicted total lung capacity (pTLC)-ratio (=pTLC donor/pTLC recipient), suggestive of oversized allografts, is associated with improved survival after lung transplantation. It is unknown whether the pTLC-ratio has a different association with survival in bilateral (BLT) versus single lung transplantation (SLT).

Concepts: Lung, Respiratory physiology, Organ transplant, Lung volumes, Lung transplantation, Spirometer

1

Atrial arrhythmia (AA) after lung transplantation (LTx) is a potentially morbid event often associated with increased length of hospital stay. Predictors of postsurgical AA, however, are incompletely understood. We characterized the incidence and predisposing risk factors for AA in patients undergoing LTx.

Concepts: Epidemiology, Pulmonology, Hospital, Pleural effusion, Organ transplant, Lung transplantation, Cardiac dysrhythmia

1

Outcomes data for high-risk donors (HRD) for transplantation are limited. We sought to elucidate the outcomes of lung transplant (LTx) recipients who received HRDs.

Concepts: Pulmonology, Pleural effusion, Organ transplant, Lung transplantation

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Appropriate exposure to Posaconazole (PSZ) was limited since the recent approval of the delayed release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300mgx1 in lung transplant patients (LT) including cystic fibrosis (CF) background.PSZ trough concentrations (C0) were determined using LCMS assay. Indicative thresholds of interest were <0.7mg/L (prophylaxis) and 1-3mg/L (curative). Tacrolimus (TRL) and everolimus (ERL) C0 measured during PSZ exposure were collected. Interaction with proton-pump inhibitors (PPI) was evaluated.We recorded 21 CFLT, 11 LT-not CF (NCFLT) and 27 non LT patients (NT) addressed to Pneumology department. Respectively for NCFLT vs CFLT vs NT: demographics were 59.2±8.4 vs 48.8±8.4 vs 63.7±16.6 kg (p=0.001*), and C0 PSZ exposure was 1.9±1.5 vs 1.1±0.8 vs 2.4±1.8mg/L (p<0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, 1x300mg-PSZ tablet administration quickly achieved similar exposure than with 3 or 4 times a day PSZ OSF used for several months. TRL C0/dose ratio (TRL C0/D) 7.4±4.4mg/L with PSZ tablets vs 4.6±0.8 with PSZ oral solution (p=0.034*). ERL C0/D was similar with both formulations. PPI had no impact on PSZ concentration (1.49±1.07mg/L without PPI, vs. 1.33±1.17mg/L with PPI, p=0.4134*). Despite high exposure, PSZ remained well tolerated (one diarrhea and one fatigue).PSZ tablets administration allows satisfactory exposure, even on CFLT patients, with lower posology. This once-a-day formulation was not impacted by PPI, extensively used in CF patients.

Concepts: Pharmacology, Pulmonology, Cystic fibrosis, Pleural effusion, Organ transplant, Lung transplantation, Pharmaceutical formulation, Tablet