Transplantation of initially rejected donor lungs using ex vivo lung perfusion: A 5-year experience.

BACKGROUND: Ex vivo lung perfusion (EVLP) is a method for the evaluation and reconditioning of high-risk donor lungs to increase the pool of potential donor lungs. METHODS: We reviewed all consecutive patients who received lung transplants from May 2012 to May 2017 with follow-up until July 2021. EVLP was used in lungs initially rejected due to inadequate oxygenation but without other contraindications. Lungs with improved oxygenation levels above the threshold were transplanted. The primary endpoint was the time to graft failure, which was defined as the time from surgery to death or re-transplantation, whichever occurred first. The secondary outcome was freedom from chronic lung allograft dysfunction. RESULTS: A total of 157 patients underwent transplantation during the study period. Thirty-nine patients received EVLP-treated donor lungs. Restricted mean graft survival time up to 7 years is 5.14 years for non-EVLP and 4.19 for EVLP, the difference being -0.95 (confidence interval [CI]-1.93 to 0.04, p = .059). The hazard ratio is 1.66 (CI 1.00-2.75, p = .046). Chronic lung allograft dysfunction was the highest contributor to mortality in both groups. There were significant differences in freedom from chronic lung allograft dysfunction at 12 and 24 months of follow-up (p = .005 and p = .030, respectively). Subgroup analyses revealed that the first patients who received EVLP in 2012-2013 had a substantially worse 5-year graft survival than those who received EVLP more recently in 2016-2017 (14.3% vs. 60.0%). For the latter, the 5-year graft survival was observed to be remarkably close to the non-EVLP group (60.8%). CONCLUSION: Long-term survival was significantly lower, and lung function was poorer among recipients in the EVLP group than in the non-EVLP group. However, the outcome of patients who received EVLP-treated lungs was observed to improve steadily after the first 2 years after EVLP was introduced in Denmark.

Felodipine and renal function in lung transplantation: A randomized placebo-controlled trial.

BACKGROUND: Calcium channel blockers may ameliorate the decline in renal function caused by calcineurin inhibitors in lung transplantation (LTX) recipients. We hypothesized that pre-operative and 12-week post-operative treatment with the calcium channel blocker felodipine would reduce the decline in glomerular filtration rate (GFR). METHODS: In this prospective, randomized, double-blind trial, 39 LTX recipients were transplanted and received placebo (n = 19; GFR, 102 ml/min/1.73 m2 [range, 91-113 ml/min/1.73 m2]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m2 [range, 88-104 ml/min/1.73 m2]). Pre-operative treatment was titrated post-operatively to 10 mg or the maximum tolerable dose. The primary end-point was the change in GFR using Cr-51-labeled EDTA from LTX to 12 weeks thereafter, and follow-up was 52 weeks. RESULTS: The treatment group showed an absolute mean decline in GFR of 31 ml/min/1.73 m2 (95% CI: -40 to 22 ml/min/1.73 m2), whereas that of the placebo group was 48 ml/min/1.73 m2 (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m2). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m2 (95% CI: 4-29 ml/min/1.73 m2; p = 0.01). Half of the patients were unable to complete the 3-month primary follow-up, and the analysis includes these patients by intention-to-treat. After 52 weeks (40 weeks after termination of treatment), the treatment effect was maintained at 12 ml/min/1.73 m2 (95% CI: 0-24 ml/min/1.73 m2, p = 0.05). The number of days with registered hypotension was significantly higher in the felodipine group than in the placebo group (39 days vs 13 days, rate ratio: 2.9 [95% CI: 1.5-5.3]). CONCLUSIONS: Use of felodipine in select patients was associated with greater preservation in renal function early (90 days) after LTX. The observed benefits were attenuated by 1 year, although trends in better renal function were noted.

Comparing Methods for Cardiac Output: Intraoperatively Doppler-Derived Cardiac Output Measured With 3-Dimensional Echocardiography Is Not Interchangeable With Cardiac Output by Pulmonary Catheter Thermodilution.

BACKGROUND: Estimation of cardiac output (CO) is essential in the treatment of circulatory unstable patients. CO measured by pulmonary artery catheter thermodilution is considered the gold standard but carries a small risk of severe complications. Stroke volume and CO can be measured by transesophageal echocardiography (TEE), which is widely used during cardiac surgery. We hypothesized that Doppler-derived CO by 3-dimensional (3D) TEE would agree well with CO measured with pulmonary artery catheter thermodilution as a reference method based on accurate measurements of the cross-sectional area of the left ventricular outflow tract. METHODS: The primary aim was a systematic comparison of CO with Doppler-derived 3D TEE and CO by thermodilution in a broad population of patients undergoing cardiac surgery. A subanalysis was performed comparing cross-sectional area by TEE with cardiac computed tomography (CT) angiography. Sixty-two patients, scheduled for elective heart surgery, were included; 1 was subsequently excluded for logistic reasons. Inclusion criteria were coronary artery bypass surgery (N = 42) and aortic valve replacement (N = 19). Exclusion criteria were chronic atrial fibrillation, left ventricular ejection fraction below 0.40 and intracardiac shunts. Nineteen randomly selected patients had a cardiac CT the day before surgery. All images were stored for blinded post hoc analyses, and Bland-Altman plots were used to assess agreement between measurement methods, defined as the bias (mean difference between methods), limits of agreement (equal to bias ± 2 standard deviations of the bias), and percentage error (limits of agreement divided by the mean of the 2 methods). Precision was determined for the individual methods (equal to 2 standard deviations of the bias between replicate measurements) to determine the acceptable limits of agreement. RESULTS: We found a good precision for Doppler-derived CO measured by 3D TEE, but although the bias for Doppler-derived CO by 3D compared to thermodilution was only 0.3 L/min (confidence interval, 0.04-0.58), there were wide limits of agreement (-1.8 to 2.5 L/min) with a percentage error of 55%. Measurements of cross-sectional area by 3D TEE had low bias of -0.27 cm (confidence interval, -0.45 to -0.08) and a percentage error of 18% compared to cardiac CT angiography. CONCLUSIONS: Despite low bias, the wide limits of agreement of Doppler-derived CO by 3D TEE compared to CO by thermodilution will limit clinical application and can therefore not be considered interchangeable with CO obtained by thermodilution. The lack of agreement is not explained by lack of agreement of the 3D technique.

First Danish experience with ex vivo lung perfusion of donor lungs before transplantation.

INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its introduction. MATERIAL AND METHODS: The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. CONCLUSION: In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted as a result of their improved function. EVLP seems to be a safe way to increase the use of marginal donor lungs. FUNDING: no funding was granted for the present paper. TRIAL REGISTRATION: not relevant.

Early laparotomy after lung transplantation: increased incidence for patients with α1-anti-trypsin deficiency.

BACKGROUND: Gastrointestinal complications after lung transplantation have been reported with incidence rates ranging from 3% to 51%, but the reasons are poorly understood. We aimed to investigate the correlations between pulmonary diseases leading to lung transplantation and early gastrointestinal complications requiring laparotomy after transplantation with outcomes for patients at increased risk. METHODS: In this study we performed a retrospective analysis of data of patients who underwent lung transplantation at our institution from 2004 to 2012. The study period was limited to the first 90 days after transplantation. RESULTS: Lung transplantation was performed in 258 patients, including 51 patients with α1-anti-trypsin deficiency (A1AD). Seventy-eight patients (30%) had an X-ray of the abdomen, and 23 patients (9%) required laparotomy during the first 90 days after transplantation. Patients with A1AD comprised 20% of the total recipients, 23% (18 of 78) of the patients who had an abdominal X-ray performed (p = 0.40), and 48% (11 of 23) of the patients who required laparotomy (p < 0.001). More than 1 of every 5 patients (11 of 51) with A1AD required laparotomy at a median 8 days after transplantation, and the estimated odds ratio for laparotomy for A1AD patients was 5.74 (CI 2.15 to 15.35). In the group of patients with A1AD who required laparotomy, the estimated hazard ratio for death was 1.62 (CI 0.57 to 4.62), the stay in the intensive care unit was prolonged, but no significant difference was observed for time on mechanical ventilation. Among pulmonary diseases and demographics of the patients, no other risk factors were identified for laparotomy. CONCLUSIONS: A1AD was the only significant risk factor identified for gastrointestinal complications that required laparotomy within 3 months after lung transplantation. There was a trend toward a higher risk of death after laparotomy in patients with A1AD, and the length of stay in the intensive care unit was significantly prolonged, whereas the time on mechanical ventilation was unaffected.

Outcome of lung transplanted patients with primary graft dysfunction.

OBJECTIVE: Primary graft dysfunction (PGD) causes significant mortality and morbidity after lung transplantation. The objectives of the study were to describe the clinical and histological sequelae of PGD. METHODS: Histology of all patients receiving single-lung transplantation 1999-2004 (n=181) was reviewed. PGD was defined as diffuse radiological infiltration of the lung allograft occurring within the first 72h postoperatively. RESULTS: One patient died intra-operatively. PGD was recorded in 63% (n=113) of 180 consecutive transplant recipients. Patients with PGD had a worse 90-day postoperative mortality (14% versus 3%, p=0.03) and 3-year survival (55% versus 77%, p=0.003). Freedom from bronchiolitis obliterans syndrome was similar in both groups. The maximal FEV(1) was significantly lower in patients with PGD, median 54% (quartiles 48-61%) predicted; compared to patients without PGD, median 59% (quartiles 54-69%) predicted (p=0.003). There was a significant linear trend in the decline of maximal FEV(1) with the presence and increasing severity of radiographic infiltrate (p=0.004). During follow-up, patients with PGD were more likely to demonstrate diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (p=0.009 and p=0.01, respectively). Histological findings of diffuse alveolar damage correlated closely with extent of radiological infiltration (p<0.0001). CONCLUSIONS: Transplant recipient survival, lung function, and histological findings of diffuse alveolar damage appear to be closely correlated with the appearance and severity of PGD.

[Opioid detoxication under general anesthesia]. / Opioidafgiftning under generel anaestesi.

Antagonist-precipitated opioid detoxification under general anaesthesia has been used extensively since its introduction in 1988. The use of antagonists was believed to shorten the detoxification period. Administration to opioid dependents is followed by a violent activation of the adrenergic system, which results in the development of an acute withdrawal syndrome in the patient. This is usually treated with clonidine. To reduce the subjective discomfort, the procedure is conducted under anaesthesia. From the existing literature, one may conclude that despite more than ten years of development there is currently no sufficient evidence of the effectiveness of antagonist-precipitated opioid detoxification under general anaesthesia conducted under modern anaesthesiological management. Randomised, clinical trials are necessary to document the advantages of this detoxification method as compared to conventional treatment.