J.W. Awori Hayanga

The surgical technique of bilateral sequential lung transplantation

Since the first successful lung transplant performed three decades ago, the technique of lung transplantation has evolved with acceptable short- and long-term outcomes such that it has become the standard for those with end stage pulmonary disease. Herein, we describe our current favored approach and discuss some of the current areas in need of further investigation as they relate to the technical aspects of the operation.

The ripple effect of a complication in lung transplantation: Evidence for increased long-term survival risk.

OBJECTIVE Lung transplantation is a life-saving procedure for patients who have end-stage lung disease. The frequency and severity of complications have not been fully characterized. We hypothesized that early in-hospital, postoperative complications decrease long-term survival. METHODS We retrospectively identified in-hospital complications in lung transplant recipients, from the period January 2007 to October 2013. Complications were graded using the extended Accordion Severity Grading System (ASGS). Complications were categorized by event and organ system. Survival analysis was performed (P < .05) using a time-dependent model. RESULTS Among 748 eligible patients, 3381 independent in-hospital, postoperative complications occurred in 92.78% of patients. Median follow-up was 5.4 years. Complications associated with significant decrease in 5-year survival were: renal (hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.40-4.48); hepatic (HR 4.08, 95% CI 2.86-5.82); cardiac (HR 1.95, 95% CI 1.56-2.45). The maximum ASGS of ≥5 (18.5% vs 73.8%), and the weighted ASGS sum >10 (2.5% vs 73.8%), were found to be significant predictors of long-term survival. Multivariate analysis identified a weighted ASGS sum of >10, and renal, cardiac, and vascular complications as predictors of decreased long-term survival. CONCLUSIONS Rigorous delineation of complications after lung transplantation showed that grade 5 ASGS in-hospital postoperative complications, and a weighted ASGS sum >10, were independent predictors of decreased long-term survival well beyond the initial perioperative period. These results may identify important targets for best practice guidelines and quality-of-care measures after lung transplantation.

Airway complications after lung transplantation: Contemporary survival and outcomes.

BACKGROUND Airway complications are rare and cause increased morbidity and mortality after lung transplantation (LT). We sought to examine risk factors associated with this complication and its impact on survival. METHODS We retrospectively evaluated United Network for Organ Sharing data from 2000 to 2012. A backward stepwise logistic regression was performed on recipient-, donor-, and transplant-related variables to select independent risk factors associated with airway complications and mortality. Survival was evaluated using the Kaplan-Meier method. RESULTS We evaluated 16,156 consecutive adult LT recipients, among whom 233 (1.4%) developed airway complications. Predictors of increased risk of airway complications included male gender (odds ratio [OR] 1.61, p = 0.001), advancing recipient age (OR 1.02, p < 0.001) and pre-transplantation admission to the intensive care unit (ICU) (OR 2.13, p < 0.001). The 30-day (89.6% vs 96.2%, p = 0.001), 90-day (69.9% vs 93.1%, p < 0.001), 1-year (54.6% vs 84.4%, p < 0.001), 3-year (38.7% vs 67.4%, p < 0.001) and 5-year (33.2% vs 54.2%, p < 0.001) survival rates were each significantly reduced in recipients with airway complications. Factors associated with an increased risk of 1-year mortality included recipient age (hazard ratio [HR] 1.01, p < 0.001), use of extracorporeal mechanical support (HR 1.5, p = 0.01), diagnosis of cystic fibrosis (HR 1.22, p = 0.01), glomerular filtration rate (GFR) 60 to 90 ml/min/1.73 m2 (HR 1.61, p < 0.001), GFR <60 ml/min/1.73 m2 (HR 1.13, p = 0.01), non-ICU hospitalization (HR 1.32, p < 0.001), pre-transplantation ICU hospitalization (HR 2.54, p < 0.001), donor with positive serology for cytomegalovirus (HR 1.16, p < 0.001) and donor with a smoking history (HR 1.19, p < 0.001). Double LT (HR 0.83, p < 0.001) was associated with a decreased risk of death. Chronic obstructive pulmonary disease/emphysema was protective compared with idiopathic pulmonary fibrosis (HR 0.85, p = 0.008). CONCLUSION Airway complications are associated with a significant mortality burden.

Extracorporeal membrane oxygenation as a bridge to lung re-transplantation: Is there a role?

BACKGROUND In this study we sought to determine survival rates after use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung re-transplantation (re-LT). METHODS Propensity-adjusted analysis was performed on data from the Scientific Registry of Transplant Recipients (SRTR) to evaluate survival in recipients between the years 1988 and 2012, based on the use of ECMO before re-LT. RESULTS A total of 854 adult re-LT recipients were identified. Extracorporeal support had been used as a bridge in 55 (6.8%) of the recipients, whereas 799 (93.2%) had undergone re-LT without the use of ECMO. Compared with non-ECMO patients, the ECMO patients were more likely to have: higher body mass index (p = 0.003); received lungs from an older donor (p = 0.04); higher total bilirubin (p = 0.002); undergone bilateral lung transplantation (p = 0.01); diabetes (p = 0.04); mechanical ventilation (p < 0.0005); and been hospitalized in the intensive care unit (p < 0.0001). They were also more likely to have a diagnosis of bronchiolitis obliterans syndrome (p < 0.0001), be on inhaled nitric oxide (p < 0.0001), and have a shorter waitlist time before re-LT (p < 0.0001). Compared with the non-ECMO group, 30-day survival for the ECMO group was lower (67.3% vs 91.2%, p = 0.0002). Obesity was identified as a predictor of increased mortality in re-LT hazard ratio 2.97 (1.18 to 7.50), p = 0.02. CONCLUSION This contemporary analysis of survival after use of ECMO as a bridge to re-LT revealed lower survival in the ECMO group.

Maintenance Belatacept-based Immunosuppression in Lung Transplantation Recipients Who Failed Calcineurin Inhibitors

Background Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure. Methods Single-center, retrospective medical record review of adult lung transplant recipients (LTR) before and after conversion to belatacept-based ISR. Patients were evaluated at fixed time points before and after belatacept initiation. Primary outcome was incidence of acute cellular rejection (ACR). Secondary outcomes included incidence of infection, chronic lung allograft dysfunction (CLAD) progression, death, change in mean arterial pressure, and estimated glomerular filtration rate. Results Eleven LTRs received belatacept with a mean of 246 (91-1064) days of follow-up after conversion. Four were changed to belatacept for thrombotic thrombocytopenic purpura, 3 for posterior reversible encephalopathy syndrome, 2 for recurrent ACR, 1 for CLAD, and 1 for renal-sparing. ACR was not different before and after belatacept (P = 0.17). Mean estimated glomerular filtration rate was significantly higher postbelatacept (32.53 vs 45.26, P = 0.04). Mean incidence of infections (24.4% vs 16.0%, P = 0.55) and mean arterial pressure (97.5 vs 92.1 P = 0.38) were not different. Progression of CLAD occurred in 2 patients. At the end of follow-up, 7 of 11 patients were alive. Conclusions Belatacept-based ISR appear to produce reasonable results in LTRs who fail CNI-based ISR. Larger prospective trials appear warranted in lung transplantation.

Setting out into practice: Preparing for the future, today

From the Division of Lung Transplantation, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa; and Department of Cardiothoracic Surgery, Western Michigan University School of Medicine, Kalamazoo, Mich. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication Nov 2, 2016; revisions received March 25, 2017; accepted for publication May 8, 2017; available ahead of print June 7, 2017. Address for reprints: J.W. Awori Hayanga, MD, MPH, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA 15213 (E-mail: jhayanga@me.com). J Thorac Cardiovasc Surg 2017;154:1340-2 0022-5223/

Rescue alemtuzumab for refractory acute cellular rejection and bronchiolitis obliterans syndrome after lung transplantation.

36.00 Copyright 2017 by The American Association for Thoracic Surgery http://dx.doi.org/10.1016/j.jtcvs.2017.05.001

Ex vivo lung perfusion: The makings of a game changer

Refractory acute cellular rejection (rACR) is associated with death and bronchiolitis obliterans syndrome (BOS) post‐lung transplantation. We report the largest cohort of lung transplant recipients (LTRs) treated with rescue alemtuzumab for rACR or BOS. RACR outcomes included burden of ACR 30 days before and 180 days after rescue assessed by a novel composite rejection standardized score (CRSS, range 0‐6) and freedom from ≥A2 ACR. BOS outcomes included freedom from BOS progression and FEV1 decline >10%. Univariate parametric and nonparametric statistical approaches were used to assess treatment response. Kaplan‐Meier method with log rank conversion was used to assess freedom from events. Fifty‐seven alemtuzumab doses (ACR 40 and BOS 17) given to 51 patients were included. Median time to rescue was 722 (IQR 42‐1403) days. CRSS declined significantly (3 vs 0.67, P<0.001) after rescue. Freedom from ≥A2 was 62.5% in rACR. Freedom from BOS progression was 52.9% at 180 days in the BOS cohort. Freedom from FEV1 decline >10% was 70% in BOS grade 1 and 14.3% in advanced BOS grades 2‐3. Infections developed in 72.5% and 76.5% of rACR and BOS groups. Rescue alemtuzumab appears useful for rACR. Patients with BOS 1 may have transient benefit, and patients with advanced BOS seem not to respond to alemtuzumab.

Bilateral Sequential Lung Transplantation: What the Anesthesiologist Needs to Know About the Surgical Approach

The use of ex vivo lung perfusion (EVLP) techniques is both contemporary and relevant. In their article, Slama et al seek to evaluate the non-inferiority of normothermic ex vivo perfusion in the process of procurement by comparing it with standard lung procurement technique. The latter technique involves standard cold preservation that has been adopted universally and was used by the authors to serve as the control group. The entire cohort was drawn from a single institution that used standardized management algorithms for both ex vivo perfusion and transplantation. This homogeneity and standardization of practice patterns allows reproducibility in the results that better mitigates the effect of confounding. The evaluated lungs were subjected to a preservation time of 4 hours per the Toronto protocol, following which lungs that had been suitably reconditioned were used for transplantation. The authors successfully used 490% of the perfused lungs for transplantation. If one were to achieve a similar yield rate in the context of marginal lungs, one would leverage tremendous expansion in the donor pool. The transplantations were performed as bilateral sequential procedures, and each procedure was supported using intraoperative venoarterial extracorporeal membrane oxygenation. This latter point constitutes a departure from standard practice in the United States, where mechanical support (extracorporeal membrane oxygenation vs cardiopulmonary bypass) is applied more judiciously and geared toward attenuating the impact of right ventricular compromise, myocardial ischemia, left ventricular dysfunction, or significant pulmonary hypertension. Perhaps more predictably, however, the authors also used extracorporeal membrane oxygenation to manage severe primary graft

Atrial arrhythmias after lung transplantation: Incidence and risk factors in 652 lung transplant recipients.

Lung transplantation is a viable option for those patients with end-stage lung disease. After careful evaluation of candidacy, a complex operation with numerous challenging components is performed. Described herein, are the salient features of this operation from the viewpoint of the surgeon. Our goal is to enhance the anesthesiologist’s understanding of the process with a view to improving multidisciplinary collaboration to improve outcomes as a whole.