Bilateral Sequential Single Lung Transplantation Research Articles

653 LAPAROSCOPIC TOUPET FUNDOPLICATION RARELY INFLUENCES THE DECLINE IN FEV1 SEEN AFTER LUNG TRANSPLANT

Abstract Lung allografts have the shortest survival of any solid organ transplant. The leading cause of chronic lung allograft dysfunction (CLAD) is bronchiolitis obliterans syndrome (BOS). The aetiology of BOS remains poorly understood, with infections, immunosuppression and gastro-oesophageal reflux disease (GORD) amongst the proposed co-factors. A recent systematic review of GORD and BOS examined six retrospective case series with relatively small numbers and conflicting results. Our dataset is the largest cohort reported to date. Methods Retrospective review of a prospectively maintained database containing 149 consecutive lung transplant recipients undergoing laparoscopic Toupet fundoplication. A single expert surgeon (>5000 procedures) with published high-quality long-term outcomes in the non-transplant population did the operations. All were referred with symptoms of GORD and/or positive 24-hour ambulatory pH study. FEV1 was measured at three time points before (6, 3 and 1 month) and after (3, 6 and 12 months) surgery. Data were analysed using random intercept generalised linear (mixed) models to examine changes in FEV1 across time, as well as graphical methods (least squares method for FEV1 trendlines and two-tailed t-test). Results Median age was 56 (IQR 44–66) years; 84/149 were male. 132 had bilateral sequential single lung transplantation. The underlying pathologies were representative—emphysema, cystic fibrosis, interstitial lung disease. 8 patients died within 6 months of fundoplication. Using a linear mixed model there was no significant change in FEV1 across time after surgery compared with the last pre-operative measurement (p = 0.48). A significant reduction in FEV1 was seen in those undergoing fundoplication after CLAD was diagnosed (1.47 L, 95% CI 1.21–1.72, p < 0.001). There was no change in trajectory of FEV1 when trendlines for each patient were analysed (p = 0.777). Conclusion As with any solid organ transplant, lung allografts unfortunately suffer failure with time. Laparoscopic Toupet fundoplication performed in a high-volume centre by an experienced surgeon did not appear to alter this. In particular, once CLAD is diagnosed it seems that the decline in function (FEV1) is accelerated and cannot be salvaged by fundoplication. A minority of patients had their declining FEV1 stabilised or improved by surgery, but it is not yet possible to predict response.

Combined Heart-Lung-Liver Transplantation for Patients With Cystic Fibrosis: The Australian Experience

Combined multivisceral transplantation has emerged as a therapeutic option for a select patient cohort; however, clinical decision-making remains complex and controversial. The aim of this study was to examine patient characteristics, operative complications, and long-term outcomes of all patients who have undergone combined heart-lung-liver transplantation (HLLTx) in Australia. In this study, we performed a retrospective analysis of all adult patients who have undergone combined HLLTx in Australia to date. Recipient clinical characteristics, waitlist, and transplant outcomes are described. Eight adult patients have received HLLTx at a single Australian transplant center. Recipients of HLLTx have typically been young (median age, 30.1 years; range, 24-37), underweight (median body mass index, 19.8 kg/m2; range, 16.2-30.4) patients with cystic fibrosis (n=8, 100%) with severe airflow obstruction (median forced expiratory volume in the first second of expiration, 24% predicted; range, 17%-48%) accompanied by liver cirrhosis confirmed on histopathology (n=8, 100%). Despite relative preservation of synthetic function and low model for end-stage liver disease scores (median, 8; range, 6-17), all recipients had complications of portal hypertension prior to transplantation, with many patients having suffered life-threatening variceal hemorrhage. In this cohort, HLLTx was associated with overall posttransplant survival of 87.5% at 30 days, 71.4% at 1 year, and 42.9% at 5 years. Listing for combined HLLTx was associated with prolonged waitlist times relative to bilateral sequential single-lung transplantation (median 556 vs 56 days, respectively), however waitlist mortality and/or delisting was comparable between groups. Taken together, these findings highlight the opportunities and challenges facing combined (heart-) lung and liver transplantation in patients with multiorgan failure.

A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia\u2013reperfusion injury after unilateral lung transplantation

BackgroundPrimary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia–reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a novel approach to assess the impact of increased pulmonary blood flow in a large porcine single-left lung transplantation model.MaterialsTwelve porcine left lung transplants were divided in two groups (n = 6, in low- (LF) and high-flow (HF) group). Donor lungs were stored for 24 h on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6 h after reperfusion with partially clamping right pulmonary artery to achieve a higher flow (target flow 40–60% of total cardiac output) to the transplanted lung compared to the LF group, where the right pulmonary artery was not clamped.ResultsSurvival at 6 h was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 h of reperfusion. injury was also present in the right native lung and showed signs compatible with the pathophysiological hallmarks of ischemia–reperfusion injury.ConclusionsPartial clamping native pulmonary artery in large animal lung transplantation setting to study the impact of low versus high pulmonary flow on the development of ischemia reperfusion is feasible. In our study, differential blood flow had no effect on IRI. However, our findings might impact future studies with extracorporeal devices and represent a specific intra-operative problem during bilateral sequential single-lung transplantation.

The Relationship Between Peak Cough Flow and Respiratory Function Testing (Spirometry), and the Factors That Influence This, Post Bilateral Sequential Single Lung Transplantation: A Cross-sectional Feasibility Study at a Single Centre Cardiothoracic Transplantation Unit

Spirometry is gold standard for detecting chronic lung allograft (CLAD) dysfunction. Peak cough flow (PCF) assesses cough strength and identifies those at risk of developing respiratory tract infections, which contribute to the development of CLAD. Normal adult PCF 440-1200 L/min, ≥ 270 L/min PCF demonstrates adequate cough, ≤ 160 L/min demonstrates inefficient cough. Study Aims: 1. To evaluate the feasibility of recruitment and PCF testing alongside standard care 2. To examine the relationship between PCF and forced vital capacity (FVC) and PCF and forced expiratory volume in one second (FEV1), and the factors that influence this post bilateral sequential single lung transplant (BSSLTx).

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.

89 Early Outcomes of Bilateral Sequential Single Lung Transplantation after Ex-Vivo Lung Evaluation and Reconditioning

Purpose Ex-vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard ISHLT criteria for transplantation (tx). This is a prospective evaluation of 11 consecutive EVLP runs performed between January 2009 and September 2010 at a single institution. Methods and Materials Lungs offered and rejected for routine tx were evaluated and procured normally if they met the inclusion criteria for EVLP. Thus obtained grafts were implanted in the EVLP circuit and reperfused according to the institutional protocol using acellular supplemented STEEN Solution™ up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 l/min/m2 with a LA pressure <5mmHg and PA pressure <15mmHg. After re-warming to 37°C, grafts were ventilated with a 6-8ml/kg(donor weight) tidal volume with a respiratory rate of 7-8/minute, an IE ratio of 1:2 and PEEP of 5-10cmH20. Hemodynamic and respiratory data was monitored continuously and the graft was underwent hourly clinical assessments. Results Donor data: n=11, age 44.81±8.82 years, cause of death: intracranial hemorrhage - 10(91%), stroke - 1(9%), history of smoking 7(64%), average pack year 19.57±8.59 years, mechanical ventilation time 98.36±91.60 hours, CXR: abnormal - 10(91%), normal - 1(9%). EVLP: Mean duration 146.04±31.06 minutes. Arterial PaO2 before termination of the circuit improved significantly compared to the last pre-retrieval value: 55.95±9.46 vs 40.4±14.92 kPa (p<0.05). After ex-vivo evaluation and reconditioning, 5 (45%) pairs of lungs were successfully transplanted. Recipient data: Age 41.8±15.69 years, underlying disease: cystic fibrosis - 2(40%), emphysema - 3(60%). Median ITU stay was 7 (range 3–72) days, median follow-up 91 (range 67–269) days, with a 30 day survival rate of 100%. There was one late death (day 203) due to pneumonia. Conclusions EVLP facilitates assessment and reconditioning of borderline lungs with a conversion rate to tx of 45% and excellent short-term survival. Ex-vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard ISHLT criteria for transplantation (tx). This is a prospective evaluation of 11 consecutive EVLP runs performed between January 2009 and September 2010 at a single institution. Lungs offered and rejected for routine tx were evaluated and procured normally if they met the inclusion criteria for EVLP. Thus obtained grafts were implanted in the EVLP circuit and reperfused according to the institutional protocol using acellular supplemented STEEN Solution™ up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 l/min/m2 with a LA pressure <5mmHg and PA pressure <15mmHg. After re-warming to 37°C, grafts were ventilated with a 6-8ml/kg(donor weight) tidal volume with a respiratory rate of 7-8/minute, an IE ratio of 1:2 and PEEP of 5-10cmH20. Hemodynamic and respiratory data was monitored continuously and the graft was underwent hourly clinical assessments. Donor data: n=11, age 44.81±8.82 years, cause of death: intracranial hemorrhage - 10(91%), stroke - 1(9%), history of smoking 7(64%), average pack year 19.57±8.59 years, mechanical ventilation time 98.36±91.60 hours, CXR: abnormal - 10(91%), normal - 1(9%). EVLP: Mean duration 146.04±31.06 minutes. Arterial PaO2 before termination of the circuit improved significantly compared to the last pre-retrieval value: 55.95±9.46 vs 40.4±14.92 kPa (p<0.05). After ex-vivo evaluation and reconditioning, 5 (45%) pairs of lungs were successfully transplanted. Recipient data: Age 41.8±15.69 years, underlying disease: cystic fibrosis - 2(40%), emphysema - 3(60%). Median ITU stay was 7 (range 3–72) days, median follow-up 91 (range 67–269) days, with a 30 day survival rate of 100%. There was one late death (day 203) due to pneumonia. EVLP facilitates assessment and reconditioning of borderline lungs with a conversion rate to tx of 45% and excellent short-term survival.

Early outcomes of bilateral sequential single lung transplantation after ex-vivo lung evaluation and reconditioning

Ex vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard International Society for Heart and Lung Transplantation criteria for transplantation. We retrospectively evaluated 13 consecutive EVLP runs between January 2009 and December 2010. Lungs rejected for routine transplantation were implanted to the EVLP circuit and reperfused using acellular supplemented Steen Solution (Vitrolife, Göteborg, Sweden) up to a target flow rate of 40% of the donor's calculated flow at a cardiac index of 3.0 liters/min/m(2); target left atrial pressure < 5 mm Hg; and pulmonary artery pressure < 15 mm Hg. Mechanical ventilation was introduced after rewarming to 32°C: tidal volume, 6 to 8 ml/kg; respiratory rate, 7 to 8 breaths/min; duration of inspiration/expiration (I/E) ratio, 1:2; and positive end-expiratory pressure, 5 to 10 cm H(2)O. Hemodynamic and respiratory data monitoring with hourly clinical assessment were performed. Donor data, conversion rate to transplantation, and recipient outcome were analyzed. Donor data (n = 13) were: age, 44.23 ± 8.33 years; female/male, 8:5; cause of death: intracranial hemorrhage, 11 (85%), stroke, 1 (7.5%), hypoxic brain injury, 1 (7.5%); smoking history, 9 (69%), 17.44 ± 8.92 pack-years; mechanical ventilation, 102.6 ± 91.92 hours; chest x-ray imaging: abnormal, 12 (92.5%); normal, 1 (7.5%). EVLP: mean 141 ± 28.83 minutes. Arterial partial pressure of oxygen/fraction of inspired oxygen 100% before termination of the circuit vs pre-retrieval value: 57.32 ± 9.1 vs 42.36 ± 14.13 kPa (p < 0.05). Six (46%) pairs of donor lungs were transplanted. Median follow-up was 297.5 days (range, 100-390 days), with 100% survival at 3 months. EVLP may facilitate assessment and/or reconditioning of borderline lungs, with a conversion rate of 46 % and good short-term survival.

Prior diabetes mellitus is associated with increased morbidity in cystic fibrosis patients undergoing bilateral lung transplantation: an ‘orphan’ area? A retrospective case–control study

The aim of this study was to determine whether pre-existing diabetes mellitus increases the risk of rejection, infection and/or death in cystic fibrosis patients undergoing bilateral sequential single-lung transplantation. A retrospective audit of 25 consecutive patients with cystic fibrosis who underwent bilateral sequential single-lung transplantation between 1 January 2003 and 31 December 2005 at a tertiary referral hospital was carried out. Although 32% patients had diabetes diagnosed before lung transplantation, 92% had random blood glucose levels > or =11.1 mmol/L requiring insulin during admission. Patients with pre-existing diabetes had increased infection-related (3.9 vs 1.2, P= 0.01) and putative rejection-related (1.4 vs 0.5, P= 0.04) hospital admissions post-transplantation compared with those without diabetes pre-transplant. During the period of observation, four of eight patients with a prior diagnosis of diabetes died compared with none of 17 patients without prior diabetes (P= 0.0055). Almost all cystic fibrosis patients develop hyperglycaemia after lung transplantation, but patients with prior diabetes have more complication-related admissions to hospital and a higher mortality rate.

Retransplantation After Single Lung Transplantation

Objective Our lung transplant program started in June 1989 with primary grafts including 21 heart-lung, 11 single lung, and 5 bilateral sequential single lung transplantation. Three patients required retransplantation for single lung and 2 patients for heart-lung grafts. The primary cause of death after lung transplantation is chronic graft dysfunction—bronchiolitis obliteran—though other causes, namely acute graft failure, have been mentioned. Retransplantation is considered to be the only treatment option. In experienced centers, the 1- and 5-year survivals are not as good as for other organ transplantations and for retransplantations the outcome is even worse. Our objective herein was to describe factors to be taken into account for retransplantation in our program, including the timing and indication for retransplantation and the presence of comorbidities. Patients and Methods In our experience of 11 single lung transplantations, 3 (27.3%) were retransplantations. The 3 patients were 3, 5, and 2 years after primary transplantation. The indications were overexpansion of the remaining lung compressing the new lung in one and bronchiolitis obliterans in the others. Results One patient with emphysema died in hospital after retransplantation because of acute myocardial infarction. One patient with lymphangioleiomyomatosis (LAM) disease died of lung complication after sudden cardiac arrest at 1.5 years after retransplantation. One patient with idiopathic pulmonary fibrosis is still alive at 5 years after retransplantation. Conclusions Bronchiolitis obliterans was a common reason for retransplantation among our patients as well as in other reports. Bronchiolitis exists with superimposed infection for years if it is the mild form. However, the clinical setting is progressively worse if it could not be controlled leading to retransplantation. At this stage, progressive deterioration of lung function must be considered because of inadequate therapy for infection. Finally, when there is infection usually both lungs are involved. The decision whether to replace the transplanted lung or the remaining lung is a concern, especially when the donor availability is scarce. In conclusion, lung retransplantation is the only treatment option for severe graft dysfunction, if there is no other therapy that can prolong life. Though bronchiolitis obliterans often is the indication for retransplantation, bronchiolitis itself is the signal of retransplantation.

Outcome of heart-lung and bilateral-sequential single lung transplantation for cystic fibrosis: a UK national study

Outcome of heart-lung and bilateral-sequential single lung transplantation for cystic fibrosis: a UK national study

Bilateral sequential single lung transplantation for pulmonary hypertension and Eisenmenger’s syndrome

Background. Lung transplantation, with and without intracardiac repair for pulmonary hypertension (PH) and Eisenmenger’s syndrome (EIS), has become an alternative transplant strategy to combined heart and lung transplantation (HLT).Methods. Thirty-five patients with PH or EIS underwent either bilateral sequential single lung transplantation (BSSLT, group I, n = 13) or HLT (group II, n = 22). Another 74 patients, who underwent BSSLT for other indications, served as controls (group III). Immediate allograft function, early and medium-term outcomes, lung function, and 2-year survival were compared between the groups.Results. Comparisons between groups I and II showed no significant difference in any variables except percent predicted forced vital capacity. Immediate allograft function was significantly inferior (p < 0.05) and the blood loss was greater (p < 0.01) in group I when compared with those in group III. However, this resulted in no significant difference in early and medium-term outcomes, and 2-year survival between the 2 groups.Conclusions. BSSLT for PH and EIS can be performed as an alternative procedure to HLT without an increase in early and medium-term morbidity and mortality. Results are comparable with BSSLT performed for other indications.

Impact of graft ischemic time on outcomes after bilateral sequential single-lung transplantation

Background. Graft ischemic time (GIT) is a potential limiting factor in lung transplantation. Methods. Seventy-four patients who underwent bilateral sequential single-lung transplantation were divided into three groups: group I, GIT less than 5 hours (n = 20); group II, GIT between 5 and 8 hours (n = 39); and group III, GIT more than 8 hours (n = 15). We compared early allograft function (ratio of arterial oxygen tension to inspired oxygen fraction and alveolar–arterial oxygen gradient), blood loss, the need for tracheostomy, the duration of ventilation, intensive care unit stay, and hospital stay. We also compared prevalences of acute and chronic rejection, airway complications, lung function test, and 2-year survival. Results. Early allograft function in group III was significantly worse than those in groups I and II. However, there was no significant difference in any other variables of early and medium-term outcomes among the three groups. No significant correlation was detected between GIT and duration of intensive care unit stay or hospital stay. Conclusions. The limitation of acceptable GIT could be extended from the traditionally approved 4 to 5 hours, to 5 to 8 hours or even longer.

Technical aspects of adult lung transplantation.

This article describes the authors' current technical preferences for the performance of isolated single lung transplantation and bilateral sequential single lung transplantation. The current techniques are the result of lessons learned in the performance of over 400 lung transplant operations at Washington University School of Medicine since 1987.

Improved sternal fixation in the transsternal bilateral thoracotomy incision

The success of bilateral sequential single-lung transplantation has led to the rebirth of the transsternal bilateral thoracotomy incision. Despite the multiple advantages of this incision over a median sternotomy for this operation, one distinct disadvantage is the high prevalence of sternal disruption at the transverse sternotomy site, which is traditionally closed with sternal wires. This disruption rate is between 20% and 40% in most institutions and can lead to significant pain and deformity in addition to slowing the postoperative recovery and increasing the risk of sternal infection. To overcome this problem we have designed and manufactured a device that provides a sound method of fixating the sternum. The device is composed of two plates, one anterior and one posterior to the sternum, that are fixed to each other and to the sternum by means of screws into internally threaded posts positioned in predrilled holes through the bone on either side of the sternotomy. All components of the device are made from titanium and a range of post lengths are available to accommodate variability in sternal thickness. The structure of the device is demonstrated. The device has now been inserted into a total of 20 patients after bilateral lung transplantation and the preliminary results suggest this is a superior technique for closure of a transverse sternotomy and support continued and routine use. (J T horac C ardiovasc S urg 1996;112:137-41)

Left atrial thrombus after lung transplantation

We report on a 16-year-old boy who developed a thrombus at the left atrial suture line after undergoing a bilateral sequential single lung transplantation. The diagnosis was made by transesophageal echocardiogram.

Techniques and results in bilateral sequential single lung transplantation. The National Heart & Lung Replacement Service.

Lung transplantation continues to evolve as a therapeutic option for patients with end-stage lung disease. Bilateral sequential single lung transplantation (BSSLTx) is a recent addition to the lung transplant surgeon's armamentarium that incorporates the benefits of single lung transplantation in patients who require double lung replacement while avoiding the morbidity inherent in the en bloc double lung transplant procedure. Between November 1992 and October 1993, 17 recipients underwent 18 bilateral BSSLTx procedures for a variety of indications. In 53% of patients, the procedure was completed without the requirement for cardiopulmonary bypass. Telescoping of the bronchial anastomosis has proved satisfactory. Induction cytolytic therapy has not been utilized. Patients received methyl prednisolone from day 1 and as maintenance prednisolone therapy. Actuarial 1-year survival is 87%; 12 of the 15 survivors are in Functional Class I. BSSLTx is an evolving transplant option for patients who require double lung replacement. Definitive clinical diffusion of the procedure will depend upon intermediate and long-term outcomes for specific recipient pathologies.