F. Ius

Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients

BACKGROUND Cold flush and static cold storage is the standard preservation technique for donor lungs before transplantations. Several research groups have assessed normothermic perfusion of donor lungs but all devices investigated were non-portable. We report first-in-man experience of the portable Organ Care System (OCS) Lung device for concomitant preservation, assessment, and transport of donor lungs. METHODS Between Feb 18, and July 1, 2011, 12 patients were transplanted at two academic lung transplantation centres in Hanover, Germany and Madrid, Spain. Lungs were perfused with low-potassium dextran solution, explanted, immediately connected to the OCS Lung, perfused with Steens solution supplemented with two red-cell concentrates. We assessed donor and recipient characteristics and monitored extended criteria donor lung scores; primary graft dysfunction scores at 0, 24, 48, and 72 h; time on mechanical ventilation after surgery; length of stays in hospital and the intensive-care unit after surgery; blood gases; and survival of grafts and patients. FINDINGS Eight donors were female and four were male (mean age 44·5 years, range 14-72). Seven recipients were female and five were male (mean age 50·0 years, range 31-59). The preharvest donor ratio of partial pressure of oxyen (PaO(2)) to fractional concentration of oxygen in inspired air (F(I)O(2)) was 463·9 (SD 91·4). The final ratio of PaO(2) to F(I)O(2) measured with the OCS Lung was 471·58 (127·9). The difference between these ratios was not significant (p=0·72). All grafts and patients survived to 30 days; all recipients recovered and were discharged from hospital. INTERPRETATION Lungs can be safely preserved with the OCS Lung, resulting in complete organ use and successful transplantation in our series of high-risk recipients. In November, 2011, we began recruitment for a prospective, randomised, multicentre trial (INSPIRE) to compare preservation with OCS Lung with standard cold storage. FUNDING TransMedics and German Federal Ministry of Education and Research.

Lung transplantation for severe pulmonary hypertension--awake extracorporeal membrane oxygenation for postoperative left ventricular remodelling.

Background Bilateral lung transplantation (BLTx) is an established treatment for end-stage pulmonary hypertension (PH). Ventilator weaning failure and death are more common as in BLTx for other indications. We hypothesized that left ventricular (LV) dysfunction is the main cause of early postoperative morbidity or mortality and investigated a weaning strategy using awake venoarterial extracorporeal membrane oxygenation (ECMO). Methods In 23 BLTx for severe PH, ECMO used during BLTx was continued for a minimum of 5 days (BLTx-ECMO group). Echocardiography, left atrial (LA) and Swan-Ganz catheters were used for monitoring. Early extubation after transplantation was attempted under continued ECMO. Results Preoperatively, all patients had severely reduced cardiac index (mean, 2.1 L/min/m2). On postoperative day 2, reduction of ECMO flow resulted in increasing LA and decreasing systemic blood pressures. On the day of ECMO explantation (median, postoperative day 8), LV diameter had increased; LA and blood pressures remained stable. Survival rates at 3 and 12 months were 100% and 96%, respectively. Data were compared to two historic control groups of BLTx without ECMO (BLTx ventilation) or combined heart-lung transplantation for severe PH. Conclusion Early after BLTx for severe PH, the LV may be unable to handle normalized LV preload. This can be effectively bridged with awake venoarterial ECMO.

Elephant trunk procedure 27 years after Borst: what remains and what is new?

The treatment of complex aortic pathology involving both the ascending and descending aortic segments at the same time represents a surgical challenge, with high postoperative morbidity and mortality rates reported. Over the past 27 years, different open surgical and endovascular techniques have been introduced and applied in various two-stage- or one-stage approaches to such cases. Thus, in 1983, Hans Borst significantly changed the traditional two-stage approach by introducing his elephant trunk technique. Leaving a segment of Dacron prosthesis reaching into the descending aorta during the first stage, the second-stage replacement of the residual dilated descending aorta was made far easier. The presence of interval mortality between the two stages, the unaffected need for two large operations to complete aortic repair, and the general failure of some patients to return for the second-stage repair set the scene for the development of one-stage procedures, both open surgical or hybrid surgical and endovascular, such as the frozen elephant trunk. However, the size of the operation, on the one hand, and the risk of spinal cord injury and need for surgical or endovascular completion during follow-up, on the other, have dampened enthusiasm. Recently, the introduction of supra-aortic debranching and endovascular aortic arch stent-graft repair has yet extended treatment to high-risk patients unsuitable to the more aggressive surgery, but mid- and long-term follow-up results are lacking. The lack of randomization and the presence of procedural and complication-related limitations for each technique do not allow for definitive conclusions about the ideal procedure to treat complex aortic pathology. However, the technical revolution experienced over the past 27 years, along with the improvement in perioperative management, has produced outstanding morbidity and mortality results even in this challenging patient population, but the decision regarding which pathology correlates with what operation remains highly debated and dependent also on regional competence.

Early donor-specific antibodies in lung transplantation: risk factors and impact on survival.

BACKGROUND The impact of early donor-specific anti-HLA antibodies (DSA) on patient and graft survival after lung transplantation remains controversial. In this study we analyzed risk factors for DSA that developed before initial hospital discharge after lung transplantation (early DSA) and compared mid-term outcomes in patients with or without DSA. METHODS Between January 2009 and August 2013, 546 patients underwent lung transplantation at our institution. One hundred (18%) patients developed early DSA (Group A) and 446 (82%) patients (Group B) did not. Patient records were retrospectively reviewed. RESULTS Retransplantation (odds ratio [OR] = 2.7, 95% confidence interval [CI] 1.1 to 6.5, p = 0.03), pre-operative HLA antibodies (OR = 2.1, 95% CI 1.2 to 3.4, p = 0.003) and primary graft dysfunction (PGD) score Grade 2 or 3 at 48 hours (OR = 2.6, 95% CI 1.5 to 4.6, p = 0.001) were associated with early DSA development. Overall, 1- and 3-year survival in Group A and B patients was 79 ± 4% vs 88 ± 2% and 57 ± 8% vs 74 ± 3%, respectively (p = 0.019). Eleven Group A (11%) and 32 Group B (7%) patients died before hospital discharge (p = 0.34). Among patients surviving beyond discharge, 1- and 3-year survival in Group A and B patients was 89 ± 4% vs 95 ± 1% and 65 ± 8% vs 80 ± 3% in Group A and B patients, respectively (p = 0.04). Multivariate analysis identified early anti-HLA Class II DSA (OR = 1.9, 95% CI 1.0 to 3.4, p = 0.04) as an independent risk factor for post-discharge mortality but not for in-hospital mortality. CONCLUSIONS Pre-operative HLA antibodies, retransplantation or post-operative PGD increase the risk of developing early DSA, which were independently associated with an increased risk for mortality.

Total aortic arch replacement with the elephant trunk technique: single-centre 30-year results

OBJECTIVES The combined disease of the aortic arch and the descending aorta (aneurysms and dissection) remains a surgical challenge. Various approaches have been used to treat this complex pathology. In the two-stage operation, at the first-stage operation, the aortic arch is replaced through a median sternotomy. Later, at the second-stage operation, the descending thoracic aorta is replaced through a lateral thoracotomy. The elephant trunk (ET) technique was introduced by H.G. Borst at our centre in March 1982, greatly simplifying the second-phase operation. We present our 30-year experience. METHODS From March 1982 to March 2012, 179 patients (112 males, age 56.4±12.6 years) received an ET procedure for the combined disease of the aortic arch and the descending aorta (91 aneurysms, 88 dissections (47 acute)). Fifty-six of these patients had undergone previous cardiac operations. Concomitant procedures were performed if necessary. The cerebral protection was done either by deep (till 1999) or moderate hypothermic circulatory arrest and selective antegrade cerebral perfusion (SACP, after 1999). RESULTS Cardiopulmonary bypass (CPB) and X-clamp times were 208.5±76.5 min and 123.7±54.8 min, respectively. The intraoperative mortality and 30-day mortality during the first-stage operation were 1.7% (3/179) and 17.3% (31/179, 15 with AADA), respectively. Perioperative stroke was 7.9% (n=14/176). Postoperative recurrent nerve palsy was present in 18.2% (32/176) and paraplegia in 5.6% (10/176). The second-stage completion operation was performed as early as possible. Fifty-seven second-stage completion procedures were performed, either surgically (n=50) or through interventional techniques (n=7). The intraoperative and 30-day mortality after the second-stage completion procedures were 5.2% (3/57) and 7.0% (4/57), respectively. The stroke, recurrent nerve palsy and paraplegia rates were 0, 0 and 7% (4/54), respectively. CONCLUSIONS The ET technique has greatly facilitated the two-stage approach to the surgical treatment of combined diseases of the aortic arch and descending aorta. The initial learning curve, acute dissections, re-do and concomitant procedures partially explain the higher mortality rate. Despite the development of new hybrid techniques, there is still a role for the classical ET in selected patients, particularly in the context of proven long-term results and cost effectiveness.

Five-year experience with intraoperative extracorporeal membrane oxygenation in lung transplantation: Indications and midterm results

BACKGROUND Since April 2010, extracorporeal membrane oxygenation (ECMO) has replaced cardiopulmonary bypass for intraoperative support during lung transplantation at our institution. The aim of this study was to present our 5-year experience with this technique. METHODS Records of patients who underwent transplantation between April 2010 and January 2015 were retrospectively reviewed. Patients who underwent transplantation without ECMO formed Group A. Patients in whom the indication for ECMO support was set a priori before the beginning of the operation formed Group B. The remaining patients in whom the indication for ECMO support was set during transplantation formed Group C. RESULTS Among 595 patients, 425 (71%) patients (Group A) did not require intraoperative ECMO; the remaining 170 (29%) patients did. Among these patients, 95 (56%) patients formed Group B, and the remaining 75 (44%) patients comprised Group C. Pulmonary fibrosis and pre-operative dilated or hypertrophied right ventricle emerged as risk factors for the indication of non-a priori intraoperative ECMO. Patients in Groups B and C showed a higher pre-operative risk profile and higher prevalence of post-operative complications than patients in Group A. Overall survival at 1 year was 93%, 83%, and 82% and at 4 years was 73%, 68%, and 69% in Groups A, B, and C (p = 0.11). The intraoperative use of ECMO did not emerge as a risk factor for in-hospital mortality or mortality after hospital discharge. CONCLUSIONS Intraoperative ECMO filled the gap between pre-operative and post-operative ECMO in lung transplantation. Although complications and in-hospital mortality were higher in patients who received ECMO, survival was similar among patients who underwent transplantation with or without ECMO.

Limited long-term durability of the cryolife o'brien stentless porcine xenograft valve

Background— Despite the fact that early and midterm hemodynamic and clinical results of the Cryolife O’Brien (CLOB) stentless valve have been reported to be favorable, the long-term durability and clinical results of this valve are largely unknown. Accordingly, we analyzed 10-year outcomes after aortic valve replacement with this valve. Methods and Results— From January 1994 to September 2004, 185 patients (67, 73, and 75 years, 25th, 50th, and 75th quartiles, respectively; 38% older than 75 years; 56% females) underwent aortic valve replacement with the CLOB valve. Sixty-eight percent of patients were in NYHA class 3 to 4. Standard EuroSCORE was 7.1±2.7. Pure aortic stenosis accounted for 42% (n=79), and pure insufficiency for 12% of cases (n=22). Concomitant surgery: 28% coronary artery bypass (n=51), 11% mitral valve replacement/annuloplasty (n=21), and 2% ascending aorta replacement (n=3). Sixty-one percent of patients received a 23-mm valve or smaller size. Follow-up was 100% completed, and cumulative follow-up was 65 months/patient. The 30-day mortality was 5.4% (none were valve related). Actuarial survival at 5 and 10 years were 68% and 40%, respectively. Actuarial freedom from structural valve deterioration was 91% at 5 years and dropped to 44% at 10 years. Actuarial freedom from reoperation was 94% at 5 years and declined to 57% at 10 years. Conclusions— In a population with a high prevalence of elderly females with small aortic root, the CLOB valve demonstrated satisfactory clinical results till 8-years. Afterward, a significant increase in hazard for structural valve deterioration and reoperation occurred in late follow-up.

Preemptive treatment with therapeutic plasma exchange and rituximab for early donor-specific antibodies after lung transplantation.

OBJECTIVE De novo donor-specific anti-human leukocyte antigen antibodies develop in a high proportion of lung transplant recipients early after lung transplantation. We recently showed that de novo donor-specific antibodies (DSA) occurrence is associated with significantly increased mortality. Here, we studied the efficacy of a preemptive treatment protocol. METHODS A retrospective observational study was conducted on all lung transplantations at Hanover Medical School between January 2009 and May 2013. RESULTS Among the 500 transplant recipients, early DSA developed in 86 (17%). Of these, 56 patients (65%; Group A) received therapeutic plasma exchange, and 30 patients (35%; Group B) did not. Among Group A patients, 51 also received rituximab. Between groups, there was no statistically significant difference in mortality, incidence of pulsed steroid therapies, rejections diagnosed by biopsy specimen, incidence of bronchitis obliterans syndrome (BOS), or infections requiring hospitalization at 1 year and 3 years. Also, there were no statistically significant differences after matching 21 Group A with 21 Group B patients through propensity score analysis. Significantly more Group A patients (65%) than Group B patients (34%) cleared DSA at hospital discharge (p = 0.01). At the last control after transplantation (median, 14 months; interquartile range, 5-24 months), 11 Group A (22%) and 9 Group B patients (33%) still showed DSA (p = 0.28). CONCLUSIONS Preemptive treatment with therapeutic plasma exchange and rituximab led to improved elimination of DSA early after lung transplantation (p = 0.01). However, spontaneous elimination in untreated Group B patients also occurred frequently. This treatment protocol was not associated with significantly improved outcome.

Veno-veno-arterial extracorporeal membrane oxygenation for respiratory failure with severe haemodynamic impairment: technique and early outcomes

OBJECTIVES Patients with respiratory failure may benefit from veno-venous and veno-arterial extracorporeal membrane oxygenation (ECMO) support. We report on our initial experience of veno-veno-arterial (v-v-a) ECMO in patients with respiratory failure. METHODS Between January 2012 and February 2014, 406 patients required ECMO support at our institution. Here, we retrospectively analysed the characteristics and outcomes of patients commenced on either veno-venous or veno-arterial ECMO due to respiratory failure, and then switched to v-v-a ECMO. RESULTS Ten (2%) patients proceeded to v-v-a ECMO. The underlying conditions were acute respiratory distress syndrome (n = 3), end-stage pulmonary fibrosis (n = 5) and respiratory failure after major thoracic surgery (n = 1) and Caesarean section (n = 1). In all of these patients, ECMO was initially started as veno-venous (n = 9) or veno-arterial (n = 1) ECMO but was switched to a veno-veno-arterial (v-v-a) approach after a mean of 2 (range, 0-7) days. Reasons for switching were: haemodynamic instability (right heart failure, n = 5; pericardial tamponade, n = 1; severe mitral valve regurgitation, n = 1; haemodynamic instability following cardiopulmonary resuscitation, n = 1 and evidence of previously unknown atrial septal defect with pulmonary hypertension and Eisenmenger syndrome, n = 1) and upper-body hypoxaemia (n = 1). ECMO-related complications were bleeding (n = 3) and leg ischaemia (n = 2). Seven patients were successfully taken off ECMO with 4 being bridged to recovery and a further 3 to lung transplantation after a mean of 11 (range, 9-18) days. Five patients survived until hospital discharge and all of them were alive at the end of the follow-up. CONCLUSIONS Veno-veno-arterial ECMO is a technically feasible rescue strategy in treating patients presenting with combined respiratory and haemodynamic failure.

C1-esterase-inhibitor for primary graft dysfunction in lung transplantation.

Background Primary graft dysfunction (PGD) is the most important cause of early morbidity and mortality in lung transplantation (LTX) with an incidence of 8% to 20%. We hypothesized that application of C1-esterase-inhibitor (C1-INH) in LTX-recipients showing early signs of severe PGD would attenuate the condition. Methods Starting as of May 2010, all recipients showing a PaO2/FiO2 ratio of less than 100 as early sign of PGD at first measurement in the OR were immediately treated with C1-INH. Postoperative courses of C1-INH-treated recipients were compared with a subgroup of recipients that developed severe PGD (PGD3-group) within 72 hours after LTX but did not receive C1-INH. Additionally, a third group consisting of all remaining recipients was assembled. Results A total of 275 LTX were performed between May 2010 and September 2012 at our center. Among these, 24 patients (8.7%) revealed a first PaO2/FiO2 ratio less than 100 and were treated with C1-INH (C1-INH-group). The PGD3-group consisted of 14 patients; the control cohort consisted of 237 patients. PGD scores were significantly higher in the C1-INH-group and PGD3-group as compared with the control group at all times postoperatively. ICU stay was longest in the PGD3 cohort and prolonged in C1-INH patients compared with the control group (29 [2–70] vs. 9 [2–83] vs. 3 [1–166] days, P=0.002). One-year survival in the PGD3-cohort was 71.4%, the C1-INH-treated-group had a one-year-survival of 82.5%, the control group had the best outcome (95%) (P=0.001). Conclusion Treatment of PGD with C1-INH led to acceptable outcome. Although survival in the C1-INH treated patients was lower than in the remaining collective, it was as good or better, compared with the PGD3 group and as what is internationally regarded as reasonable after LTX.