G. Warnecke

Extracorporeal Membrane Oxygenation in Nonintubated Patients as Bridge to Lung Transplantation

We report on the use of veno‐arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18–35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation.

Bridge to Thoracic Organ Transplantation in Patients with Pulmonary Arterial Hypertension Using a Pumpless Lung Assist Device

We describe a novel technique of pumpless extracorporeal life support in four patients with cardiogenic shock due to end‐stage pulmonary hypertension (PH) including patients with veno‐occlusive disease (PVOD) using a pumpless lung assist device (LAD). The device was connected via the pulmonary arterial main trunk and the left atrium, thereby creating a septostomy‐like shunt with the unique addition of gas exchange abilities in parallel to the lung. Using this approach, all four patients were successfully bridged to bilateral lung transplantation and combined heart–lung transplantation, respectively. Although all patients presented in cardiogenic shock, hemodynamic unloading of the right ventricle using the low‐resistance LAD stabilized the hemodynamic situation immediately so that no pump support was subsequently required.

Vascular Complications in Patients Undergoing Femoral Cannulation for Extracorporeal Membrane Oxygenation Support

BACKGROUND Extracorporeal membrane oxygenation (ECMO) is a well-established treatment for severe cardiopulmonary failure. Patients undergoing ECMO support through femoral vessels are prone to vascular complications. The aim of this study was to evaluate such complications to outline basic technical principles for their prevention. METHODS From January 2005 to December 2009, 174 patients underwent ECMO support through cannulation of the femoral vessels. The primary outcome was any vascular complication. Secondary outcomes were 30-day mortality and 1-year survival. A logistic regression analysis including ECMO duration, peripheral arterial disease, ECMO access (percutaneous versus open), and diabetes mellitus identified predictors for vascular complications. RESULTS The venoarterial mode was used in 143 patients (82%), and venovenous in 31 patients (18%). Of the 17 (10%) observed vascular complications, 15 (88%) occurred in patients with venoarterial access, whereas 2 (12%) occurred after venovenous access (p=0.50) Two patients who had extremity ischemia required limb amputation. Thirty-day mortality and 1-year survival rates were 63% and 26%, respectively. Peripheral arterial disease was the only strong predictor of vascular complications (odds ratio, 6.95; 95% confidence interval, 1.89 to 25.59; p=0.003). Vascular complications were not associated with early or late mortality. CONCLUSIONS The incidence of vascular complications in venovenous cannulation was low, whereas in arterial cannulation, it is still considerable. Peripheral arterial disease remains a risk factor, and early involvement of vascular surgeons for open vascular exposure or alternative vascular access sites can be recommended. Vascular complications after ECMO support are not associated with higher mortality rates.

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.

Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow‐up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including “restrictive allograft syndrome (RAS)”, “neutrophilic CLAD (nCLAD)” and “rapid decliners”. At follow‐up, 8 patients demonstrated ≥10% improvement in FEV1, 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1. Patients fulfilling criteria for “rapid decliners” (n = 21, p = 0.005), RAS (n = 22, p = 0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n = 44, p = 0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression‐free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.

Extracorporeal membrane oxygenation instead of invasive mechanical ventilation in patients with acute respiratory distress syndrome

Dear Editor, Invasive mechanical ventilation with or without additional extracorporeal membrane oxygenation (ECMO) support represents standard treatment for patients with acute respiratory distress syndrome (ARDS). An ‘‘awake ECMO’’ strategy in order to avoid intubation and mechanical ventilation has been implemented as a bridge to lung transplantation in patients with chronic lung disease [1, 2] but has been used only occasionally in patients with ARDS [3]. We conducted a single-center, uncontrolled pilot trial designed to assess the feasibility of veno-venous ECMO in awake, non-intubated, spontaneously breathing patients with ARDS (www.clinical.govNCT01669 863 ). Patients between 18 and 75 years old presenting with moderate or severe ARDS were eligible. The main exclusion criteria were severe bleeding disorders and uncontrolled sepsis with multi-organ failure involving at least two organ systems. The Institutional Review Board (IRB) of Hannover Medical School approved and supervised the study and all patients provided written informed consent prior to ECMO insertion. Six patients with severe ARDS were enrolled as planned; four of them were immunocompromised. Patient characteristics and outcome parameters are shown in Table 1. All patients suffered from severe ARDS with PaO2/FiO2 ratios at most 100 mmHg while receiving noninvasive ventilation. Gas exchange patterns improved immediately after ECMO insertion and noninvasive ventilation could be stopped within 1 h in two patients. Three patients (patients 1, 4, and 5) were successfully weaned from ECMO after 10, 5, and 7 days, respectively, and discharged from the ICU without needing invasive mechanical ventilation. Patient 2 was also successfully weaned from ECMO support but developed respiratory failure due to an iatrogenic pneumothorax 2 days later and required intubation as a result. A protracted ICU course ensued, complicated by ventilatorassociated pneumonia and sepsis. The patient was eventually discharged from the ICU after 50 days. Patient 3 improved rapidly on ECMO support, but became increasingly agitated and confused. On the 7th day on ECMO support, he intentionally removed his jugular cannula, resulting in emergency intubation and brief cardiopulmonary resuscitation. He subsequently died 10 days later from

Executive summary. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK

The European Paediatric Pulmonary Vascular Disease (PVD) Network is a registered, non-profit organisation that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of paediatric pulmonary hypertensive vascular disease, including specific forms such as pulmonary arterial hypertension (PAH)-congenital heart disease, pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, persistent PH of the newborn, and related cardiac dysfunction. Methods The writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990–2015) and held five face-to-face meetings with votings. Clinical trials, guidelines, and reviews limited to paediatric data were searched using the terms ‘pulmonary hypertensioń’ and 5–10 other keywords, as outlined in the other nine articles of this special issue. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on paediatric data only, or on adult studies that included >10% children. Results A total of 9 original consensus articles with graded recommendations (COR/LOE) were developed, and are summarised here. The topics included diagnosis/monitoring, genetics/biomarker, cardiac catheterisation, echocardiography, cardiac magnetic resonance/chest CT, associated forms of PH, intensive care unit/ventricular assist device/lung transplantation, and treatment of paediatric PAH. Conclusions The multipaper expert consensus statement of the European Paediatric PVD Network provides a specific, comprehensive, detailed but practical framework for the optimal clinical care of children with PH.

Health-related quality of life after solid organ transplantation: a prospective, multiorgan cohort study.

Background Short-term posttransplantation survival and health-related quality of life (HRQoL) is exceptionally high for all patients after organ transplantation; however, predictors of the HRQoL outcome are not well understood. Trajectories of patients’ perceived benefit/burden ratio associated with the transplant procedure may differ when taking the organ type for transplantation into account. Methods A prospective, single-center cohort study assessed the trajectories of 354 patients after kidney (n=165), liver (n=53), heart (n=24), and lung (n=112) transplantation at 2, 6, 12, and 24 months with respect to psychosocial outcomes (HRQoL, anxiety, depression, social support, and work performance). Results Mean age was 50±13 years, and 61.6% were male in the overall sample. Demographics differed with respect to organ type. HRQoL measured by the mean SF-36 Physical Component Scale was 36.8 (95% confidence interval, 35.7–37.8) and 48.9 (95% confidence interval, 47.2–49.7) for the Psychosocial Component Scale for the entire sample at 2 months and showed a marginal decrease until 24 months after transplantation. Overall, HRQoL increased for all organ types with differing trajectories. Liver patients reported the lowest HRQoL benefit for the majority of the physical (P⩽0.01) and psychosocial (P⩽0.01) SF-36 subscales. Anxiety (17.4%) and depression (13.8%) were prevalent in the overall sample. Depression symptoms impaired HRQoL outcomes in both SF-36 components and unemployment impacted the SF-36 psychosocial outcomes. Conclusions HRQoL improved after transplantation for all four types of transplant, but the trajectories were different. Regular screening for depression symptoms may diminish psychologic disorders and distress after transplantation and thus may further improve outcomes.

Impact of CLAD Phenotype on Survival After Lung Retransplantation: A Multicenter Study

Chronic lung allograft dysfunction (CLAD) remains a major problem after lung transplantation with no definitive treatment except redo lung transplantation (re‐LTx) in selected candidates. However, CLAD is not a homogeneous entity and different phenotypes exist. Therefore, we aimed to evaluate the effect of CLAD phenotypes on survival after re‐LTx for CLAD. Patients who underwent re‐LTx for respiratory failure secondary to CLAD in four LTx centers between 2003 and 2013 were included in this retrospective analysis. Bronchiolitis obliterans syndrome (BOS) and restrictive CLAD (rCLAD) were distinguished using pulmonary function, radiology and explant lung histopathology. Patient variables pre‐ and post‐re‐LTx were collected and analyzed. A total of 143 patients underwent re‐LTx for CLAD resulting in 94 BOS (66%) and 49 rCLAD (34%) patients. Unadjusted and adjusted survival after re‐LTx for rCLAD was worse compared to BOS (HR = 2.60, 1.59–4.24; p < 0.0001 and HR = 2.61, 1.51–4.51; p = 0.0006, respectively). Patients waiting at home prior to re‐LTx experienced better survival compared to hospitalized patients (HR 0.40; 0.23–0.72; p = 0.0022). Patients with rCLAD redeveloped CLAD earlier and were more likely to redevelop rCLAD. Survival after re‐LTx for rCLAD is worse compared to BOS. Consequently, re‐LTx for rCLAD should be critically discussed, particularly when additional peri‐operative risk factors are present.