Olaf Wiesner

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.

Renal function and survival in 200 patients undergoing ECMO therapy

BACKGROUND Extracorporeal membrane oxygenation (ECMO) is increasingly used in the intensive care unit (ICU) setting to improve gas exchange in patients with acute respiratory distress syndrome as well as in patients pre- and post-heart and lung transplantation. In this clinical setting, acute kidney injury (AKI) is frequently observed. So far, it is unknown how AKI affects the survival of critically ill patients receiving ECMO support and whether veno-veno and veno-arterial ECMO have different effects on kidney function. METHODS This is a retrospective analysis of patients undergoing ECMO treatment in medical and surgical ICUs in a tertiary care centre. We evaluated all patients undergoing ECMO treatment at our centre between 1 January 2005 and 31 December 2010. Data from all 200 patients (83F/117M), median age 45 (17-83) years, were obtained by chart review. Follow-up data were obtained for up to 3 months. RESULTS Three-month survival of all patients was 31%. Of the 200 patients undergoing ECMO treatment, 60% (120/200) required renal replacement therapy (RRT) for AKI. While patients without RRT showed a 3-month survival of 53%, the survival of patients with AKI requiring RRT was 17% (P = 0.001). Longer duration of RRT was associated with a higher mortality. CONCLUSIONS AKI requiring RRT therapy in patients undergoing ECMO treatment increases mortality in ICU patients. Future studies have to clarify whether it is possible to identify patients who benefit from the combination of ECMO and RRT.

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.

Are metallic stents really safe? A long-term analysis in lung transplant recipients

Airway complications affect 20% of all lung transplant recipients. Self-expandable metallic stents (SEMS) are one treatment option but their use in benign airway disorders is controversial. We studies the long-term safety of SEMS in lung transplant recipients. Between January 1998 and February 2008, all lung transplant recipients with SEMS were analysed retrospectively at a single centre. Complications were recorded until September 2008. In 65 (9.2%) out of 706 recipients, 111 (91% noncovered) bronchial SEMS were implanted a median (range) 133 (55–903) days after lung transplantation; follow-up was 777 (7–3.655) days. Clinical improvement was noted in 80% of recipients. The forced expiratory volume in 1 s increased by (mean±sd) 21±33%. Most frequent early complications were migration (3%) and mucus plugging (11%). No procedure-related deaths were noted. Re-stenosis occurred in 34 (52%) out of 65 recipients 85 (7–629) days after insertion. In multivariate analysis, stent insertion before post-operative day 90 was independently associated with an increased risk of re-stenosis (HR 3.29, 95% CI 1.50–7.18; p = 0.003). In 40% of recipients, new bacterial airway colonisation occurred after SEMS insertion. In SEMS patients, 5-yr survival was significantly lower than in the total cohort (60% versus 76%; p = 0.02). Late complications in lung transplant recipients treated with SEMS are frequent. The major problems are re-stenosis and airway colonisation.

Altered expression of membrane-bound and soluble CD95/Fas contributes to the resistance of fibrotic lung fibroblasts to FasL induced apoptosis.

BackgroundAn altered susceptibility of lung fibroblasts to Fas-induced apoptosis has been implicated in the pathogenesis of pulmonary fibrosis; however, the underlying mechanism is not completely understood. Here, we studied the susceptibility of lung fibroblasts, obtained from patients with (f-fibs) and without pulmonary fibrosis (n-fibs), to FasL- (CD95L/APO-1) induced apoptosis in relation to the expression and the amounts of membrane-bound and soluble Fas. We also analysed the effects of tumor necrosis factor-β on FasL-induced cell death.MethodsApoptosis was induced with recombinant human FasL, with and without prior stimulation of the fibroblasts with tumor necrosis factor-α and measured by a histone fragmentation assay and flow cytometry. The expression of Fas mRNA was determined by quantitative PCR. The expression of cell surface Fas was determined by flow cytometry, and that of soluble Fas (sFas) was determined by enzyme-linked immunosorbent assay.ResultsWhen compared to n-fibs, f-fibs were resistant to FasL-induced apoptosis, despite significantly higher levels of Fas mRNA. F-fibs showed lower expression of surface-bound Fas but higher levels of sFas. While TNF-α increased the susceptibility to FasL-induced apoptosis in n-fibs, it had no pro-apoptotic effect in f-fibs.ConclusionsThe data suggest that lower expression of surface Fas, but higher levels of apoptosis-inhibiting sFas, contribute to the resistance of fibroblasts in lung fibrosis against apoptosis, to increased cellularity and also to increased formation and deposition of extracellular matrix.

Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection

IntroductionVirus-associated hemophagocytic syndrome (VAHS) is a severe complication of various viral infections often resulting in multiorgan failure and death. The purpose of this study was to describe baseline characteristics, development of VAHS, related treatments and associated mortality rate of consecutive critically ill patients with confirmed 2009 influenza A (H1N1) infection and respiratory failure.MethodsWe conducted a prospective observational study of 25 critically ill patients with 2009 influenza A (H1N1) infection at a single-center intensive care unit in Germany between 5 October 2009 and 4 January 2010. Demographic data, comorbidities, diagnosis of VAHS, illness progression, treatments and survival data were collected. The primary outcome measure was the development of VAHS and related mortality. Secondary outcome variables included duration of mechanical ventilation, support of extracorporeal membrane oxygenation and duration of viral shedding.ResultsVAHS developed in 9 (36%) of 25 critically ill patients with confirmed 2009 influenza A (H1N1) infection, and 8 (89%) of them died. In contrast, the mortality rate in the remaining 16 patients without VAHS was 25% (P = 0.004 for the survival difference in patients with or without VAHS by log-rank analysis). The patients were relatively young (median age, 45 years; interquartile range (IQR), 35 to 56 years of age); however, 18 patients (72%) presented with one or more risk factors for a severe course of illness. All 25 patients received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia, with a median duration of mechanical ventilation of 19 days (IQR, 13 to 26 days). An additional 17 patients (68%) required extracorporeal membrane oxygenation for a median of 10 days (IQR, 6 to 19 days).ConclusionsThe findings of this study raise the possibility that VAHS may be a frequent complication of severe 2009 influenza A (H1N1) infection and represents an important contributor to multiorgan failure and death.

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

Extracorporeal Membrane Oxygenation Watershed

A 55-year-old, previously healthy man was admitted to another hospital with deep-venous thrombosis in both legs and massive pulmonary embolism verified by chest computed tomography (CT). He presented with severe dyspnea and hypotension refractory to inotropes. Fibrinolytic therapy with recombinant tissue plasminogen activator was initiated, but the patient further deteriorated and required cardiopulmonary resuscitation for a period of 30 minutes. After return of spontaneous circulation, he remained in cardiogenic shock despite the use of inotropes and vasopressors, which is why our hospital was contacted. Our mobile extracorporeal membrane oxygenation (ECMO) team was dispatched and the patient received veno-arterial ECMO support with a 24 French venous cannula inserted via the right femoral vein and advanced into the right atrium and a 17 French arterial cannula inserted into the right femoral artery and advanced into the right iliacal artery. With an ECMO blood flow of 4.5 L/min, hemodynamics stabilized and the patient was transported to Hannover Medical School. Here, the patient was mechanically ventilated with an inspiratory oxygen fraction of 1.0 …

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.

Extracorporeal membrane oxygenation in a nonintubated patient with acute respiratory distress syndrome.

To the Editors: Endotracheal intubation and mechanical ventilation are mainstays in the management of patients with acute respiratory distress syndrome (ARDS), but this treatment strategy exposes the patient to several risks and complications. A small number of ARDS patients can be treated with noninvasive ventilation and these patients have less ventilator-associated pneumonia and a lower mortality rate [1]. However, failure to improve oxygenation with noninvasive ventilation indicates the need for endotracheal intubation [1]. In patients with severe respiratory failure, extracorporeal membrane oxygenation (ECMO) is increasingly being used on top of mechanical ventilation to facilitate oxygenation and protective ventilation [2]. A novel concept is the use of ECMO in awake, spontaneously breathing patients to avoid the complications of invasive ventilation. So far, “awake ECMO” has been used predominantly in patients with end-stage lung disease as bridge to lung transplantation [3, 4]. The use of awake ECMO as …