Chronic obstructive pulmonary disease is one of the leading causes of death worldwide.1 Consecutively, it may cause progressive lung emphysema leading to dyspnea and loss of exercise capacity. Increase of total lung capacity due to massive pulmonary hyperinflation leads to impaired diaphragmatic breathing resulting in breathing pump failure. Lung volume reduction surgery (LVRS) represents a well-established and accepted treatment option for end-stage lung emphysema in carefully selected patients with severe chronic hyperinflation.2 During acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with global or partial respiratory failure, mechanical ventilation is often required in patients failing or not tolerating noninvasive ventilation (NIV). However, mechanical ventilation is associated with an increased complication and mortality rate.3 Extracorporeal CO2 removal (ECCO2R) has been successfully applied in patients with AECOPD as bridge to recovery.3 Recently, we reported our experience with different modes of venovenous extracorporeal lung support during oncologic thoracic surgical resection.4 Here, we first describe the application of low-flow venovenous ECCO2R (LFVV-ECCO2R) as bridge to LVRS in patients with end-stage lung emphysema experiencing severe hypercapnia with acute failure of the respiratory pump.
Patients and Methods
Patients’ demographics are summarized in Table 1. Between March and October 2015, n = 4 patients (mean age 58 ± 4 years, range 53–63 years; male/female 3/1) with end-stage lung emphysema experiencing severe hypercapnia with acute failure of the respiratory pump were admitted to our department. In all patients, no signs of AECOPD were present.
In n = 2 patients (cases 1 and 2, Table 1), mechanical ventilation over temporary tracheostomy was performed for 52 and 19 days, respectively. Both patients were supported by a pressure control mode of ventilation. In both cases, high inspiratory peak pressures were required, and protective lung ventilation was therefore not possible. Despite aggressive mechanical ventilation, hypercapnia persisted and ECCO2R was considered. In case 2 (Table 1), non–small-cell lung cancer of the right upper lobe (cT3N0) was additionally diagnosed and staged (Figure 1). One patient (case 3, Table 1) was previously evaluated twice for endoscopic lung volume reduction (ELVR), which was rejected because of severe collateral ventilation. Several acute episodes of exacerbation were documented. In May 2014, left-sided pleural empyema was diagnosed and surgically treated by thoracotomy with pleurectomy and decortication of the lung elsewhere. The patient required intermittent NIV for 16 hours daily and long-term oxygen therapy (LTOT) with 6–8 L O2/min. The current hospital admission was due to severe hypercapnia (paCO2 83.8 mm Hg, pH 7.18) and acute respiratory pump failure with increasing dyspnea and marked muscle fatigue and no clinical or laboratory signs of infection. The patient presented with severe anxiety and fear of death. Despite NIV and reduction of hypercapnia (paCO2 61.3 mm Hg, pH 7.39), dyspnea and anxiety persisted. To avoid mechanical ventilation, ECCO2R was considered and offered to the patient.
In case 4 (Table 1), ELVR via valve implantation in the right upper lobe was performed. Subsequently, the patient developed pneumonia leading to sepsis and hypercapnic respiratory failure before transferal to our department. Before valve implantation, the patient required intermittent NIV therapy for 12 hours daily as well as LTOT with 4–6 L O2/min.
Because ventilation perfusion lung scan was not possible to be performed under these conditions, preoperative CT scan with volumetric quantification of the emphysematic target zones was performed in all patients (Figure 2).
Extracorporeal CO2 Removal Application
All patients received single-site cannulation LFVV-ECCO2R. For this purpose, a 24 Fr TwinPort double-lumen cannula (NovaPort twin, Novalung, Germany) was inserted percutaneously into the right femoral vein, as we have previously described.5 For systemic anticoagulation, unfractionated heparin was administered intravenously with a target activated partial thromboplastin time of 45–50 seconds. Single-site LFVV-ECCO2R was initiated using the iLA-active system (Novalung, Germany) with a mean blood flow of 0.8 (0.6–1.0) L/min and a mean sweep gas flow of 4 L/min2–6 to establish transmembranous gas exchange. Mean preoperative ECCO2R duration was 14 (1–42) days.
All patients underwent unilateral LVRS. Surgical access included lateral thoracotomy (n = 3) and video-assisted thoracoscopic surgery (n = 1). The mean length of the procedure was 81 ± 26 min (range 38–105 min).
Surgical procedures included anatomic lobectomy of the left upper lobe (n = 1) and right upper lobe (n = 3). In case 2, radical lymph node dissection was performed as well because of the previously diagnosed and staged non–small-cell lung cancer. In case 4, the implanted endobronchial valves were extracted preoperatively via rigid bronchoscopy (Table 2).
During surgery, ECCO2R enabled protective single lung ventilation with a mean peak inspiratory pressure (PIP) of 22 (18–26) cm H2O and normocapnia in all patients.
Postoperative Mortality and Outcome
Mean postoperative ECCO2R duration was 4 days.1–8 After removal, local pressure was applied for 10 minutes onto the ECCO2R insertion site. The postoperative period was uneventful but prolonged because of intensive respiratory therapy. Chest tubes were removed after a mean of 4 days.2–5
Median intensive care unit stay was 12 (range 7–16) days. All patients are still alive. In both patients with previous continuous aggressive mechanical ventilation (cases 1 and 2), phases of spontaneous breathing without mechanical support were possible for increasing periods of time. Both patients were transferred to the respiratory weaning unit and successfully decannulated after 5 and 3 weeks, respectively. The remaining two patients (cases 3 and 4) were able to perform a 6 minute walking test (6-MWT) with a distance of 289 and 243 m, respectively, at discharge. Preoperatively, both patients were not able to perform any ambulatory activity because of massive dyspnea at rest. Moreover, no further NIV therapy was required, and LTOT was reduced to 2 L O2/min in both cases after surgery (Table 3). Mean postoperative follow-up was 11 (7–15) months. None of the patients required hospital readmission or mechanical ventilation during the follow-up period. After 6 months, all patients were seen at our outpatient clinic for 6-MWT. All patients were able to perform the test with a walking distance of 128, 156, 311, and 272 m, respectively.
Use of ECCO2R as bridge to lung transplantation is a well-established concept with promising results.6 This includes the application of high-flow venovenous or veno-arterial ECMO, and pumpless arterio-venous interventional lung assist (iLA) as reported by us and others.7–9 Recently, application of pumpless arterio-venous iLA was described in patients with AECOPD to avoid mechanical ventilation.3 In these patients with severe hypercapnia, the iLA provided sufficient CO2 removal leading to normocapnia and normalization of the pH value, thereby avoiding mechanical ventilation. However, arterial cannulation is associated with a relative high rate of severe complications including limb ischemia and compartment syndrome.10 In the past years, a new generation of single-site venovenous ECCO2R cannulae was developed. These easily insertable cannulae provide sufficient CO2 removal with a low complication rate. Previously, our group reported the safe and efficient application of single-site cannulation LFVV-ECCO2R for intraoperative support in patients with severely impaired preoperative pulmonary function undergoing major oncologic lung resections.4,5
In the current work, single-site LFVV-ECCO2R was used in patients with end-stage lung emphysema presenting with severe hypercapnia and acute failure of the respiratory pump as bridge to LVRS. Preoperatively, ECCO2R facilitated protective mechanical ventilation in n = 2 patients requiring aggressive ventilator support before ECCO2R. Moreover, mechanical ventilation was avoided in n = 2 patients.
Single lung ventilation is challenging in patients with extensive emphysema. Often, high intraoperative inspiratory pressures are required to achieve sufficient gas exchange. In our cohort, ECCO2R enabled intraoperative protective mechanical ventilation, which may have helped to avoid postoperative prolonged air leak, which did not occur leading to early chest tube removal.
Lung volume reduction surgery represents an important and well-accepted treatment option for patients with end-stage lung emphysema and consecutive massive pulmonary hyperinflation.2 The national emphysema treatment trial showed a significant improvement of the exercise capacity and lung function parameters in patients undergoing LVRS compared with optimal medical therapy.2 Recently, ELVR by implanting endobronchial valves has been reported.11 The endobronchial valves lead to complete atelectasis of a whole lobe or segment. Despite short-term improvement of the lung function, these valves are associated with a number of major complications, such as pneumothorax and recurrent infections.12 In our series, ELVR was performed in one patient. In this case, severe pneumonic infection led to sepsis and hypercapnic respiratory failure. Usually, nonanatomic stapled wedge resections “apical shaving” are performed to achieve surgical LVR. However, in our experience, recurrent infections occur more frequently in the residual lung tissue, which in most cases lead to a deterioration of the patients postoperatively. Moreover, persisting air leaks represent one of the most frequent complications after LVRS. In this series, the patients underwent radical anatomical resections including unilateral upper lobe resection. Performing anatomic resections of the target zones diminishes the risk of recurrent infection in the “residual” lung tissue and reduces the air leaks because manipulation of the lung parenchyma during anatomic resections is markedly less than nonanatomic wedge resections. The decision for performing unilateral LVRS is the high-risk constellation of the patients in this series to minimize the risk of postoperative complications. This radical surgical approach provided a marked improvement in all patients, as shown above.
Venovenous single-site cannulation ECCO2R is a safe and effective bridging tool to LVRS in patients with end-stage lung emphysema experiencing severe hypercapnia with acute failure of the breathing pump. In such patients, radical surgery leads to instant intrathoracic decompression and, therefore, a significant improvement of the performance status. In addition, it facilitates respiratory weaning and consecutively may help improve quality of life in patients with end-stage lung disease. We would not advocate placing all patients with hypercapnic respiratory failure on ECCO2R and subsequently performing LVRS. This procedure should only be considered when severe emphysema with accompanying respiratory failure is present.
1. Criner GJ, Cordova F, Sternberg AL, Martinez FJThe National Emphysema Treatment Trial (NETT): Part I: Lessons learned about emphysema.Am J Respir Crit Care Med2011184763770
2. Kluge S, Braune SA, Engel M, et al.Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing noninvasive ventilation.Intensive Care Med20123816321639
3. Kostron A, Horn-Tutic M, Franzen D, et al.Repeated lung volume reduction surgery
is successful in selected patients.Eur J Cardiothorac Surg201548710715
4. Redwan B, Semik M, Dickgreber N, Ziegeler S, Fischer SSingle site cannulation veno-venous extracorporeal lung support during pulmonary resection in patients with severely compromised pulmonary function.ASAIO J201561366369
5. Redwan B, Ziegeler S, Freermann S, et al.Intraoperative veno-venous extracorporeal lung support in thoracic surgery: A single-centre experience.Interact Cardiovasc Thorac Surg201521766772
6. Chiumello D, Coppola S, Froio S, Colombo A, Del Sorbo LExtracorporeal life support as bridge to lung transplantation: A systematic review.Crit Care20151919
7. Fischer S, Hoeper MM, Bein T, et al.Interventional lung assist: A new concept of protective ventilation in bridge to lung transplantation.ASAIO J200854310
8. Fischer S, Hoeper MM, Tomaszek S, et al.Bridge to lung transplantation with the extracorporeal membrane ventilator Novalung in the veno-venous mode: The initial Hannover experience.ASAIO J200753168170
9. Bein T, Weber F, Philipp A, et al.A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia.Crit Care Med20063413721377
10. Fischer S, Simon AR, Welte T, et al.Bridge to lung transplantation with the novel pumpless interventional lung assist device NovaLung.J Thorac Cardiovasc Surg2006131719723
11. Sciurba FC, Ernst A, Herth FJ, et al.VENT Study Research GroupA randomized study of endobronchial valves for advanced emphysema.N Engl J Med201036312331244
12. Valipour A, Herth FJ, Burghuber OC, et al.VENT Study GroupTarget lobe volume reduction and COPD outcome measures after endobronchial valve therapy.Eur Respir J201443387396