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Use of Endobronchial Valves for Native Lung Hyperinflation Associated With Respiratory Failure in a Single-Lung Transplant Recipient for Emphysema
Original Research INTERVENTIONAL PULMONOLOGY
Use of Endobronchial Valves for Native Lung Hyperinflation Associated With Respiratory Failure in a Single-Lung Transplant Recipient for Emphysema* Maria M. Crespo, MD; Bruce A. Johnson, MD; Kenneth R. McCurry, MD; Rodney J. Landreneau, MD, FCCP; and Frank C. Sciurba, MD, FCCP
Emphysema is a common indication for adult pulmonary transplantation. Double-lung transplantation is increasingly the preferred approach because severe posttransplant native lung hyperinflation (NLH) following single-lung transplantation may compromise allograft lung function. We describe successful emergency use of bronchoscopic lung volume reduction using endobronchial valves (EBVs) [Zephyr; Emphasys Medical; Redwood, CA] in a single-lung transplant recipient who was critically ill with ventilator dependence from complications of NLH and at excessive risk for lung volume reduction surgery or pneumonectomy. Following placement of 17 valves in all segments of the native lung, atelectasis of the native lung was accompanied by volume expansion of the allograft. Immediately following valve placement, peak airway pressure decreased and alveolar ventilation increased. The patient was subsequently weaned from mechanical ventilation. This report suggests the need for clinical trials to evaluate the effectiveness of EBVs in single-lung transplant recipients with less critical functional impairment associated with NLH. (CHEST 2007; 131:214 –216) Key words: bronchoscopy; emphysema; endobronchial valve; lung transplant; native lung hyperinflation; volume reduction Abbreviations: BLVR ⫽ bronchoscopic lung volume reduction; EBV ⫽ endobronchial valve; NLH ⫽ native lung hyperinflation
is a common indication for adult pulE mphysema monary transplantation. Double-lung transplantation is increasingly the preferred approach because severe posttransplant native lung hyperinflation (NLH) *From the Divisions of Pulmonary, Allergy and Critical Care Medicine (Drs. Crespo, Johnson, and Sciurba) and Cardiothoracic Surgery (Drs. McCurry and Landreneau).University of Pittsburgh, Pittsburgh, PA. Drs. Crespo, Landreneau, and Sciurba are investigators in the Endobronchial Valve for Emphysema Palliation Trial (Emphasys Medical, Inc). Drs. Johnson and McCurry have no conflicts of interest to disclose. Manuscript received May 4, 2006; revision accepted July 7, 2006. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Maria M. Crespo, MD, University of Pittsburgh Medical Center, Division of Pulmonary, Allergy and, Critical Care Medicine, NW 628 Montefiore University Hospital, 3459 Fifth Ave, Pittsburgh, PA 15213; e-mail: [email protected] DOI: 10.1378/chest.06-1171 214
following single-lung transplantation may compromise allograft lung function.1,2 We report successful bronchoscopic lung volume reduction (BLVR) in a singlelung transplant recipient with emphysema resulting in resolution of severe lung NLH and respiratory failure.3 Case Report A 60-year-old man with a history of emphysema due to ␣1-antitrypsin deficiency underwent right single-lung transplantation 7 years prior to presentation. His posttransplant course was not significant for infection or chronic rejection. His lung function had been stable for 5 years; his last spirometry (FEV1, 56% of predicted; FVC, 54% of predicted) was performed 6 months prior to hospital admission. Immunosuppression included tacrolimus and azathioprine without prednisone, and enzyme-replacement therapy with prolastin was continued. Chest radiography demonstrated NLH with a mediastinal shift. He presented to his local hospital with sudden-onset respiratory failure requiring mechanical ventilation and was started empirically on broad-spectrum antibiotics for an infiltrate in the Original Research
Table 1—Thoracic Volumes Estimated From CT Scans Before and After EBV Placement* Thoracic Volume, L (% Predicted of Total Lung Capacity) Time of Scan Before EBV After EBV
Total
Left Lung
Right Lung
8.50 (121) 5.93 (94)
5.96 (95) 3.77 (60)
1.62 (26) 2.16 (34)
*Thoracic volumes were calculated by summing the volumes of 0.5-cm tomographic slices of each hemithorax. The area of the tomographic slices was determined using radiology software (Stentor; San Francisco, CA) and the freehand region-of-interest tool. The patient was sedated and placed on mechanical ventilation to an inspiratory tidal volume of 450 using a positive end-expiratory pressure of 5 cm H2O during both studies.
Ventilator-associated complications included bronchopleural fistula in the native left lung requiring tube thoracostomy, resulting in a persistent air leak for 3 weeks. Furthermore, hemoptysis persisted despite bronchial artery coil embolization. Notably, bronchial balloon catheter occlusion at the bleeding subsegments was successful at temporary tamponade of the persistent hemoptysis but had no impact on radiographic hyperinflation or on refractory respiratory failure. The patient was believed to be at an unacceptable risk level for lung volume reduction surgery or pneumonectomy. After remaining ventilator dependent for 10 weeks and believing that all standard therapeutic options had been exhausted, discussions with the family centered around compassionate withdrawal of ventilator support. The Food and Drug Administration and our institutional review board were petitioned for emergency use of one-way endobronchial valves (EBVs) [Zephyr; Emphasys Medical; Redwood, CA) to treat the severe NLH. The valves consist of a silicon-coated, self-expanding nitinol retainer supporting a unidi-
Table 2—Ventilator Settings and Measurements and Arterial Blood Gas Measures Before and After EBV Placement* Variables
Figure 1. Representative slices of high-resolution, noncontrast, chest CT scans before (top, A) and after (bottom, B) EBV placement.
native left lung base. Echocardiography showed normal biventricular function and moderate pulmonary hypertension. Ultrasound studies showed a left leg deep vein thrombosis, and an inferior vena cava filter was placed when intractable hemoptysis required discontinuation of IV heparin. Three weeks following hospital admission, he was transferred to our facility due to refractory ventilator dependence and hemoptysis. Chest CT scan revealed NLH associated with mediastinal shift and volume loss in the allograft (Fig 1, top, A; Table 1) and a left lower lobe infiltrate. Bronchoscopy identified active bleeding from the native left lower lobe without endobronchial lesions. Transbronchial biopsies from the allograft indicated minimal rejection without infection. Allograft BAL, native lung bronchial washings, and blood culture results were consistently sterile. 99mTc-macroaggregated albumin perfusion scanning demonstrated no significant focal defects with 73% of perfusion to the allograft. www.chestjournal.org
Fraction of inspired oxygen, % Positive endexpiratory pressure, cm H2O Tidal volume, L Total exhaled minute volume, L Inspiratory flow rate, L/min Peak inspiratory pressure, cm H2O pH Pco2, mm Hg Po2, mm Hg
Before EBV
After EBV
67 (2.1)
68 (2.7)
5
p Value† NS
5
450 12.2 (0.1)
450 13.0 (0.3)
0.03
85 (2.4)
84 (2.5)
NS
33 (1.4)
28 (0.9)
0.01
7.34 (0.008) 51 (1.5) 94 (8.8)
7.39 (0.009) 43 (0.9) 85 (5.0)
⬍ 0.001 ⬍ 0.001 NS
*Data are presented as mean values (SE) recorded over 3 days before and 3 days after EBV placement for lung function (n ⫽ 13 before EBV, n ⫽ 15 after EBV) and arterial blood gases (n ⫽ 8 before EBV, n ⫽ 14 after EBV). NS ⫽ not significant. †Mann-Whitney U test. CHEST / 131 / 1 / JANUARY, 2007
215
rectional silicone flap valve. Seventeen valves (standard size, 5 to 7 mm) were placed in all segments of the native left lung through the channel of a 3.1-mm fiberoptic bronchoscope under general anesthesia. Visual atelectasis was confirmed by quantitative CT analyses demonstrating decreases in volume of the native left lung and increase in allograft volume (Fig 1; Table 1). Furthermore, the native lung air leak stopped immediately, and hemoptysis gradually resolved. Ventilatory and gas exchange data shown in Table 2 reveal decreased peak airway pressures associated with improved alveolar ventilation. The patient began effective weaning trials within 1 week of valve placement and was discontinued from positive pressure ventilation within 5 weeks of valve placement, whereupon he was accepted for transfer to an outside rehabilitation center.
Comment NHL associated with impairment in allograft function after single-lung transplantation for emphysema is a frequent problem. Prior reports of lung volume reduction surgery of the native lung for this condition suggest significant morbidity.4,5 We report successful BLVR in a single-lung transplant recipient with emphysema resulting in resolution of severe lung NLH and respiratory failure. Also noteworthy in this case, valve placement further resulted in successful resolution of bronchopleural fistula and hemoptysis. BLVR in the context of single-lung transplantation may not be associated with factors inhibiting optimal response in traditional emphysema patients. First, when complete native lung occlusion is performed, as in our patient; collateral ventilation preventing effective volume reduction in the occluded segments should not be an issue. Furthermore, the presence of a well-functioning allograft to reexpand after decompression of NLH
216
should have mechanical advantages beyond what is seen when residual emphysema is present in the nonoccluded lung. While we demonstrated successful treatment of one patient, the risks, benefits, and patient selection factors in this heterogeneous group of individuals remain to be determined. Infectious complications, which were not observed in our case, must be closely monitored in future applications. Additionally, discrimination between allograft compression from NLH and volume loss associated with obliterative bronchiolitis must be considered. However, an important positive feature of BLVR is that is potentially reversible. We propose a systematic phase I trial evaluation of this approach in a less morbid group of single-lung transplant patients. References 1 Ahya VN, Kawut SM. Noninfectious pulmonary complications after lung transplantation. Clin Chest Med 2005; 26: 613– 622 2 Moy ML, Loring SH, Ingenito EP, et al. Causes of allograft dysfunction after single lung transplantation for emphysema: extrinsic restriction versus intrinsic obstruction; Brigham and Women’s Hospital Lung Transplantation Group. J Heart Lung Transplant 1999; 18:986 –993 3 Wan YP, Toma TP, Geddes DM, et al. Bronchoscopic lung volume reduction for end-stage emphysema: report on the first 98 patients. Chest 2006; 129:518 –526 4 Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003; 348: 2059 –2073 5 Schulman LL, O’Hair DP, Cantu E, et al. Salvage by volume reduction of chronic allograft rejection in emphysema. J Heart Lung Transplant 1999; 18:107–112
Original Research
Use of Endobronchial Valves for Native Lung Hyperinflation Associated With Respiratory Failure in a Single-Lung Transplant Recipient for Emphysema* Maria M. Crespo, MD; Bruce A. Johnson, MD; Kenneth R. McCurry, MD; Rodney J. Landreneau, MD, FCCP; and Frank C. Sciurba, MD, FCCP
Emphysema is a common indication for adult pulmonary transplantation. Double-lung transplantation is increasingly the preferred approach because severe posttransplant native lung hyperinflation (NLH) following single-lung transplantation may compromise allograft lung function. We describe successful emergency use of bronchoscopic lung volume reduction using endobronchial valves (EBVs) [Zephyr; Emphasys Medical; Redwood, CA] in a single-lung transplant recipient who was critically ill with ventilator dependence from complications of NLH and at excessive risk for lung volume reduction surgery or pneumonectomy. Following placement of 17 valves in all segments of the native lung, atelectasis of the native lung was accompanied by volume expansion of the allograft. Immediately following valve placement, peak airway pressure decreased and alveolar ventilation increased. The patient was subsequently weaned from mechanical ventilation. This report suggests the need for clinical trials to evaluate the effectiveness of EBVs in single-lung transplant recipients with less critical functional impairment associated with NLH. (CHEST 2007; 131:214 –216) Key words: bronchoscopy; emphysema; endobronchial valve; lung transplant; native lung hyperinflation; volume reduction Abbreviations: BLVR ⫽ bronchoscopic lung volume reduction; EBV ⫽ endobronchial valve; NLH ⫽ native lung hyperinflation
is a common indication for adult pulE mphysema monary transplantation. Double-lung transplantation is increasingly the preferred approach because severe posttransplant native lung hyperinflation (NLH) *From the Divisions of Pulmonary, Allergy and Critical Care Medicine (Drs. Crespo, Johnson, and Sciurba) and Cardiothoracic Surgery (Drs. McCurry and Landreneau).University of Pittsburgh, Pittsburgh, PA. Drs. Crespo, Landreneau, and Sciurba are investigators in the Endobronchial Valve for Emphysema Palliation Trial (Emphasys Medical, Inc). Drs. Johnson and McCurry have no conflicts of interest to disclose. Manuscript received May 4, 2006; revision accepted July 7, 2006. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Maria M. Crespo, MD, University of Pittsburgh Medical Center, Division of Pulmonary, Allergy and, Critical Care Medicine, NW 628 Montefiore University Hospital, 3459 Fifth Ave, Pittsburgh, PA 15213; e-mail: [email protected] DOI: 10.1378/chest.06-1171 214
following single-lung transplantation may compromise allograft lung function.1,2 We report successful bronchoscopic lung volume reduction (BLVR) in a singlelung transplant recipient with emphysema resulting in resolution of severe lung NLH and respiratory failure.3 Case Report A 60-year-old man with a history of emphysema due to ␣1-antitrypsin deficiency underwent right single-lung transplantation 7 years prior to presentation. His posttransplant course was not significant for infection or chronic rejection. His lung function had been stable for 5 years; his last spirometry (FEV1, 56% of predicted; FVC, 54% of predicted) was performed 6 months prior to hospital admission. Immunosuppression included tacrolimus and azathioprine without prednisone, and enzyme-replacement therapy with prolastin was continued. Chest radiography demonstrated NLH with a mediastinal shift. He presented to his local hospital with sudden-onset respiratory failure requiring mechanical ventilation and was started empirically on broad-spectrum antibiotics for an infiltrate in the Original Research
Table 1—Thoracic Volumes Estimated From CT Scans Before and After EBV Placement* Thoracic Volume, L (% Predicted of Total Lung Capacity) Time of Scan Before EBV After EBV
Total
Left Lung
Right Lung
8.50 (121) 5.93 (94)
5.96 (95) 3.77 (60)
1.62 (26) 2.16 (34)
*Thoracic volumes were calculated by summing the volumes of 0.5-cm tomographic slices of each hemithorax. The area of the tomographic slices was determined using radiology software (Stentor; San Francisco, CA) and the freehand region-of-interest tool. The patient was sedated and placed on mechanical ventilation to an inspiratory tidal volume of 450 using a positive end-expiratory pressure of 5 cm H2O during both studies.
Ventilator-associated complications included bronchopleural fistula in the native left lung requiring tube thoracostomy, resulting in a persistent air leak for 3 weeks. Furthermore, hemoptysis persisted despite bronchial artery coil embolization. Notably, bronchial balloon catheter occlusion at the bleeding subsegments was successful at temporary tamponade of the persistent hemoptysis but had no impact on radiographic hyperinflation or on refractory respiratory failure. The patient was believed to be at an unacceptable risk level for lung volume reduction surgery or pneumonectomy. After remaining ventilator dependent for 10 weeks and believing that all standard therapeutic options had been exhausted, discussions with the family centered around compassionate withdrawal of ventilator support. The Food and Drug Administration and our institutional review board were petitioned for emergency use of one-way endobronchial valves (EBVs) [Zephyr; Emphasys Medical; Redwood, CA) to treat the severe NLH. The valves consist of a silicon-coated, self-expanding nitinol retainer supporting a unidi-
Table 2—Ventilator Settings and Measurements and Arterial Blood Gas Measures Before and After EBV Placement* Variables
Figure 1. Representative slices of high-resolution, noncontrast, chest CT scans before (top, A) and after (bottom, B) EBV placement.
native left lung base. Echocardiography showed normal biventricular function and moderate pulmonary hypertension. Ultrasound studies showed a left leg deep vein thrombosis, and an inferior vena cava filter was placed when intractable hemoptysis required discontinuation of IV heparin. Three weeks following hospital admission, he was transferred to our facility due to refractory ventilator dependence and hemoptysis. Chest CT scan revealed NLH associated with mediastinal shift and volume loss in the allograft (Fig 1, top, A; Table 1) and a left lower lobe infiltrate. Bronchoscopy identified active bleeding from the native left lower lobe without endobronchial lesions. Transbronchial biopsies from the allograft indicated minimal rejection without infection. Allograft BAL, native lung bronchial washings, and blood culture results were consistently sterile. 99mTc-macroaggregated albumin perfusion scanning demonstrated no significant focal defects with 73% of perfusion to the allograft. www.chestjournal.org
Fraction of inspired oxygen, % Positive endexpiratory pressure, cm H2O Tidal volume, L Total exhaled minute volume, L Inspiratory flow rate, L/min Peak inspiratory pressure, cm H2O pH Pco2, mm Hg Po2, mm Hg
Before EBV
After EBV
67 (2.1)
68 (2.7)
5
p Value† NS
5
450 12.2 (0.1)
450 13.0 (0.3)
0.03
85 (2.4)
84 (2.5)
NS
33 (1.4)
28 (0.9)
0.01
7.34 (0.008) 51 (1.5) 94 (8.8)
7.39 (0.009) 43 (0.9) 85 (5.0)
⬍ 0.001 ⬍ 0.001 NS
*Data are presented as mean values (SE) recorded over 3 days before and 3 days after EBV placement for lung function (n ⫽ 13 before EBV, n ⫽ 15 after EBV) and arterial blood gases (n ⫽ 8 before EBV, n ⫽ 14 after EBV). NS ⫽ not significant. †Mann-Whitney U test. CHEST / 131 / 1 / JANUARY, 2007
215
rectional silicone flap valve. Seventeen valves (standard size, 5 to 7 mm) were placed in all segments of the native left lung through the channel of a 3.1-mm fiberoptic bronchoscope under general anesthesia. Visual atelectasis was confirmed by quantitative CT analyses demonstrating decreases in volume of the native left lung and increase in allograft volume (Fig 1; Table 1). Furthermore, the native lung air leak stopped immediately, and hemoptysis gradually resolved. Ventilatory and gas exchange data shown in Table 2 reveal decreased peak airway pressures associated with improved alveolar ventilation. The patient began effective weaning trials within 1 week of valve placement and was discontinued from positive pressure ventilation within 5 weeks of valve placement, whereupon he was accepted for transfer to an outside rehabilitation center.
Comment NHL associated with impairment in allograft function after single-lung transplantation for emphysema is a frequent problem. Prior reports of lung volume reduction surgery of the native lung for this condition suggest significant morbidity.4,5 We report successful BLVR in a single-lung transplant recipient with emphysema resulting in resolution of severe lung NLH and respiratory failure. Also noteworthy in this case, valve placement further resulted in successful resolution of bronchopleural fistula and hemoptysis. BLVR in the context of single-lung transplantation may not be associated with factors inhibiting optimal response in traditional emphysema patients. First, when complete native lung occlusion is performed, as in our patient; collateral ventilation preventing effective volume reduction in the occluded segments should not be an issue. Furthermore, the presence of a well-functioning allograft to reexpand after decompression of NLH
216
should have mechanical advantages beyond what is seen when residual emphysema is present in the nonoccluded lung. While we demonstrated successful treatment of one patient, the risks, benefits, and patient selection factors in this heterogeneous group of individuals remain to be determined. Infectious complications, which were not observed in our case, must be closely monitored in future applications. Additionally, discrimination between allograft compression from NLH and volume loss associated with obliterative bronchiolitis must be considered. However, an important positive feature of BLVR is that is potentially reversible. We propose a systematic phase I trial evaluation of this approach in a less morbid group of single-lung transplant patients. References 1 Ahya VN, Kawut SM. Noninfectious pulmonary complications after lung transplantation. Clin Chest Med 2005; 26: 613– 622 2 Moy ML, Loring SH, Ingenito EP, et al. Causes of allograft dysfunction after single lung transplantation for emphysema: extrinsic restriction versus intrinsic obstruction; Brigham and Women’s Hospital Lung Transplantation Group. J Heart Lung Transplant 1999; 18:986 –993 3 Wan YP, Toma TP, Geddes DM, et al. Bronchoscopic lung volume reduction for end-stage emphysema: report on the first 98 patients. Chest 2006; 129:518 –526 4 Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med 2003; 348: 2059 –2073 5 Schulman LL, O’Hair DP, Cantu E, et al. Salvage by volume reduction of chronic allograft rejection in emphysema. J Heart Lung Transplant 1999; 18:107–112
Original Research