- Email: [email protected]
LUNG REDUCTION SURGERY IN CHRONIC OBSTRUCTIVE LUNG DISEASE
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OBSTRUCTIVE LUNG DISEASES, PART I
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LUNG REDUCTION SURGERY IN CHRONIC OBSTRUCTIVE LUNG DISEASE Robert M. Rogers, MD, Frank C. Sciurba, MD, and Robert J. Keenan, MD
HISTORICAL BACKGROUND No health provider has witnessed a patient with severe emphysema struggle for each breath without hoping for a dramatic intervention that could relieve that struggle. Medical interventions to date have modified the course and symptoms of these patients but have produced no dramatic changes. Surgeons as well have devised numerous surgical techniques, including costochondrectomy, transverse sternotomy, thorocoplasty, and phrenic nerve paralysis, which, although dramatic, were ineffective.20One surgical procedure introduced in the 1950s by Brantigan and colleagues7“to prevent expiratory collapse of small airways by resecting peripheral lung tissue with hope that this would restore elastic tension of the remaining lung and the radial tension around the airways to prevent their collapse on expiration” made good physiologic sense then and now. Brantigan’s data following the surgery did not show any improvement in standard pulmonary functions and carried a high mortality (i.e./ 27%). Rogers and established that this surgery produced improvement in airway conductance, lung volumes, and conductance volume ratios. They compared the physiologic results of surgical resection of large bullae, lobes, or wedge resection and lung reduction surgery for Dr. Sciurba is funded by the George H. Love Foundation. From the Pulmonary, Allergy, and Critical Care Division (RMR, FCS) and the Division of Thoracic Surgery (RJK), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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diffuse emphysema. They used the airway conductance measured in the body plethysmograph, reasoning that it more closely simulated normal breathing of patients than did the forced expiratory maneuver. The latter required maximum effort and in no way simulated normal breathing. They showed a consistent improvement in airway conductance and conductance volume ratios in patients with large bullae as well as in patients with diffuse emphysema. In the patients who had resection of segments or lobes of the lung, there was no change or a reduction in conductance and conductance volume ratio. Although these findings were promising, the authors followed the individuals over time and showed that the subjects with diffuse emphysema tended to drift back to the preoperative levels of function over 12 to 18 months (Fig. 1).The authors concluded "bullectomy in patients with severe diffuse chronic obstructive emphysema cannot be supported by us on a basis of present data. All such patients in our study returned towards their pre-operative condition over a period of time. To establish whether a patient with large bullae also has diffuse obstructive emphysema is still a most difficult problem to which we have not found an easy answer."35 Over
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Figure 1. Data from a patient with severe emphysema who underwent unilateral multiplewedge resection utilizing Brantigan's techniques. Note the initial drop in lung volume (solid circles) and rise in airway conductance (open circles) following surgery. Over a period of months these values returned towards baseline. Solid circle = thoracic gas volume; open circle = conductance.
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the next several decades, lung reduction surgery was abandoned only 24, 39, 41 to be reexamined again in recent years by several investigators.1b, WHAT IS NEW TODAY
There are many reasons to reexamine lung reduction surgery. New technologic developments have rekindled interest in this procedure because it did produce a definitive improvement in airway conductance and a decrease in symptoms in the patients studied. There were, however, many problems during the 1960s, including high morbidity and mortality because of underdeveloped critical care medicine and other factors. Many of these issues are now resolved. Understanding of Pathology and Pathophysiology
The fundamental pathology and pathophysiology of emphysema is better understood. Imaging techniques have vastly improved, allowing clinicians to determine better the pathologic distribution with the radiographic images. The definitive definitions of emphysema and its subgroupings into paraseptal, panlobular, and central lobular emphysema were emerging but now are firmly established. Until recently, it was virtually impossible to image the lung in such a way that one could determine the extent and type of emphysema. The only tools available in the 1960s were the standard chest film and quantitative lung scans,% to localize avascular areas, thus assisting the surgeon in tailoring the procedure for the patient. The currently available computed tomography techniques afford the clinician the ability to localize and quantify the degree and extent of the emphysema and the amount of normal or nearnormal tissue intervening between the emphysematous areas. Pulmonary Function Testing
Pulmonary function testing has become more sophisticated, readily available, reproducible, and automated so that a test can be more accurately performed. In addition, better normal values, better quality control in production of equipment, and better trained physicians and technicians now exist. Some of these tests were still limited to the research laboratory in the 1960s. For instance, today the diffusing capacity test is a common clinical test used in most hospitals. In the 1960s, it was basically a research test available only in major teaching hospitals. This is also true of the body plethysmographic measure of airway resistance, conductance, and lung volume. Cardiopulmonary exercise testing was also in its infancy in the 1960s but is now standard in most cardiac and pulmonary laboratories. Although the "art" of pulmonary function testing has not been completely removed, especially with the more
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sophisticated tests, the standard tests are readily available, reproducible, and reliable in most pulmonary function laboratories. Advanced Surgical Techniques
Excision of large bullae, occupying at least one third of the volume of the affected lung, for relief of compressive symptoms causing dyspnea is well established. The surgical approach to these giant bullae is reviewed elsewhere21,31*35 and is not reviewed in detail in this article. Attention has refocused on the potential benefits of surgical resection of diffusely emphysematous tissue in an effort to reduce dypsnea and improve exercise tolerance. This effort is based on the pioneering work of Brantigan and c011eagues,7-~who postulated that denervation of the lung and removal of wedges of diseased tissue would reduce the overall volume of the lung, reshape its configuration, improve the elastic recoil of the lung and its effect on large and small airways, and improve the diaphragmatic excursion. This early experiment was successful in some patients, but the considerable morbidity associated with Brantigan’s standard thoracotomy technique led to the abandonment of 34, 35 the pr~cedure.~, A resurgence of interest in surgical treatment of emphysema patients followed the introduction of video-assisted thoracic surgery. This approach avoids the necessity of thoracotomy and significantly reduces morbidity otherwise accompanying surgical intervention for selected pulmonary problems.24 Two techniques using the thoracoscopic approach for diffuse emphysema, laser ablation and stapled lung reduction, have been reported. Wakabayashi and colleagues,4’ in 1991, first described a unilateral laser ablation procedure in a small group of patients, although the perioperative rate of complications was significant.* The technique involves use of a neodymium:yttrium aluminum garnet (Nd:YAG) laser fiber inserted through one of the thoracoscopic ports. The laser energy is applied to the surface of the lung using either a contact probe or in a noncontact (free beam) mode. The aim of the treatments was to diffusely scarcify the lung surface to inhibit reexpansion. Results from three seriesu,~ 5 , using exclusive laser ablation suggest symptomatic benefit but modest objective improvement in pulmonary function. It is the authors’ opinion from personal communication that most centers have abandoned the laser approach because of disappointing results. The authors’ group has reported its experience using thoracoscopic stapled lung reduction.” The initial focus was on a unilateral approach, with lung reduction being performed on the lung most severely affected by the emphysematous process as determined roentgenographically (by chest film, computed tomography [CT] scan, and ventilation/perfusion nuclear scintigraphy). The areas of the lung to be resected were primarily determined by the preoperative roentgenographic findings, particularly density mask images of the CT scan, which highlighted the areas of
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worst anatomic disease as well as zones of more normal lung, and the single photon emission computed tomography (SPECT) perfusion study projected in a three-dimensional view, which identified zones of significant hypoperfusion. These areas were focused on during the resection particularly when the ventilation had shown washout abnormalities. Strips of lung tissue are resected along the leading edges of each lobe, such as along the fissures or anteriorly and posteriorly to the apex of the upper lobe and along the basal segments or superior segment of the lower lobe. As noted, the extent of resection in each area is determined by the perfusion studies. The lung can periodically be partially inflated during the procedure to estimate the extent of resection accomplished in each lobe of the lung so as to gauge the progress of the procedure and to avoid overresection. The aim is to resect approximately 20% to 30% of the lung volume. The authors have adopted the practice of performing bilateral thoracoscopic lung reduction procedures that can be accomplished in a single operating session.z4aThis approach is also advocated by McKenna and Cooper and P a t t e r s ~ n ’have ~ modified Brantigan’s original technique and reported on 46 patients who had undergone median sternotomy and stapled resection of emphysematous tissue. Patients experienced improvements in pulmonary function and symptoms. Following a standard median sternotomy incision, the pleura is incised and the lung is deflated with one-lung ventilation directed to the contralateral side. Excision is directed to those areas that remain distended, generally the upper lobes. These areas are grasped, and successive applications of a linear stapler-cutter device are made to resect an inverted ”horseshoe” of tissue over the apex of the upper lobe. The procedure is repeated on the other side with the aim of being able to resect approximately 20% to 30% of each lung. Early postoperative extubation, usually in the operating room, is achieved in more than 90% of patients. Air leaks requiring the chest tubes for longer than 5 days is the single most common postoperative complication, affecting 30% to 48% of patients in reported series. Use of bovine pericardial strips to buttress the staple lines as advocated by CooperI4has reduced but not eliminated this problem. Nevertheless, the majority of air leaks seal within 2 weeks. To reduce further the risk of prolonged air leaks at the completion of surgery, the chest tubes are placed on only water seal without suction. An apical space may be present on the first postoperative chest films; however, this is rarely a problem because the patient’s underlying emphysema keeps the lung from collapsing, and the space often resolves within 2 to 3 days. If a space persists longer than 3 days, a small amount of suction ( - 10 cm HzO) can be added. Other significant reported complications include pneumonia (9% to l6%), gastrointestinal disturbance (2% to 15%), respiratory failure (2.5% to 13%), and need for surgical exploration (2.5% to 10.5%). Although definitions between series are variable, the reported early (< 60 days) and late mortality ranges from 2.4% to 5.5% and 2% to 7.1%.
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As noted, the surgical approach has changed from the standard thoracotomy, which allowed limited visualization of the lung, to procedures that allow more complete visualization of all segments of the lung, including bilateral or unilateral thoracoscopic surgery and median sternotomy. The bilateral approach has yielded a greater reduction in lung volume, and it potentially eliminates some of the deterioration that occurs with unilateral surgery (i.e., the nonoperated side expands, preventing optimal expansion of the operated lung). In studies cited earlier, almost all the patients who regressed back to their baseline airway conductance or symptoms had undergone unilateral resect i o n ~ .34,~35, Based on this information, the authors believe that there is a justifiable reason to reexamine this procedure. PHYSIOLOGIC BASIS FOR LUNG REDUCTION SURGERY
The precise mechanism for the clinical improvement noted in patients following lung reduction surgery is yet to be established. There are several areas of potential benefit for which evidence has accumulated: lung elastic recoil and airflow, respiratory muscle function, and cardiovascular function. One must keep in mind, however, that there is a great deal of interaction and overlap in each category. Lung Elastic Recoil and Airflow Lung elastic recoil has been shown to influence airway resistance. When it is artifically increased by strapping the chest wall, airway resistance (RA) falls and airway conductance (GA= 1 / b ) increases.” Abnormalities in lung elastic recoil play a fundamental role in the pathophysiology of mechanical respiratory impairment associated with emphysema. Many investigators have described the relationship between loss of elastic recoil and expiratory flow limitation leading to 17, 19, 28, 32 These thoracic hyperinflation in patients with emphy~ema.’~, models relate the abnormally low expiratory flow rates in emphysema to both the reduced alveolar driving pressure and the dynamic increases in expiratory resistance associated with a loss in elastic airway support. Black and colleagues4showed that most, but not all, of the resistance to airflow seen in patients with alphal-antiprotease deficiency could be attributed to loss of elastic recoil. Total lung capacity and functional residual capacity increase in part because of a reduction in the inward recoil forces directed by the lung parenchyma on the chest wall. Furthermore, because of extremely low end-expiratory flows, the prolonged expiration frequently ceases above the usual end-expiratory lung volume at which chest wall and lung recoil would be balanced. Forced expiration below functional residual
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capacity is further impaired because of dynamic airway collapse, which further increases residual volume. The disproportionate increase in residual volume and functional residual capacity compared to total lung capacity limits the inspiratory capacity of the lungs. These changes are accentuated during exercise as expiratory time shortens and patients are forced to breathe at higher lung volumes to maximize expiratory flow.*’ These factors are the dominant basis for exercise intolerance in emphysema patients. In other words, these patients reach their ventilatory limitation (approximated by M W in Fig. 2), thus stopping exercise before achieving maximal cardiovascular stress, which is the basis for exercise termination in most other normal and disease populations. The authors’ group39documented an increase in lung elastic recoil in patients who had lung reduction surgery at 3 months following surgery. The authors believe this identifies an important pathophysiologic basis for the subjective and objective improvements described following lung reduction surgery (Fig. 3). Increases in maximal static elastic recoil pressure and coefficient of retraction (maximal elastic recoil adjusted for total lung capacity) were highly significant and corresponded to the
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Figure 2. Mechanism of improved exercise tolerance in an individual following lung reduction surgery. Prior to bilateral lung reduction surgery minute ventilation (thick solid line) approaches maximal voluntary ventilation ( M W ) (thin solid line) at very low exercise intensity. Three months following surgery minute ventilation (thick dashed lines) approaches M W (thin dashedlines) at a much higher level allowing dramatic increases in exercise tolerance.
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Figure 3. Static transpulmonary pressure versus total lung capacity. The preoperative values (solid circles) are shifted up and to the left, with the total lung capacity being 140% of predicted. Three months following a unilateral lung reduction stapling procedure the curve is shifted down and to the right (open cides) and the maximum pressure has gone from 10.5 to about 12.5 cm H,O. The Xs represent a normal volume-versus-pressure relationship.
16 of 20 patients who had shifts to the right in the volume versus transpulmonary pressure compliance curve. The one patient in the series who experienced deterioration in elastic recoil and clinical decline following surgery had comparatively normal preoperative recoil measurements and likely had significant airways disease in addition to severe emphysema. This poor outcome, however, is consistent with the results observed in several bullectomy series that identified the presence of airways disease as a risk factor for poor clinical outcome. The expected impact of improved lung recoil on improving airways resistance (Fig. 4) and expiratory flow rates and secondarily reducing lung volumes was also observed. A disproportionate reduction in residual volume compared to total lung capacity was also observed as would be expected consequent to improvements in end-expiratory flow. The reduced end-expiratory lung volume elicited improvements in inspiratory capacity and vital capacity. A more optimal respiratory muscle configuration consequent to these lung volume changes should result in improved respiratory muscle efficiency. extends the previous work of Rogers and colleagues;M* 35 This which suggested that the mechanism of improvement following lung reduction surgery was related to improved elastic recoil. Other studies evaluating the effects of surgery on patients with giant bullae are varied.
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Figure 4. In the same patient as in Figure 3, three months following surgery, the conductance versus volume curve has shifted up towards the normal slope and has intercepted the lung-volume line at a lower volume, albeit still considerably higher than normal. Solid circle = pre-op; open circle = 3 months post-op.
This variation has been explained by the quality of the underlying parenchyma, which expands to fill the void (i.e., normal compressed lung or diffuse emphysema). Large bullae as opposed to small bullae or cysts are often at maximal inflation and do not actively participate in the pressure volume curve but act as space-occupying regions that partially compress areas of underlying lung. Following classic bullectomy, patients with normal compressed lung demonstrate increased elastic recoil and improved compliance because of both the renewed contribution of these normal units to the overall pressure volume relationship and tethering of the parenchyma.22, 31* 35 If the compressed lung is emphysematous, reexpansion of these regions may result in only regional improvements in compliance and gas exchange but have less dramatic effect on overall mechanics? 31 and that effect may only be transient because of stress relaxation of the emphysematous tissue over time.% In contrast to giant bullae, the areas of confluent emphysema removed by lung reduction surgery are less commonly associated with compression of lobes of the lung but are more likely to exert this effect on regions within lobes. Furthermore, because some of these areas may
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participate in airflow, even on a diminished basis, they contribute to the overall pressure volume curve as high compliance units. The authors suggest that the improved elastic recoil following this procedure is in part due to elimination of these high compliance regions and in part by regional tethering of smaller airways in the lung parenchyma. The varying magnitude of improvement in recoil observed in the authors’ series39may be explained by individual variations in disease pattern, some patients presenting with disease dominated by multiple maximally inflated regions with underlying lung compression and others presenting with disease dominated by variably ventilated regions of confluent panacinar emphysema. Furthermore, the regional changes described previously may result in improved ventilation-perfusion matching, thus resulting in the improved arterial oxygenation found in some series.
Respiratory Muscles Muscle function is most efficient when the muscle fiber is at its ideal length so that it develops maximum tension with minimal energy expenditure. The diaphragm in patients with emphysema and hyperinflation is forced downward and appears flat on the chest film, and hence these muscle fibers as well as intercostal fibers are shortened. Because of this shortened length, they have decreased force and efficiency. Furthermore, the vector forces of these fibers are no longer directed to optimize thoracic inflation. This thoracic hyperinflation with its resulting decreased inspiratory muscle efficiency may be corrected by improvements in elastic recoil and expiratory flow, thus reducing lung volume. Further inefficiencies in inspiratory muscle activity may result from positive alveolar pressures at end-expiration intrinsic positive end-expird o r y pressure (PEEP). Intrinsic PEEP is a term used to indicate incomplete expiration before inspiration occurs, at which time the alveolar pressure is presumed to be positive. The consequence of intrinsic PEEP is an inspiratory threshold load that would increase the work of breathing because significant respiratory muscle activity is necessary to lower alveolar pressure even before airflow into the lungs occurs. Although end-expiratory esophageal pressure does not precisely define the degree of intrinsic PEEP, which is the difference between lung elastic recoil and chest wall relaxation pressures at end-expiration, it does provide a minimum for this value. Before lung reduction surgery, eight patients in the authors’ series of 20 had positive esophageal pressures and would be presumed to have positive alveolar pressure at end-expiration. Seven of the eight subjects had a negative conversion following surgery, which strongly suggests a reduction in intrinsic PEEP.39Hence by decreasing intrinsic PEEP, muscle function may be improved. Proving that the muscles of respiration are more efficient presents a more difficult problem because of the interactions of all of the beneficial effects noted previously. Ideally, one would like to
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have measurements of the oxygen cost of breathing before and after surgery; this difficult measurement has not been made to date. Cardiovascular Function
Little has been written on the effects of lung reduction surgery on cardiac function. It has been assumed that cor pulmonale is a significant contraindication to this procedure, even though Brantigan and Rogers and o t h e r ~ ’ , did ~ , ~not ~ believe that it was. If pulmonary hypertension is the result of compression of normal pulmonary vessels (i.e., zone 1 of WesP2)and lack of tethering or expansion of these vessels, it is conceivable that the cardiac function after surgery would improve. If pulmonary hypertension is due to lack of capillaries, which have been destroyed by the progression of the emphysematous process, removal of further capillaries would obviously worsen right-sided heart function. Although this question has not been definitively answered, the authors have data on right-sided heart function in 20 patients before and 3 months after lung reduction surgery. The majority showed either no change or improvement in right ventricular function, which ‘the authors suggest is due to capillary recruitment, secondary to improved mechanics in regional lung zones, which were previously subjected to compression by hyperinflated alveoli, or due to improved elastic recoil, which would tether vessels as well as airways (Fig. 5). Many but not all of the subjects also had an increase in diffusing capacity for carbon monoxide (DLco). Furthermore, the reduced end-expiratory esophageal pressure, hence, pericardial pressures, described previously might improve right ventricular filling. Appropriate selection of patients who have improvement in cardiac function is still problematic. It is the senior author’s impression that a major problem encountered in the 1960s was unrecognized coronary artery disease, which, if significant, might account for increased morbidity and mortality in the postoperative period. Today‘s ability to identify and quantify left-sided and right-sided cardiac function makes the selection of patients much easier. A recent article by the authors is intended to document a physiologic basis for the short-term clinical improvements in a select group of patients following lung reduction Long-term improvements have not yet been established. In fact, deterioration over time has occurred despite initial improvements following unilateral lung reduction surgery.”, 35 Also, patients with underlying emphysema exhibited accelerated clinical deterioration following classic bullectomy compared with patients with normal underlying lung18,31, possibly related to postoperative stress relaxation of underlying smaller bullae.= All of these reports, however, precede the introduction of the newer surgical and diagnostic techniques. In a preliminary report,% the authors showed sustained improvement in lung elastic recoil in 12 patients at 3 months and 1 year, although 5 of 12 patients had a lower value for lung elastic recoil at 1 year.
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Figure 5. A 63-year-old male before (A and s)and 3 months following (C and 0)unilateral right-sided lung reduction surgery. Note the shift back towards normal in the ipsilateral major fissure (A) as well as the contralateralmajor fissure (C) associated with re-expansion of the relatively preserved lower lobe parenchyma following surgery. Also note the increased caliber of the major pulmonary vessels (B),which we feel is due to the increase in lung elastic recoil following surgery. The patient had excellent physiologic and symptomatic improvement as well.
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Figure 5. Continued
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RESULTS TO DATE
The widespread acceptance of this procedure has clearly preceded publication of large series, peer-reviewed scientific papers. Historically, such an approach to innovative surgical advances is common (i.e., introduction of coronary artery bypass surgery or various transplantation procedures). The current direction of the surgical community with respect to lung reduction surgery is driven by several large descriptive clinical series that have been presented at professional meetings and that have generated ongoing academic discussion long before formal publication. Close scrutiny of these data with respect to patient outcome is essential to answer the following relevant questions: Do the benefits outweigh the risk of surgery? What is the duration of improvement after surgery? What is the role of laser compared to stapling and unilateral compared with bilateral procedures? Patterns are already beginning to emerge in the available data to answer some of these questions. In assessing the available data, one must be cautious and take into account variations in the data collection and manner of presentation among centers. For instance, mortality expressed, as a 30-day figure is less relevant and often lower than in-hospital mortality or 3-month mortality because death is often due to respiratory complications resulting in prolonged mechanical ventilation. Additionally, incomplete follow-up rates may have an impact on results, especially if dissatisfied or more severely disabled patients do not return for follow-up testing, thus skewing the data. Every effort should be made to obtain complete follow-up data and at least to characterize the patients not returning for follow-up testing. Even less meaningful are mean data presented serially with variable numbers of patients at various preoperative and postoperative time points. Furthermore, outcomes presented as only mean data without distribution of change cannot distinguish between a scenario resulting in dramatic improvements in relatively few patients from that resulting in consistent moderate improvement in most patients. Finally, statistically sign$cunt changes do not necessarily translate into clinically relevant change considering the potential for serious complications. Other relevant variations between studies include differences in patient selection, such as physiologic severity or anatomic disease distribution, which are not always clearly defined in the methods. Studies that mix the analysis of patients having more classic giant bullous disease with patients having more diffuse disease may unfairly bias the outcome with respect to evaluation of the less defined lung reduction procedure. Although the impact of variability in the administration of pulmonary rehabilitation before and after lung reduction surgery has received a lot of attention, such therapy would not be expected to influence spirometry, lung volume, or arterial oxygenation measurements, although assessment of dyspnea and exercise tolerance outcomes could be affected. Before widespread application of the available results occurs, one must take into account that available data are generally from large
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centers with surgical and support services experienced in dealing with lung transplant and complicated thoracic surgery patients. Even in these centers, the learning curve is steep, and, furthermore, anecdotal reports available to the authors suggest the potential for a poorer physiologic response and greater complication rate in less experienced centers. An interesting observation made by Brantigan and more recently observed by several investigators is the finding of more consistent or disproportionate improvement in subjective patient symptoms in comparison to routine measurements of pulmonary function. Although this observation may be attributed to a placebo effect, it is equally likely that outcome parameters such as FEV,, which is measured during a forced expiration without consideration of lung volume status, most likely do not reflect the full physiologic and clinical improvements elicited after the procedure. It is conceivable that the perceived symptomatic improvement is a result of the cumulative change in a variety of specific physiologic outcome indices, which may improve at times independently of each other and which may not be routinely measured. Such parameters may include arterial oxygen tension and other indicators of ventilation perfusion matching, expiratory flow indices, resting and exercise dead space proportion, resting and exercise diffusion measurements, pulmonary vascular resistance and right ventricular function parameters, lung volume measurements, nutritional parameters, assessment of intrinsic PEEP, and other indicators of respiratory muscle efficiency. Table 1 summarizes the results of recent published literature, literature in press and available by personal communication, and expansion of the authors’ unpublished data. The authors’ initial experience with a unilateral thoracoscopic purely laser approach was disappointing and has been abandoned. Reports in the literature have confirmed relatively minor improvements in mean FEV, (range 13% to 18%) and arterial oxygenation following a purely laser approach.23,25, 27 One report that describes a more significant response to what the title describes as a laser approach in fact includes thoracoscopic stapling procedures and patients with giant bullae in its statistical analysis.40Although some authors have argued that the specific laser techniques are critical to obtaining optimal outcome, this appears to be more relevant with respect to complications than to physiologic improvements. The authors’ experience and the available data suggest that the most dramatic improvements occur following the bilateral stapling procedure and that improvements of similar magnitude occur in the hands of experienced surgeons whether a thoracoscopic or open procedure is performed. The largest series evaluating the bilateral stapling procedure identified a 57”/0improvement in FEV,, a 30% decrease in residual volume, 9 mm Hg improvement in arterial oxygen tension, and increases in exercise durati011.I~Subsequent analyses at the authors’ institution and elsewhere have identified significantly better improvements in FEV,, residual volume, and arterial oxygen tension in patients undergoing bilateral compared with unilateral stapling procedures (see Table l).24a A recently presented abstract describing outcome in patients with upper lobe pre-
+21% + 19% + 5% + 17%
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Procedures Bilateral stapling Unilateral* laser ? stapling Unilateral laser only Unilateral laser only Unilateral stapling Unilateral stapling Unilateral stapling Bilateral stapling
'Various techniques. $Some large bullae included in series. $Some data sets incomplete. FEV, = Forced expiratory volume in 1 second; FVC = forced vital capacity; RV = residual volume; TLC = total lung capacity.
Little et atzs McKenna et alz7 McKenna et alz7 Keenan et aIz4 Hazelrigg et a123 Keenan et aIz4.
Cooper et all5 WakabayashP
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Table 1. SUMMARY OF RESULTS
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dominant disease showed significantly greater improvement in FEV, in patients undergoing bilateral stapling (82%) compared with unilateral stapling (29%) or unilateral laser (6%)." These findings are further supported with unpublished results from the authors' institution comparing consecutive patients undergoing either bilateral or unilateral stapling procedures. Significantly greater improvement in FEV, (41% versus 26%), residual volume (32% versus 14%), arterial oxygen tension (7 versus 0 mm Hg), and transitional dyspnea index (5.9 versus 4.7) occurred following the bilateral procedure. The duration of benefit is still unknown, but it should be noted that the deterioration in airway conductance, lung volumes, and conductance volume ratios occurred in subjects undergoing unilateral lung reduction surgery. Preliminary data suggest the potential for long-term symptomatic improvement in selected ~atients.3~ In his final paper, Brantigan7 suggested that only bilateral lung reduction surgery patients maintained significant improvement. The modest data to date suggest this is indeed the case with current surgical techniques. PATIENT SELECTION
The basis for successful bullectomy was first outlined by Baldwin and colleagues' and confirmed by others.', 26 These previously dogmatic principles maintain that bullae resections can be successful only if the intervening lung is not emphysematous. The authors believe that these guidelines maintain relevance in the determination of candidacy for lung reduction surgery despite the fact that many of the individuals being considered for bullectomies had emphysema in the intervening lung. Based on these principles, the centers with greatest experience can easily choose patients who are very good to excellent or very poor candidates. Patients with the most heterogeneous disease, such that relatively normal underlying lung is compressed by discrete but severe emphysematous tissue, appear to have the greatest potential for improvement. The other extreme, commonly known as vanishing lung, wherein nearly the entire thorax is diffusely and severely involved with panlobular emphysema with little compression of more normal areas, defines a patient who is at highest risk. Such patients often have simultaneous severe hypercapnea, low DLCO,and enlarged pulmonary arteries on imaging studies. The majority of patients lie between the two extremes described or may have diffuse but moderate involvement, for which the criteria for candidacy are less clear. The appropriate radiologic imaging can assist in the determination of regions with the most normal lung such that resection occurs in the least functional, highly compliant, most poorly ventilated, and least perfused areas of the lung. When these latter areas are resected, it is hoped that the more normal tissue expands, opening up those airways and vessels allowing better ventilation and perfusion matching.
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The authors cannot speak with great accuracy on the best candidates for lung reduction surgery but share with the reader their experience to date. The reader must recognize that these statements are subject to change as more data accumulate. Reasons to refuse surgery are as follows: 1. Diffuse involvement on CT (i.e., no areas of relatively normal lung). 2. Individuals with a diffusing capacity below 25%, which suggests loss of a significant degree of capillary beds. 3. An elevated PaCo2 at rest to greater than 50 mm Hg, especially if associated with relatively diffuse disease and following exclusion of associated primary sleep-disordered breathing. In one study, the combination of Paco2 greater than 50 mm Hg and diffusing capacity less than 25% of predicted was 83% specific for determining a poor 4. Patients with accompanying disease that would impair their ability to withstand surgery, such as severe left ventricular dysfunction, symptomatic coronary artery disease, neuromuscular disease, and myopathy. 5. Patients with pulmonary artery systolic pressures greater than 50 nun Hg in the absence of heterogeneous disease associated with clear areas of lung compression. These patients are considered to be at excessive risk. Whether the presence of pulmonary hypertension should exclude subjects from surgery is still unclear because lung reduction surgery, as noted previously, could improve right-sided heart function by improving the caliber of the vessels, thus decreasing pulmonary vascular resistance. 6. Patients with chronic obstructive disease dominated by chronic bronchitis or bronchiectasis or other airway disease and patients with significant superimposed pulmonary fibrosis despite the presence of emphysema. The authors performed esophageal balloon measurements on all candidates to determine lung pressure-volume relationships. The authors consider preservation of lung elastic recoil (maximal static recoil pressure > 15 cm HzO or coefficient of retraction > 2.5 cm H,O/L) to be indicative of disproportionate airways or fibrotic disease and a relative contraindication to surgery. 7. Patients with dominant cardiovascular rather than pulmonary mechanical limitation as determined by cardiopulmonary exercise testing. These patients are also considered to be unlikely to achieve dramatic symptomatic improvement following a procedure that has a large impact on pulmonary mechanical function. Although severe deconditioning alone is undoubtedly present in all patients, this would be unlikely to dominate exercise termination in these individuals in the absence of significant superimposed cardiovascular impairment.
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Other criteria such as advanced age over 75, severe exercise intolerance (6-minute walk distance less than 400 feet and maximal oxygen consumption < 10 mL/min/kg), and severe resting hypoxemia less than 45 mm Hg on room air need to be scrutinized closely as potential predictors of poor outcome. Finally, no patient at this time should be subject to this procedure unless the patient is fully informed that despite the real potential for improvement, uncertainties exist regarding appropriate selection and long-term outcome as well as the potential for mortality and serious morbidity. REHABILITATION
There is a great deal of discussion as to whether pulmonary rehabilitation involving exercise training affects survival after lung reduction surgery. The impact of exercise training on dyspnea and exercise performance in patients with chronic obstructive pulmonary disease is undisputed (except by the insurance agencies) based on recent literature.I2,33 It is also known that level of conditioning is an independent predictor of morbidity and mortality following other thoracic surgery proced~res.~, Exercise training thus makes theoretic sense by optimizing the patient’s cardiopulmonary reserve such that the patient is better capable of tolerating the metabolic demands imposed by the perioperative period. In some cases, in fact, sufficient symptomatic improvement may occur following training such that the patient no longer chooses to undergo surgery. There are insufficient data, or rationale for that matter, to deny surgery to patients unwilling or unable to complete a prolonged preoperative rehabilitation program. Although patients with even advanced lung disease have been shown to benefit from exercise training, the degree of improvement is limited in these patients because of the mechanical impairment to breathing, which may limit full participation in a rigorous training program. In fact, one could make a strong argument that training should be deferred until following the procedure when pulmonary mechanical reserve has improved such that patients can now more rigorously stress their cardiac and peripheral muscle to produce a more significant training effect (see Fig. 5). Only time and randomized trials will determine whether such training is truly necessary or advisable before surgery is performed. CONCLUSIONS AND FUTURE DIRECTIONS
It is exciting and sobering to think that lung reduction surgery offers a palliative procedure that may benefit severely disabled patients with diffuse pulmonary emphysema. Some of the same problems that faced the early investigators, however, still plague clinicians. Fortunately, today better tools are available for diagnosis, physiologic and
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radiologic evaluation, preoperative and postoperative surgical care and intervention. These tools should also allow clinicians to define better the optimal surgical approach and to select patients who will benefit most. Although the precise surgical approach to be used is still being debated, the available data support the following: (1) Laser alone is no longer recommended by the majority of surgeons and physicians involved in this research. (2) Some patients may benefit from unilateral surgery but not all. (3) Bilateral resection of lung tissue is the best approach whether through a sternotomy or video-assisted thoracoscopy to get maximum benefit and probably less morbidity. To a great extent at present, the approach a particular surgeon takes depends on his or her experience and expertise. The final answer, however, awaits definitive studies with long-term follow-up. Issues that remain unresolved include: 1. What are the prognostic indicators for good versus bad outcome? 2. Where should the surgery be performed and by whom? 3. How should the data be collected and collated to be sure that it can be generalized to the right setting for the patients? 4. What is the duration of symptomatic and physiologic improvement offered by the various surgical approaches? 5. What is the ultimate impact of this procedure on long-term survival? 6. Are the expenses incurred by the patients and insurance agencies warranted for the degree of improvement attainable through this procedure?
References 1. Baldwin E deF, Harden KA, Green DG, et al: Pulmonary insufficiency: 1V. A study of 16 cases of large pulmonary air cysts or bullae. Medicine 29:169, 1950 2. Barker SJ, Clarke C, Trivedi N, et al: Anesthesia for thoracoscopic laser ablation of bullous emphysema. Anesthesiology 78:44-50, 1993 3. Bechard D, Wetstein L: Assessment of oxygen consumption as a preoperative criterion for lung resection. Ann Thorac Surg 4434449,1987 4. Black LF, Hyatt RE, Stubbs SE: Mechanism of expiratory airflow limitation in chronic obstructive pulmonary disease associated with alpha, antitrypsin deficiency. Am Rev Respir Dis 105891, 1974 5. Bollinger CT, Jordan P, Soler M, et al: Exercise capacity as a predictor of postoperative complications in lung resection candidates. Am J Respir Crit Care Med 151:14721480, 1995 6. Boushy SF, Billig DM, Kohen R Changes in pulmonary function after bullectomy. Am J Med 4791&923,1969 7. Brantigan OC, Kress MB, Mueller EA: The surgical approach to pulmonary emphysema. Dis Chest 39:485501, 1961 8. Brantigan OC, Mueller E: Surgical treatment of pulmonary emphysema. Am Surg 23789404, 1957 9. Brantigan OC, Mueller E, Kress MB A surgical approach to pulmonary emphysema. Am Rev Respir Dis 80194-202,1959 10. Brenner M, McKenna RJ, Gelb AF, et al: Volume reduction surgery for emphysema: A prospective controlled trial. Chest 108:96, 1995
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11. Caro, CG, Butler J, DuBois AB: Some effects of restriction of chest cage expansion on pulmonary function in man: An experimental study. J Clin Invest 39573, 1960 12. Casaburi R, Patessio A, Ioli F, et al: Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis 132236-240, 1985 13. Christie R B The elastic properties of the emphysematous lung and their significance. J Clin Invest 13295-321, 1934 14. Cooper J D Technique to reduce air leaks after resection of emphysematous lung. Ann Thorac Surg 571038-1039, 1994 15. Cooper JD, Patterson GA: Lung-volume reduction surgery for severe emphysema. Chest Surg Clin North Am 5815-831, 1995 16. Cooper JD, Trulock EP, Triantafillou AN, et al: Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 109:106116, 1995 17. Dayman H: Mechanics of airflow in health and emphysema. J Clin Invest 3011751190,1951 18. Fitzgerald MX, Keelan PJ, Cugell DW, et al: Long-term results of surgery for bullous emphysema. J Thorac Cardiovasc Surg 68:566-587, 1974 19. Fry DL, Hyatt RE: Pulmonary mechanics. Am J Med 29672489,1960 20. Gaensler EA, Cugell DW, Knudson RJ, et al: Surgical management of emphysema. Clin Chest Med 4M3-463, 1983 21. Gaensler EA, Jederlinic PJ, Fitzgerald MX: Patient work-up for bullectomy. J Thorac h a g 1:75-93, 1986 22. Gelb AF, Gold WM, Nadel JA: Mechanisms limiting airflow in bullous lung disease. Am Rev Respir Dis 107571-578, 1973 23. Hazelrigg S, Boley T, Henkle J, et al: Thoracoscopic laser bullectomy: A prospective study with three month results. J Thorac Cardiovasc Surg 1996, in press 24. Keenan RJ, Landreneau RJ, Sciurba FC, et al: Unilateral thoracoscopic surgical approach for diffuse bullous emphysema. J Thorac Cardiovasc Surg 111:308-316, 1996 24a. Keenan RJ, Sciurba F, Landreneau R, et al: Superiority of bilateral versus unilateral thoracoscopic approaches to lung reduction surgery [abstract]. Am J Respir Crit Care Med 1996, in press 25. Little AG, Swain JA, Nino JJ, et al: Reduction pneumoplasty for emphysema: Early results. AM Surg 222:365-374, 1995 26. Lourenzi GA, Turino GM, Fishrnan AP: Bullous disease of the lung. Am J Med 32:378, 1962 27. McKenna RJ Jr, Brenner M, Mullin M, et al: A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema. J Thorac Cardiovasc Surg 111:317-322, 1996 28. Mead J, Turner JM, Macklem PT,et al: Significance of the relationship between lung recoil and maximum expiratory flow. J Appl Physiol 2295-108, 1967 29. Pellegrino R, Brusasco V, Rodarte JR, et al: Expiratory flow limitation and regulation of end-expiratory lung volume during exercise. J Appl Physiol 74:2552-2558, 1993 30. Pierce JA, Growdon JH: Physical properties of the lungs in giant cysts. N Engl J Med 267369-173, 1962 31. Pride NB, Barter CE, Hugh-Jones P: The ventilation of bullae and the effect of their removal on thoracic gas volumes and tests of overall pulmonary function. Am Rev Respir Dis 10783-98, 1973 32. Pride NB, Permutt S, Riley RL, et al: Determinants of maximal expiratory flow from the lungs. J Appl Physiol 23:646-662, 1967 33. Ries AL, Kaplan RM, Limberg TM, et al: Pulmonary rehabilitation on physiologic and psychosocial outcomes in chronic obstructive pulmonary disease. Ann lntern Med 12823, 1995 34. Rogers RM: Stress-relaxation in pulmonary emphysema and its relation to airway conductance. Am Rev Respir Dis 101:43&440, 1970 35. Rogers RM, DuBois AB, Blakemore WS Effect of removal of bullae on airway conductance and conductance volume ratios. J Clin Invest 472569-2579, 1968 36. Rogers RM, Kuhl DE, Hyde RW, et al: Measurement of the vital capacity and
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perfusion of each lung by fluoroscopy and macroaggregated albumin lung scanning: An alternative to bronchospirometry for evaluating individual lung function. Ann Intern Med 67947-956, 1967 Roue C, Ma1 H, Sleiman CH, et al: Surgical treatment of emphysema without giant bullae. Am J Respir Crit Care Med 151:A12, 1995 Sciurba FC, Rogers RM, Keenan RJ, et al: Impact of unilateral thoracoscopic lung reduction surgery on lung elastic recoil one year following surgery [abstract]. Am J Respir Dis 1996, in press Sciurba FC, Rogers RM, Keenan RJ, et al: Improved lung elastic recoil and pulmonary function after lung reduction surgery for diffuse emphysema. N Engl J Med 1996, in press Wakabayashi A: Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous emphysema. AM Thorac Surg 60:93&942,1995 Wakabayashi A, Brenner M, Kayaleh RA, et al: Thoracoscopic carbon dioxide laser treatment of bullous emphysema. Lancet 3378814383, 1991 West J B Ventilation/Blood Flow and Gas Exchange. Oxford, Blackwell Scientific Publications, 1971
Address repripit reqrtests to Robert M. Rogers, MD Pulmonary, Allergy, and Critical Care Division University of Pittsburgh 440 Scaife Hall Pittsburgh, PA 15261
OBSTRUCTIVE LUNG DISEASES, PART I
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LUNG REDUCTION SURGERY IN CHRONIC OBSTRUCTIVE LUNG DISEASE Robert M. Rogers, MD, Frank C. Sciurba, MD, and Robert J. Keenan, MD
HISTORICAL BACKGROUND No health provider has witnessed a patient with severe emphysema struggle for each breath without hoping for a dramatic intervention that could relieve that struggle. Medical interventions to date have modified the course and symptoms of these patients but have produced no dramatic changes. Surgeons as well have devised numerous surgical techniques, including costochondrectomy, transverse sternotomy, thorocoplasty, and phrenic nerve paralysis, which, although dramatic, were ineffective.20One surgical procedure introduced in the 1950s by Brantigan and colleagues7“to prevent expiratory collapse of small airways by resecting peripheral lung tissue with hope that this would restore elastic tension of the remaining lung and the radial tension around the airways to prevent their collapse on expiration” made good physiologic sense then and now. Brantigan’s data following the surgery did not show any improvement in standard pulmonary functions and carried a high mortality (i.e./ 27%). Rogers and established that this surgery produced improvement in airway conductance, lung volumes, and conductance volume ratios. They compared the physiologic results of surgical resection of large bullae, lobes, or wedge resection and lung reduction surgery for Dr. Sciurba is funded by the George H. Love Foundation. From the Pulmonary, Allergy, and Critical Care Division (RMR, FCS) and the Division of Thoracic Surgery (RJK), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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diffuse emphysema. They used the airway conductance measured in the body plethysmograph, reasoning that it more closely simulated normal breathing of patients than did the forced expiratory maneuver. The latter required maximum effort and in no way simulated normal breathing. They showed a consistent improvement in airway conductance and conductance volume ratios in patients with large bullae as well as in patients with diffuse emphysema. In the patients who had resection of segments or lobes of the lung, there was no change or a reduction in conductance and conductance volume ratio. Although these findings were promising, the authors followed the individuals over time and showed that the subjects with diffuse emphysema tended to drift back to the preoperative levels of function over 12 to 18 months (Fig. 1).The authors concluded "bullectomy in patients with severe diffuse chronic obstructive emphysema cannot be supported by us on a basis of present data. All such patients in our study returned towards their pre-operative condition over a period of time. To establish whether a patient with large bullae also has diffuse obstructive emphysema is still a most difficult problem to which we have not found an easy answer."35 Over
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Figure 1. Data from a patient with severe emphysema who underwent unilateral multiplewedge resection utilizing Brantigan's techniques. Note the initial drop in lung volume (solid circles) and rise in airway conductance (open circles) following surgery. Over a period of months these values returned towards baseline. Solid circle = thoracic gas volume; open circle = conductance.
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the next several decades, lung reduction surgery was abandoned only 24, 39, 41 to be reexamined again in recent years by several investigators.1b, WHAT IS NEW TODAY
There are many reasons to reexamine lung reduction surgery. New technologic developments have rekindled interest in this procedure because it did produce a definitive improvement in airway conductance and a decrease in symptoms in the patients studied. There were, however, many problems during the 1960s, including high morbidity and mortality because of underdeveloped critical care medicine and other factors. Many of these issues are now resolved. Understanding of Pathology and Pathophysiology
The fundamental pathology and pathophysiology of emphysema is better understood. Imaging techniques have vastly improved, allowing clinicians to determine better the pathologic distribution with the radiographic images. The definitive definitions of emphysema and its subgroupings into paraseptal, panlobular, and central lobular emphysema were emerging but now are firmly established. Until recently, it was virtually impossible to image the lung in such a way that one could determine the extent and type of emphysema. The only tools available in the 1960s were the standard chest film and quantitative lung scans,% to localize avascular areas, thus assisting the surgeon in tailoring the procedure for the patient. The currently available computed tomography techniques afford the clinician the ability to localize and quantify the degree and extent of the emphysema and the amount of normal or nearnormal tissue intervening between the emphysematous areas. Pulmonary Function Testing
Pulmonary function testing has become more sophisticated, readily available, reproducible, and automated so that a test can be more accurately performed. In addition, better normal values, better quality control in production of equipment, and better trained physicians and technicians now exist. Some of these tests were still limited to the research laboratory in the 1960s. For instance, today the diffusing capacity test is a common clinical test used in most hospitals. In the 1960s, it was basically a research test available only in major teaching hospitals. This is also true of the body plethysmographic measure of airway resistance, conductance, and lung volume. Cardiopulmonary exercise testing was also in its infancy in the 1960s but is now standard in most cardiac and pulmonary laboratories. Although the "art" of pulmonary function testing has not been completely removed, especially with the more
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sophisticated tests, the standard tests are readily available, reproducible, and reliable in most pulmonary function laboratories. Advanced Surgical Techniques
Excision of large bullae, occupying at least one third of the volume of the affected lung, for relief of compressive symptoms causing dyspnea is well established. The surgical approach to these giant bullae is reviewed elsewhere21,31*35 and is not reviewed in detail in this article. Attention has refocused on the potential benefits of surgical resection of diffusely emphysematous tissue in an effort to reduce dypsnea and improve exercise tolerance. This effort is based on the pioneering work of Brantigan and c011eagues,7-~who postulated that denervation of the lung and removal of wedges of diseased tissue would reduce the overall volume of the lung, reshape its configuration, improve the elastic recoil of the lung and its effect on large and small airways, and improve the diaphragmatic excursion. This early experiment was successful in some patients, but the considerable morbidity associated with Brantigan’s standard thoracotomy technique led to the abandonment of 34, 35 the pr~cedure.~, A resurgence of interest in surgical treatment of emphysema patients followed the introduction of video-assisted thoracic surgery. This approach avoids the necessity of thoracotomy and significantly reduces morbidity otherwise accompanying surgical intervention for selected pulmonary problems.24 Two techniques using the thoracoscopic approach for diffuse emphysema, laser ablation and stapled lung reduction, have been reported. Wakabayashi and colleagues,4’ in 1991, first described a unilateral laser ablation procedure in a small group of patients, although the perioperative rate of complications was significant.* The technique involves use of a neodymium:yttrium aluminum garnet (Nd:YAG) laser fiber inserted through one of the thoracoscopic ports. The laser energy is applied to the surface of the lung using either a contact probe or in a noncontact (free beam) mode. The aim of the treatments was to diffusely scarcify the lung surface to inhibit reexpansion. Results from three seriesu,~ 5 , using exclusive laser ablation suggest symptomatic benefit but modest objective improvement in pulmonary function. It is the authors’ opinion from personal communication that most centers have abandoned the laser approach because of disappointing results. The authors’ group has reported its experience using thoracoscopic stapled lung reduction.” The initial focus was on a unilateral approach, with lung reduction being performed on the lung most severely affected by the emphysematous process as determined roentgenographically (by chest film, computed tomography [CT] scan, and ventilation/perfusion nuclear scintigraphy). The areas of the lung to be resected were primarily determined by the preoperative roentgenographic findings, particularly density mask images of the CT scan, which highlighted the areas of
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worst anatomic disease as well as zones of more normal lung, and the single photon emission computed tomography (SPECT) perfusion study projected in a three-dimensional view, which identified zones of significant hypoperfusion. These areas were focused on during the resection particularly when the ventilation had shown washout abnormalities. Strips of lung tissue are resected along the leading edges of each lobe, such as along the fissures or anteriorly and posteriorly to the apex of the upper lobe and along the basal segments or superior segment of the lower lobe. As noted, the extent of resection in each area is determined by the perfusion studies. The lung can periodically be partially inflated during the procedure to estimate the extent of resection accomplished in each lobe of the lung so as to gauge the progress of the procedure and to avoid overresection. The aim is to resect approximately 20% to 30% of the lung volume. The authors have adopted the practice of performing bilateral thoracoscopic lung reduction procedures that can be accomplished in a single operating session.z4aThis approach is also advocated by McKenna and Cooper and P a t t e r s ~ n ’have ~ modified Brantigan’s original technique and reported on 46 patients who had undergone median sternotomy and stapled resection of emphysematous tissue. Patients experienced improvements in pulmonary function and symptoms. Following a standard median sternotomy incision, the pleura is incised and the lung is deflated with one-lung ventilation directed to the contralateral side. Excision is directed to those areas that remain distended, generally the upper lobes. These areas are grasped, and successive applications of a linear stapler-cutter device are made to resect an inverted ”horseshoe” of tissue over the apex of the upper lobe. The procedure is repeated on the other side with the aim of being able to resect approximately 20% to 30% of each lung. Early postoperative extubation, usually in the operating room, is achieved in more than 90% of patients. Air leaks requiring the chest tubes for longer than 5 days is the single most common postoperative complication, affecting 30% to 48% of patients in reported series. Use of bovine pericardial strips to buttress the staple lines as advocated by CooperI4has reduced but not eliminated this problem. Nevertheless, the majority of air leaks seal within 2 weeks. To reduce further the risk of prolonged air leaks at the completion of surgery, the chest tubes are placed on only water seal without suction. An apical space may be present on the first postoperative chest films; however, this is rarely a problem because the patient’s underlying emphysema keeps the lung from collapsing, and the space often resolves within 2 to 3 days. If a space persists longer than 3 days, a small amount of suction ( - 10 cm HzO) can be added. Other significant reported complications include pneumonia (9% to l6%), gastrointestinal disturbance (2% to 15%), respiratory failure (2.5% to 13%), and need for surgical exploration (2.5% to 10.5%). Although definitions between series are variable, the reported early (< 60 days) and late mortality ranges from 2.4% to 5.5% and 2% to 7.1%.
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As noted, the surgical approach has changed from the standard thoracotomy, which allowed limited visualization of the lung, to procedures that allow more complete visualization of all segments of the lung, including bilateral or unilateral thoracoscopic surgery and median sternotomy. The bilateral approach has yielded a greater reduction in lung volume, and it potentially eliminates some of the deterioration that occurs with unilateral surgery (i.e., the nonoperated side expands, preventing optimal expansion of the operated lung). In studies cited earlier, almost all the patients who regressed back to their baseline airway conductance or symptoms had undergone unilateral resect i o n ~ .34,~35, Based on this information, the authors believe that there is a justifiable reason to reexamine this procedure. PHYSIOLOGIC BASIS FOR LUNG REDUCTION SURGERY
The precise mechanism for the clinical improvement noted in patients following lung reduction surgery is yet to be established. There are several areas of potential benefit for which evidence has accumulated: lung elastic recoil and airflow, respiratory muscle function, and cardiovascular function. One must keep in mind, however, that there is a great deal of interaction and overlap in each category. Lung Elastic Recoil and Airflow Lung elastic recoil has been shown to influence airway resistance. When it is artifically increased by strapping the chest wall, airway resistance (RA) falls and airway conductance (GA= 1 / b ) increases.” Abnormalities in lung elastic recoil play a fundamental role in the pathophysiology of mechanical respiratory impairment associated with emphysema. Many investigators have described the relationship between loss of elastic recoil and expiratory flow limitation leading to 17, 19, 28, 32 These thoracic hyperinflation in patients with emphy~ema.’~, models relate the abnormally low expiratory flow rates in emphysema to both the reduced alveolar driving pressure and the dynamic increases in expiratory resistance associated with a loss in elastic airway support. Black and colleagues4showed that most, but not all, of the resistance to airflow seen in patients with alphal-antiprotease deficiency could be attributed to loss of elastic recoil. Total lung capacity and functional residual capacity increase in part because of a reduction in the inward recoil forces directed by the lung parenchyma on the chest wall. Furthermore, because of extremely low end-expiratory flows, the prolonged expiration frequently ceases above the usual end-expiratory lung volume at which chest wall and lung recoil would be balanced. Forced expiration below functional residual
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capacity is further impaired because of dynamic airway collapse, which further increases residual volume. The disproportionate increase in residual volume and functional residual capacity compared to total lung capacity limits the inspiratory capacity of the lungs. These changes are accentuated during exercise as expiratory time shortens and patients are forced to breathe at higher lung volumes to maximize expiratory flow.*’ These factors are the dominant basis for exercise intolerance in emphysema patients. In other words, these patients reach their ventilatory limitation (approximated by M W in Fig. 2), thus stopping exercise before achieving maximal cardiovascular stress, which is the basis for exercise termination in most other normal and disease populations. The authors’ group39documented an increase in lung elastic recoil in patients who had lung reduction surgery at 3 months following surgery. The authors believe this identifies an important pathophysiologic basis for the subjective and objective improvements described following lung reduction surgery (Fig. 3). Increases in maximal static elastic recoil pressure and coefficient of retraction (maximal elastic recoil adjusted for total lung capacity) were highly significant and corresponded to the
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Figure 2. Mechanism of improved exercise tolerance in an individual following lung reduction surgery. Prior to bilateral lung reduction surgery minute ventilation (thick solid line) approaches maximal voluntary ventilation ( M W ) (thin solid line) at very low exercise intensity. Three months following surgery minute ventilation (thick dashed lines) approaches M W (thin dashedlines) at a much higher level allowing dramatic increases in exercise tolerance.
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Figure 3. Static transpulmonary pressure versus total lung capacity. The preoperative values (solid circles) are shifted up and to the left, with the total lung capacity being 140% of predicted. Three months following a unilateral lung reduction stapling procedure the curve is shifted down and to the right (open cides) and the maximum pressure has gone from 10.5 to about 12.5 cm H,O. The Xs represent a normal volume-versus-pressure relationship.
16 of 20 patients who had shifts to the right in the volume versus transpulmonary pressure compliance curve. The one patient in the series who experienced deterioration in elastic recoil and clinical decline following surgery had comparatively normal preoperative recoil measurements and likely had significant airways disease in addition to severe emphysema. This poor outcome, however, is consistent with the results observed in several bullectomy series that identified the presence of airways disease as a risk factor for poor clinical outcome. The expected impact of improved lung recoil on improving airways resistance (Fig. 4) and expiratory flow rates and secondarily reducing lung volumes was also observed. A disproportionate reduction in residual volume compared to total lung capacity was also observed as would be expected consequent to improvements in end-expiratory flow. The reduced end-expiratory lung volume elicited improvements in inspiratory capacity and vital capacity. A more optimal respiratory muscle configuration consequent to these lung volume changes should result in improved respiratory muscle efficiency. extends the previous work of Rogers and colleagues;M* 35 This which suggested that the mechanism of improvement following lung reduction surgery was related to improved elastic recoil. Other studies evaluating the effects of surgery on patients with giant bullae are varied.
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Figure 4. In the same patient as in Figure 3, three months following surgery, the conductance versus volume curve has shifted up towards the normal slope and has intercepted the lung-volume line at a lower volume, albeit still considerably higher than normal. Solid circle = pre-op; open circle = 3 months post-op.
This variation has been explained by the quality of the underlying parenchyma, which expands to fill the void (i.e., normal compressed lung or diffuse emphysema). Large bullae as opposed to small bullae or cysts are often at maximal inflation and do not actively participate in the pressure volume curve but act as space-occupying regions that partially compress areas of underlying lung. Following classic bullectomy, patients with normal compressed lung demonstrate increased elastic recoil and improved compliance because of both the renewed contribution of these normal units to the overall pressure volume relationship and tethering of the parenchyma.22, 31* 35 If the compressed lung is emphysematous, reexpansion of these regions may result in only regional improvements in compliance and gas exchange but have less dramatic effect on overall mechanics? 31 and that effect may only be transient because of stress relaxation of the emphysematous tissue over time.% In contrast to giant bullae, the areas of confluent emphysema removed by lung reduction surgery are less commonly associated with compression of lobes of the lung but are more likely to exert this effect on regions within lobes. Furthermore, because some of these areas may
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participate in airflow, even on a diminished basis, they contribute to the overall pressure volume curve as high compliance units. The authors suggest that the improved elastic recoil following this procedure is in part due to elimination of these high compliance regions and in part by regional tethering of smaller airways in the lung parenchyma. The varying magnitude of improvement in recoil observed in the authors’ series39may be explained by individual variations in disease pattern, some patients presenting with disease dominated by multiple maximally inflated regions with underlying lung compression and others presenting with disease dominated by variably ventilated regions of confluent panacinar emphysema. Furthermore, the regional changes described previously may result in improved ventilation-perfusion matching, thus resulting in the improved arterial oxygenation found in some series.
Respiratory Muscles Muscle function is most efficient when the muscle fiber is at its ideal length so that it develops maximum tension with minimal energy expenditure. The diaphragm in patients with emphysema and hyperinflation is forced downward and appears flat on the chest film, and hence these muscle fibers as well as intercostal fibers are shortened. Because of this shortened length, they have decreased force and efficiency. Furthermore, the vector forces of these fibers are no longer directed to optimize thoracic inflation. This thoracic hyperinflation with its resulting decreased inspiratory muscle efficiency may be corrected by improvements in elastic recoil and expiratory flow, thus reducing lung volume. Further inefficiencies in inspiratory muscle activity may result from positive alveolar pressures at end-expiration intrinsic positive end-expird o r y pressure (PEEP). Intrinsic PEEP is a term used to indicate incomplete expiration before inspiration occurs, at which time the alveolar pressure is presumed to be positive. The consequence of intrinsic PEEP is an inspiratory threshold load that would increase the work of breathing because significant respiratory muscle activity is necessary to lower alveolar pressure even before airflow into the lungs occurs. Although end-expiratory esophageal pressure does not precisely define the degree of intrinsic PEEP, which is the difference between lung elastic recoil and chest wall relaxation pressures at end-expiration, it does provide a minimum for this value. Before lung reduction surgery, eight patients in the authors’ series of 20 had positive esophageal pressures and would be presumed to have positive alveolar pressure at end-expiration. Seven of the eight subjects had a negative conversion following surgery, which strongly suggests a reduction in intrinsic PEEP.39Hence by decreasing intrinsic PEEP, muscle function may be improved. Proving that the muscles of respiration are more efficient presents a more difficult problem because of the interactions of all of the beneficial effects noted previously. Ideally, one would like to
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have measurements of the oxygen cost of breathing before and after surgery; this difficult measurement has not been made to date. Cardiovascular Function
Little has been written on the effects of lung reduction surgery on cardiac function. It has been assumed that cor pulmonale is a significant contraindication to this procedure, even though Brantigan and Rogers and o t h e r ~ ’ , did ~ , ~not ~ believe that it was. If pulmonary hypertension is the result of compression of normal pulmonary vessels (i.e., zone 1 of WesP2)and lack of tethering or expansion of these vessels, it is conceivable that the cardiac function after surgery would improve. If pulmonary hypertension is due to lack of capillaries, which have been destroyed by the progression of the emphysematous process, removal of further capillaries would obviously worsen right-sided heart function. Although this question has not been definitively answered, the authors have data on right-sided heart function in 20 patients before and 3 months after lung reduction surgery. The majority showed either no change or improvement in right ventricular function, which ‘the authors suggest is due to capillary recruitment, secondary to improved mechanics in regional lung zones, which were previously subjected to compression by hyperinflated alveoli, or due to improved elastic recoil, which would tether vessels as well as airways (Fig. 5). Many but not all of the subjects also had an increase in diffusing capacity for carbon monoxide (DLco). Furthermore, the reduced end-expiratory esophageal pressure, hence, pericardial pressures, described previously might improve right ventricular filling. Appropriate selection of patients who have improvement in cardiac function is still problematic. It is the senior author’s impression that a major problem encountered in the 1960s was unrecognized coronary artery disease, which, if significant, might account for increased morbidity and mortality in the postoperative period. Today‘s ability to identify and quantify left-sided and right-sided cardiac function makes the selection of patients much easier. A recent article by the authors is intended to document a physiologic basis for the short-term clinical improvements in a select group of patients following lung reduction Long-term improvements have not yet been established. In fact, deterioration over time has occurred despite initial improvements following unilateral lung reduction surgery.”, 35 Also, patients with underlying emphysema exhibited accelerated clinical deterioration following classic bullectomy compared with patients with normal underlying lung18,31, possibly related to postoperative stress relaxation of underlying smaller bullae.= All of these reports, however, precede the introduction of the newer surgical and diagnostic techniques. In a preliminary report,% the authors showed sustained improvement in lung elastic recoil in 12 patients at 3 months and 1 year, although 5 of 12 patients had a lower value for lung elastic recoil at 1 year.
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Figure 5. A 63-year-old male before (A and s)and 3 months following (C and 0)unilateral right-sided lung reduction surgery. Note the shift back towards normal in the ipsilateral major fissure (A) as well as the contralateralmajor fissure (C) associated with re-expansion of the relatively preserved lower lobe parenchyma following surgery. Also note the increased caliber of the major pulmonary vessels (B),which we feel is due to the increase in lung elastic recoil following surgery. The patient had excellent physiologic and symptomatic improvement as well.
LUNG REDUCTION SURGERY IN CHRONIC OBSTRUCTIVE LUNG DISEASE
Figure 5. Continued
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a1
RESULTS TO DATE
The widespread acceptance of this procedure has clearly preceded publication of large series, peer-reviewed scientific papers. Historically, such an approach to innovative surgical advances is common (i.e., introduction of coronary artery bypass surgery or various transplantation procedures). The current direction of the surgical community with respect to lung reduction surgery is driven by several large descriptive clinical series that have been presented at professional meetings and that have generated ongoing academic discussion long before formal publication. Close scrutiny of these data with respect to patient outcome is essential to answer the following relevant questions: Do the benefits outweigh the risk of surgery? What is the duration of improvement after surgery? What is the role of laser compared to stapling and unilateral compared with bilateral procedures? Patterns are already beginning to emerge in the available data to answer some of these questions. In assessing the available data, one must be cautious and take into account variations in the data collection and manner of presentation among centers. For instance, mortality expressed, as a 30-day figure is less relevant and often lower than in-hospital mortality or 3-month mortality because death is often due to respiratory complications resulting in prolonged mechanical ventilation. Additionally, incomplete follow-up rates may have an impact on results, especially if dissatisfied or more severely disabled patients do not return for follow-up testing, thus skewing the data. Every effort should be made to obtain complete follow-up data and at least to characterize the patients not returning for follow-up testing. Even less meaningful are mean data presented serially with variable numbers of patients at various preoperative and postoperative time points. Furthermore, outcomes presented as only mean data without distribution of change cannot distinguish between a scenario resulting in dramatic improvements in relatively few patients from that resulting in consistent moderate improvement in most patients. Finally, statistically sign$cunt changes do not necessarily translate into clinically relevant change considering the potential for serious complications. Other relevant variations between studies include differences in patient selection, such as physiologic severity or anatomic disease distribution, which are not always clearly defined in the methods. Studies that mix the analysis of patients having more classic giant bullous disease with patients having more diffuse disease may unfairly bias the outcome with respect to evaluation of the less defined lung reduction procedure. Although the impact of variability in the administration of pulmonary rehabilitation before and after lung reduction surgery has received a lot of attention, such therapy would not be expected to influence spirometry, lung volume, or arterial oxygenation measurements, although assessment of dyspnea and exercise tolerance outcomes could be affected. Before widespread application of the available results occurs, one must take into account that available data are generally from large
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centers with surgical and support services experienced in dealing with lung transplant and complicated thoracic surgery patients. Even in these centers, the learning curve is steep, and, furthermore, anecdotal reports available to the authors suggest the potential for a poorer physiologic response and greater complication rate in less experienced centers. An interesting observation made by Brantigan and more recently observed by several investigators is the finding of more consistent or disproportionate improvement in subjective patient symptoms in comparison to routine measurements of pulmonary function. Although this observation may be attributed to a placebo effect, it is equally likely that outcome parameters such as FEV,, which is measured during a forced expiration without consideration of lung volume status, most likely do not reflect the full physiologic and clinical improvements elicited after the procedure. It is conceivable that the perceived symptomatic improvement is a result of the cumulative change in a variety of specific physiologic outcome indices, which may improve at times independently of each other and which may not be routinely measured. Such parameters may include arterial oxygen tension and other indicators of ventilation perfusion matching, expiratory flow indices, resting and exercise dead space proportion, resting and exercise diffusion measurements, pulmonary vascular resistance and right ventricular function parameters, lung volume measurements, nutritional parameters, assessment of intrinsic PEEP, and other indicators of respiratory muscle efficiency. Table 1 summarizes the results of recent published literature, literature in press and available by personal communication, and expansion of the authors’ unpublished data. The authors’ initial experience with a unilateral thoracoscopic purely laser approach was disappointing and has been abandoned. Reports in the literature have confirmed relatively minor improvements in mean FEV, (range 13% to 18%) and arterial oxygenation following a purely laser approach.23,25, 27 One report that describes a more significant response to what the title describes as a laser approach in fact includes thoracoscopic stapling procedures and patients with giant bullae in its statistical analysis.40Although some authors have argued that the specific laser techniques are critical to obtaining optimal outcome, this appears to be more relevant with respect to complications than to physiologic improvements. The authors’ experience and the available data suggest that the most dramatic improvements occur following the bilateral stapling procedure and that improvements of similar magnitude occur in the hands of experienced surgeons whether a thoracoscopic or open procedure is performed. The largest series evaluating the bilateral stapling procedure identified a 57”/0improvement in FEV,, a 30% decrease in residual volume, 9 mm Hg improvement in arterial oxygen tension, and increases in exercise durati011.I~Subsequent analyses at the authors’ institution and elsewhere have identified significantly better improvements in FEV,, residual volume, and arterial oxygen tension in patients undergoing bilateral compared with unilateral stapling procedures (see Table l).24a A recently presented abstract describing outcome in patients with upper lobe pre-
+21% + 19% + 5% + 17%
+ 6%
+ 25% -11 - 32
NA NA - 16
-11
+ 30% + 21 Yo
+ 18% + 13% + 33% + 27% + 14% + 41Yo
- 32 - 13
FVC
FEV,
- 17
-5
-6
- 14 NA NA
-5
- 14
TLC
+4
+4 +7
NA NA +1
+ + +
NA NA
-k
+ +
Dyspnea'
+ + +
NA NA NA
+
+
Exercise'
Procedures Bilateral stapling Unilateral* laser ? stapling Unilateral laser only Unilateral laser only Unilateral stapling Unilateral stapling Unilateral stapling Bilateral stapling
'Various techniques. $Some large bullae included in series. $Some data sets incomplete. FEV, = Forced expiratory volume in 1 second; FVC = forced vital capacity; RV = residual volume; TLC = total lung capacity.
Little et atzs McKenna et alz7 McKenna et alz7 Keenan et aIz4 Hazelrigg et a123 Keenan et aIz4.
Cooper et all5 WakabayashP
RV
% Change
% Change
Table 1. SUMMARY OF RESULTS
28/55 26/30 36/38 40157 681141 17/35
46/49 96-202/500$
Total
N FOIIOW-UP/
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dominant disease showed significantly greater improvement in FEV, in patients undergoing bilateral stapling (82%) compared with unilateral stapling (29%) or unilateral laser (6%)." These findings are further supported with unpublished results from the authors' institution comparing consecutive patients undergoing either bilateral or unilateral stapling procedures. Significantly greater improvement in FEV, (41% versus 26%), residual volume (32% versus 14%), arterial oxygen tension (7 versus 0 mm Hg), and transitional dyspnea index (5.9 versus 4.7) occurred following the bilateral procedure. The duration of benefit is still unknown, but it should be noted that the deterioration in airway conductance, lung volumes, and conductance volume ratios occurred in subjects undergoing unilateral lung reduction surgery. Preliminary data suggest the potential for long-term symptomatic improvement in selected ~atients.3~ In his final paper, Brantigan7 suggested that only bilateral lung reduction surgery patients maintained significant improvement. The modest data to date suggest this is indeed the case with current surgical techniques. PATIENT SELECTION
The basis for successful bullectomy was first outlined by Baldwin and colleagues' and confirmed by others.', 26 These previously dogmatic principles maintain that bullae resections can be successful only if the intervening lung is not emphysematous. The authors believe that these guidelines maintain relevance in the determination of candidacy for lung reduction surgery despite the fact that many of the individuals being considered for bullectomies had emphysema in the intervening lung. Based on these principles, the centers with greatest experience can easily choose patients who are very good to excellent or very poor candidates. Patients with the most heterogeneous disease, such that relatively normal underlying lung is compressed by discrete but severe emphysematous tissue, appear to have the greatest potential for improvement. The other extreme, commonly known as vanishing lung, wherein nearly the entire thorax is diffusely and severely involved with panlobular emphysema with little compression of more normal areas, defines a patient who is at highest risk. Such patients often have simultaneous severe hypercapnea, low DLCO,and enlarged pulmonary arteries on imaging studies. The majority of patients lie between the two extremes described or may have diffuse but moderate involvement, for which the criteria for candidacy are less clear. The appropriate radiologic imaging can assist in the determination of regions with the most normal lung such that resection occurs in the least functional, highly compliant, most poorly ventilated, and least perfused areas of the lung. When these latter areas are resected, it is hoped that the more normal tissue expands, opening up those airways and vessels allowing better ventilation and perfusion matching.
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The authors cannot speak with great accuracy on the best candidates for lung reduction surgery but share with the reader their experience to date. The reader must recognize that these statements are subject to change as more data accumulate. Reasons to refuse surgery are as follows: 1. Diffuse involvement on CT (i.e., no areas of relatively normal lung). 2. Individuals with a diffusing capacity below 25%, which suggests loss of a significant degree of capillary beds. 3. An elevated PaCo2 at rest to greater than 50 mm Hg, especially if associated with relatively diffuse disease and following exclusion of associated primary sleep-disordered breathing. In one study, the combination of Paco2 greater than 50 mm Hg and diffusing capacity less than 25% of predicted was 83% specific for determining a poor 4. Patients with accompanying disease that would impair their ability to withstand surgery, such as severe left ventricular dysfunction, symptomatic coronary artery disease, neuromuscular disease, and myopathy. 5. Patients with pulmonary artery systolic pressures greater than 50 nun Hg in the absence of heterogeneous disease associated with clear areas of lung compression. These patients are considered to be at excessive risk. Whether the presence of pulmonary hypertension should exclude subjects from surgery is still unclear because lung reduction surgery, as noted previously, could improve right-sided heart function by improving the caliber of the vessels, thus decreasing pulmonary vascular resistance. 6. Patients with chronic obstructive disease dominated by chronic bronchitis or bronchiectasis or other airway disease and patients with significant superimposed pulmonary fibrosis despite the presence of emphysema. The authors performed esophageal balloon measurements on all candidates to determine lung pressure-volume relationships. The authors consider preservation of lung elastic recoil (maximal static recoil pressure > 15 cm HzO or coefficient of retraction > 2.5 cm H,O/L) to be indicative of disproportionate airways or fibrotic disease and a relative contraindication to surgery. 7. Patients with dominant cardiovascular rather than pulmonary mechanical limitation as determined by cardiopulmonary exercise testing. These patients are also considered to be unlikely to achieve dramatic symptomatic improvement following a procedure that has a large impact on pulmonary mechanical function. Although severe deconditioning alone is undoubtedly present in all patients, this would be unlikely to dominate exercise termination in these individuals in the absence of significant superimposed cardiovascular impairment.
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Other criteria such as advanced age over 75, severe exercise intolerance (6-minute walk distance less than 400 feet and maximal oxygen consumption < 10 mL/min/kg), and severe resting hypoxemia less than 45 mm Hg on room air need to be scrutinized closely as potential predictors of poor outcome. Finally, no patient at this time should be subject to this procedure unless the patient is fully informed that despite the real potential for improvement, uncertainties exist regarding appropriate selection and long-term outcome as well as the potential for mortality and serious morbidity. REHABILITATION
There is a great deal of discussion as to whether pulmonary rehabilitation involving exercise training affects survival after lung reduction surgery. The impact of exercise training on dyspnea and exercise performance in patients with chronic obstructive pulmonary disease is undisputed (except by the insurance agencies) based on recent literature.I2,33 It is also known that level of conditioning is an independent predictor of morbidity and mortality following other thoracic surgery proced~res.~, Exercise training thus makes theoretic sense by optimizing the patient’s cardiopulmonary reserve such that the patient is better capable of tolerating the metabolic demands imposed by the perioperative period. In some cases, in fact, sufficient symptomatic improvement may occur following training such that the patient no longer chooses to undergo surgery. There are insufficient data, or rationale for that matter, to deny surgery to patients unwilling or unable to complete a prolonged preoperative rehabilitation program. Although patients with even advanced lung disease have been shown to benefit from exercise training, the degree of improvement is limited in these patients because of the mechanical impairment to breathing, which may limit full participation in a rigorous training program. In fact, one could make a strong argument that training should be deferred until following the procedure when pulmonary mechanical reserve has improved such that patients can now more rigorously stress their cardiac and peripheral muscle to produce a more significant training effect (see Fig. 5). Only time and randomized trials will determine whether such training is truly necessary or advisable before surgery is performed. CONCLUSIONS AND FUTURE DIRECTIONS
It is exciting and sobering to think that lung reduction surgery offers a palliative procedure that may benefit severely disabled patients with diffuse pulmonary emphysema. Some of the same problems that faced the early investigators, however, still plague clinicians. Fortunately, today better tools are available for diagnosis, physiologic and
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radiologic evaluation, preoperative and postoperative surgical care and intervention. These tools should also allow clinicians to define better the optimal surgical approach and to select patients who will benefit most. Although the precise surgical approach to be used is still being debated, the available data support the following: (1) Laser alone is no longer recommended by the majority of surgeons and physicians involved in this research. (2) Some patients may benefit from unilateral surgery but not all. (3) Bilateral resection of lung tissue is the best approach whether through a sternotomy or video-assisted thoracoscopy to get maximum benefit and probably less morbidity. To a great extent at present, the approach a particular surgeon takes depends on his or her experience and expertise. The final answer, however, awaits definitive studies with long-term follow-up. Issues that remain unresolved include: 1. What are the prognostic indicators for good versus bad outcome? 2. Where should the surgery be performed and by whom? 3. How should the data be collected and collated to be sure that it can be generalized to the right setting for the patients? 4. What is the duration of symptomatic and physiologic improvement offered by the various surgical approaches? 5. What is the ultimate impact of this procedure on long-term survival? 6. Are the expenses incurred by the patients and insurance agencies warranted for the degree of improvement attainable through this procedure?
References 1. Baldwin E deF, Harden KA, Green DG, et al: Pulmonary insufficiency: 1V. A study of 16 cases of large pulmonary air cysts or bullae. Medicine 29:169, 1950 2. Barker SJ, Clarke C, Trivedi N, et al: Anesthesia for thoracoscopic laser ablation of bullous emphysema. Anesthesiology 78:44-50, 1993 3. Bechard D, Wetstein L: Assessment of oxygen consumption as a preoperative criterion for lung resection. Ann Thorac Surg 4434449,1987 4. Black LF, Hyatt RE, Stubbs SE: Mechanism of expiratory airflow limitation in chronic obstructive pulmonary disease associated with alpha, antitrypsin deficiency. Am Rev Respir Dis 105891, 1974 5. Bollinger CT, Jordan P, Soler M, et al: Exercise capacity as a predictor of postoperative complications in lung resection candidates. Am J Respir Crit Care Med 151:14721480, 1995 6. Boushy SF, Billig DM, Kohen R Changes in pulmonary function after bullectomy. Am J Med 4791&923,1969 7. Brantigan OC, Kress MB, Mueller EA: The surgical approach to pulmonary emphysema. Dis Chest 39:485501, 1961 8. Brantigan OC, Mueller E: Surgical treatment of pulmonary emphysema. Am Surg 23789404, 1957 9. Brantigan OC, Mueller E, Kress MB A surgical approach to pulmonary emphysema. Am Rev Respir Dis 80194-202,1959 10. Brenner M, McKenna RJ, Gelb AF, et al: Volume reduction surgery for emphysema: A prospective controlled trial. Chest 108:96, 1995
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11. Caro, CG, Butler J, DuBois AB: Some effects of restriction of chest cage expansion on pulmonary function in man: An experimental study. J Clin Invest 39573, 1960 12. Casaburi R, Patessio A, Ioli F, et al: Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis 132236-240, 1985 13. Christie R B The elastic properties of the emphysematous lung and their significance. J Clin Invest 13295-321, 1934 14. Cooper J D Technique to reduce air leaks after resection of emphysematous lung. Ann Thorac Surg 571038-1039, 1994 15. Cooper JD, Patterson GA: Lung-volume reduction surgery for severe emphysema. Chest Surg Clin North Am 5815-831, 1995 16. Cooper JD, Trulock EP, Triantafillou AN, et al: Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg 109:106116, 1995 17. Dayman H: Mechanics of airflow in health and emphysema. J Clin Invest 3011751190,1951 18. Fitzgerald MX, Keelan PJ, Cugell DW, et al: Long-term results of surgery for bullous emphysema. J Thorac Cardiovasc Surg 68:566-587, 1974 19. Fry DL, Hyatt RE: Pulmonary mechanics. Am J Med 29672489,1960 20. Gaensler EA, Cugell DW, Knudson RJ, et al: Surgical management of emphysema. Clin Chest Med 4M3-463, 1983 21. Gaensler EA, Jederlinic PJ, Fitzgerald MX: Patient work-up for bullectomy. J Thorac h a g 1:75-93, 1986 22. Gelb AF, Gold WM, Nadel JA: Mechanisms limiting airflow in bullous lung disease. Am Rev Respir Dis 107571-578, 1973 23. Hazelrigg S, Boley T, Henkle J, et al: Thoracoscopic laser bullectomy: A prospective study with three month results. J Thorac Cardiovasc Surg 1996, in press 24. Keenan RJ, Landreneau RJ, Sciurba FC, et al: Unilateral thoracoscopic surgical approach for diffuse bullous emphysema. J Thorac Cardiovasc Surg 111:308-316, 1996 24a. Keenan RJ, Sciurba F, Landreneau R, et al: Superiority of bilateral versus unilateral thoracoscopic approaches to lung reduction surgery [abstract]. Am J Respir Crit Care Med 1996, in press 25. Little AG, Swain JA, Nino JJ, et al: Reduction pneumoplasty for emphysema: Early results. AM Surg 222:365-374, 1995 26. Lourenzi GA, Turino GM, Fishrnan AP: Bullous disease of the lung. Am J Med 32:378, 1962 27. McKenna RJ Jr, Brenner M, Mullin M, et al: A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema. J Thorac Cardiovasc Surg 111:317-322, 1996 28. Mead J, Turner JM, Macklem PT,et al: Significance of the relationship between lung recoil and maximum expiratory flow. J Appl Physiol 2295-108, 1967 29. Pellegrino R, Brusasco V, Rodarte JR, et al: Expiratory flow limitation and regulation of end-expiratory lung volume during exercise. J Appl Physiol 74:2552-2558, 1993 30. Pierce JA, Growdon JH: Physical properties of the lungs in giant cysts. N Engl J Med 267369-173, 1962 31. Pride NB, Barter CE, Hugh-Jones P: The ventilation of bullae and the effect of their removal on thoracic gas volumes and tests of overall pulmonary function. Am Rev Respir Dis 10783-98, 1973 32. Pride NB, Permutt S, Riley RL, et al: Determinants of maximal expiratory flow from the lungs. J Appl Physiol 23:646-662, 1967 33. Ries AL, Kaplan RM, Limberg TM, et al: Pulmonary rehabilitation on physiologic and psychosocial outcomes in chronic obstructive pulmonary disease. Ann lntern Med 12823, 1995 34. Rogers RM: Stress-relaxation in pulmonary emphysema and its relation to airway conductance. Am Rev Respir Dis 101:43&440, 1970 35. Rogers RM, DuBois AB, Blakemore WS Effect of removal of bullae on airway conductance and conductance volume ratios. J Clin Invest 472569-2579, 1968 36. Rogers RM, Kuhl DE, Hyde RW, et al: Measurement of the vital capacity and
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perfusion of each lung by fluoroscopy and macroaggregated albumin lung scanning: An alternative to bronchospirometry for evaluating individual lung function. Ann Intern Med 67947-956, 1967 Roue C, Ma1 H, Sleiman CH, et al: Surgical treatment of emphysema without giant bullae. Am J Respir Crit Care Med 151:A12, 1995 Sciurba FC, Rogers RM, Keenan RJ, et al: Impact of unilateral thoracoscopic lung reduction surgery on lung elastic recoil one year following surgery [abstract]. Am J Respir Dis 1996, in press Sciurba FC, Rogers RM, Keenan RJ, et al: Improved lung elastic recoil and pulmonary function after lung reduction surgery for diffuse emphysema. N Engl J Med 1996, in press Wakabayashi A: Thoracoscopic laser pneumoplasty in the treatment of diffuse bullous emphysema. AM Thorac Surg 60:93&942,1995 Wakabayashi A, Brenner M, Kayaleh RA, et al: Thoracoscopic carbon dioxide laser treatment of bullous emphysema. Lancet 3378814383, 1991 West J B Ventilation/Blood Flow and Gas Exchange. Oxford, Blackwell Scientific Publications, 1971
Address repripit reqrtests to Robert M. Rogers, MD Pulmonary, Allergy, and Critical Care Division University of Pittsburgh 440 Scaife Hall Pittsburgh, PA 15261