The Current Status of Lung Volume Reduction Operations for Emphysema

Transcription

1 The Current Status of Lung Volume Reduction Operations for Emphysema Keith S. Naunheim, MD, and Mark K. Ferguson, MD Departments of Surgery, St. Louis University, St, Louis, Missouri, and The University of Chicago, Chicago, Illinois In the 1990s, the concept of surgical therapy was introduced once again for the treatment of end-stage emphysema. The earliest reports touted laser ablation of emphysematous lung as definitive therapy. Although some discernable benefit was reported, this was associated with significant operative morbidity. In 1993, the concept of parenchymal resection or "lung volume reduction" was reintroduced as treatment for end-stage lung disease. Over the ensuing 3 years, different techniques and approaches have evolved at different institutions. Lung volume reduction has been performed bilaterally and unilaterally through multiple approaches including sternotomy, thoracotomy, and thoracoscopy. The results of these various approaches are reviewed and compared. Lung volume reduction appears to be a beneficial procedure when performed in carefully selected patients by personnel and at institutions that are experienced in the care of patients with end-stage emphysema. (Ann Thorac Surg 1996;62:601-12) E mphysema is a progressive, disabling disease that affects almost two million people in the United States [11. It is one of several diseases that are collectively referred to as chronic obstructive pulmonary disease (COPD), a category that is the fourth leading cause of death in the United States. The prevalence of COPD is rising, especially among women, a fact that is largely attributable to patterns of tobacco use dating back to the World War It era. Chronic obstructive pulmonary disease is one of only two major diseases (the other being lung cancer) for which the annual mortality rate is increasing, with the death rate rising 64 /i. between 1980 and 1992 [11. The high rate of mortality and the large number of patients affected have made the therapy of emphysema and COPD a focus of attention for many years. Standard therapy for emphysema has a limited impact on patients' quality of life and survival, and most patients become increasingly symptomatic over time. The limitations of medical therapy led to the introduction of other forms of therapy, including surgical intervention, with the hope of achieving symptomatic improvement in selected patients [2-4]. Originally described by Brantigan and Mueller [5] in 1957, the concept of lung volume reduction ILVR] for emphysema held promise as a unique and potentially effective mechanism for improving the mechanics of air exchange in patients with severely emphysematous lungs. The reintroduction of this operation bv Cooper and others [6] in 1995 stimulated interest in surgery for emphysema and resulted in a large number of uncontrolled trials of this therapy. The increasing use of LVR for emphysema has provided a large volume of data from which the short-term outcomes of surgical therapy can be analyzed. The put- Add~,s r~'print requests to Dr Naunheim, Department ot SurgeD', St. Louis ~ niversity Hospital, 3635 Vista Ave at Grand Blvd, PO Box 15250, St. Louis, MO poses of this report are to review the background of operations for emphysema, to compare outcomes of laser and resectional techniques as well as results after unilateral and bilateral operations, and to discuss the potential limitations of and future directions for surgical therapy for emphysema. Background Pathology Patients with emphysema have an abnormal enlargement of the alveoli and alveolar ducts and destruction of the alveolar walls. Alveoli become confluent in patterns classified as centriacinar emphysema (which more often affects the apical lung segments) and panacinar emphysema (which more often affects the basilar lung segments), both of which are common among cigarette smokers, and distal acinar emphysema, which is associated with the development of large bullae without significant airflow obstruction (most often evident in young adults with spontaneous pneumothorax) [7]. In patients with end-stage emphysema the centriacinar and panacinar forms often become confluent, and the distribution of disease between the upper and lower lung zones is relatively uniform [8]. As emphysema becomes severe, airflow obstruction develops that is associated with bronchial abnormalities. Reversible inflammation in bronchioles accounts for some airway obstruction [9], and pulmonary parenchymal destruction results in loss of mechanical support for the airways, permitting their collapse and causing airway obstruction [10]. Airway obstruction results in gas trapping within the lungs, a hallmark of emphysema. The discovery of the relationship between alpha 1- antitrypsin deficiency and emphysema led to the hypothesis that emphysema results from an imbalance between proteases and antiproteases in the lung, leading to de by The Society of Thoracic Surgeons [$15.00 Published by Elsevier Science lnc Pll S (96)

2 602 REVIEW NAUNHEIM AND FERGUSON Ann Thorac Surg LUNG VOLUME REDUCTION 1996;62: struction of alveolar septa [11]. Numerous animal models of emphysema have been described that support this hypothesis [12]. Studies in humans demonstrate increased elastin peptide concentrations in patients with emphysema [13]. Cigarette smoke has been shown to increase elastolytic activity, inhibit lung fibroblast proliferation, cause an increase in tissue susceptibility to elastase, and inactivate antielastases [14-20]. These findings support the hypothesis that cigarette smoke results in an imbalance in elastase-antilelastase that causes destruction of the microarchitecture of the lung, resulting in emphysema. Pathophysiology The function of respiratory muscles is profoundly altered in patients with emphysema. Tonic contraction of the accessory muscles of respiration and the intercostal muscles causes them to operate at an unfavorable position on the length-tension curve [21]. The curvature of the diaphragm is reduced, resulting in its inability to generate negative intrathoracic pressure. Contraction of a flattened diaphragm draws in the lower rib cage, in which case the diaphragm functions as an expiratory muscle and adversely affects the efficiency of breathing [21, 22]. The elastic recoil of the thoracic cage normally is directed outward and participates in the inspiratory process. In patients with severe hyperinflation thoracic elastic recoil is directed inward, adding to the elastic load that the muscles of respiration must work against. Loss of alveolar wall integrity leads to loss of pulmonary capillary surface area and is sometimes associated with the development of pulmonary hypertension. Elevated pulmonary vascular resistance in emphysema stems from disruption of the microcirculation, which by itself is not sufficient to generate resting pulmonary hypertension. The resistance to pulmonary blood flow in patients with emphysema is closely and inversely correlated with the diffusing capacity of the lungs for carbon monoxide, suggesting that a severe disturbance in gas exchange is also a necessary precursor to the development of pulmonary hypertension [23, 24]. Prognosis The prognosis in patients with emphysema or COPD is related to a number of factors. Positive correlations with survival have been demonstrated for forced expiratory volume in 1 second (FEV1) O2, reversibility of airflow obstruction, exercise capacity, diffusing capacity, vital capacity, and the presence of atopy. Negative correlations have been reported for age, decreasing FEV 1 on serial testing, resting heart rate, arterial carbon dioxide tension, pulmonary artery pressure, total lung capacity, perceived dyspnea, continued smoking, and malnutrition [25-34]. In patients with severe emphysema, characterized by an FEV1 less than 30% of predicted, the 1-year and 5-year survival rates average 90% and 40%, respectively (Fig 1) [28, 33]. In patients who require hospitalization for management of COPD, the hospital survival rate is about 80% and the 1-year survival rate for patients older than 65 years is only 41% [35, 36]. % Survival,oo 60' 40 20' I l l l I I o 4 Years Fig 1. Su~ffval in patients diagnosed with chronic obstructive pulmonary disease who have a forced expiratory volume in 1 second less than 30% qf predicted [28, 33]. Medical Therapy Standard therapy for emphysema includes cessation of smoking and reduction of exposure to environmental pollutants that are thought to contribute to the development of emphysema. Influenza vaccination is important in reducing the risk of viral pneumonia, and protein replacement therapy is useful for patients with alpha 1- antitrypsin deficiency. Many patients also require pharmacologic therapy for symptomatic management, which includes bronchodilator drugs such as sympathomimetics, anticholinergics, and theophylline, mucolytics, intermittent courses of antibiotics when bacterial infection is suspected, and steroids. Noninvasive ventilation may be used for acute exacerbations of airway obstruction to avoid intubation with mechanical ventilation and its associated complications [37]. Intubation and mechanical ventilation is appropriate in patients who have had a severe and acute exacerbation of their symptoms that is thought to be reversible. Long-term oxygen therapy is indicated for patients with hypoxemia. It results in prolongation of survival, improved pulmonary hemodynamics, reduced heart work, increased exercise capacity, decreased work of breathing, beneficial neuropsychological effects, and an improvement in the quality of sleep [381. Most patients with moderate to severe emphysema benefit from a program of cardiopulmonary rehabilitation. Exercise training decreases total hospital stay and recurrent hospitalization rates in patients with COPD [39-41[. Controlled trials of graded exercise with appropriate monitoring of heart rate, oxygen saturation, and blood pressure demonstrate significant improvement in exercise capacity, exercise endurance, and dyspnea [42-51]. There is also some evidence that a patient's quality of life and sense of well-being are enhanced as a result of exercise rehabilitation. The mechanisms of improvement

3 Ann Thorac Surg REVIEW NAUNHEIM AND FERGUSON ;62: LUNG VOLUME REDUCTION are variously ascribed to enhanced aerobic capacity, increased muscle strength, desensitization to the sense of dyspnea, and improved techniques of performance [39]. Specific training of respiratory muscles does not provide substantial benefit [52]. Elderly patients benefit from supervised exercise programs to an extent that is similar to that seen in younger patients [43, 53]. Nutritional counseling and support are important elements in the success of cardiopulmonary rehabilitation, because most patients with end-stage emphysema are protein-calorie malnourished [54-56]. It is important to note that, despite the functional improvements that result from pulmonary rehabilitation in patients with severe emphysema, important improvements do not occur in these patients in either spirometric measurements or gas exchange indices [44-46, 49-51]. Surgical Therapy History Because of the poor quality of life and limited survival in patients with end-stage emphysema, a variety of surgical approaches have been introduced for patients who have responded inadequately to medical therapy. These techniques have been extensively reviewed elsewhere [2-4] and will be only briefly summarized here. Based on the concept that the rib cage was too rigid and small to permit complete expansion of an emphysematous lung, early in the 20th century efforts were aimed at lessening the stiffness of the chest wall by resecting costal cartilages and perichondrium. Favorable results were reported by a few individuals, who demonstrated a mild increase in vital capacity and a decrease in dyspnea, but the outcomes were unpredictable. The recognition that hyperexpansion of the lung was the root of mechanical problems in emphysema led to the ill-advised concept of thoracoplasty and phrenicectomy, a procedure that more often than not resulted in worsening dyspnea for the victim of the operation. Attempts to elevate a chronically depressed diaphragm resulted in the application of abdominal compression devices or pneumoperitoneum, neither of which could be pursued long-term and both of which failed to produce convincing clinical improvement. Pleural operations also were devised, including pleurectomy to stimulate ingrowth of new blood vessels into the lung, but no evidence was ever presented that they produced any measurable improvements. Curiously, operations were also devised for the nervous system in attempts to reduce bronchoconstriction or to relieve dyspnea. The fact that these operations had no apparent physiologic basis was certainly part of the reason for their failures. Transplantation In recent years lung transplantation has provided successful palliation for selected patients with far-advanced emphysema. Originally introduced for end-stage restrictive lung disease in 1986, the technique of single-lung transplantation was applied to patients with COPD in 1989 [57]. Currently COPD is the most common indica- tion for transplantation, comprising between one-third and one-half of all indications for lung transplantation [58]. The optimal type of transplant procedure, single- or double-lung transplantation, for patients with emphysema is controversial [59-64]. Short-term survival rate is favorable at about 90%, and at 4 years the mean survival rate of recipients with COPD of about 60% is equal to or slightly greater than that of the entire lung transplant population [65, 66]. There are, however, several concerns regarding the use of lung transplantation, many of which are not limited to patients with emphysema. Transplantation entails a 1- to 21/2-year waiting period for an appropriate donor, during which time the annual mortality for patients awaiting a transplant is 10%. The cost of the operation, subsequent monitoring, and long-term immunosuppression is extraordinarily high, and no formal analysis of the costbenefit relationships of this procedure has been performed. Long-term irnmunosuppression is associated with the development of hematologic malignancies in some patients, and is also associated with an increased risk of infectious complications throughout the recipient's life. Obliterative bronchiolitis develops in the transplanted lung of many patients, which results in severe dyspnea and often requires retransplantation. For these reasons, alternative methods of surgically managing patients with end-stage emphysema have been sought. Lung Volume Reduction Operations Operations on the lung were introduced for patients with diffuse emphysema by Brantigan and Mueller [5] in the late 1950s. They theorized that under normal conditions the elasticity of the expanded lung is transmitted to relatively pliable bronchi, which are held open by a circumferential elastic pull. In patients with emphysema, this elasticity is lost, resulting in impairment of the circumferential pull holding open the bronchioles. They postulated that by a surgical reduction in lung volume, the radial traction on the bronchi would be restored, reducing expiratory airflow obstruction and relieving dyspnea. Initially, few data were presented that supported their conclusion that the LVR operation was beneficial [5, 67]. Subsequent publications provided little additional objective support for the concept of LVR, and the procedure was not adopted by the medical and surgical communities as a treatment for generalized emphysema [68-70]. The reintroduction by Cooper and others of LVR for diffuse emphysema in 1995 was prompted by several factors. Their increasing experience with transplantation for emphysema demonstrated the safety of one-lung ventilation in these patients. They found that the configuration of the chest wall in patients receiving transplants for emphysema returned to a more normal, less expanded state in the early postoperative period [71]. There was a growing experience with bilateral lung operations through a sternotomy, and new techniques for limiting air leaks after operations on giant bullae had been reported [72-75]. The operation was based on the concept that an improvement in symptoms and performance

4 604 REVIEW NAUNHEIM AND FERGUSON Ann Thorac Surg LUNG VOLUME REDUCTION 1996;62: could be achieved by reversing some of the pathophysiologic effects of emphysema [6]. Early results of LVR have substantiated many of their expectations. Interestingly, LVR recently has been shown to be an effective bridge to lung transplantation [76, 77]. The concept of using LVR as a staging procedure for patients who are experiencing progressive deterioration in lung function is an intriguing one that deserves further investigation. Whether transplantation or LVR is the better choice for patients who qualify for either procedure is an even more complicated question. Data show that early functional results of single-lung transplantation are superior to those of bilateral LVR, a finding that is tempered by the higher cost, the need for immunosuppression, and a higher mortality during intermediate follow-up associated with transplantation [78]. Current Status of Lung Volume Reduction Indications At present, LVR procedures are believed to be most appropriate in patients with "pure" emphysema unadulterated by other forms of COPD. Such patients are characterized by severe respiratory functional impairment, which usually corresponds to a grade 3 to 4 (out of 4) level on the Modified Medical Research Council dyspnea scale. The radiologic picture includes hyperinflated lungs on chest roentgenograms with flattened diaphragms and an increased anteroposterior diameter. The emphysema may be bullous or nonbullous, and can be demonstrated on a high-resolution computed tomographic scan. Patients with giant bullae and associated collapsed parenchyma, although known to improve after bullectomy, are not considered to be part of this patient population and are not considered in this discussion. Spirometry and lung volume measurements performed via plethysmography reveal severe airway obstruction with an increased amount of trapped gas as demonstrated by markedly elevated residual volumes. Such patients nearly always desaturate with exercise, and most are hypoxic at rest. Preoperative Workup The preoperative workup currently performed at most centers can be divided into investigations dealing with thoracic imaging and those that measure functional status. In addition to the standard initial workup (medical history, physical examination, serum chemistries, electrocardiogram, and urinalysis), most programs obtain anteroposterior radiographs in the inspiratory and expiratory phases. Computed tomography of the chest is performed to better define the structural changes associated with the emphysema, as well as to rule out occult carcinoma. Most institutions include a quantitative ventilation/perfusion scan in the initial assessment. This allows the practitioner to identify regional differences in perfusion and ventilation, and allows for selection of the most dysfunctional portion of lung (least perfusion, greatest gas retention) as the "target area" to be ablated. Finally, Doppler echocardiography is used to evaluate both left-sided and right-sided cardiac function. Assessment of regional wall motion valvular function helps rule out a cardiac cause for the dyspnea. Examination of the right heart is undertaken to identify changes that might indicate significant elevations in pulmonary artery pressures (pulmonary valve regurgitation, tricuspid regurgitation, right ventricular hypertrophy, right ventricular dilatation). If pulmonary hypertension is suspected, then a right heart catheterization is performed to confirm or refute this suspicion. Although several investigational imaging techniques have been used in LVR candidates (single-photon emission computed tomographic scans, cine-magnetic resonance imaging), these are not widely used by the thoracic community. The functional parameters measured include complete pulmonary function testing with and without bronchodilators. This must include both spirometry and lung volumes as measured by plethysmography. Volumes measured by gas retention techniques tend to underestimate the degree of trapped gas and residual volume in severe emphysema. The 6-minute walk test has been used for many years in the assessment of functional status after lung transplantation and has been commonly used at many institutions in the lung reduction candidates. The test is reliable, reproducible, and relatively easy to perform. Finally, formal cardiopulmonary exercise testing has been undertaken at many sites to assess the candidate's cardiopulmonary status in depth. Once the above testing has been performed, candidates are evaluated for the final selection process. The current inclusion and exclusion criteria generally agreed upon at the present time are as follows: Inclusion criteria 1. Diagnosis of emphysema 2. Disabling dyspnea (Modified Medical Research Council dyspnea grade 3 or 4) 3. Postbronchodilator FEV~ <35% predicted 4. Residual volume (by plethysmography) >200% predicted 5. Total lung capacity (by plethysmography) >120% predicted 6. Hyperinflated lungs on chest radiograph 7. Regional heterogeneity of perfusion on radionuclide scan, providing the opportunity for excision of hyperinflated, relatively functionless areas 8. Ability to participate in preoperative pulmonary rehabilitation Exclusion criteria 1. Age >80 years 2. Any tobacco use (inhaled or oral) within 6 months 3. Pulmonary artery hypertension (systolic >45 mm Hg, mean >35 mm Hg) 4. Resting carbon dioxide tension >55 mm Hg 5. Irreversible obesity (>1.25 ideal body weight or cachexia (<0.75 ideal body weight) 6. Unstable coronary artery disease 7. Other life limiting medical disease (eg, uncon-

5 Ann Thorac Surg REVIEW NAUNHEIM AND FERGUSON ;62: LUNG VOLUME REDUCTION trolled malignancy, severe congestive heart failure, severe cirrhosis, renal failure requiring dialysis) 8. Ventilator dependence 9. Chronic bronchitis, bronchiectasis, or asthma The vast majority of patients who are referred for LVR procedures prove not to be appropriate candidates. The acceptance rates for candidates in current reports ranges from 6% to 37% [79, 80]. Preoperative Preparation Once a patient is accepted as a candidate for operation, there are several items that must be addressed to appropriately prepare the patient for the operation. Many patients are receiving substantial doses of steroids. During the preoperative period, the goal is to wean the patient off their oral steroid dosage if at all possible. At the very least, most investigators would like the patient taking less than 20 mg of prednisone per day. Inhaled steroid can be substituted and often helps manage this weaning process. Patients are asked to participate in a formal supervised pulmonary rehabilitation program including attention to proper breathing exercises, pulmonary toilet, upper body strengthening, nutritional repletion, and overall conditioning using a treadmill, stationary bicycle, or other exercise machine. During exercise oxygen saturation should be monitored, and supplemental oxygen is administered to maintain the oxygen saturation at 90% or greater. The goal of conditioning is 30 minutes of uninterrupted exercise on a treadmill or bicycle. An evaluation is sent to the physician every 2 weeks so that he or she can follow the progress and identify when the goals have been met. Although all investigators believe preoperative pulmonary rehabilitation is highly desirable, not all believe it is absolutely necessary. There are those physicians who will not operate on a patient unless such conditions are met [71, 79, 80], and also those who attempt to enroll all patients in a rehabilitation program but will proceed with surgical intervention even if the patient cannot meet the specified goals [81, 82, 83]. Operative Rationale Emphysema is caused by a chronic inflammatory process within the lung parenchyma that results in destruction of the alveolar walls with abnormal permanent enlargement of the air spaces distal to the terminal bronchioles. This parenchymal destruction leads to a decrease in the circumferential "tethering" effect by the normal lung parenchyma on the terminal bronchioles. It is this radial tethering that tends to hold the small airway open throughout the expiratory cycle until a balance is achieved between the chest wall and lung elastic recoil forces at end-expiration. The combination of a lessened alveolar driving force (due to alveolar destruction) and decreased tethering leads to early closure of the small airways during expiration with resultant poor expiratory flow and hyperinflation. The gas trapped within the lung A B Fig 2. (A) Radionucleide perfusion scan demonstrating bilateral apical hypoperfusion. (B) Radionucleide ventilation scan demonstrating apical gas retention. tends to limit the inspiratory capacity and markedly impairs the patient's maximal breathing capacity as evidenced by very low maximum voluntary ventilation indices. The operative rationale for LVR is based on the ablation or resection of the most diseased portions of emphysematous lungs. The ideal patient is believed to be one in whom clear "target zones" appear on the ventilation and perfusion scans. Such zones are characterized by markedly decreased perfusion limited to a single region in both lungs (Fig 2A). Ideally, this regional hypoperfusion would correlate with a site of gas retention on the ventilation scan (Fig 2B). It is important to note that the remainder of the lung should demonstrate relatively good perfusion if the patient is to be considered an appropriate candidate. Hypoperfusion not limited to a single region of the lung (ie, homogeneous or diffuse

6 606 REVIEW NAUNHE1M AND FERGUSON Ann Thorac Surg LUNG VOLUME REDUCTION 1996;62: Table 1. Preoperative Profile No. of Six-Minute Preoperative First Author Modality Patients FEV 1 (% pred) RV (% pred) Walk fit) Oxygen Use Wakabayashi [86] CO 2 laser (25%) % Little [87] Nd:YAG laser (...) % Hazelrigg [88] Nd:YAG laser (23%) 5.52 (256%) % McKenna [82] Nd:YAG laser (...) 5.10 (...)... 75% Eugene [89] Both (...) 5.07 (...)... 82% Wakabayashi [90] Both (25%)... (197%)... 70% Keenan [91] Resection (30%) 5.10 (239%) % McKenna [82] Resection (...) 5.40 (...)... 69% Naunheirn [83] Resection (26%) 5.13 (235%) % McKenna [92] Resection (25%) 4.80 (...)... 56% Bingisser [93] Resection (28%) 5.80 (25%) 1,608 (12-rain) 35% Cooper [71] Resection (25%) 5.90 (285%) 1,175 90% Miller [79] Resection (19%) 5.50 (290%) 1,106 71% Daniel [94] Resection (25%) 6.10 (...)... 54% Miller [80] Resection (...) % Argenziano [811 Resection (23%) 4.00 (...) % FEV 1 - forced expiratory_ volume in 1 second; Nd:YAG neodymium:yttrium-aluminum garnet; %, pred - percent predicted; RV = residual volume. changes) is generally believed to be a contraindication to LVR. The purpose of the LVR is to resect the dysfunctional "target zones" and thus reduce the amount of trapped gas (as demonstrated by a decrease in residual volume measurements). There are at least four mechanisms purported to be responsible for the respiratory improvement that occurs after LVR procedures. It is important to remember that these physiologic mechanisms are all interrelated. ELASTIC RECOIL. Brantigan's original work suggested that resection of portions of the lung would improve the elastic recoil as the lung reexpanded to fill the enlarged chest cage. This improvement in elastic recoil would lead to a reinstitution of the circumferential tethering of the small airways causing a decreased expiratory airway resistance and improved expiratory flows. Reports by Sciurba and associates [841 and Miller and colleagues [79] document just such changes in lung elastic recoil and expiratory airway resistance, respectively. VENT1LATION/PERFUSION MISMATCH, The retention of inspired gas in areas of decreased perfusion (characterized as the so-called target zone) may lead to elevated systemic levels of carbon dioxide. Such dilated, hyperinflated regions may lead to atelectasis of adjacent areas of less diseased lung resulting in perfused but hypoventilated lung, a condition that results in shunting with systemic hypoxia. Resection of this sort of dysfunctional lung may lead to improvements in hypoxia and hypercarbia by removing the areas with the worst ventilation/ perfusion mismatch. RESPIRATORY MUSCULATURE. The hyperinflation that results from emphysema leads to severe distention of the chest and diaphragmatic flattening. All muscle, including the diaphragmatic and intercostal muscles, has an optimal length at which it develops maximal tension. The distended chest and flattened diaphragms result in decreased efficiency and strength of the inspiratory musculature in patients with emphysema. Resection of dysfunctional lung leads to a reduced volume of the lung and allows the distended chest cage to return to its more normal diameter, and the diaphragm to resume its domed shape, thus improving the efficiency of the respiratory "pump." CARDIOVASCULAR HEMODYNAMICS. It has been suggested that LVR may have some salutatory effects on right heart function by virtue of recruitment of hypoperfused pulmonary artery capillaries after expansion of atelectatic lung. In addition, it is recognized that patients with end-stage emphysema who suffer from "auto-positive end-expiratory pressure" may deteriorate acutely when placed on mechanical ventilatory support due to a phenomenon of air trapping that results in a form of "pulmonary tamponade." Markedly elevated intrathoracic pressures can decrease systemic venous return with a disastrous consequences. This concept of impaired hemodynamics due to variations in intrathoracic pressure has been championed by Dahan and colleagues [85]. It is likely a combination of the above factors that leads to physiologic improvement after LVR. The relative roles of the above mechanisms are at the present time unknown and may vary from patient to patient. Results of LVR that have been published or presented or that are "in press" are listed in Tables I and 2, and are arranged according to whether they were performed using laser ablation, stapled resection of lung tissue, or a combination of the two modalities. It is evident from the

7 Ann Thorac Surg REVIEW NAUNHEIM AND FERGUSON ;62: LUNG VOLUME REDUCTION Table 2. Postoperative Results Operative Mortality LOS FEV~ RV Six-Minute Postoperative First Author Approach (%) (days) Increase Decrease Walk Increase Oxygen Use Wakabayashi [86] Unilat-VATS % Little [871 Unilat-VATS % Hazelrigg [88] Unilat-VATS % 11%... 65% McKenna [82] Unilat-VATS % % Eugene [89] Unilat-VATS % 12%... 64% Wakabayashi [90] Unilat-VATS % 12% Keenan [91] Unilat-VATS % 16% 14% 63% McKenna [82] Unilat-VATS % % Naunheim [83] Unilat-VATS % 33% 20% 40% McKenna [92] Bilat-VATS % % Bingisser [93] Bilat-VATS % 24% 39% 30% Cooper [71] Bilat-open /'i, 32% 19% 27% Miller [79] Bilat-open % 29% 29% 18% Daniel [941 Bilat-open % 30%... 41% Miller [80] Both-open % % 18% Argenziano [81] Both-open % %... Bilat = bilateral; FEV~ forced expiratod, volume in 1 second; LOS length of stay; RV = residual volume; Unilat unilateral; VATS - video-assisted thoracic surgery-. limited data that the groups of patients selected for these procedures are similar, and that all have severe manifestations of emphysema. Laser Therapy The reports of Wakabayshi and associates [86] and Barker and colleagues [95] were the first to suggest laser ablation as a method for the treatment of end-stage emphysema. These retrospective studies described the same 22 patients treated with thoracoscopic application of free-beam carbon dioxide laser to shrink emphysematous lung tissue. Overall, the operative mortality rate was 16% (4/22), with two early and two late deaths. All patients required mechanical ventilation for a mean of 5 days, and large air leaks were noted universally. Mean chest tube duration was 13 days. Follow-up at 1 month was reported in 11 of 18 survivors who were noted to have a 27% increase in FEV 1 [95] and an increase in maximal time on the exercise treadmill from 5 to 8 minutes [86]. Two prospective, uncontrolled studies were carried out in an attempt to confirm the beneficial effect of laser ablation. Little and colleagues [87] performed unilateral thoracoscopic laser ablation using a free-beam neodymium:yttrium-aluminum garnet (Nd:YAG) laser in 55 patients. The hospital mortality rate was 5.5%, and the mean hospital stay was 12.9 days. The investigators noted significant improvement in subjective dyspnea in 32 patients followed up at least 3 months, a 15% increase in mean FEV1, and a 4-point increase in mean arterial oxygen tension (59 to 63 mm Hg). Air leaks were noted to be a significant problem, and moderate to severe subcutaneous emphysema developed in 45% of patients. The second prospective study was a multiinstitutional effort reported by Hazelrigg and associates [88]. In this study, video-assisted thoracic surgical (VATS) ablation of emphysematous tissue was undertaken in 141 patients using an Nd:YAG laser with a sapphire contact tip. The hospital mortality rate was 5.7%, and there were five late deaths (3.5%) after discharge. Median hospital stay was 11 days, primarily due to a prolonged (>5 days) air leak in 31% of patients. Follow-up was available in 68 patients at 3 months and revealed significant improvement in subjective dyspnea, a 24% increase in the 6-minute walk, a 14% increment in FEV1, and an 18% decline in the number of patients requiring oxygen. Hazelrigg and associates concluded these changes were modest when compared with those achieved by performing a stapled resection, and they abandoned the use of the laser technique. In a prospective, controlled study, McKenna and colleagues [82] randomized patients to undergo either a unilateral stapled resection or a unilateral laser ablation for the treatment of emphysema. The preoperative profile of the patients was similar, but the results were significantly different. Patients undergoing stapled resection had a significantly greater improvement in FEV1, as well as a much decreased need for supplemental oxygen. McKenna and colleagues concluded that a unilateral stapled resection was more effective for the treatment of emphysema than the laser ablation using an Nd:YAG contact tip. Although there are marked variations among authors regarding the laser technique (CO 2 versus Nd:YAG, free-beam versus contact) it appears that laser ablation of emphysematous lung tissue has beneficial effects in patients with end-stage emphysema. Unfortunately, although rehabilitation was used occasionally in these

8 608 REVIEW NAUNHEIM AND FERGUSON Ann Thorac Surg LUNG VOLUME REDUCTION 1996;62: studies, it was not routinely and systematically performed in the preoperative period. Thus, it is not possible to ascribe all the improvements in subjective dyspnea and functional capacity to the operation alone because such changes are known to occur with a formal pulmonary rehabilitation program. However, the improvements in spirometric values and increments in oxygenation indices are not known to be produced by a program of rehabilitation, and can be ascribed to the VATS laser procedures. Combined Modality Two recent articles document results achieved by combining the technique of stapled lung resection and laser ablation. Eugene and associates [89] performed both stapled lung resections and free-beam laser ablation of diseased lung using both potassium-titanyl-phosphate and Nd:YAG lasers in 28 patients. These procedures were performed using a video-assisted approach incorporating both standard thoracoscopy ports and a minithoracotorny. There were no operative deaths, but three late deaths occurred (11% late mortality rate). Prolonged air leak occurred in 42% of patients. Subjective improvement was found in 79% of patients, and 22% of oxygendependent patients could discontinue their oxygen use. There was also an increase of 34% in the FEV 7 after 3 to 6 months. No parameters of functional capacity were reported. A recent report by Wakabayshi [90] documents 500 consecutive procedures in 443 patients using stapled resection combined with Nd:YAG ablation of bullous disease. The overall mortality rate was 5.4%. Ventilatory support averaged 22 hours, and the mean hospital stay was 18 days. Follow-up was obtained in 203 patients, 87% of whom felt their breathing was better than before operation. The reason for the lack of follow-up in the other patients was not stated. At follow-up, the average increase in FEV~ was 26%, and this was statistically significant. Blood gas data and functional capacity changes were available in 81 patients. There was no change in oxygen tension or carbon dioxide tension, although the mean treadmill test duration rose from 5 minutes to 8 minutes. Although these two reports demonstrate that combinations of stapled resection and laser ablation lead to significant improvement, it is uncertain how much is due to the ablation and how much to the stapled resection. These reports do not provide details regarding the extent of either the resection or the ablation, and thus are of limited application for surgeons trying to replicate these techniques. Resection The initial report by Cooper and associates [6] in 1995 outlined results of the sternotomy approach for bilateral stapled resection in 20 patients with end-stage emphysema. There was no operative mortality, an 82% increase in FEV 1, a 6 mm Hg increase in oxygen tension, a marked diminution in oxygen use, and a significant improvement in quality of life. These remarkable results spurred many investigators to institute LVR programs. Some investigators thought that a minimally invasive approach would potentially benefit this fragile patient population by minimizing the postoperative pain and pulmonary morbidity. Early reports are available from Keenan [91], McKenna [82], Naunheim [83], and their associates regarding prospective evaluations of unilateral LVR using VATS techniques. These clinical series document that a unilateral VATS LVR procedure can be performed with acceptable morbidity and mortality rates (2.5% to 5.3%), and that one can appreciate significant improvements in FEV1 values (27% to 35% increase) and functional capacity (6-rninute walk 14% to 20% improved), and a marked decrease in oxygen utilization. Once satisfied with the efficacy of this approach, some surgeons began performing bilateral simultaneous LVR procedures with VATS techniques. McKenna and associates [92] performed a retrospective analysis comparing the results of consecutive patients undergoing bilateral and unilateral VATS procedures. The preoperative profile and operative morbidity were similar between the two groups, and the bilateral procedure was superior with regard to the degree of spirornetric improvement, relief of dyspnea, and the ability to discontinue oxygen supplementation. McKenna and associates concluded that a bilateral VATS approach is warranted when bilateral target zones exist, and there are no contraindications to operative intervention. For patients with unilateral disease or those with specific contraindications (prior thoracotomy, pleurodesis) on one side, a unilateral LVR is still beneficial. European investigators have also confirmed the salutary effects of thoracoscopic lung reduction procedures. Bingisser and colleagues [93] used a simultaneous bilateral VATS approach in 20 patients with no operative mortality. They demonstrated a 38% increase in FEV 1 with a concomitant 39% increase in functional capacity as measured by a 12-minute walk test. Many other investigators have pursued the open approach championed by Cooper. Miller [79], Daniel [94[, Miller [80[, and their associates have all performed bilateral LVR procedures via the sternotomy approach with acceptable operative mortality (3.8% to 10%) and morbidity rates. However, it is important to remember that this is an extremely fragile patient subset in whom a nearperfect operation with expert perioperative management is required lest prohibitive morbidity arise. Unpublished anecdotal data have arisen from multiple sites documenting mortality rates up to 50% at some institutions using this approach. It is clear that this operation can be undertaken with significant but acceptable risk by an experienced team of thoracic physicians (surgical and medical) at well-equipped tertiary medical centers. There is good evidence of at least short-term benefit to patients from the operation, and it is realistic to hope that at least intermediate-term benefit will be derived from the procedure. We believe that the current complexities of total care associated with the procedure are such that LVR is an appropriate procedure to be performed only by thoracic surgeons who are working as part of a multidisci-

9 Ann Tharac Surg REVIEW NAUNHEIM AND FERGUSON ;62: LUNG VOLUME REDUCTION plinary team in selected hospitals from which it is realistic to expect further evaluation of LVR. Analysis of the above-mentioned investigators' experiences with bilateral LVR documents marked improvement in spirometric indices, functional capacity, dyspnea scores, and oxygenation parameters. Efforts to elucidate the physiologic mechanisms responsible for these improvements are just now being reported. Sciurba's [84], Miller's [79], and Klepetko's [96] groups have documented significant improvements in work or breathing, intrinsic positive end-expiratory pressure, elastic recoil, dynamic compliance, and airway resistance. The relative contribution to improvement of these ventilatory mechanics vis-a-vis changes in ventilation perfusion mismatch and chest wall mechanics remains to be determined. The results of bilateral reduction procedures appear to be better than those achieved via a unilateral VATS approach. However, it must also be remembered that although all patients undergoing sternotomy had bilateral target zones to work upon, a significant percentage of unilateral VATS patients had only unilateral disease or a contraindication to the bilateral approach, and thus the results may not be directly comparable. The data do suggest, however, that the bilateral approach may be preferable in patients with bilateral target zones. Cooper and Patterson [71] have recently updated Cooper's series to include the first 100 patients at his institution undergoing LVR, and some changes in outcome have occurred. As the selection criteria were broadened, the operative mortality has risen to 5%, and the spirometric improvement in FEV 1 decreased from 82% to 57%. However, the patients continue to demonstrate consistent improvement in 6-minute walk capacity (25% increment), oxygen tension increment (9 mm Hg), and relief of dyspnea. Another recent report from Cooper's group [94] documents that the beneficial effects noted at 3 and 6 months are maintained, and show no significant decline through a 1-year follow-up period. This report also notes that the actuarial 1-year survival stands at 94%, a surprisingly high figure considering the natural history of patients with emphysema as severe as those operated on. Finally, Argenziano and colleagues [81] have recently reported on a series of 85 patients, many of whom would be refused operation at other programs due to prohibitive risk as defined by the exclusion criteria and other guidelines. Nine of the 85 patients (11%) had intrathoracic neoplasms identified and resected during the lung reduction. Thirty-five patients (41%) were unable to complete preoperative rehabilitation, and 9 patients (11%) had a carbon dioxide tension greater than 55 mm Hg. Argenziano and colleagues performed 27 open unilateral reductions, 14 sternotomy bilateral reductions, and 44 bilateral reductions via a "clam-shell" incision, which has become their approach of choice. The operative mortality rate was 7.1% (6/84, 1 still hospitalized), and the median hospital stay was 17 days. At 3 months, improvements were noted in FEV 1 (61% increase), 6-minute walk (62% increase), and dyspnea index. The marked improvement in 6-minute walk is quite difficult to critically assess because nearly half their patients did not have the benefit of preoperative rehabilitation, and it is uncertain how much of that improved function might have been obtained had they pursued a rehabilitation regimen. Nonetheless, these investigators demonstrated that a significant improvement can be obtained even in patients who fall outside the criteria identifying "optimal" candidates. Controversies A great deal of controversy exists regarding the operative techniques used to achieve LVR. The most prominent of these controversies are the operative approach, the method of ablation, and the amount of tissue to be ablated. Perhaps the least important of these controversies is the operative approach. Although a great deal has been made of the differences between thoracoscopy, thoracotomy, and sternotomy, the most important aspect of LVR is what is accomplished within the chest cavity, not how one gets there. Acceptable results have been documented for both the thoracoscopic [82, 83, 91] and open [71, 79, 80] approaches. Although further studies may demonstrate some differences in operative morbidity, each of the approaches has been demonstrated to be acceptable. The method of parenchymal ablation has also varied. The most commonly used method at present is a stapled excision of lung tissue. Although the laser has been used both in a free-beam fashion and with contact probes to effect parenchymal ablation, this technique has been abandoned by most practitioners. Similarly, the argon beam coagulator, although reported to be demonstrated effective in a small number of patients, has not been widely accepted [97[. Finally, there has been disagreement as to whether a bilateral or unilateral LVR procedure should be undertaken. Practitioners of VATS have most commonly performed unilateral procedures, but recently simultaneous bilateral thoracoscopic lung reductions have been performed [92, 93]. Surgeons who use the sternotomy approach commonly perform bilateral reductions simultaneously, and many believe this is the optimal approach. It is likely that these two approaches will eventually be used selectively in an attempt to match the extent of the procedure to the individual patient. Patients with primarily unilateral disease may indeed not benefit from a bilateral procedure, and those with a contraindication to operation on one side (eg, prior thoracotomy, pleurodesis) may also be better suited to a unilateral operation. Patients with bilateral target zones and no contraindication to operation on either side will likely be treated with simultaneous reductions of both lungs. Summary The data presented in the available reports allow some conclusions regarding LVR. First, it appears to provide significant short-term improvement in respiratory status in carefully selected patients. Although pulmonary rehabilitation alone has been demonstrated to improve dyspnea and functional status to some extent, LVR provides benefit in these areas far out of proportion to that found

10 610 REVIEW NAUNHEIM AND FERGUSON Ann Thorac Surg LUNG VOLUME REDUCTION 1996;62: from rehabilitation programs. In addition, it significantly improves spirometric indices and patient oxygen saturation, two benefits never reported for rehabilitation. However, to provide this benefit reliably and reproducibly, LVR must be performed in an organized and systematic fashion. It is imperative that a multidisciplinary team experienced in the care of end-stage emphysema patients be assembled. This team must include not only qualified thoracic surgeons, pulmonologists, and anesthesiologists, but the critical ancillary personnel such as nurses, respiratory therapists, and physical therapists who deliver minute-to-minute care in the hospital setting. There must be an institutional commitment to provide the resources necessary for such an integrated program. In institutions in which this has not been approached in such an organized fashion, very disappointing results have occurred. Even in the ideal setting, it must be recognized that there is significant morbidity and mortality that will result from this aggressive surgical approach to a very fragile patient population. Although the idea of LVR procedures is decades old, the current implementation of this concept is in its infancy. As occurred early in the experience with coronary artery bypass, the published reports appear to provide as many questions than they do answers. Now, 25 years after the introduction of myocardial revascularization, investigations are still ongoing in attempts to optimize this form of therapy. It is likely that a similar time scale will be needed for the evolution of LVR. At present, data demonstrate that LVR can be performed with acceptable morbidity and mortality, and markedly improves the respiratory status and quality of life in end-stage emphysema patients in the short-term. Over the next decade, investigatory efforts need to be directed to address specific issues in each of three areas: patient selection, operative technique, and results. Questions to be answered include, but are not limited, to the following: Patient Selection 1. Contraindications--Is there an upper age limit? Are active bronchitis, bronchiectasis, and pulmonary hypertension absolute contraindications? Are there patients who are too compromised to undergo LVR? 2. Parenchymal disease--is heterogeneous perfusion absolutely necessary or will patients with homogenous perfusion benefit somewhat? Are the results for patients with apical lung reduction the same as those with basilar lung reduction? 3. Rehabilitation--Is rehabilitation an absolute necessity before LVR, and if so, what is the optimal amount? Technical 1. Air leak management--is a buttressed staple line always necessary, and what is the ideal material? What is the role of pleurodesis and pleural tents? 2. Laser--Is it possible that the laser will be useful as an adjunct to stapling to help improve or sustain the beneficial effect of LVR? 3. Ablation--What is the optimal amount of tissue to be removed, and how should this be measured? 4. Approach--When, if ever, should a VATS approach be used instead of an open approach? What patients, if any, should preferentially have a unilateral procedure performed? Results 1. Duration--What is the duration of symptomatic improvement? 2. Survival--Is there a survival benefit for LVR? 3. Cost--Does LVR reduce medication and hospitalization utilization and, if so, how is the overall cost affected? Lung volume reduction is an exciting new tool for the treatment of patients with end-stage emphysema. The answers to these and other questions will arise as our understanding of the physiology evolves, and as the surgical procedure becomes further refined. References 1. 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