INTRODUCTION

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Lung volume reduction surgery (LVRS) has been shown to improve pulmonary function, gas exchange, exercise performance, dyspnea, and quality of life in select patients with moderate to severe emphysema (1). Nevertheless, the improvement after LVRS is not universal and the postoperative complications are not trivial (3, 10). Disappointing results from LVRS are either due to failure to alter the course of emphysema or to perioperative morbidity and mortality (1, 3, 10, 12, 17). Perioperative complications reported in LVRS studies ranged from 30 to 87% (3, 10, 20), and include pulmonary problems, such as bronchopleural fistula, lower respiratory tract infections, and respiratory failure, or nonpulmonary complications such as cardiovascular or cerebrovascular abnormalities, or thoracic and gastrointestinal hemorrhage.

Previous investigators have noted a high association between respiratory failure after LVRS and mortality; however, few have performed risk factor analysis to identify predictors of poor perioperative outcome (3, 5, 10, 17). Keenan and colleagues (3) reported that the presence of preoperative hypercapnia and a severely reduced diffusion capacity had a specificity of 86% in predicting serious postoperative complications. Two other groups of investigators have also concluded that preoperative hypercapnia heralds poorer perioperative outcome (10, 17). In contrast, others (5, 6) have found no difference in outcome between patients with and without severe hypercapnia.

Prolonged postoperative respiratory failure is believed to be a major contributor to the morbidity (increased risk of nosocomial pneumonia and prolonged air leaks) after LVRS, but its impact on mortality is not known. Herein we sought to determine the incidence of acute respiratory failure post-LVRS, its impact on patient mortality, and the types and risks of preoperative factors that lead to its occurrence.

	METHODS

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Study Population

We retrospectively reviewed the records of all patients with severe chronic obstructive pulmonary disease (COPD) who underwent LVRS at our institution from February 1995 to February 1998 (n = 87). The institutional review board waived the need for informed consent. We classified patients into two groups: patients with and without respiratory failure after LVRS. We defined postoperative respiratory failure as dependency on mechanical ventilation for greater than 24 h after LVRS or the need for reintubation before hospital discharge.

Patients were included if they had evidence of severe airflow obstruction (FEV₁ < 30% predicted), hyperinflation by pulmonary function studies (TLC > 120% of predicted) and by chest X-ray and high-resolution chest computed tomography (CT), in addition to documented ventilation perfusion mismatch in planned resected lung tissue by quantitative ventilation-perfusion lung scan. All of the patients had stopped smoking at least 6 mo before evaluation and remained symptomatic despite optimal medical therapy. Patients were excluded if they had refractory severe hypoxemia (ratio of arterial oxygen tension to fraction of inspired oxygen [Pa_O2/FI_O2] < 150), severe pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg), psychological dysfunction, or if they were in severe debilitated state (total body weight < 70% of ideal). All patients were encouraged to complete 8 wk of preoperative pulmonary rehabilitation before undergoing surgery. All LVRS were performed by one experienced cardiothoracic surgeon, who is United Network of Organ Sharing (UNOS)-certified and performs heart, lung, and heart-lung transplantation. We obtained preoperative, intraoperative, and postoperative clinical data from the medical records.

Preoperative Data Collection

Preoperative variables analyzed included patient demographics, cardiac history, percent ideal body weight (%IBW), systemic steroid use, serum albumin, lung function, cardiopulmonary exercise testing and 6-min walk distance (6-MWD), pulmonary hemodynamics, and echocardiographic findings.

Pulmonary Function and Cardiopulmonary Exercise Testing (CPET)

Pulmonary function testing was performed (System 6200 Autobox DL Plethysmograph; SensorMedics Corporation, Yorba Linda, CA) following American Thoracic Society guidelines, and the thoracic gas volumes were determined by plethysmography. Only postbronchodilator results are reported.

Symptom-limited maximal CPET data (maximal minute ventilation, maximal tidal volume, total exercise time, and maximal oxygen consumption [O₂max] and 6-MWD were recorded when available. CPET was performed using incremental treadmill exercise to symptom-limited maximum (Precor 9.4sp; Precor Inc., Bothell, WA) and data were recorded by a metabolic cart (SensorMedics 2900) following American Heart Association guidelines (21). During the test, supplemental oxygen was usually individualized for each patient to prevent oxygen desaturation. The 6-min walk test was performed on a day different than exercise testing.

Right Heart Catheterization

Pulmonary hemodynamics and echocardiogram were also recorded when available. Echocardiographic Doppler imaging was performed using transthoracic views. Right heart catheterization was performed in the cardiac catheterization suite using the standard technique of a balloon-tipped pulmonary artery flotation catheter. The cardiologist performing the procedure interpreted all tracings. Cardiac output was measured using the thermodilution method.

Intraoperative Data Collection

Intraoperative data analyzed included the method of performing LVRS, i.e., median sternotomy (MS) versus video-assisted thoracoscopic surgery (VATS), the type of concomitant surgery, the duration of surgery (from induction to reversal of anesthesia), and the development of intraoperative complications.

Postoperative Data Collection

Postoperative data obtained included location of extubation (operating room versus recovery room), postoperative arterial blood gases (ABG), presence of air leaks, or other postoperative complications, disposition and survival outcome, and total length of hospitalization. For patients who developed respiratory failure, we recorded time of reintubation, prerespiratory failure ABG, and cause of respiratory failure.

Statistical Analysis

The variables are presented as mean ± SD. Comparisons between the group of patients who developed respiratory failure and those who did not were performed by unpaired Student's t test for normally distributed continuous data, Mann-Whitney U test for nonparametric data, ² test, and Fisher exact test, when over 20% of the expected values were less than five (for categorical data). Statistical computations were done on Sigmastat Version 2.0 (SPSS Inc., San Rafael, CA). Univariate and multivariate logistic regressions were used to estimate the relationship of individual factors with the occurrence of respiratory failure. p < 0.05 was considered statistically significant.

	RESULTS

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Patient Characteristics

Eighty-seven patients with severe emphysema had LVRS during the 3-yr period; 72 cases were analyzed. Thirteen patients were excluded because of respiratory failure (ventilator-dependent before surgery) or lung transplant before LVRS was performed; two records were incomplete and could not be analyzed. Twenty-one of the 72 patients (29%) developed acute respiratory failure after LVRS. Baseline demographic characteristics and physiologic data of the two groups are shown in Tables 1234. Respiratory failure patients were older and had a higher incidence of preoperative coronary artery disease compared with those who did not develop acute respiratory failure. There was no difference between the two groups in terms of other demographic or physiologic variables. Both groups had evidence of at most only mild pulmonary hypertension preoperatively (Table 3). Nine patients (43%) in the respiratory failure group, and 18 patients (35%) in the group not developing respiratory failure were hypercapnic before LVRS (Pa_CO2 > 45 mm Hg).

Perioperative Outcome

Perioperative data and complications are shown in Tables 5 and 6. Of the 21 patients with acute respiratory failure after LVRS, five patients developed hypoxemic and nine patients hypercapnic respiratory failure. Seven patients were intubated because of hemodynamic instability, four of whom had cardiac ischemia. Except for one patient, all were ventilator-dependent or required reintubation within 1 to 48 h postoperatively, and three patients required tracheostomies for prolonged ventilatory support. Postoperative patients developing respiratory failure had longer anesthesia time, more concomitant procedures performed, higher complication rates, longer hospitalization, and higher hospital mortality compared with those without respiratory failure.

Concomitant procedures included seven coronary artery bypass graft surgeries, one left ventricular reduction (Batista procedure), and a resection of a left thigh tumor. The overall mortality in the 72 patients was 9.7%; all seven patients who died were in the respiratory failure group, two of whom had coronary artery bypass grafting.

Risk Factor Analysis

Results of univariate logistic regression results are shown in Table 7. Age, presence of coronary artery disease, duration of surgery, and performance of concomitant procedures were significantly related to the occurrence of respiratory failure. There was a trend toward relationships between history of congestive heart failure, inspiratory capacity, maximal inspiratory mouth pressure, and surgery via median sternotomy and increased risk of respiratory failure; however, these relationships were not statistically significant. In the multivariate logistic regression model, duration of surgery was the only independent variable associated with respiratory failure after LVRS. However, the small number of patients and the frequency distribution of concomitant procedures (concomitant procedure occurred only in the acute respiratory failure group) precluded adding this variable to the multivariate logistic model.

	DISCUSSION

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In this study, almost one-third of patients undergoing LVRS developed respiratory failure immediately postprocedure, with 33% of this group dying as a result of their perioperative complication. Preoperative static pulmonary physiologic studies, gas exchange values, exercise test performance, and central pulmonary hemodynamics failed to identify patients at risk for serious postoperative complications. Older age, presence of coronary artery disease, and combined surgical procedures were more specific in predicting postoperative respiratory failure; all patients with combined surgery developed respiratory failure.

Respiratory failure has been reported to occur between 0- 17% in patients undergoing LVRS (Table 8). Hypercapnia, severe pulmonary disease, and poor functional performance have been suggested as markers of poor postoperative outcome (3, 10, 17). Wakabayashi (10) analyzed risk factors for 3-mo mortality and postoperative respiratory failure in 443 patients after Nd:YAG laser LVRS. Poor functional status, oxygen tension less than 44 mm Hg, and carbon dioxide tension greater than 60 mm Hg were all associated with increased 3-mo mortality and the need for tracheostomy. Szekely (17) and Keenan (3) demonstrated a worse postoperative outcome in hypercapnic patients (Pa_CO2 > 45 and > 50 mm Hg, respectively) on preoperative evaluation. In Keenan's patients, the combination of preoperative hypercapnia and reduced single-breath diffusing capacity of the lungs for carbon monoxide (DL_CO) ( 25%) was 86% specific for serious postoperative complications. Using the ratio of DL_CO to alveolar ventilation (DL_CO/A) rather than DL_CO, if we apply the same cutoff values, the specificity for serious complication is 94%; however, the sensitivity of Keenan's criteria in our patients is only 5%.

Hypercapnia, however, has not always been identified as a marker of increased risk after LVRS. Argenziano and colleagues (5) evaluated high-risk patient groups characterized by severe hypercapnia (mean Pa_CO2 66.9 ± 8.8 mm Hg), steroid-dependency (mean daily prednisone use 24.1 ± 2.6 mg), severe pulmonary dysfunction (mean FEV₁ 368 ± 61 ml), and inability to complete pulmonary rehabilitation. Perioperative mortality and respiratory failure in their study was 7% and 8%, respectively; 57% of mortality was caused by progressive respiratory failure, and most patients developing complications were not associated with any of the high-risk groups.

The incidence of acute respiratory failure in our study was higher than previously reported, and physiologic variables, including hypercapnia, were not found to be good predictors of poor postoperative outcome. Patient selection and discordant definition of respiratory failure may account in part for the discrepancy between our results and previous investigations. First, acute respiratory failure was not clearly defined in the majority of the studies (1, 2, 5, 18). Second, our patient population differed from the other case series; patients with coronary artery disease and those who underwent concomitant surgical procedures were included. Except for Thurnheer and colleagues (22) other investigators excluded patients with active cardiac disease (1, 10, 19).

The duration of the surgery was the only variable that independently predicted the occurrence of respiratory failure; however, the small number of patients precluded further adjustment of the data to differentiate independent risk factors. It is likely that the presence of ischemic heart disease and performance of a concomitant surgical procedure are major contributors to the development of respiratory failure because of the strong association between duration of surgery and concomitant surgeries. Moreover, the same frequency of acute respiratory failure and higher postoperative complications have been observed in patients undergoing concomitant cardiac operations and pulmonary resection for various types of pulmonary pathology (pulmonary nodules and malignancies) (23, 24). The impact of the intraoperative events is better understood by analyzing the cause of the respiratory failure. Although postoperative respiratory failure was associated with high morbidity and mortality, patients who suffered from hemodynamic instability or developed hypoxemic respiratory failure, rather than hypercapnic respiratory failure, had the worse outcome. Five of the seven patients with hemodynamic instability and two of the five patients with severe hypoxemia died, and none of the patients who developed postoperative hypercapnic respiratory failure died. Kotloff and colleagues suggested that there is an association between postoperative respiratory failure and median sternotomy (18). In our study, even when patients who underwent concomitant procedures were excluded, we did not find such an association, and repeated analysis excluding patients with simultaneous surgeries demonstrated that only age (> 60 yr) and race (being black) were associated with the development of respiratory failure. Again, selection differences, rather than surgical approach, probably account for the discrepancy between our results and those of Kotloff, who did not describe race and comorbidities in his case series.

Our study is limited by being a single-center retrospective case series and therefore subject to inherent selection and treatment biases. However, currently there is no comprehensive data that allows one to evaluate the true risks versus benefits of combined LVRS and cardiac surgeries in patients with severe heart and lung disease. Two case reports, one combining LVRS with thoracic aortic aneurysm resection and the other with coronary artery bypass grafting and mitral valve reconstruction, suggest the feasibility of such an approach (25, 26). Our data, however, warn against the indiscriminate performance of LVRS coupled with other surgical procedures. In our patients who did not develop respiratory failure or serious postoperative complications, two of the four patients known to have coronary artery disease had coronary revascularization 1 and 4 yr before LVRS. In the study by Thurnheer and colleagues (22), three of five patients with coronary artery disease underwent coronary revascularization before LVRS, and one of these three patients died on the second postoperative day.

In summary, we have demonstrated that respiratory failure after LVRS is associated with a high mortality and extensive morbidity. We have also demonstrated that preoperative pulmonary physiologic and hemodynamic measurements do not aid in predicting postoperative respiratory failure in patients with severe emphysema undergoing LVRS. Older age, ischemic heart disease, factors related to the operative procedure, and possibly race are important determinants of respiratory failure requiring mechanical ventilation after LVRS. Our findings suggest that some patients undergoing complex cardiac surgeries requiring cardiopulmonary bypass combined with LVRS may be too high a risk to develop serious postoperative complications (respiratory failure 100%, mortality 25%). The fact that both debilitating diseases can be treated during a one-stage combined surgery is appealing, but this case series casts doubt on the benefits of this approach.