Joseph P. Mathew
1. For the anesthesiologist, lung volume reduction surgery is a challenging procedure and the tailoring of the anesthetic management requires profound knowledge of the pathophysiology of COPD, ventilatory mechanics in awake and anesthetized COPD patients and pain management in thoracic surgery. A variety of different approaches to LVRS have been proposed; these include median sternotomy, thoracosternotomy, standard thoracotomy and video-assisted thoracosopic surgery (VATS) with both unilateral and bilateral approaches.
2. Potential candidates for LVRS undergo extensive evaluation in order to mitigate perioperative risks and contain perioperative complications. Important physiologic variables when evaluating a patient are FEV1 and DLCO, the RV/TLC ratio, PCO2 and oxygen use. The ideal operative candidate should have an FEV1 of 20% to 35% predicted without very severe reductions in DLCO (<20% predicted), a RV/TLV more than 0.67, a PCO2 less than 45 mm Hg, and no or low level supplemental oxygen use.
3. Intraoperative management is centered on minimizing further insult due to induction of general anesthesia and institution of positive pressure ventilation. Ventilatory management during one-lung ventilation (OLV) aims to balance competitive priorities: maintaining adequate oxygenation, minimizing intrinsic PEEP, minimizing barotrauma and maximizing CO2 elimination.
4. Intraoperative hypotension may be due to sympathetic blockade from local anesthetics administered through the thoracic epidural catheter, vasodilatory effects of the induction agents, hypovolemia, myocardial ischemia, dynamic hyperinflation or infrequent but possible catastrophic causes such as tension pneumothorax.
5. Tracheal extubation immediately after surgery is an important aim after LVRS in order to minimize the risk of developing or exacerbating an air leak and avoid the deleterious hemodynamic effects of positive pressure ventilation. Adequate pain control achieved with minimal respiratory depression in LVRS patients is vital to the success of the surgical procedure. Inadequate pain control will result in splinting, poor respiratory effort, and inability to cough and clear secretions leading to airway closure, atelectasis, shunting and hypoxemia.
The patient is a 68-year-old male with advanced emphysema who is scheduled for lung volume reduction surgery (LVRS). He is an ex-smoker who has recently undergone preoperative pulmonary rehabilitation. He has concurrent coronary artery disease and hypertension. Medications include aspirin, valsartan and lovastatin.
Vital signs: BP 140/70, HR 72, and room air oxygen saturation 91%.
Laboratory examination is notable for blood urea nitrogen of 30 mg/dL and creatinine of 1.9 mg/dL. Pulmonary function tests reveal a FEV1 of 0.9 L (30% predicted), FVC of 3.6 L (50% predicted), TLC 7.1L (110% predicted) and DLCO 22% predicted.
Chronic obstructive pulmonary disease (COPD) is characterized by progressive and largely irreversible airflow limitation caused primarily by exposure to tobacco smoke, and less commonly by other noxious stimuli or by alpha1-antitrypsin deficiency. COPD is one of the leading causes of death and disability worldwide. It is expected that by the year 2020, COPD will become the third leading cause of death worldwide.1
The main goals of therapy in COPD patients are focused on relieving symptoms, preventing lung function decline, preventing exacerbations of the disease, and improving exercise capacity and quality of life. In spite of the advances in medical therapy, smoking cessation is the single most effective intervention shown to alter the rate of progression of COPD.2 Supplemental oxygen therapy in patients with severe COPD and hypoxemia has also been shown to have beneficial effects such as prolonged survival, improvement in cardiac function, and improved exercise tolerance.3
The failure of medical management of COPD to produce significant impact on outcomes has led to the development of lung volume reduction surgery (LVRS) in the past century. In selected patients with severe emphysema, LVRS was associated with prolonged survival, improvement in exercise capacity and quality of life, and improvement in lung function and dyspnea.4 Given the high perioperative mortality and morbidity associated with LVRS, the survival benefit depends on adequate patient selection and containment of perioperative complications associated with anesthesia and surgery.
For the anesthesiologist, lung volume reduction surgery is a challenging procedure and the tailoring of the anesthetic management requires profound knowledge of the pathophysiology of COPD, ventilatory mechanics in awake and anesthetized COPD patients and pain management in thoracic surgery. This chapter summarizes the impact of anesthesia and surgery on lung function in COPD patients, preoperative evaluation and criteria for optimal patient selection and intraoperative and postoperative anesthetic management.
PATHOPHYSIOLOGY OF COPD
The cardinal abnormality in COPD is an irreversible reduction in maximal expiratory flow due to chronic bronchitis, emphysema, or both. Chronic bronchitis is defined as cough and sputum production for most days over 3 months for 2 consecutive years. It is thought to result from the innate immune response to inhaled toxic particles and gases, particularly to tobacco smoke, which results in inflammation of the epithelium of the central airways and mucus-producing glands. The airway inflammation is associated with increased mucus production, reduced mucociliary clearance, and increased permeability of the airspace epithelial barrier.5 While hyperproduction of mucus may not have a significant impact on smokers with normal lung function, in patients with severe COPD it contributes to the further decline of airflow during expiration.
Emphysema is defined as enlargement of the airspaces distal to the terminal bronchioles due to destruction of the alveolar walls. Destruction of the normal lung parenchyma causes a reduction of the elastic recoil resulting in a progressive deterioration of the maximal expiratory airflow. Emphysema may exist in a centrilobular or a panlobular form. The centrilobular (also known as centriacinar) form results from dilatation or destruction of the respiratory bronchioles, is more closely associated with tobacco smoking and has predominantly an upper lobe distribution.6 The panlobular (also known as panacinar) form, results in more even dilatation and destruction of the entire acinus, is associated with alpha1-antitrypsin deficiency and has predominantly a lower lobe distribution (Figures 15–1, 15–2, 15–3).
Figure 15–1. A chest radiograph of a patient with diffuse severe emphysema.
Figure 15–2. A chest radiograph of a patient with severe emphysema and upper lobe predominance.
Figure 15–3. A computed tomograph of a patient with pan-lobular emphysema left greater than right.
On pulmonary function testing, the expiratory airflow limitation is first identified as a reduction in the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC). The diagnosis of COPD as established by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) requires an FEV1/FVC ratio of less than 0.7. Patients are then stratified into four categories from mild to very severe disease based on the severity of FEV1 impairment7 (Table 15–1).
Table 15–1. Physiologic Classification of the Severity of Chronic Obstructive Pulmonary Disease*
Expiratory airflow limitation results in air trapping and hyperinflation with increases in total lung capacity (TLC) and residual volume (RV), and an elevated RV/TLC ratio. As the disease progresses and the recoil of the lungs becomes diminished, the functional residual capacity (FRC) moves rightwards toward the flat portion of the compliance curve of the lungs, to the detriment of pulmonary mechanics. Therefore, the patient with hyperinflation has difficulty with inspiration because the respiratory system moves on a relatively flat portion of its compliance curve and consequently there is increased elastic work of breathing. As COPD progresses, static hyperinflation gets progressively worse, and the operational lung volumes increase toward a threshold that may even result in resting dyspnea.8 Further elevation in operational lung volumes, superimposed on static hyperinflation occurs during exercise when ventilatory requirements are increased. Due to airflow obstruction and shortened expiratory time during exercise, expiration cannot be completed and inhalation is triggered due to the urge to inspire before FRC is reached. This respiratory pattern leads to “stacking” of breaths and a gradual hyperinflation of the lungs, known as dynamic hyperinflation. Similar exacerbations of hyperinflation occur with increased respiratory rate associated with anxiety and hypoxemia.
The loss of acinar structure and disruption of the alveolar-capillary structure lead to ventilation-perfusion (V/Q) mismatch and impairment of gas exchange. Also, as the hyperinflation develops nonuniformly, the normal parenchyma may become compressed and underexpanded, causing a further increase in the V/Q mismatch. Due to the higher diffusability of carbon dioxide (CO2), the CO2elimination is well-preserved until V/Q abnormalities are severe. As the disease advances, there is an increase in physiologic dead-space secondary to under-perfused alveoli, and the subsequent impairment of CO2 clearance results in hypercapnic respiratory failure. Also, air trapping and hyperinflation place the diaphragm and other inspiratory muscles at severe mechanical disadvantage, producing alveolar hypoventilation and contributing to hypercapnia. Chronic CO2 retention occurs slowly and a compensated respiratory acidosis is noted on arterial blood gas analysis. Acute CO2 retention, however, is a sign of impending respiratory failure and occurs with superimposed respiratory infection and bronchospasm.
Pulmonary hypertension is a frequent complication in the natural history of COPD. It progresses over time and its severity correlates with the degree of airflow obstruction and the impairment of pulmonary gas exchange. However, the rate of progression is slow and the degree of pulmonary hypertension in COPD is of low-to-moderate magnitude, rarely exceeding 35 to 40 mm Hg9 of mean pulmonary artery pressure. Usually right ventricular function is mildly impaired with preservation of cardiac output. Acute exacerbations in right ventricular afterload in the settings of hypoxia, hypercapnia, or compression of intraalveolar vessels due to dynamic hyperinflation may result in right ventricular failure. Elevated mean alveolar pressure associated with dynamic hyperinflation may compress intra-alveolar vessels, increasing pulmonary vascular resistances and right ventricular output impedance. With progressive right ventricular dysfunction, left shifting of the interventricular septum can impair cardiac output further due to ventricular interdependence.10 Patients with severe COPD and pulmonary hypertension show structural and functional changes in pulmonary muscular arteries and precapillary vessels that explain the irreversible increase of pulmonary vascular resistance. Long-term oxygen therapy may slow down the progression of pulmonary hypertension, however, pulmonary artery pressures rarely return to normal and the structural abnormalities of the pulmonary vessels remain unaltered.9
COPD is also associated with high rates of other comorbid illnesses such as cardiovascular disease, malnutrition, peripheral muscle weakness and osteoporosis. Cardiovascular disease is a major cause of death in patients with COPD. There are several reasons for the association between COPD and cardiovascular disease including a major shared risk factor (smoking), use of beta-agonist medications that may stimulate the cardiovascular system, and systemic inflammation.11,12 Enhanced systemic inflammation may also explain nonpulmonary COPD characteristics such as skeletal muscle dysfunction, cachexia, and malnutrition.8
SURGICAL TECHNIQUES FOR LUNG VOLUME REDUCTION SURGERY
Brantigan developed the concept of LVRS in the 1950s when he described resection of 30% of the hyperinflated lung and autonomic denervation through thoracotomy in an attempt to improve expiratory flow.13 LVRS was not performed widely as it was associated with a very high surgical mortality at that time. In 1995, Cooper and colleagues reported dramatic improvements in pulmonary function and no mortality in 20 patients undergoing simultaneous bilateral LVRS using a median sternotomy with resection of 30% of each lung.14
A variety of different approaches to LVRS have been proposed; these include median sternotomy, thoracosternotomy, standard thoracotomy, and video-assisted thoracosopic surgery (VATS) with both unilateral and bilateral approaches (Figure 15–4). The areas for surgical removal are identified before surgery by computed tomography and radionuclide ventilation-perfusion scanning. Methods for sealing the site of resected lung include the use of staples or laser (neodymium-yttrium aluminum garnet or Nd-YAG).15
Figure 15–4. A chest radiograph (A) and computed tomograph (B) of a patient with a left giant bulla for unilateral lung reduction.
MEDIAN STERNOTOMY VS VATS
Questions regarding the high perioperative mortality in LVRS patients shown in an analysis of the Medicare claims data (23% at 1 year)16 and the cost effectiveness and high rehospitalization rates associated with LVRS led to the funding of the National Emphysema Treatment Trial (NETT), the largest randomized trial of LVRS performed to date. The NETT was designed to compare short- and long-term outcomes of best medical therapy for emphysema with best medical therapy plus LVRS. It also included randomized and nonrandomized comparisons of the median sternotomy and VATS for LVRS. This subanalysis showed that functional results as well as morbidity and mortality were comparable for LVRS by VATS or median sternotomy. The VATS approach, however, allowed earlier recovery at a lower cost than median sternotomy.17 Most studies comparing median sternotomy and VATS have yielded conflicting results. Wisser et al compared median sternotomy versus bilateral VATS in a sequential, nonrandomized study and showed similar postoperative morbidity and mortality and no difference in functional and physiologic results.18 In contrast, Roberts et al compared the complications associated with bilateral LVRS through VATS or median sternotomy. They found that although the operating time was greater for the VATS group, the median sternotomy group had a higher incidence of life-threatening complications, longer stay in the intensive care unit, ventilator days, and percent requiring reintubation.19 In a study predating the NETT, Kotloff et al compared the short-term outcomes following bilateral LVRS performed through median sternotomy (80 patients) and VATS (40 patients). All patients in both groups were extubated at the completion of surgery, but 17.5% of patients in the median sternotomy group and 2.5% in the VATS group subsequently required reintubation at some point during the postoperative course. There was no significant difference in duration of air leaks or length of hospital stay and the functional outcomes achieved with either technique were similar. Thirty-day operative mortality was 4.2% for the median sternotomy group and 2.5% for the VATS group. However, total in-hospital mortality was 13.8% for the median sternotomy group, while it remained 2.5% for the VATS group.20
UNILATERAL VS BILATERAL
Bilateral VATS for lung volume reduction is preferred over the unilateral approach. Multiple studies have shown that the bilateral procedure produces greater overall improvement than a unilateral procedure.21,22 McKenna et al compared unilateral and bilateral VATS procedures and showed that the bilateral procedure provided greater oxygen independence (68% vs 35%), prednisone independence (86% vs 56%), greater improvement in the FEV1 and an improvement in the perceived degree of dyspnea than the unilateral procedure with comparable mortality and morbidity.22 However, given the improvement associated with unilateral surgery, unilateral operation may still be offered in some patients who are not candidates for a bilateral operation due to prior thoracic intervention or inappropriate anatomy for bilateral LVR. Similar functional outcome with sustained improvement of FEV1, 6-minute walk test and gas exchange was shown in other studies.23,24 The excellent results seen in the postoperative period with the use of bilateral LVRS may not lead to improved long-term survival. A large multi-institutional retrospective study comparing long-term survival in patients undergoing either bilateral or unilateral thoracoscopic lung volume reduction found that there was no significant difference between the two groups in regard to operative mortality or late death at 1 year, 2 years, or 3 years.25
STAPLES VS LASER
McKenna et al also showed in a prospective blindly randomized study that patients in whom lung volume reduction surgery is done with staples and buttressing with bovine pericardium have a lower morbidity (fewer delayed pneumothoraces), as well as greater improvement in oxygen independence, lung function, and overall lifestyle and dyspnea scale, than patients treated with contact laser (Nd-YAG).26
Usually, after induction of anesthesia and intubation, the patient is positioned supine with the arms supported above the head utilizing an ether screen. This position offers satisfactory exposure not only for VATS but median sternotomy, as well as anterior/lateral thoracotomy on both sides.27 For the VATS approach three ports are used on each side, two in the submammary crease and one axillary port. A horseshoe-shaped specimen is removed from the superior portion of the lung avoiding direct tissue handling in order to prevent damage to friable lung tissue with its attendant risk of postoperative air leak.27
Mechanisms for Improvement in Respiratory Function after LVRS
The possible mechanisms by which LVRS might provide benefit are not known with certainty. Numerous studies are now available regarding the short-term results of LVRS on pulmonary function, however the results are sometimes conflicting and cover a large range of reported values due to difference in study design, patient selection, surgical technique, presence or absence of pulmonary rehabilitation or pulmonary bronchodilator administration at the time of measurement.
As mentioned above, LVRS results in marked improvement in several parameters characterizing lung function. An overview of the results available in the literature shows that in the majority of patients, LVRS leads to an improvement of FEV1 accompanied by an increase in the FVC. Moreover, there is a decrease in total lung capacity (TLC) and residual volume (RV).20,22-24,26,28-31 The improvement in FEV1 is possibly due to an improvement in elastic recoil, a reduction in expiratory flow limitation and a decrease in dynamic hyperinflation shown by many investigators.29,32,33 Resection of the emphysematous, nonfunctional lung tissue should also allow the healthier lung tissue to expand and improve expiratory flow by reducing lung compliance, premature airway closure and end-expiratory volume.34 However, despite improvements in FEV1, postoperative changes in the FEV1/FVC ratio are very small or absent, suggesting that FEV1 increases not only because of an improvement of the expiratory flow but also because of the increase in FVC.34
The reports on the changes in resting arterial blood gases are less consistent, ranging from improvements in arterial partial pressure of oxygen (PaO2) and decreases in arterial partial pressure of carbon dioxide (PaCO2) to little change28 or even worsening of these parameters.35 While some studies link the change in oxygenation to an increase in mean alveolar ventilation,31,36 other studies suggest that the improved oxygenation is due to a reduction in ventilation-perfusion heterogeneity.35 In a follow-up study on a large cohort of subjects enrolled in the NETT, LVRS was found to increase PaO2 and decrease self-reported oxygen use at rest and on exertion.37 Few studies have reported the impact of LVRS on lung diffusing capacity for carbon monoxide (DLCO), however the improvement in DLCO shown appears to be modest.30,38
Emphysema leads to an increase in the lung volume at which the respiratory muscles operate, which reduces their mechanical effectiveness and leads to diminished inspiratory muscle force. Due to hyperinflation, muscle fibers have shortened inspiratory muscle pre-contraction length, which diminishes the pressure generated at a given level of tension.34 Also in patients with chronic inflation, the zone of diaphragmatic apposition, which is the area of the diaphragm immediately apposed to the ribcage, is markedly reduced32 potentially reducing the ability of the diaphragm to generate adequate inspiratory volume change. Numerous studies have shown an improvement in the respiratory muscle strength and interaction after LVRS as shown in an increase of the diaphragm length,39 increase in the maximal transdiaphragmatic pressures,39,40 reduction in maximal inspiratory pressure and reduction in dyspnea.40
The reported changes in pulmonary vascular function after LVRS are inconsistent, with some studies showing no change or improvement in pulmonary artery pressures and right ventricular function, and others showing worsening of pulmonary hypertension.33,41,42 These controversial results are due to possible opposing effects of LVRS on the pulmonary vascular function. Resection of perfused lung can increase the already impaired pulmonary vascular resistance while on the other hand a decrease in vascular resistance might occur through recruitment of vessels in the reexpanding lung tissue or through improvement in elastic recoil, which may increase radial traction on extra-alveolar vessels.43
The multiple effects of lung volume reduction surgery are summarized in Table 15–2.
Table 15–2. Physiological Effects of Lung Volume Reduction Surgery
Outcome and Complications
LVRS is associated with higher but acceptable mortality and morbidity than other general thoracic surgical procedures. Awareness and understanding of the potential complications associated with LVRS are some of the keys to minimizing their occurrence.44 Mortality rates associated with LVRS reported in the literature range from 2.5% to 13%.18,25,31,45 The 90-day mortality rate for LVRS in the NETT for the surgical group overall was 7.9%, much less than the mortality rate reported by Medicare.
Pulmonary complications are the most frequent after LVRS. Pneumonia occurs in about 7% to 14% of the patients. Respiratory failure requiring reintubation occurs in 5% to 10% of the patients, and if postoperative reintubation occurs, more than half of the patients will fail to wean from the ventilator.44 However, the most common complication after LVRS is prolonged air leak, defined here as an air leak that lasts at least 7 days following the procedure. This complication occurs in approximately 40% to 60% of patients and is associated with a more protracted and prolonged hospital stay. There does not seem to be any significant difference in the incidence of air leak after VATS and median sternotomy procedures.44 Within the NETT, an air leak occurred at some point in 90% of bilateral LVRS patients; the median duration of an air leak was 7 days, and 12% had a persistent air leak even 30 days postoperatively.46 Risk factors for post-LVRS air leak include Caucasian race, lower FEV1 or diffusion capacity, use of inhaled steroids, upper-lobe predominant emphysema and presence of moderate to marked pleural adhesions. Factors such as surgical approach or use of buttressing material at the staple line did not affect the presence or duration of air leak46 (Figure 15–5).
Figure 15–5. A patient with pneumonia and subcutaneous emphysema due to a postsurgical air leak after unilateral lung reduction.
Cardiac complications are the second most common cause of perioperative morbidity and mortality after lung resection surgery. Major cardiac morbidity, defined as intraoperative or postoperative arrhythmia requiring treatment, myocardial infarction or pulmonary embolus in the 30 days after lung volume reduction surgery, had an incidence of 20% in the NETT.47 The most common cardiac complication is arrhythmia-requiring treatment. Atrial arrhythmias can occur in up to 20% of the patients and are associated with fluid overload, atelectasis and hypoxia.44
Bronchoscopic Lung Volume Reduction
Given the potential benefit of LVRS on quality of life, survival and exercise capacity in selected patients with heterogeneous emphysema, several minimally invasive techniques have emerged in order to achieve lung volume reduction without open thoracotomy. Bronchoscopic lung volume reduction (BLVR) allows clinicians to collapse areas of severe emphysema. Several BLVR systems have emerged and are currently under clinical trials. Endobronchial one-way valve systems are deployed into segmental or subsegmental bronchi of emphysematous, hyperinflated lung. They are designed to prevent inspiratory airflow but to allow air and secretions to move from the alveoli to the central airways, therefore resulting in progressive deflation and collapse of the lung distal to the valve.48,49 Complications include migration of the device, hemoptysis, pneumothorax, postobstructive pneumonia, and failure of the lung to collapse due to collateral ventilation.
The Endobronchial Valve for Emphysema Palliation Trial (VENT) is the first prospective randomized multicenter trial to evaluate endobronchial valves. The preliminary results showed that the procedure has an acceptable safety profile.34 The study showed that endobronchial-valve treatment induced modest improvements in lung function, exercise tolerance, and symptoms at the cost of more frequent exacerbations of COPD, pneumonia, and hemoptysis after implantation.50
The Exhale Airway Stents for Emphysema (EASE) trial, a double-blinded, randomized, sham-controlled device study for patients with emphysema/COPD was designed to evaluate the safety and effectiveness of the Airway Bypass procedure with Exhale Drug-Eluting Stents. The prospectively defined clinical endpoints of the trial were FVC and the modified Medical Research Council (mMRC) dyspnea score, a measure of the impact of breathlessness on quality of life. Early results showed statistically significant improvement only in mMRC dyspnea score.51
Fibrin-based glue, with subsequent collapse and remodeling of emphysematous lung, can also achieve occlusion of airways. In an open-label, phase II study of 50 patients with advanced upper lobe emphysema, a fibrinogen-thrombin hydrogel was administered to eight subsegmental sites (four in each upper lobe). Significant improvement was noted in the primary outcome, residual volume to total lung capacity ratio (RV/TLC), and also in secondary outcomes such as improvement in FEV1, symptom scores, and health-related quality of life.52
PREOPERATIVE ASSESSMENT AND PATIENT SELECTION
Potential candidates for LVRS undergo extensive evaluation in order to mitigate perioperative risks and contain perioperative complications. The patient selection criteria are rigorous, involving both functional and radiological assessment with the goals of identifying the patients that are most likely to benefit from the procedure with an acceptable risk, optimizing medical status and customizingperioperative risk reduction strategies. The criteria for lung resection in patients with emphysema have developed over time. Before the NETT there was a high variability in the reported results due to differences in patient population, study design, surgical technique and perioperative management. The NETT, a multi-institutional randomized study sponsored jointly by the National heart, Lung and Blood Institute and the Center for Medicare and Medicaid Services, provided reliable estimates of risk and benefit from LVRS and established criteria selection for patients who will benefit most from lung volume reduction.
The clinical evaluation of the patients should be focused on identifying the clinical manifestations of the lung disease, presence of comorbid conditions, active cigarette smoking, corticosteroid use, and nutritional status. Medical contraindications include any conditions that increase the perioperative risk or predict a short-life expectancy due to non-emphysema illnesses. Advanced age has also been suggested as a risk factor for an unacceptable outcome.30,53 Previous studies of the LVRS population showed that patients aged 70 years or older are at risk for an increased perioperative morbidity and mortality53 or for less postoperative improvement in lung function.54 Although the NETT did not identify age as a prognostic factor for operative mortality, patients with advanced age were at higher risk for major pulmonary morbidity and cardiovascular complications.47
Based on mechanisms of lung function improvement after LVRS, it is expected that the patients that benefit most have clinical manifestations of lung disease consistent with parenchymal destruction typical for emphysema with mild or minimal airway disease. Therefore, a history of recurrent bronchial infection with clinically significant daily sputum production might identify patients with primarily intrinsic disease who would not benefit from lung volume reduction. Prior thoracic surgery, which might lead to the formation of pleural adhesions and pleural or interstitial disease, are viewed as exclusion criteria for LVRS.
Careful assessment for cardiac disease before selection for surgery is also necessary as LVRS carries a significant risk of cardiac stress and intraoperative myocar-dial infarctions have been reported.55,56Coronary artery disease (CAD) is frequent among patients with COPD, as the two diseases share cigarette smoking as a common risk factor and a high prevalence of CAD has been shown angiographically in the LVRS patient population.57 The evaluation of patients with advanced emphysema for the presence and extent of coronary artery disease presents a clinical challenge, as these patients may have poor functional capacity due to the underlying lung disease. However, keeping in mind that elective pulmonary resection surgery is deemed an “intermediate risk” procedure by the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on perioperative cardiovascular examination for noncardiac surgery,58 the medical consultant needs to assess the functional status, severity, and stability of cardiac symptoms in a patient who has CAD or heart failure and proceed with noninvasive testing whenever indicated. Patients who have evidence of significant ischemia on noninvasive testing usually undergo coronary angiography; those who have left main or triple-vessel disease are potential candidates for surgical revascularization, whereas those who have single-or double-vessel disease may undergo PCI with or without stenting or be managed medically. Successful LVRS and coronary artery bypass grafting or LVRS and valve replacement have been performed with improvements in pulmonary function similar to those reported after isolated LVRS procedures.59-62 A recent myocardial infarction (within the past 30 days) represents a major risk factor for perioperative risk complications. Although in the past it was believed that elective surgery should be delayed for 6 months after a myocardial infarction based on Goldman’s original risk index, the ACC/AHA guidelines have decreased this interval to 4 to 6 weeks for a medically stable, fully investigated and optimized patient.58,63
Another issue with potential perioperative implications is pulmonary hypertension. The degree of pulmonary hypertension in COPD is usually of low to moderate magnitude, with mean pulmonary artery pressures rarely exceeding 35 to 40 mm Hg,9 and although right ventricular function is generally preserved, multiple perioperative clinical scenarios (hypoxia, hypercapnia, dynamic hyperinflation) can lead to right ventricular failure. It is accepted that a peak systolic pulmonary artery pressure more than 45 mm Hg or mean pulmonary artery pressure more than 35 mm Hg is a relative contraindication to LVRS.64 As echocardiography is frequently inaccurate in patients with advanced lung disease and tends to considerably overestimate the degree of pulmonary hypertension65 a right heart catheterization is sometimes required in order to rule out significant pulmonary hypertension.
As smoking cessation has a significant positive impact on the rate of decline of FEV1, wound healing and postoperative recovery, candidates for LVRS should be nonsmokers for at least 6 months prior to surgery.66,67 Patients dependent on high-dose corticosteroids therapy may be at risk for delayed wound healing, prolonged postoperative leaks and infectious complications. Also, these patients may have an important coexisting intrinsic inflammatory airway disease component contributing to their airflow obstruction and therefore may not benefit significantly from LVRS. A daily prednisone dose of more than 20 mg (or equivalent) was one of the exclusion criteria in the NETT.34 Nutritional status in patients with advanced emphysema is of great concern. Approximately 50% of patients undergoing LVRS for emphysema have a deficient nutritional status identifiable by a low BMI, which is associated with increased postoperative morbidity.68,69 Although patients with advanced emphysema are rarely overweight, obesity also confers a higher postoperative risk of mortality and morbidity; a BMI greater than 31.1 kg/m2 in men and 32.3 kg/m2 in women was one of the exclusion criteria in the NETT.34
Assessment of the risk for postoperative pulmonary complications is crucial to evaluating the patient with advanced emphysema being considered for LVRS; therefore the selection criteria rely on pulmonary function tests. As shown in the NETT subgroup analysis one of the predictors of major pulmonary morbidity was percent-predicted FEV1. The criteria vary from series to series, but the majority of the investigators agree patients with an FEV1 higher than 35% to 45% predicted are not surgical candidates. A higher postbronchodilator FEV1 would not justify the risks associated with LVRS. Before the NETT, there was no consensus regarding the lower acceptable limit for FEV1. The NETT defined a group of patients with severe emphysema who should not have surgery because of an exceptionally high risk for death after LVRS with little chance of functional benefit. This group of patients had an FEV1 less than 20% of the predicted value and either homogenous (diffuse) emphysema on chest computed tomography (CT) or a DLCO less than 20% of predicted. The 30-day mortality in this subgroup of NETT patients was 16%, while 30-day mortality in patients with all three high-risk characteristics reached 25%. Based on this data obtained during interim analysis, the NETT investigators ceased the enrollment of patients with low FEV1 who had either homogenous emphysema on the chest CT scan or a low carbon monoxide diffusing capacity.70
In the analysis of risk factors for operative morbidity and mortality in the NETT patients not considered to be high risk, FEV1 and DLCO together with age were found to be risk factors for major pulmonary morbidity, defined as tracheostomy, failure to wean from mechanical ventilation, reintubation, pneumonia, and mechanical ventilation for 3 days or more. Other investigators have also suggested that a low DLCO increases the risk of mortality and morbidity with the lower limit varying from 10%71 to 30%.72 Another respiratory parameter investigated is the RV/TLC ratio. Analysis of a physiologic model proposed by Fessler and Permutt suggested that an increase in RV/TLC might be the best predictor of improvement in expiratory flow rates after LVRS. In this model the greatest impact of LVRS results from the relatively greater reduction in RV than in TLC with a consequent increase in vital capacity (VC) and an appropriate resizing of the lungs to the chest cavity.73 A study of LVRS patients based on this physiologic model using multi-variate logistic regression identified the RV/TLC ratio as the only preoperative predictor of improvement in FVC and FEV1. In these patients, 68% of the change in FEV1 was attributed to change in FVC. The patients with RV/TLC >0.67 had significantly greater absolute and percent improvements in FEV1 and FVC and a significantly greater decrease in residual volume (RV).74 Although post-rehabilitation postbronchodilator TLC more than 100% predicted and RV less than 150% predicted were part of the inclusion criteria, the NETT did not identify lung volume as a predictor of mortality or cardiopulmonary morbidity after LVRS.47
Arterial blood gas abnormalities have also been suggested as predictive of a bad outcome with significant controversies surrounding this issue. Data regarding oxygenation are contradictory. Although McKenna et al showed no association between preoperative room air blood gas PaO2 and postoperative change in FEV1 or dyspnea score, they reported significantly worse outcome for patients using 4 L of supplemental oxygen at rest before the operation.54 The NETT excluded patients with oxygen requirement greater than 6 L/min to maintain oxygen saturation more than 90% during exercise.70
As patients with COPD have varying degrees of hypercapnia, the data regarding the prognostic value of preoperative PaCO2 on perioperative mortality and morbidity are conflicting. Many investigators have proposed excluding patients with hypercapnia from surgical treatment due to an unacceptable postoperative outcome. Szekely et al found a PaCO2 greater than 45 mm Hg as a strong predictor of mortality within 6 months and prolonged hospital stay.75 Other investigators consider a PaCO2 greater than 50 mm Hg20,76 or 55 mm Hg71 associated with adverse outcomes. Other studies have shown similar outcomes in patients with hypercapnia (PaCO2 >45 to 55 mm Hg) when compared with patients with normocapnia.77,78 The NETT data did not reveal hypercapnia to be a predictor of worse outcome, however patients with a PaCO2 greater than 60 mm Hg (55 mm Hg in Denver) were excluded from the trial, by trial design.47
The NETT investigators did not identify poor exercise tolerance as a predictor of operative mortality or cardiopulmonary morbidity, however the investigators required a postrehabilitation 6-minute-walk distance of over 140 m as a measure of functional status.47
In summary, important physiologic variables when evaluating a patient for LVRS are FEV1 and DLCO, the RV/TLC ratio, PCO2 and oxygen use. The ideal operative candidate should have an FEV1 of 20% to 35% predicted without very severe reductions in DLCO (<20% predicted), a RV/TLV more than 0.67, a PCO2 less than 45 mm Hg, and no or low level supplemental oxygen use.
High-resolution computer tomography (HRCT) is a powerful tool for evaluation of pulmonary emphysema and has become the radiographic study of choice in evaluation potential LVRS patients. CT permits quantitative analysis of the severity of pulmonary emphysema and allows judgment of the heterogeneity of the disease. The NETT has established thoracic imaging as a crucially important tool in the evaluation of patients considered for LVRS. In the NETT, the magnitude and distribution of the emphysema in the participating patients was classified by HRCT as predominantly upper-lobe or non-upper-lobe using a visual scoring scale according to the study protocol.79
As mentioned in the section above, an initial report, based on interim analysis of the mortality data by the Data and Safety Monitoring Board, identified an increased risk of surgical mortality in patients with severe obstruction (FEV1 ≤ 20% predicted) and either diffuse emphysema on HRCT or a DLCO less than or equal to 20% predicted79 and ceased enrollment of patients with these characteristics.
In the analysis of patients not at high-risk during a mean follow-up period of 29 months, the only individual base-line factors associated with differences in mortality between the treatment groups were the craniocaudal distribution of emphysema (presence or absence of upper-lobe predominance) and baseline exercise capacity (low or high, with the cutoff point for defining low baseline exercise capacity at the 40th percentile, ie, 25 Watts for women and 40 Watts for men).70 When patients were divided into four subgroups on the basis of combinations of upper-lobe or non-upper-lobe emphysema and low or high exercise capacity at base line, there was strong evidence of differential effects on the primary endpoints of the NETT (ie, survival and exercise capacity at 24 months). The patients with upper-lobe disease and low baseline exercise capacity had the most survival advantage and improvement in exercise capacity from LVRS. LVRS did not show any survival advantage when compared with medical therapy in patients with upper-lobe disease and high baseline exercise capacity and in patients with non-upper-lobe disease and low baseline exercise capacity, but there was difference in the functional outcome. LVRS resulted in improved exercise capacity and health related quality of life in the patients with upper-lobe predominant disease and high-exercise capacity. In the patients with non-upper-lobe disease and low exercise capacity LVRS resulted only in improvement in the health-related quality of life. Patients who had non-upper-lobe predominant disease and high exercise capacity and underwent LVRS had a higher risk of death than those in the medical therapy group and there was difference in the improvement in the exercise capacity or health-related quality of life compared with the medical group70,80 (Figure 15–6).
Figure 15–6. Kaplan-Meier estimates of the probability of death as a function of the number of months after randomization in the National Emphysema Treatment Trial (NETT). The study found no overall survival benefit of surgery over medical therapy, and a higher risk of death with surgery in high-risk patients and in patients with non-upper lobe disease and high exercise tolerance. (From: National Emphysema Treatment Trial Research Group. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348(21):2059-2073, with permission. © 2003 Massachusetts Medical Society. All rights reserved.)
A follow-up study sought to identify preoperative predictors of operative mortality, pulmonary and cardiovascular morbidity by using univariate and multivariate logistic regression and found that non-upper-lobe predominant emphysema was a predictor of both operative mortality and cardiovascular morbidity.47 Extended follow-up of the patients to a median period of 4.3 years compared the differences in survival, exercise capacity, and health-related quality of life between those patients undergoing LVRS and those receiving optimal medical therapy.4 A survival advantage was noted in the entire surgical group with 0.11 deaths per person-year compared with the medical group in which there were 0.13 deaths per person-year, despite the expected higher earlier postoperative mortality in the LVRS group. Improvement was also more likely in the LVRS than in the medical group for maximal exercise through 3 years and for health-related quality of life through 4 years.4 In subgroup analysis, the additional follow-up data also confirmed the beneficial effects of LVRS in patients with upper-lobe-predominant emphysema and low post-rehabilitation exercise capacity. After LVRS, this subgroup of patients demonstrated improved survival and exercise throughout 3 years, and health-related quality of life through 5 years. Upper-lobe predominant and high-exercise capacity LVRS patients obtained no survival advantage but were likely to have significant and sustained improvements in exercise capacity and disease-specific quality of life. At 3 years there was no benefit with regard to survival, quality of life, or exercise capacity in the patients with non-upper-lobe emphysema and either high or low exercise capacity.
A summary of the criteria for determination of candidacy for lung volume reduction surgery is presented in Table 15–3.
Table 15–3. Criteria for Determination of Candidacy for Lung Volume Reduction Surgery
Even the ideal candidate for LVRS has a substantial risk for mortality and morbidity after undergoing this elective surgical procedure. Therefore, meticulous perioperative management is paramount, starting with the preoperative preparation of the patient. Pulmonary rehabilitation attempts to optimize functional status and to improve physical and psychological symptoms, and plays a critical role in preparing selected patients for LVRS. In the patients enrolled in the NETT who underwent 6 to 10 weeks of pulmonary rehabilitation pre-randomization, significant improvements in exercise capacity, dyspnea, and health-related quality of life were observed consistently.81
Cigarette smoking has a wide range of effects on pulmonary, cardiovascular and immune functions, wound healing, hemostasis, drug metabolism, and mental status, all of which may impact postoperative outcome.82,83 Also, smoking cessation is the only long-term intervention that has been shown to slow the rate of decline in lung function.2 Thus, patients considered candidates for LVRS should be nonsmokers for 6 months prior to surgery.66
A large proportion of patients with COPD may have partially reversible airways disease and maximal medical therapy with long-acting bronchodilators and mucolytics should be continued, including on the day of the surgery. COPD exacerbations should be treated aggressively and surgery should be delayed at least 4 to 6 weeks after resolution of the exacerbation to allow stabilization.66 The patients must be free of respiratory infections for at least 3 weeks before lung volume reduction surgery and must require no antibiotic therapy preoperatively.84 Despite clear evidence that systemic steroids are indicated only for short courses during COPD exacerbations,85 the reported use of systemic steroids in stable patients with moderate and severe COPD is high.86 However, systemic steroids have been linked to possible increased risks for perioperative delayed wound healing and infectious complications and the NETT investigators found that systemic corticosteroid use increased postoperative cardiovascular morbidity.47 Therefore, systemic corticosteroids should be weaned off or decreased to the lowest possible tolerated dosage before surgery.
As anxiety is associated with tachypnea, dynamic hyperinflation and dyspnea, psychological preparation plays a crucial role in optimizing the overall preoperative status of the patient. Judicious anxiolytic therapy may be necessary in the perioperative period.
Important advancements in monitoring, anesthetic agents, perioperative pain management, and in understanding of the physiological responses to surgical and anesthetic insults, has provided the anesthesiologist with a clinical armamentarium which allows implementing medical interventions aimed to improve postoperative outcome. More important than the specific agents and techniques used is devising an anesthetic plan tailored to the specific needs and goals of every patient.
Adverse Effects of Anesthesia on Respiratory Function
General anesthesia has multiple adverse effects on respiratory mechanics and blood gas exchange irrespective of the anesthetic agent used or whether the patient is breathing spontaneously or is being mechanically ventilated.87 By changing the body position from upright to supine in an average healthy subject there is a decrease in the FRC by 0.8 to 1.0 L, with a further decrease by 0.4 to 0.5 L after induction of anesthesia. The decrease seems to be related to loss of respiratory muscle tone, shifting the balance between the elastic recoil force of the lung and the outward forces of the chest wall to a lower chest and lung volume.87 Compliance of the respiratory system is also decreased during general anesthesia (from 95 to 60 mL/cm H2O) mostly due to a decrease in the lung compliance.
Atelectasis appears in around 90% of patients who are anesthetized irrespective of the type of surgery. It occurs both during spontaneous breathing and after muscle paralysis, regardless of whether intravenous or inhalational anesthetics are used and involves up to 15% to 20% of the lung, mostly in the dependent areas. In addition to atelectasis, intermittent airway closure may reduce ventilation in the dependent areas of the lungs, resulting in worsening of the V/Q mismatch with increased number of low V/Q units. A three-compartment lung model can thus be constructed to explain oxygenation impairment during anesthesia. The model consists of one compartment with normal ventilation and perfusion, one with airway closure that impedes ventilation, and one of collapsed lung with no ventilation at all resulting in increased intrapulmonary shunt.87 The alveolar-arterial oxygen gradient (pA-aO2) increases during general anesthesia, irrespective of the type of anesthetic agent and mode of ventilation (spontaneous or mechanically ventilated)82 probably as a result of atelectasis, a greater V/Q mismatch, and attenuation of the hypoxic pulmonary vasoconstriction response. Ventilation of the lungs with pure oxygen might worsen the pA-aO2 by promoting atelectasis through alveolar collapse in the low V/Q units.
Patients with COPD with already impaired gas exchange in the awake state experience further worsening of gas exchange during anesthesia. The mechanisms of gas exchange impairment may be different than in patients with healthy lungs. Patients with COPD develop minimal or no atelectasis during anesthesia, experience only a minor decrease in FRC and a small shunt. There is, however, a large dispersion of V/Q ratios with a further increase in V/Q mismatch and a widened perfusion distribution.88 The preservation of FRC during anesthesia in patients with COPD might be explained by the chronic airflow obstruction, which leads to air trapping, intrinsic PEEP and loss of lung elastic recoil, and increased stiffness of the chest wall.82 Carbon dioxide elimination might also be impaired during anesthesia due to increased distribution of ventilation to areas of the lungs with high V/Q ratio.
General anesthetic agents modulate respiratory function though various mechanisms: impaired respiratory drive, decreased muscular tone, and impaired mucociliary clearance at the level of the airways and attenuation of the hypoxic pulmonary vasoconstriction (HPV) reflex. All inhalational agents, opioids, and most intravenous anesthetic agents attenuate hypoxic and hypercapnic ventilatory reflexes in a dose-dependent manner. This effect might be more pronounced and prolonged in patients with COPD.10 Inhibition of HPV by inhalational anesthesia is well-recognized. Halothane and nitrous oxide clearly inhibit HPV in a dose-dependent manner;89 however, the newer inhalation anesthetics isoflurane, desflurane, and sevoflurane appear to be neutral toward HPV or at least not cause a significant depression in clinically relevant doses. None of the intravenous anesthetic agents interfere with the HPV response and intravenous anesthesia with propofol has been proposed as means of avoiding HPV modulation, although research published in the last decade has been controversial.90-92 Other factors such as surgical manipulation, cardiac output, increased pulmonary artery pressure from elevated airway pressure, hypoxia, hypercarbia, heart failure, or preexisting lung disease may overcome HPV and have a greater influence on intrapulmonary shunt.
Prolonged exposure to general anesthesia may alter the immune defenses and gas exchange by depressing the alveolar macrophage function, interfering with surfactant production, slowing of mucociliary clearance and increasing the permeability of the alveolar capillary barrier.82
Intra-thoracic procedures produce marked alteration in respiratory function leading to a restrictive pattern of breathing which gradually improves in 4 to 10 days postoperatively. This pulmonary restrictive syndrome is characterized by reduction in lung volumes and alteration in the mechanics of the chest wall and diaphragm. Postoperative atelectasis, increased airway resistance due to low lung volumes, accumulated secretions and bronchospasm, diaphragmatic dysfunction, and respiratory muscle injury may all contribute to increased work of breathing in the postoperative period.82
A summary of the effects of anesthesia on respiratory function is presented in Table 15–4.
Table 15–4. Effects of Anesthesia on Respiratory Function
Induction and Maintenance of General Anesthesia
Most anesthesia practitioners avoid sedative premedication in order to avoid respiratory depression in this already critically compromised group of patients and prolongation of emergence at the end of the procedure. However, small doses of benzodiazepines can be administered in patients being treated chronically with benzodiazepines or if increased anxiety related to the upcoming surgery results in tachypnea with the potential of dynamic hyperinflation.
Monitoring for LVRS should include standard monitoring as recommended by the American Society of Anesthesiologists Standards for Intraoperative Monitoring and an indwelling arterial catheter for rapid-response hemodynamic monitoring and intermittent blood gas sampling and analysis. Because of the potential for hemodynamic instability on induction of general anesthesia, the intra-arterial blood pressure monitoring should be established prior to induction. Central venous catheters may be employed for administration of vasoactive medication that cannot be administered through a peripheral line. The placement of the central venous catheter should be done after induction of general anesthesia, due to the discomfort that the patient might experience in the Trendelenburg position.55 More controversial is the use of pulmonary artery (PA) catheters and transesophageal echocardiography (TEE). The routine use of pulmonary artery catheters is not supported by current literature.93,94 Central venous pressure and PA pressures may be inaccurate secondary to intrinsic and extrinsic positive end-expiratory pressure (PEEP), lateral decubitus position and open chest. In patients with significant coronary artery disease or pulmonary hypertension, pertinent intraoperative assessment of the right and left heart function can be provided by TEE.55 However, at the conclusion of the surgical procedure attention should be paid to potential upper airway edema from the insertion and intraoperative manipulation of the TEE probe. As the patients undergoing LVRS receive little or no amnestic agents and may receive insufficient anesthetic agents due to potential hemodynamic instability, brain function monitoring may be helpful to target an adequate depth of anesthesia.82 The intraoperative use of in-line flow-volume loop monitoring may be helpful in detecting the presence of intrinsic PEEP by the failure of the expiratory flow to return to zero before initiation of a new breath.95
If thoracic epidural analgesia will be employed for postoperative pain control, a thoracic epidural catheter should be placed before induction of general anesthesia. The spread of the neural blockade should be checked before induction to ensure proper placement and to avoid respiratory failure due to inadequate pain control.
Multiple agents are available for induction and maintenance of anesthesia. The choice of the anesthetic agent used for induction is mostly determined by the medical condition of the patient. Slow, careful titration of the anesthetic agents and vasoactive drugs during induction may provide better hemodynamic stability. Achievement of an adequate depth of anesthesia before laryngoscopy and intubation is paramount, as intubation in an inadequately anesthetized patient can lead to severe bronchospasm.84 The anesthetic plan for maintenance is formulated with the goal of extubation of the patient at the end of the procedure. Historically, potent inhalational agents have been the agents of choice in providing anesthesia for thoracic surgical cases given their ease of titration and their potent bronchodilator properties. However, patients undergoing LVRS may benefit from a total intravenous anesthesia (TIVA) approach. Although current literature does not support a clear physiologic advantage of using one technique over another in patients with relatively normal lung function, avoiding modulation of HPV with TIVA may be clinically significant in patients with marginal lung function. More importantly though, patients with COPD undergoing LVRS have increased dead space, and therefore the uptake and distribution of the inhalational agents is unpredictable and the end-tidal volatile anesthetic concentration inaccurate.10Furthermore, premature airway closing during expiration and air trapping may hinder elimination of the volatile anesthetic, delaying awakening and extubation. The most common drugs used for TIVA are remifentanil and propofol as a continuous infusion, which allow rapid recovery and more predictable emergence at the end of the procedure. The intravenous administration of opioids, with the exception of ultrashort-acting ones, should be limited in order to avoid postoperative respiratory depression. Intermediate-acting muscle relaxants devoid of hemodynamic effects and easily reversible are recommended. As patients with severe COPD may evidence increased sensitivity to neuromuscular blocking agents, the degree of neuromuscular blockade should be monitored.55 Local anesthetics or a combination of local anesthetic and narcotics may be administered through the thoracic epidural catheter allowing for a smooth emergence in the absence of pain or respiratory depression.
Besides its well-known adverse effects (higher incidence of myocardial ischemia and wound infection, coagulopathy), hypothermia may result in shivering leading to an increased production of carbon dioxide and delayed extubation. Therefore, the use of warming devices is recommended to maintain normothermia.
Hypotension may occur at any time following induction or during maintenance of general anesthesia and may represent a diagnostic dilemma. Causes of hypotension include sympathetic blockade from local anesthetics administered through the thoracic epidural catheter, vasodilatory effects of the induction agents, hypovolemia, myocardial ischemia, dynamic hyperinflation, or infrequent but possible catastrophic causes such as tension pneumothorax. Air trapping and dynamic hyperinflation resulting in decreased venous return is one of the most common causes of hypotension upon institution of positive pressure ventilation. If this is the etiology of hypotension, disconnecting the endotracheal tube from the breathing circuit and allowing the lung volumes to decrease will result in resolution of hypotension. An extreme form of air trapping and auto-PEEP can have a “tamponade” effect on the heart. Such patients show a progressive increase in central venous pressure, pulmonary hypertension, and proportionally increased pulmonary capillary wedge pressures. This results in a low cardiac output state with progressive systemic hypotension and drastic reduction in oxygen delivery to tissues. If the condition is not recognized and corrected rapidly, the patient may expire.96 In order to correct or avoid auto-PEEP, airflow obstruction should be aggressively corrected by confirming the correct position of the endotracheal tube, removing secretions and administering inhaled bronchodilators. Optimizing the ventilatory parameters by increasing the expiratory time and decreasing the respiratory rate may allow more time for lung deflation. The abrupt development of cardiovascular collapse unresponsive to volume infusion and vasopressor administration and unexplained by auto-PEEP and/or malposition of the endotracheal tube should raise the suspicion of a pneumothorax. Due to positive pressure ventilation, a pneumothorax becomes rapidly a tension pneumothorax and represents a true emergency. This complication needs immediate detection and treatment by aborting the surgical procedure, re-expanding the operative lung, and immediately inserting a chest tube in the contralateral chest.96
One-Lung Ventilation in Patients with Severe Chronic Obstructive Pulmonary Disease
Most of the techniques of lung isolation and considerations related to OLV discussed in detail in Chapters 3 and 4 apply to the patients undergoing LVRS. However, there are some unique aspects related to the ventilatory management of OLV in these patients.
OLV can be accomplished by any of the usual techniques: DLT, single-lumen tube with bronchial blocker or Univent tube. Although increased airflow resistance through a DLT compared with a single-lumen tube or a Univent tube during OLV97 might worsen auto-PEEP, DLTs tend to be the favored method for lung separation in LVRS by most practitioners. Bronchial blockers are more prone to dislodgement, provide slower deflation of the operative lung due to the small size of the central lumen, and do not permit suctioning of the operative lung. Irrespective of the method used for lung separation, fiberoptic bronchoscopy should be used for confirmation of appropriate positioning.
Because of decreased elastic recoil of the lung and chronic airflow obstruction, the deflation of the operative lung might be delayed; therefore one should proceed with OLV as early as possible in order to maximize the time available for lung deflation. Intraoperative ventilatory management during OLV aims to balance competitive priorities: maintaining adequate oxygenation, minimizing intrinsic PEEP, minimizing barotrauma, and maximizing CO2 elimination.
Some investigators have found that oxygenation is preserved for a longer period of time in patients with severe emphysema as compared with patients with normal lung function after initiation of OLV.98Explanations include: (1) slow deflation of the operative lung after institution of OLV serving as a reservoir of oxygen, (2) preexisting reduced perfusion to the operative lung secondary to altered HPV in the presence of chronic, irreversible disease in the pulmonary vessels, (3) kinked pulmonary vessels in the deflated, operative lung that inhibit perfusion, (4) development of auto-PEEP in the dependent lung with decreased atelectasis formation and preserved FRC.99 The position of the patient during surgery might also influence the degree of hypoxemia during OLV. Bardoczky et al found a significantly higher PaO2 and lower PA-aO2 in patients with mild pulmonary hyperinflation when OLV was performed in the lateral position compared with the supine position. They also found that PaO2 was significantly greater when OLV was initiated after turning the patients into the lateral decubitus position.100 These results are conflicting with the study by Fiser et al, who studied OLV in the supine and lateral position and did not find significant changes in PaO2 during OLV when the position of the patient was changed from supine to lateral decubitus. However, in their study OLV was initiated in the supine position and maintained continuously, even during turning and positioning of the patient.101
Most practitioners have adopted the lung-protective ventilatory strategy with small tidal volumes (TV) (5-7 mL/kg when ventilating two lungs and 3-4 mL/kg when ventilating a single lung), peak inspiratory pressure below 35 cm H2O, inspiratory/expiratory ratio between 1:3 to 1:5, and low respiratory rates. This ventilatory strategy is aimed at preventing dynamic hyperinflation, minimizing the risk of disruption of suture lines or lung tissue and avoiding the intraoperative occurrence of pneumothorax or air leaks. However, it may lead to hypoventilation and hypercapnia. Permissive hypercapnia with PaCO2 levels up to 70 mm Hg may be well-tolerated for short periods of time, assuming a reasonable cardiovascular reserve and in particular right ventricular function.89 Inotropic support might be required in more compromised patients. Significant respiratory acidosis, however, has numerous potential adverse effects such as increased intracranial pressure, decreased myocardial contractility, pulmonary hypertension, diaphragmatic dysfunction, and cardiac arrhythmias. When significant acidosis develops (pH <7.20) maneuvers should be instituted to maximize minute ventilation, communication should be initiated with the surgeon, and two-lung ventilation should be resumed whenever possible. In this clinical situation when carbon dioxide elimination is impaired, administration of sodium bicarbonate with the aim to normalize the pH value is not recommended as it might worsen the intracellular acidosis. Due to increased dead space, the gradient between the end-tidal CO2 and PaCO2 is increased and unpredictable, therefore frequent arterial blood gas sampling and analysis is recommended.10
PEEP is commonly applied to the ventilated lung to try to improve oxygenation during OLV but is an unreliable therapy and occasionally causes PaO2 to decrease further. Slinger et al showed that the effects of the application of 5 cm of PEEP on oxygenation during OLV has a variable effect on oxygenation depending on the relation between the plateau end-expiratory pressure and the inflection point of the static compliance curve. When the application of PEEP causes the end-expiratory pressure to increase from a low level toward the inflection point, oxygenation is likely to improve. Conversely, if the addition of PEEP causes an increased inflation of the ventilated lung that raises the equilibrium end-expiratory pressure beyond the inflection point, oxygenation is likely to deteriorate.102 The application of external PEEP in patients with severe COPD has generally been discouraged due to the potential risk of barotrauma. Because of the heterogenous nature of auto-PEEP, patients with preexisting auto-PEEP have an unpredictable response to application of external PEEP. The increase in total PEEP after application of external PEEP is not consistent and depends on the level of auto-PEEP.103 However, the application of low level extrinsic PEEP during weaning from mechanical ventilation might improve the lung mechanics and reduce work of breathing by shifting the effort from the patient, who has to exert a certain inspiratory effort in order to overcome the auto-PEEP, to the ventilator.104 Intraoperative PEEP titration is difficult and may not be feasible as determination of the inflection point or auto-PEEP requires in-line spirometry.
Although there is no unequivocal evidence that one mode of ventilation may be more beneficial than the other, pressure-controlled ventilation (PCV) may diminish the risk of barotrauma by limiting peak and plateau airway pressures. Also, the decelerating flow pattern results in more homogenous distribution of the tidal volume and improved dead space ventilation.105 The concern surrounding PCV relates to the impact that inspiratory resistance and auto-PEEP may have on delivered TV leading to unpredictable low TV and unintended hypoventilation.105
At the end of the procedure the operative lung is inflated gradually to a peak inspiratory pressure less than 20 cm H2O in order to prevent disruption of the staple line. During reinflation of the operative lung it is helpful to clamp the lumen serving the dependent lung to limit overdistension and significant hypotension.89
Tracheal extubation immediately after surgery is an important aim after LVRS in order to minimize the risk of developing or exacerbating an air leak and avoid the deleterious hemodynamic effects of positive pressure ventilation. Successful extubation however depends on multiple factors: adequate pain control, reversal of neuromuscular blockade, absence of significant bronchospasm and secretions, absence of significant hypercapnia and acidosis, and absence of respiratory depression due to residual anesthetic agents. Strategies for optimization of the patient prior to extubation are presented in Table 15–5.
Table 15–5. Strategies to Avoid Delayed or Failed Extubation after Lung Volume Reduction Surgery
Due to underlying ventilatory problem in patients with COPD, extubation can be attempted even in the presence of moderate respiratory acidosis. Most patients demonstrate a pattern of recovery from the moderate hypercapnic acidosis within 1 or 2 hours following extubation.96 Worsening of respiratory acidosis after extubation may resolve by employing noninvasive ventilation. Occasionally, extubation must be delayed due to severe hypercapnic acidosis. Delaying extubation is preferred over aggressive ventilation, which carries the risk of barotrauma and air leaks.10
Some investigators recommend changing the DLT to an SLT at the end of the procedure in order to facilitate “toilet” bronchoscopy and reduce airflow resistance in the spontaneously breathing patient prior to extubation. The benefits of this maneuver have to be weighted against the risk of manipulating the airway, taking into consideration the fact that when both lumens of the DLT are used the airflow resistance is only slightly higher compared to an SLT.97
As postoperative respiratory failure and tracheal re-intubation carry significant morbidity, LVRS patients have to be monitored very closely after extubation and any deterioration in their respiratory status has to be treated very aggressively. The patient should be placed in a steep sitting position to facilitate diaphragmatic excursions, nebulized bronchodilators should be administered immediately after extubation, pain control should be optimized and aggressive chest physiotherapy should be initiated promptly.
Pain Management In Lung Volume Reduction Surgery
The importance of adequate pain control in LVRS patients cannot be overstated. Effective, enduring pain control is vital to the success of the surgical procedure. Inadequate pain control in these high-risk patients will result in splinting, poor respiratory effort, inability to cough and clear secretions leading to airway closure, atelectasis, shunting, and hypoxemia. Also, it is paramount that adequate pain control is achieved with minimal respiratory depression.
Common surgical approaches used in LVRS, VATS, and midline sternotomy are usually associated with less acute postoperative pain than a thoracotomy incision. Although comparative studies of various modalities of pain control in LVRS do not exist, some conclusions could be extrapolated from studies on pain control in thoracic surgery. Regional analgesia techniques are widely employed in thoracic surgery due to their narcotic-sparing effects. Thoracic epidural analgesia (TEA) with a continuous infusion of local anesthetics with or without opioids is the favored modality of postoperative pain control after LVRS by most practitioners. TEA provides a better quality pain control compared to parenteral opioids106 and may reduce the incidence of myocardial infarction in the perioperative period.107 Good evidence indicates that TEA reduces the incidence of respiratory complications after thoracic surgery. In a meta-analysis, Ballantyne et al showed that, while epidural opioids had only a tendency to reduce pulmonary complications overall when compared with systemic opioids, epidural local anesthetics increased PaO2 and decreased the incidence of pulmonary infections and pulmonary complications overall.108 However, there is concern that by blocking the nerve supply to the intercostal muscles, local anesthetics could impair postoperative respiratory function. Gruber et al showed that this does not occur to a clinically significant degree. In a group of 12 patients undergoing LVRS thoracic epidural blockade with bupivacaine 0.25% did not adversely affect ventilatory mechanics, breathing pattern, gas exchange or inspiratory muscle power.109 Improved gastrointestinal motility and postoperative gut function was observed in patients with thoracic epidural analgesia especially when the splanchnic fibers (T5-T10) were blocked. This may be of importance given the fact that a small number of LVRS patients may develop postoperative ileus, which can be compounded by the use of parenteral opioids and can lead to diaphragmatic dysfunction, respiratory failure and reintubation.
Nonsteroidal anti-inflammatory drugs (NSAIDs) can be used as adjuvants in postoperative pain control. Ketorolac tromethamine (Toradol) is the most potent analgesic in the NSAID class available in an intravenous form in the United States. Given that ketorolac binds to both isoforms of the cyclooxygenase, its potential adverse effects include decreased renal perfusion, inhibition of platelet aggregation, and predisposition to peptic ulcer disease and gastrointestinal bleeding.110
Other potential techniques for pain control in LVRS patients include intrathecal morphine, intercostal nerve blockade, paravertebral nerve blockade, and pleural catheters. Paravertebral blockade provides comparable pain relief with epidural analgesia in thoracic surgery, has a better side-effect profile and is associated with a reduction in pulmonary complications.111 However, local anesthetic toxicity may be of concern due to the bilateral nature of the surgical approach in thoracoscopic LVRS, and due to the fact that a greater amount of local anesthetic is used for paravertebral blockade. Also, one of the possible complications associated with paravertebral blockade is the development of a pneumothorax, which could manifest after the institution of positive pressure ventilation and have extreme consequences.
Irrespective of the technique used, a very clear plan for pain control has to be designed and discussed with the patient, the surgical team and the acute pain service if available.
When performed on appropriately selected patients, LVRS is associated with prolonged survival, improvement in exercise capacity and quality of life, and improvement in lung function and respiratory symptoms. It is essential that the thoracic anesthesiologist have a clear understanding of the indications and contraindications for surgery, the pathophysiology of COPD, and the management of one-lung ventilation in this high risk group of patients; also paramount to successful patient outcomes is a well-planned and executed plan for postoperative analgesia.
1. Pauwels R. Global initiative for chronic obstructive lung diseases (GOLD): time to act. Eur Respir J. 2001;18(6):901-902.
2. Buist AS, Sexton GJ, Nagy JM, Ross BB. The effect of smoking cessation and modification on lung function. Am Rev Respir Dis. 1976;114(1):115-122.
3. Anthonisen NR. Long-term oxygen therapy. Ann Intern Med. 1983;99(4):519-527.
4. Naunheim KS, Wood DE, Mohsenifar Z, et al. Long-term follow-up of patients receiving lung-volume-reduction surgery versus medical therapy for severe emphysema by the National Emphysema Treatment Trial Research Group. Ann Thorac Surg. 2006;82(2):431-443.
5. Macnee W. Pathogenesis of chronic obstructive pulmonary disease. Clin Chest Med. 2007;28(3):479-513, v.
6. Kim WD, Eidelman DH, Izquierdo JL, Ghezzo H, Saetta MP, Cosio MG. Centrilobular and panlobular emphysema in smokers. Two distinct morphologic and functional entities. Am Rev Respir Dis. 1991;144(6):1385-1390.
7. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 15 2007;176(6):532-555.
8. Cooper CB, Dransfield M. Primary care of the patient with chronic obstructive pulmonary disease-part 4: understanding the clinical manifestations of a progressive disease. Am J Med. 2008;121(7 Suppl):S33-45.
9. Barbera JA, Peinado VI, Santos S. Pulmonary hypertension in chronic obstructive pulmonary disease. Eur Respir J. 2003;21(5):892-905.
10. Hartigan PM, Pedoto A. Anesthetic considerations for lung volume reduction surgery and lung transplantation. Thorac Surg Clin. 2005;15(1):143-157.
11. Au DH, Lemaitre RN, Curtis JR, Smith NL, Psaty BM. The risk of myocardial infarction associated with inhaled beta-adrenoceptor agonists. Am J Respir Crit Care Med. 2000;161(3 Pt 1):827-830.
12. Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ. 22 2000;321(7255):199-204.
13. Brantigan OC, Mueller E. Surgical treatment of pulmonary emphysema. Am Surg. 1957;23(9):789-804.
14. Cooper JD, Trulock EP, Triantafillou AN, et al. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J Thorac Cardiovasc Surg. 1995;109(1):106-116; discussion 116-109.
15. Stirling GR, Babidge WJ, Peacock MJ, et al. Lung volume reduction surgery in emphysema: a systematic review. Ann Thorac Surg. 2001;72(2):641-648.
16. Huizenga HF, Ramsey SD, Albert RK. Estimated growth of lung volume reduction surgery among Medicare enrollees: 1994 to 1996. Chest. 1998;114(6):1583-1587.
17. McKenna RJ, Jr., Benditt JO, DeCamp M, et al. Safety and efficacy of median sternotomy versus video-assisted thoracic surgery for lung volume reduction surgery. J Thorac Cardiovasc Surg. 2004;127(5):1350-1360.
18. Wisser W, Tschernko E, Senbaklavaci O, et al. Functional improvement after volume reduction: sterno-tomy versus videoendoscopic approach. Ann Thorac Surg. 1997;63(3):822-827; discussion 827-828.
19. Roberts JR, Bavaria JE, Wahl P, Wurster A, Friedberg JS, Kaiser LR. Comparison of open and thoracoscopic bilateral volume reduction surgery: complications analysis. Ann Thorac Surg. 1998;66(5):1759-1765.
20. Kotloff RM, Tino G, Bavaria JE, et al. Bilateral lung volume reduction surgery for advanced emphysema. A comparison of median sternotomy and thoracoscopic approaches. Chest. 1996;110(6):1399-1406.
21. Hazelrigg SR, Boley TM, Grasch A, Shawgo T. Surgical strategy for lung volume reduction surgery. Eur J Cardiothorac Surg. 1999;16 Suppl 1:S57-60.
22. McKenna RJ, Jr., Brenner M, Fischel RJ, Gelb AF. Should lung volume reduction for emphysema be unilateral or bilateral? J Thorac Cardiovasc Surg. Nov 1996;112(5):1331-1338; discussion 1338-1339.
23. Argenziano M, Thomashow B, Jellen PA, et al. Functional comparison of unilateral versus bilateral lung volume reduction surgery. Ann Thorac Surg. 1997;64(2):321-326; discussion 326-327.
24. Eugene J, Dajee A, Kayaleh R, Gogia HS, Dos Santos C, Gazzaniga AB. Reduction pneumonoplasty for patients with a forced expiratory volume in 1 second of 500 milliliters or less. Ann Thorac Surg. 1997;63(1):186-190; discussion 190-182.
25. Naunheim KS, Kaiser LR, Bavaria JE, et al. Long-term survival after thoracoscopic lung volume reduction: a multiinstitutional review. Ann Thorac Surg. 1999;68(6):2026-2031; discussion 2031-2022.
26. McKenna RJ, Jr., Brenner M, Gelb AF, et al. A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema. J Thorac Cardiovasc Surg. 1996;111(2):317-321; discussion 322.
27. Vigneswaran WT, Podbielski FJ. Single-stage bilateral, video-assisted thoracoscopic lung volume reduction operation. Ann Thorac Surg. 1997;63(6):1807-1809.
28. Flaherty KR, Martinez FJ. Lung volume reduction surgery for emphysema. Clin Chest Med. 2000;21(4):819-848.
29. Gelb AF, Zamel N, McKenna RJ, Jr., Brenner M. Mechanism of short-term improvement in lung function after emphysema resection. Am J Respir Crit Care Med. 1996;154(4 Pt 1):945-951.
30. Hazelrigg S, Boley T, Henkle J, et al. Thoracoscopic laser bullectomy: a prospective study with three-month results. J Thorac Cardiovasc Surg. 1996;112(2):319-326; discussion 326-317.
31. Miller JI, Jr., Lee RB, Mansour KA. Lung volume reduction surgery: lessons learned. Ann Thorac Surg. 1996;61(5):1464-1468; discussion 1468-1469.
32. Marchand E, Gayan-Ramirez G, De Leyn P, Decramer M. Physiological basis of improvement after lung volume reduction surgery for severe emphysema: where are we? Eur Respir J. 1999;13(3):686-696.
33. Sciurba FC, Rogers RM, Keenan RJ, et al. Improvement in pulmonary function and elastic recoil after lung-reduction surgery for diffuse emphysema. N Engl J Med. 1996;334(17):1095-1099.
34. Mamary A, Criner G. Lung volume reduction surgery and bronchoscopic lung volume reduction in severe emphysema. Respiratory medicine: COPD update. 2008;4:44-59.
35. Albert RK, Benditt JO, Hildebrandt J, Wood DE, Hlastala MP. Lung volume reduction surgery has variable effects on blood gases in patients with emphysema. Am J Respir Crit Care Med. 1998;158(1):71-76.
36. Tschernko EM, Wisser W, Hofer S, et al. The influence of lung volume reduction surgery on ventilatory mechanics in patients suffering from severe chronic obstructive pulmonary disease. Anesth Analg. 1996;83(5):996-1001.
37. Snyder ML, Goss CH, Neradilek B, et al. Changes in arterial oxygenation and self-reported oxygen use after lung volume reduction surgery. Am J Respir Crit Care Med. 15 2008;178(4):339-345.
38. Naunheim KS, Keller CA, Krucylak PE, Singh A, Ruppel G, Osterloh JF. Unilateral video-assisted thoracic surgical lung reduction. Ann Thorac Surg. 1996;61(4):1092-1098.
39. Lando Y, Boiselle PM, Shade D, et al. Effect of lung volume reduction surgery on diaphragm length in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999;159(3):796-805.
40. Martinez FJ, de Oca MM, Whyte RI, Stetz J, Gay SE, Celli BR. Lung-volume reduction improves dyspnea, dynamic hyperinflation, and respiratory muscle function. Am J Respir Crit Care Med. 1997;155(6):1984-1990.
41. Haniuda M, Kubo K, Fujimoto K, Aoki T, Yamanda T, Amano J. Different effects of lung volume reduction surgery and lobectomy on pulmonary circulation. Ann Surg. 2000;231(1):119-125.
42. Haniuda M, Kubo K, Fujimoto K, et al. Effects of pulmonary artery remodeling on pulmonary circulation after lung volume reduction surgery. Thorac Cardiovasc Surg. 2003;51(3):154-158.
43. Sciurba FC. Preoperative predictors of outcome following lung volume reduction surgery. Thorax. 2002;57 Suppl 2:II47-II52.
44. McKenna RJ, Jr. Complications after lung volume reduction surgery. Chest Surg Clin N Am. 2003;13(4):701-708.
45. Kotloff RM, Tino G, Palevsky HI, et al. Comparison of short-term functional outcomes following unilateral and bilateral lung volume reduction surgery. Chest. 1998;113(4):890-895.
46. DeCamp MM, Blackstone EH, Naunheim KS, et al. Patient and surgical factors influencing air leak after lung volume reduction surgery: lessons learned from the National Emphysema Treatment Trial.Ann Thorac Surg. 2006;82(1):197-206; discussion 206-197.
47. Naunheim KS, Wood DE, Krasna MJ, et al. Predictors of operative mortality and cardiopulmonary morbidity in the National Emphysema Treatment Trial. J Thorac Cardiovasc Surg. 2006;131(1):43-53.
48. Hopkinson NS, Toma TP, Hansell DM, et al. Effect of bronchoscopic lung volume reduction on dynamic hyperinflation and exercise in emphysema. Am J Respir Crit Care Med. 2005;171(5):453-460.
49. Venuta F, de Giacomo T, Rendina EA, et al. Bronchoscopic lung-volume reduction with one-way valves in patients with heterogenous emphysema. Ann Thorac Surg. 2005;79(2):411-416; discussion 416-417.
50. Sciurba FC, Ernst A, Herth FJ, et al. A randomized study of endobronchial valves for advanced emphysema. The New England Journal of Medicine. 2010;363(13):1233-1244.
52. Criner GJ, Pinto-Plata V, Strange C, et al. Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results. Am J Respir Crit Care Med. 2009;179(9):791-798.
53. Glaspole IN, Gabbay E, Smith JA, Rabinov M, Snell GI. Predictors of perioperative morbidity and mortality in lung volume reduction surgery. Ann Thorac Surg. 2000;69(6):1711-1716.
54. McKenna RJ, Jr., Brenner M, Fischel RJ, et al. Patient selection criteria for lung volume reduction surgery. J Thorac Cardiovasc Surg. 1997;114(6):957-964; discussion 964-957.
55. Brister NW, Barnette RE, Kim V, Keresztury M. Anesthetic considerations in candidates for lung volume reduction surgery. Proc Am Thorac Soc. 2008;5(4):432-437.
56. Hogue CW, Jr., Stamos T, Winters KJ, Moulton M, Krucylak PE, Cooper JD. Acute myocardial infarction during lung volume reduction surgery. Anesth Analg. 1999;88(2):332-334.
57. Thurnheer R, Muntwyler J, Stammberger U, et al. Coronary artery disease in patients undergoing lung volume reduction surgery for emphysema. Chest. 1997;112(1):122-128.
58. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. J Am Coll Cardiol. 2007;50(17):1707-1732.
59. Choong CK, Abu-Omar Y, Agarwal A, et al. Concomitant bilateral lung volume reduction surgery and aortic valve replacement: multidisciplinary strategies in achieving a successful outcome. J Thorac Cardiovasc Surg. 2009;137(6):1551-1552.
60. Choong CK, Naylor J, Vuylsteke A, et al. Successful combined bilateral lung volume reduction and coronary artery bypass grafting surgery: implications and advantages. J Thorac Cardiovasc Surg. 2009;137(6):1552-1554.
61. Schmid RA, Stammberger U, Hillinger S, et al. Lung volume reduction surgery combined with cardiac interventions. Eur J Cardiothorac Surg. 1999;15(5):585-591.
62. Whyte RI, Bria W, Martinez FJ, Lewis P, Bolling SF. Combined lung volume reduction and mitral valve reconstruction. Ann Thorac Surg. 1998;66(4):1414-1416.
63. Cohn SL. Preoperative cardiac evaluation of lung resection candidates. Thorac Surg Clin. 2008;18(1):45-59.
64. Martinez FJ, Flaherty KR, Iannettoni MD. Patient selection for lung volume reduction surgery. Chest Surg Clin N Am. 2003;13(4):669-685.
65. Arcasoy SM, Christie JD, Ferrari VA, et al. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med. 2003;167(5):735-740.
66. DeCamp MM, Jr, Lipson D, Krasna M, Minai OA, McKenna RJ, Jr, Thomashow BM. The evaluation and preparation of the patient for lung volume reduction surgery. Proc Am Thorac Soc. 2008;5(4):427-431.
67. Yusen RD, Lefrak SS, Trulock EP. Evaluation and preoperative management of lung volume reduction surgery candidates. Clin Chest Med. 1997;18(2):199-224.
68. Mazolewski P, Turner JF, Baker M, Kurtz T, Little AG. The impact of nutritional status on the outcome of lung volume reduction surgery: a prospective study. Chest. 1999;116(3):693-696.
69. Nezu K, Yoshikawa M, Yoneda T, et al. The effect of nutritional status on morbidity in COPD patients undergoing bilateral lung reduction surgery. Thorac Cardiovasc Surg. 2001;49(4):216-220.
70. Fishman A, Martinez F, Naunheim K, et al. A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema. N Engl J Med. 2003;348(21):2059-2073.
71. Yusen RD, Lefrak SS. Evaluation of patients with emphysema for lung volume reduction surgery. Washington University Emphysema Surgery Group. Semin Thorac Cardiovasc Surg. 1996;8(1):83-93.
72. Geddes D, Davies M, Koyama H, et al. Effect of lung-volume-reduction surgery in patients with severe emphysema. N Engl J Med. 27 2000;343(4):239-245.
73. Fessler HE, Permutt S. Lung volume reduction surgery and airflow limitation. Am J Respir Crit Care Med. 1998;157(3 Pt 1):715-722.
74. Fessler HE, Scharf SM, Permutt S. Improvement in spirometry following lung volume reduction surgery: application of a physiologic model. Am J Respir Crit Care Med. 1 2002;165(1):34-40.
75. Szekely LA, Oelberg DA, Wright C, et al. Preoperative predictors of operative morbidity and mortality in COPD patients undergoing bilateral lung volume reduction surgery. Chest. 1997;111(3):550-558.
76. Keenan RJ, Landreneau RJ, Sciurba FC, et al. Unilateral thoracoscopic surgical approach for diffuse emphysema. J Thorac Cardiovasc Surg. 1996;111(2):308-315; discussion 315-306.
77. O’Brien GM, Furukawa S, Kuzma AM, Cordova F, Criner GJ. Improvements in lung function, exercise, and quality of life in hypercapnic COPD patients after lung volume reduction surgery. Chest. 1999;115(1):75-84.
78. Wisser W, Klepetko W, Senbaklavaci O, et al. Chronic hypercapnia should not exclude patients from lung volume reduction surgery. Eur J Cardiothorac Surg. 1998;14(2):107-112.
79. Patients at high risk of death after lung-volume-reduction surgery. N Engl J Med. 11 2001;345(15):1075-1083.
80. Edwards MA, Hazelrigg S, Naunheim KS. The National Emphysema Treatment Trial: summary and update. Thorac Surg Clin. 2009;19(2):169-185.
81. Ries AL, Make BJ, Lee SM, et al. The effects of pulmonary rehabilitation in the national emphysema treatment trial. Chest. Dec 2005;128(6):3799-3809.
82. Licker M, Schweizer A, Ellenberger C, Tschopp JM, Diaper J, Clergue F. Perioperative medical management of patients with COPD. Int J Chron Obstruct Pulmon Dis. 2007;2(4):493-515.
83. Warner DO. Perioperative abstinence from cigarettes: physiologic and clinical consequences. Anesthesiology. 2006;104(2):356-367.
84. Tschernko EM. Anesthesia considerations for lung volume reduction surgery. Anesthesiol Clin North America. 2001;19(3):591-609.
85. Niewoehner DE, Erbland ML, Deupree RH, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group. N Engl J Med. 24 1999;340(25):1941-1947.
86. Barr RG, Celli BR, Martinez FJ, et al. Physician and patient perceptions in COPD: the COPD Resource Network Needs Assessment Survey. Am J Med. 2005;118(12):1415.
87. Hedenstierna G, Edmark L. The effects of anesthesia and muscle paralysis on the respiratory system. Intensive Care Med. 2005;31(10):1327-1335.
88. Gunnarsson L, Tokics L, Lundquist H, et al. Chronic obstructive pulmonary disease and anaesthesia: formation of atelectasis and gas exchange impairment. Eur Respir J. 1991;4(9):1106-1116.
89. Lohser J. Evidence-based management of one-lung ventilation. Anesthesiol Clin. 2008;26(2):241-272, v.
90. Beck DH, Doepfmer UR, Sinemus C, Bloch A, Schenk MR, Kox WJ. Effects of sevoflurane and propofol on pulmonary shunt fraction during one-lung ventilation for thoracic surgery. Br J Anaesth. 2001;86(1):38-43.
91. Pilotti L, Torresini G, Crisci R, De Sanctis A, De Sanctis C. Total intravenous anesthesia in thoracotomy with one-lung ventilation. Minerva Anestesiol. Jul-1999;65(7-8):483-489.
92. Pruszkowski O, Dalibon N, Moutafis M, et al. Effects of propofol vs sevoflurane on arterial oxygenation during one-lung ventilation. Br J Anaesth. 2007;98(4):539-544.
93. Buettner AU, McRae R, Myles PS, et al. Anaesthesia and postoperative pain management for bilateral lung volume reduction surgery. Anaesth Intensive Care. 1999;27(5):503-508.
94. Triantafillou AN. Anesthetic management for bilateral volume reduction surgery. Semin Thorac Cardiovasc Surg. 1996;8(1):94-98.
95. Bardoczky GI, d’Hollander AA, Cappello M, Yernault JC. Interrupted expiratory flow on automatically constructed flow-volume curves may determine the presence of intrinsic positive end-expiratory pressure during one-lung ventilation. Anesth Analg. 1998;86(4):880-884.
96. Keller CA, Naunheim KS. Perioperative management of lung volume reduction patients. Clin Chest Med. 1997;18(2):285-300.
97. Slinger PD, Lesiuk L. Flow resistances of disposable double-lumen, single-lumen, and Univent tubes. J Cardiothorac Vasc Anesth. 1998;12(2):142-144.
98. Aschkenasy SV, Hofer CK, Zalunardo MP, et al. Patterns of changes in arterial PO2 during one-lung ventilation: a comparison between patients with severe pulmonary emphysema and patients with preserved lung function. J Cardiothorac Vasc Anesth. 2005;19(4):479-484.
99. Grichnik KP, Clark JA. Pathophysiology and management of one-lung ventilation. Thorac Surg Clin. 2005;15(1):85-103.
100. Bardoczky GI, Szegedi LL, d’Hollander AA, Moures JM, de Francquen P, Yernault JC. Two-lung and one-lung ventilation in patients with chronic obstructive pulmonary disease: the effects of position and F(IO)2. Anesth Analg. 2000;90(1):35-41.
101. Fiser WP, Friday CD, Read RC. Changes in arterial oxygenation and pulmonary shunt during thoracotomy with endobronchial anesthesia. J Thorac Cardiovasc Surg. 1982;83(4):523-531.
102. Slinger PD, Kruger M, McRae K, Winton T. Relation of the static compliance curve and positive end-expiratory pressure to oxygenation during one-lung ventilation. Anesthesiology. 2001;95(5):1096-1102.
103. Slinger PD, Hickey DR. The interaction between applied PEEP and auto-PEEP during one-lung ventilation. J Cardiothorac Vasc Anesth. 1998;12(2):133-136.
104. Smith TC, Marini JJ. Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction. J Appl Physiol. Oct 1988;65(4):1488-1499.
105. Nichols D, Haranath S. Pressure control ventilation. Crit Care Clin. 2007;23(2):183-199, viii-ix.
106. Block BM, Liu SS, Rowlingson AJ, Cowan AR, Cowan JA, Jr., Wu CL. Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA. 2003;290(18):2455-2463.
107. Beattie WS, Badner NH, Choi P. Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis. Anesth Analg. 2001;93(4):853-858.
108. Ballantyne JC, Carr DB, deFerranti S, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg. 1998;86(3):598-612.
109. Gruber EM, Tschernko EM, Kritzinger M, et al. The effects of thoracic epidural analgesia with bupivacaine 0.25% on ventilatory mechanics in patients with severe chronic obstructive pulmonary disease. Anesth Analg. 2001;92(4):1015-1019.
110. Koehler RP, Keenan RJ. Management of postthoracotomy pain: acute and chronic. Thorac Surg Clin. 2006;16(3):287-297.
111. Davies RG, Myles PS, Graham JM. A comparison of the analgesic efficacy and side-effects of paravertebral vs epidural blockade for thoracotomy–a systematic review and meta-analysis of randomized trials. Br J Anaesth. 2006;96(4):418-426.