David J. Ficke
Jerome M. Klafta
1. All patients being considered for lung resection should have pulmonary function tests including spirometry and a DLCO (diffusing capacity of the lung for carbon monoxide) test, from which the predicted postoperative values are calculated. If the results are unfavorable, a measure of exercise capacity or peak oxygen consumption should be obtained.
2. Cardiac evaluation of the thoracic surgical patient should include surgeons, anesthesiologists, and cardiologists. Higher levels of perioperative risk may be acceptable because of the potential curative benefit of surgery for non-small-cell lung cancer.
3. A thorough history of cancer therapy that considers chemotherapy, radiation, and an evaluation of the paraneoplastic effects of the cancer identifies other potential perioperative vulnerabilities.
A 69-year-old man is scheduled for a left pneumonectomy. A CT-guided biopsy 6 days ago revealed adenocarcinoma. He is obese and has hypertension, type 2 diabetes mellitus, osteoarthritis, and a 55 pack-year smoking history. When a mass was seen on his chest x-ray 2 weeks ago, he quit smoking. Pulmonary function tests show a moderately obstructive ventilatory defect with an FEV1 of 63% of predicted. He blames limited exercise tolerance on his “bad knees” and has never been evaluated by a cardiologist. How should this case be managed? Are there any other tests that would be helpful for stratifying his perioperative risk?
Thoracic surgery can have profound effects on cardiopulmonary function in the operating room, in the immediate postoperative setting, and in the long-term. The scope of thoracic surgery ranges from a thoracoscopic sympathectomy for a healthy 20-year-old patient to an extrapleural pneumonectomy for an 80-year-old with coronary disease and emphysema. Ever since the first pneumonectomy was described in 1933,1 physicians have been looking for a simple, effective way to evaluate patients to optimize outcomes. This chapter focuses primarily on the preoperative evaluation of patients who need pulmonary resection, but the principles apply for other thoracic surgeries as well. Esophageal surgery, for example, does not involve resection of lung tissue, but because esophageal pathology is associated with smoking, patients frequently have concurrent pulmonary disease. Several other considerations are noteworthy for esophageal surgery including the frequent presence of reflux and aspiration, poor nutritional status, and preoperative chemotherapy or radiation.
Understanding the surgical approach is critical to preparing for thoracic surgery. For example, if a patient has had coronary bypass surgery with an internal mammary artery, he is at high risk for myocardial ischemia during an ipsilateral extrapleural pneumonectomy. The unique physiology and pathophysiology of pulmonary resection necessitates several other considerations.
Pulmonary resection is generally performed on patients with lung cancer, which accounts for 160,000 deaths per year in the United States.2 Five-year survival—only 15% for all lung cancers—is 49% for patients with surgically resectable, localized disease. It is likely that surgery is responsible for most of the long-term survivors. Lung cancers double in size within 30 to 500 days,3 and faster growing tumors are associated with poorer prognosis.4 Because of the aggressive nature of lung cancer, many patients (and physicians) are willing to accept higher levels of risk than they might for other types of surgery. Preoperative evaluation, ideally, should not significantly delay a surgery that is potentially curative.
We next provide a framework for the evaluation of the thoracic surgery patient with focus on the respiratory and cardiovascular systems, the potential physiologic impact of other cancer therapies such as chemotherapy and radiation, as well as other unique considerations for thoracic surgery.
Minimally invasive techniques, particularly video-assisted thoracic surgery (VATS), have become increasingly popular in the past decade. A video-assisted thoracoscopic lobectomy may have fewer and less severe complications than the same procedure performed by a conventional thoracotomy,5,6 but preoperative evaluation of patients should be similar for both open and minimally invasive procedures. The removal of lung parenchyma and the physiologic changes this brings to the cardiorespiratory systems are not significantly different with either surgical technique–lung tissue is still removed. In addition, with VATS there is always the potential for conversion to an open procedure. Therefore, no distinction is made in this chapter between minimally invasive or open techniques with regard to preoperative risk stratification.
EVALUATION OF RESPIRATORY FUNCTION
The majority of pulmonary resections for lung cancer are performed in patients with some degree of respiratory impairment. Historically, maximum voluntary ventilation (MVV) was used to determine fitness for pulmonary resection.7 MVV is defined as the maximal amount of air a patient can inhale and exhale in 12 seconds. In 1955, Gaensler found that patients with low MVV had a higher mortality, and subsequent studies have confirmed a correlation between MVV and perioperative mortality.8,9 Because one of the limitations of MVV is that it depends entirely on effort, it has largely been replaced by other tests.
Spirometry has become the primary method by which patients are evaluated before thoracic surgery. Spirometry, which is relatively noninvasive, evaluates lung mechanics without the need for expensive equipment. The patient exhales air as fast as possible into a device that measures the pressure, flow, and volume of air exhaled. Several spirometric tests have been shown to correlate with outcome in thoracic surgery. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) are two such tests, with FEV1 having the highest predictive value for complications.10-12 Guidelines from the American College of Chest Physicians (ACCP)13 and the British Thoracic Society (BTS)14 suggest that after maximum bronchodilator therapy, an FEV1 more than 2 L before a pneumonectomy or FEV1more than 1.5 L before a lobectomy is sufficient for a patient to tolerate surgery, assuming no significant dyspnea on exertion or no interstitial lung disease. The difficulty with using an absolute number for cutoffs is that FEV1 depends on age, gender, and patient size. Because absolute values may unnecessarily exclude an elderly, small woman from surgery, FEV1 and FVC are reported as a percentage of predicted value, which takes other factors into account. These same guidelines recommend an FEV1 of more than 80% as sufficient to tolerate either pneumonectomy or lobectomy without further workup.
If a patient does not meet the above criterion, a more detailed approach is needed to estimate the patient’s predicted postoperative FEV1 (ppo-FEV1). Several methods can be used to estimate ppo-FEV1. The most basic (the anatomic method)15 involves counting the number of segments to be removed. See Figure 9–1.
Figure 9–1. Example of anatomic method for calculating predicted postoperative FEV1. RUL = right upper lobe, RML = right middle lobe, RLL = right lower lobe, LUL = left upper lobe, LLL = left lower lobe
The calculation is as follows:
One advantage of this method is that postoperative lung mechanics can be calculated after a second lobectomy or completion pneumonectomy. An alternative method using radionuclide perfusion16,17may be better at predicting the ppo-FEV1 after pneumonectomy than the anatomic method, which may underestimate the actual ppo-FEV1.18
The risk of perioperative complications increases when the ppo-FEV1 less than 40%.19,20 The ACCP guidelines13 suggest that patients with a ppo-FEV1 less than 40% undergo exercise testing for further risk stratification (see below). A low ppo-FEV1 is not an absolute contraindication to resection; Linden et al21 showed that patients with a ppo-FEV1 less than 35% could tolerate lung resections. In fact, the newly published guidelines of the European Respiratory Society and the European Society of Thoracic Surgery (ERS/ESTS) recommend a ppo-FEV1 of 30% as the threshold to define high-risk patients.22Emerging studies also show that patients with extremely poor lung function may benefit from combined lung volume reduction surgery (LVRS) and resection of a malignant tumor.23 It appears that the ideal candidate for combined LVRS and lung cancer resection has upper lobe emphysema with a tumor in the emphysematous upper lobe (see Chapter 15 on LVRS.). As anesthetic, surgical, and postoperative techniques improve, continuing studies are needed to determine the lowest spirometry values compatible with an acceptable surgical risk.
Unlike the measures of respiratory mechanics obtained by spirometry, other tests evaluate the capacity for gas exchange in the alveoli, including arterial oxygenation (PaO2), arterial carbon dioxide (PaCO2), and the diffusing capacity for carbon monoxide (DLCO). Historically, a PaO2 less than 60 mm Hg breathing ambient air has been considered a contraindication for pulmonary resection. This number should be interpreted cautiously because PaO2 may improve after lung resection when ventilation-perfusion matching has improved.24 Similarly, a PaCO2 more than 45 mm Hg has historically been the upper limit of acceptable hypercapnea before lung resection, but some studies have shown that complications do not necessarily increase with a PaCO2 more than 45 mm Hg.25
Because of the limitations of PaO2 and PaCO2 values, DLCO is now considered the most useful test for evaluating gas exchange in the alveoli. The value is relatively easy to obtain and is often performed with other pulmonary function tests. To measure DLCO, the patient inhales a small amount of carbon monoxide and air and holds his breath for 10 seconds. When the patient exhales, the amount of exhaled carbon monoxide is measured and the diffusing capacity is calculated as the difference between the inhaled and exhaled amount.
In a retrospective analysis, Ferguson et al26 found that DLCO correlated with surgical morbidity and mortality, perhaps even more so than FEV1. The predicted postoperative DLCO (ppo-DLCO) can be calculated in the same manner as ppo-FEV1 (see page 152). In another recent study, ppo-DLCO correlated with morbidity and mortality even in patients with normal spirometric values.27
As with ppo-FEV1, several studies have shown that if the ppo-DLCO is less than 40%, perioperative risk is significantly increased.19,28 The ACCP guidelines13 suggest further risk stratification with formal exercise testing in patients with a ppo-DLCO less than 40%. Several groups have suggested that a product of % ppo-FEV1 × % ppo-DLCO less than 1650 may be even more sensitive for revealing patients at high risk for perioperative complications.28,29
Split Lung Function Tests and Ventilation-Perfusion Scans
Given the strain on the cardiopulmonary system after pulmonary resection, a number of techniques have been developed to try to simulate this change and predict the body’s response to the resection of a portion of lung parenchyma. Techniques involving temporary occlusion of a bronchus or pulmonary artery have been described.30 If a pulmonary artery or lobar branch is occluded and pulmonary artery pressure does not change significantly, it is presumed that the remaining pulmonary vasculature is able to accommodate. These tests are invasive, resource intensive, and not widely used. They also may be misleading because pulmonary artery pressure may remain constant due to a failing right ventricle rather than accommodation of the pulmonary vasculature.31
Ventilation-perfusion scintigraphy scans (V/Q scans) have also been used in preoperative assessment to determine the relative contribution of each lung to overall ventilation.32 A V/Q scan has two parts. The first part measures ventilation after a patient inhales a radioactive isotope that shows which parts of the lung are ventilated. The second part measures the perfusion of the lung after a separate radioactive isotope is injected to reveal which areas of the lung are perfused. V/Q scans appear to have reasonable correlation for predicting ppo-FEV1 and ppo-FVC.33 With this technique, an obstructed or underperfused area of lung parenchyma can be detected and the ppo-FEV1 adjusted accordingly. If a patient has a ppo-FEV1 less than 40% by the anatomic method, a V/Q scan may adjust the ppo-FEV1upwards. For example, if the patient from Figure 9–1 had a V/Q scan that showed his left lung received only 42% of the perfusion, then his revised ppo-FEV1 would be 0.63 × (1–0.42) or 36.5%. If the revised ppo-FEV1 still identifies the patient as high risk, exercise testing is generally recommended for further risk stratification (see page 155).
Flow-volume loops are occasionally obtained before thoracic surgery to supplement other tests and are performed in the same manner as spirometry. They may be useful in the evaluation of a mediastinal mass.34 (See also Chapter 12 on mediastinal masses.) A flow-volume loop can identify an intrathoracic airway obstruction by showing airflow limitation in the expiratory limb. Flow-volume loops were ordered frequently in the past, before more sophisticated imaging techniques of the intrathoracic airway were developed. Despite other advances in imaging, flow-volume loops have value because they measure airflow limitations throughout the entire respiratory cycle rather than at a single point in time. If a patient has few or no comorbidities and does not describe positional dyspnea or coughing, these tests are often omitted.
Patients may also undergo exercise testing before thoracic surgery. Rather than measuring isolated respiratory mechanics or gas exchange, exercise testing examines the function of the integrated cardiopulmonary system. Historically, stair climbing has been used as one functional assessment of overall cardiorespiratory status. The ability to climb three flights of stairs indicated the ability to tolerate a lobectomy; climbing five flights of stairs indicated the ability to tolerate a pneumonectomy. Surgical complications and mortality have been shown to correlate with inability to climb stairs.35
The lack of standardization for stair climbing makes the test somewhat problematic: the speed of ascent, duration of climbing, and number of stairs per flight may vary. Nevertheless, stair climbing still provides an easy, inexpensive estimate of the patient’s exercise tolerance. In one study, patients who climbed fewer than 12 meters owing to symptoms of dyspnea had increased complications and mortality compared to those who could climb higher than 22 meters.36 When combined with pulse oximetry, stair climbing may increase the sensitivity of predicting postoperative complications.37
A more objective measurement of exercise tolerance is the measure of maximal oxygen consumption (VO2max), the gold standard for evaluation of exercise tolerance. The patient exercises—often on a treadmill—while wearing a mask that measures the volume and concentration of inhaled and exhaled gases. Many studies have shown that postoperative complications and mortality increase as preoperative VO2max decreases.38-41 A VO2max less than 10 mL/kg/min is a marker for increased risk of complications and mortality. Patients with a low ppo-FEV1 or ppo-DLCO with a VO2max between 10 and 15 mL/kg/min also have a high rate of adverse events. Indeed the ACCP guidelines recommend that patients with a VO2max less than 10 mL/kg/min or a VO2max less than 15 mL/kg/min with both ppo-FEV1 less than 40% and ppo-DLCO less than 40% be counseled about nonstandard surgery (ie, segmentectomy) or nonoperative therapies.13
Measuring VO2max is time-consuming and resource intensive. Several other methods have been devised as alternatives for formal measurement of VO2max. The 6-minute walk test,42 which measures how far a patient can walk in 6 minutes, correlates well with VO2max and predicts complications after pulmonary resection.43,44 A distance of less than 2000 feet (610 meters) correlates to a VO2max of less than 15mL/kg/min.45
The shuttle walk test is another surrogate for VO2max. In this test, the patient walks between two markers 10 meters apart, paced by an audio signal, until too tired to continue.46 The shuttle walk test is used frequently in the nonsurgical assessment of pulmonary exercise tolerance. This test shows reasonable correlation to VO2max.47 Somewhat limited data suggest that a patient unable to complete 25 shuttles on two occasions is likely to have a VO2max less than 10 mL/kg/min.48
Summary Recommendations for Respiratory Evaluation
Given the poor prognosis of cancer without surgery and patients’ willingness to accept higher levels of risk, every effort should be made to optimize the medical condition of a patient so that surgery can be considered. All patients should have spirometry and DLCO testing. If the FEV1 and DLCO are more than 80% predicted, no further evaluation is needed. For patients with FEV1 less than 80% or DLCO less than 80%, a ppo-FEV1 and ppo-DLCO should be calculated using the anatomic method. If either ppo-FEV1 or ppo-DLCO is less than 40%, a V/Q scan can be considered to further refine predicted postoperative function. Alternatively, formal exercise testing with measurement of VO2max should be performed. If the institution does not have the capacity to measure VO2max, either stair climbing, the shuttle walk test, or the 6-minute walk test can be substituted. For those patients who, after exercise testing, are still at high risk for complications or death, nonstandard surgery (segmentectomy, combined LVRS/cancer resection) or nonoperative therapy should be discussed. A decision is made on a case by case basis. The algorithm in Figure 9–2 summarizes these recommendations.
Figure 9–2. Preoperative physiologic assessment for lung resection. (Data modified from Figure 1 in Colice GL, Shafazand S, Griffin JP, et al.13)
Although guidelines exist for cardiac evaluation before noncardiac surgery49,50 (see also Figure 9–3), they are not specific to thoracic surgery. The objective of this section is to clarify some important aspects that are specific to thoracic surgical patients.
Figure 9–3. ACC/AHA guidelines for preoperative cardiac evaluation for noncardiac surgery. Thoracic surgery is categorized as an intermediate risk procedure, and preoperative cardiac evaluation is generally not indicated unless the patient exhibits an active cardiac condition, even in the presence of multiple risk factors for coronary disease. (Reprinted with permission from Circulation. 2007;116:e418-e500. ©2007 American Heart Association, Inc.)
In general, the guidelines of the American College of Cardiology and the American Heart Association (ACC/AHA) classify intrathoracic surgery as a procedure of intermediate cardiac risk. That is, the risk of cardiac death or nonfatal myocardial infarction is 1% to 5%.49 In our view, this is somewhat of an oversimplification. Even among pulmonary operations, not all resections will generate the same amount of stress on the cardiovascular system. An extrapleural pneumonectomy, for example, with its potential for blood loss and major effects on pulmonary vascular resistance, is a higher risk surgery than a wedge resection.
The revised ACC/AHA guidelines49 recommend that if a thoracic surgical patient has an exercise tolerance of at least 4 metabolic equivalents (the ability to walk up one flight of steps), no further coronary evaluation is necessary, even in the presence of multiple risk factors, unless such evaluation would change management. As with ordering any test, the physician should consider what is to be done with the results. A positive stress test is often followed by cardiology consultation and coronary angiography. If a flow-limiting obstruction is found during angiography, then angioplasty and stenting is considered. Stents obligate the patient to a period of anticoagulation, which may necessitate delaying surgery (see below).
Stress testing is still warranted for a patient with significant risk factors and poor exercise tolerance as an additional means of risk stratification.
We recommend involving a cardiologist in a multidisciplinary approach for patients considered at high risk for cardiovascular complications after thoracic surgery to help define the pathology, further quantify risk, and optimize preoperative management.
Patients with a flow-limiting coronary obstruction have an area of myocardium at risk for ischemia that perhaps could be relieved by stenting. Some enthusiasm for stenting in patients with stable coronary disease has been tempered by the COURAGE trial, which showed no significant reduction in death or rate of acute coronary syndrome with bare metal stents compared to medical therapy.51 This trial, however, did not specifically focus on the perioperative setting, nor did it evaluate drug-eluting stents. As perioperative ischemia has a different pathophysiology than nonperioperative ischemia (supply-demand ratio mismatch rather than a plaque rupture and acute thrombus, in most cases), many practitioners still consider relieving the flow-limiting obstruction with stents.
When a stent is placed, the patient is obligated to a period of anticoagulation with multiple platelet-inhibiting drugs. Prematurely stopping platelet inhibitors can lead to acute thrombosis of the stent and ST elevation myocardial infarction. The practitioner must weigh the risk of stopping anticoagulation before a surgical procedure with the risk of delaying surgery. This decision is best made in consultation with a cardiologist. Compared to bare-metal stents (BMS), drug-eluting stents (DES) take a longer period of time to endothelialize,52 which makes them prone to thrombosis for longer. Because of reports of acute thrombosis in patients 1 year after placement of DES,53 the ACC/AHA have revised the guidelines on antiplatelet therapy after coronary stents. Dual antiplatelet therapy is recommended for at least 1 month after BMS placement, and for 1 year following a DES.54 Again, in patients with recent stents, the risk of discontinuing antiplatelet therapy must be weighed against the risk of delaying potentially curative surgery or operating on an anticoagulated patient and necessarily foregoing postoperative epidural analgesia.
For patients at risk for perioperative myocardial ischemia, beta blockers are often recommended. Beta blockers have traditionally been withheld in patients with airway obstruction because of the concern that beta-2 blockade causes additional bronchoconstriction. However, beta-1 specific blockers are routinely used safely, eliminating this concern. Beta blockers have many potential benefits in the perioperative setting: they lower myocardial oxygen demand by lowering heart rate, decrease arrhythmias, prevent plaque rupture by decreasing sympathetic tone, and increase diastolic time thus increasing myocardial oxygen supply.
Initial trials for beta blockade before noncardiac surgery were encouraging.55 Recent data, however, have dampened this enthusiasm. The POISE trial56 studied 8300 patients at risk for atherosclerosis who had noncardiac surgery. Although incidence of cardiovascular death and nonfatal myocardial infarction was decreased, total mortality, stroke, and hypotension were found more often in the group treated with beta blockers. The major criticism of that study is that the patients in the beta blocker group were started on high dose beta blockers on the day of surgery. In the DECREASE IV trial57 beta blockers were started preoperatively (median 34 days) and titrated to a heart rate of 50 to 70 bpm. Risk of death and nonfatal MI decreased without increased morbidity in patients given beta blockers. The ACC/AHA guidelines on perioperative beta blockade,58 updated in 2009, recommend that patients who are already taking beta blockers continue them perioperatively. Patients at risk for myocardial ischemia who have not been taking beta blockers before intermediate-risk surgery may be considered for beta blockade titrated to blood pressure and heart rate, but their care should be managed in conjunction with a consulting cardiologist.
Besides beta blockade, patients at risk for myocardial ischemia are often placed on lipid-lowering therapy with statins. Statins have anti-inflammatory and plaque-stabilizing effects in addition to their effects on cholesterol (also known as pleiotropic effects). Preliminary observational trials suggest that statins may reduce perioperative risk in noncardiac surgery.59,60 DECREASE III,61 a randomized, controlled trial, found that fluvastatin reduced the risk of perioperative ischemia in patients undergoing vascular surgery. DECREASE IV57 showed a trend toward improved outcome in the group treated with fluvastatin as well. Additional prospective, randomized trials are needed to further evaluate these potential benefits and the recommendation to initiate, or at least continue, statin therapy perioperatively.
Right Ventricular Impairment
In addition to the cardiovascular risks intrinsic to thoracoscopy or thoracotomy, pulmonary resection strains the cardiovascular system. Changes in preload, afterload, and contractility can cause hemodynamic instability in patients with an already compromised ventricular function. In particular, the degree of right ventricular dysfunction that occurs after lung resection is related to the change in pulmonary vascular resistance, which is proportional to the amount of lung tissue resected.62 Right heart dysfunction may develop even without preexisting right heart abnormalities.63 Many patients with a long history of smoking have some element of cor pulmonale or pulmonary hypertension that, with right ventricular dysfunction, may progress to overt right heart failure. Preoperative evaluation with echocardiography is not routinely recommended before thoracic surgery64 but should be considered when left ventricular dysfunction, valvular abnormalities,65 or pulmonary hypertension66 is suspected.
Summary Recommendations for Cardiac Evaluation
Given the frequent coexistence of pulmonary and cardiac disease, every patient should have a thorough history and physical examination. Patients with high-risk conditions (unstable angina, decompensated heart failure, arrhythmias, valvular disease, or myocardial infarction in the past 30 days) should be evaluated by a cardiologist before thoracic surgery. If the patient has known high-risk coronary disease or a low functional capacity, stress testing is warranted to further stratify the risk. Decisions about invasive testing, beta blockers, or statins should be made in conjunction with a consulting cardiologist who can continue to follow the patient’s progress beyond the immediate postoperative period. If there is a concern about pulmonary hypertension, cor pulmonale, or valvular heart disease, a preoperative echocardiogram should be performed to guide intraoperative therapy.
CHEMOTHERAPY AND RADIATION
Many thoracic surgical patients need resection of primary lung cancers, after which some are offered chemotherapy or radiation as adjuvant therapy. Other patients may have had chemotherapy or radiation before resection of a second primary lung cancer, after metastasis of another primary cancer, or for a systemic cancer. Still other patients with historically unresectable lung cancers may have undergone neoadjuvant (given before surgery) chemotherapy and radiation, in an attempt to reduce tumor size to make it resectable. Because recent studies suggest that such chemotherapy or radiation may not increase perioperative morbidity and mortality,67,68 it is likely that the number of patients undergoing surgery after chemotherapy and radiation treatment will increase.
Preoperative chemotherapy and radiation therapy may not increase immediate perioperative morbidity and mortality, but they certainly have profound effects on perioperative and anesthetic management. A careful history with particular attention to the chemotherapeutic agents used is recommended. This section will cover many of the common chemotherapeutic agents used in lung cancer, other chemotherapy agents that influence perioperative considerations, and the serious effects of radiation therapy.
Cisplatin and Carboplatin
The most common chemotherapeutic agents for the treatment of lung cancers are the platinum-based alkylating agents cisplatin and carboplatin.69,70 These drugs are inactive when administered into the circulation, but penetrate the cells by passive diffusion and inhibit DNA replication, RNA transcription, and protein synthesis. Because one of the serious adverse effects of platinum-based drugs is renal toxicity, a preoperative serum creatinine measurement is imperative. Impaired renal function may necessitate altered dosing of many anesthetic agents (ie, neuromuscular blockers). Some practitioners may opt to reduce the dose of NSAIDs such as ketorolac, or omit them altogether. Additionally, the platinum-based chemotherapies may be neurotoxic by affecting Schwann cells, which produce the myelin sheath that surrounds nerves. There have been reports of brachial plexus injuries possibly related to their neurotoxic effects.71 Any preexisting neurologic deficits should be documented, and careful attention to patient positioning is warranted.
Paclitaxel, Docetaxel, and Gemcitabine
Paclitaxel, docetaxel, and gemcitabine are relatively new chemotherapy agents that are often combined with cisplatin or carboplatin for the treatment of lung cancer.72-75 These agents can cause dose-related pulmonary toxicity in the form of pneumonitis. The pathophysiology of pneumonitis is unclear but may be related to a capillary leak.76 Pneumonitis generally resolves after treatment with glucocorticoids but can occasionally progress to pulmonary fibrosis.77,78 Surgery should be delayed until the acute pneumonitis resolves.
The anthracycline class of chemotherapy agents (doxorubicin, daunorubicin, epirubicin) is generally not used in the treatment of lung cancers. The anthracyclines are, however, frequently used in the treatment of breast cancers, sarcomas, and lymphomas, among others. The anthracyclines produce a cumulative dose-dependent cardiotoxicity, which is manifested by a nonischemic dilated cardiomyopathy.79 Formal testing of left ventricular function should be considered in patients with a history of anthracycline chemotherapy, especially if there are symptoms consistent with decreased cardiac function.80
Bleomycin is an older chemotherapeutic agent that is still used today, most commonly for germ cell tumors like testicular cancer.81 This agent causes pulmonary fibrosis in up to 10% of patients.82 The pathophysiology is not entirely clear but may be related to the development of free radicals.83 It seems, however, that increased fraction of inspired oxygen concentration (FiO2) can exacerbate or provoke the toxicity,84,85 perhaps even years after exposure to bleomycin.86 The threshold of oxygen toxicity in terms of FiO2 or duration of exposure to high oxygen concentration is unclear, and some groups do not recommend oxygen restriction during the brief perioperative period.87 In the authors’ (and editors’) opinion, it seems prudent to limit inspired oxygen to the lowest inspired concentration that adequately maintains saturation intraoperatively—a challenge during one-lung ventilation (OLV). Because the hypoxemia associated with OLV is primarily due to intrapulmonary shunt, raising the FiO2 may not improve systemic oxygenation profoundly anyway (see also Chapter 3 on the physiology of OLV).
Other Common Chemotherapeutic Agents
Many other chemotherapeutic agents including etoposide, pemetrexed, irinotecan and vinorelbine have been used in the treatment of lung cancers. These agents cause some degree of bone marrow suppression as well as nausea and vomiting. A complete blood count to assess the potential for anemia and thrombocytopenia, a complete metabolic panel, and a careful assessment of volume and nutritional status are indicated preoperatively. Because many agents produce neurotoxicity that may increase the risks of peripheral nerve injuries, special attention to patient positioning is warranted. A summary of chemotherapeutic agents and their perioperative implications appears in Table 9–1.
Table 9–1. Chemotherapeutic Agents and Their Perioperative Implications
Treatment of malignancy often involves therapeutic ionizing radiation. This treatment damages DNA in cells exposed to the radiation beams. Despite strategies to minimize or avoid damage to normal tissue cells, radiation therapy often damages noncancerous cells and may produce toxicities that have important perioperative implications.
Radiation causes endarteritis with vascular and capillary damage. Chronic tissue hypoxia leads to fibroblast proliferation and eventual scarring and fibrosis of the affected tissue. When natural anatomic planes are obliterated, surgical dissection is difficult, increasing the potential for blood loss. Occasionally surgical dissection is so difficult that resection may have to be abandoned.
Pulmonary toxicity is a common complication found 2 to 6 weeks after the conclusion of radiotherapy. It may be confused with other causes of pulmonary disease such as infection or chemotherapy-induced pulmonary toxicity.88 Indeed, radiation therapy with concurrent chemotherapy may increase the risk of developing pulmonary toxicity.89 Pulmonary toxicity generally starts as hyperemia and increased pulmonary secretions, and later progresses to pneumonitis.90 Occasionally, pneumonitis leads to irreversible pulmonary fibrosis.90 Patients with a history of radiation therapy should be questioned about pulmonary symptoms. Any recent dyspnea or change in symptoms requires further investigation. If a patient has acute, radiation-induced pneumonitis, surgery is ideally delayed until pneumonitis resolves. Radiation pneumonitis is often treated with a prolonged steroid taper, so patients with a history of pneumonitis may be at risk for adrenal insufficiency. Patients with extensive pulmonary fibrosis from radiation are probably not good surgical candidates. Exercise tolerance will generally be impaired and standard preoperative spirometry will likely show a restrictive defect.91
Besides pulmonary toxicity, radiation can cause cardiac toxicity in the form of myocardial fibrosis and diastolic dysfunction,92 valvular abnormalities,93 dysrhythmias,94 and accelerated coronary artery disease if the radiation window included the heart. A careful history combined with an assessment of exercise tolerance is generally sufficient to rule out significant radiation-induced cardiotoxicity. Although the pathophysiology of the cardiotoxicity is unique, the standard method for cardiac evaluation described earlier should properly identify patients with radiation-induced cardiac injury.
Pulmonary rehabilitation is frequently used in the nonsurgical treatment of patients with severe chronic obstructive pulmonary disease (COPD) to reduce symptoms. Rehabilitation does not directly impact lung mechanics per se, but improves a patient’s exercise tolerance for a higher workload without lactic acidosis.95 Pulmonary rehabilitation often consists of supervised exercise for 3 to 4 hours a day for 6 to 12 weeks. Smaller studies suggest that preoperative pulmonary rehabilitation is beneficial, particularly before lung-volume reduction surgery.96,97 Because pulmonary rehabilitation takes time and resources, its use preoperatively depends on the institution. It may be too time-consuming before resection of malignant lesions. The benefits of short-term pulmonary rehabilitation have not yet been thoroughly studied.
Active cigarette smoking has long been known to be a risk factor for pulmonary complications after surgery.98,99 Cigarette smoking decreases ciliary function; increases sputum production, airway reactivity, and carboxyhemoglobin levels; and impedes wound healing, all of which affect pulmonary complications. The timing of smoking cessation before surgery, however, has been a subject of some controversy. Older studies suggest no decrease in pulmonary complications (and perhaps a paradoxical increase) if smoking cessation is within 4 to 8 weeks before surgery.100,101 We do know that carboxyhemoglobin levels decrease (and thus shift the oxy-hemoglobin curve rightward favoring delivery of oxygen to the tissues) within 12 hours of smoking cessation.102 Two recent studies did not show an increase in pulmonary complications with smoking cessation within 4 weeks of surgery.103,104 In our opinion, with additional data suggesting no increase in harm, smoking cessation should be encouraged. Not doing so may neglect a powerful incentive for a patient’s overall health. Further studies may help to define the optimal timing of smoking cessation with respect to pulmonary complications.
PERIOPERATIVE RESPIRATORY MEDICATIONS
Chronic lung disease such as COPD is a known risk factor for postoperative pulmonary complications.105 Controlling the obstructive symptoms preoperatively with medications such as bronchodilators is recommended.106,107 Long-acting bronchodilators and inhaled steroids should be continued on the morning of surgery. Acute shortness of breath or sputum production from an exacerbation of COPD should prompt postponement of an elective thoracic procedure until breathing is back to the patient’s baseline.
In the intensive care setting, systemic glucocorticoids are often given to patients who are difficult to wean from mechanical ventilation or to patients with acute respiratory distress syndrome (ARDS). Some clinicians have suggested giving steroids prophylactically in the perioperative setting. As in ARDS, in which the data on steroid use are conflicting, changes in doses and dosing schedules may confound any potential benefit. The limited data available do not support prophylactic use of steroids before thoracic surgery.108
Patients with metastatic lung cancer generally do not undergo pulmonary resection but may need other thoracic surgeries such as pleurodesis or airway or esophageal stenting. Lung cancer may metastasize to any organ in the body, but several locations are more common and warrant special consideration including the liver, adrenals, bone, and brain. In one autopsy study, hepatic metastases were found in more than 50% of patients with lung cancer.109 The lesions are frequently asymptomatic until late in the course of the disease. They may be detected by liver enzyme abnormalities or CT or PET scans. Metastases to the adrenal gland, often asymptomatic, do not interfere with the patient’s ability to secrete glucocorticoids or mineralocorticoids. Bony metastases can cause pain and hypercalcemia. Patients with metastases to bone are likely to be taking narcotics for pain and require an evaluation of serum calcium to rule out hypercalcemia. Metastasis to a thoracic vertebra may complicate epidural placement for postoperative pain. Finally, brain metastases may cause focal neurologic deficits and seizures. Antiepileptic medicines should be continued in the perioperative period.
METABOLIC AND PARANEOPLASTIC EFFECTS OF CANCER
In addition to the possibility of metastases, any patient with cancer should be evaluated for metabolic and paraneoplastic symptoms, particularly patients with small-cell lung cancer. Many patients with cancer are malnourished, so a complete metabolic panel is indicated. As mentioned previously, bony metastases can cause hypercalcemia, which can lead to cardiac arrhythmias. If a patient is malnourished, obtaining an ionized calcium level may be useful to account for calcium’s binding to albumin.
The syndrome of inappropriate anti-diuretic hormone secretion (SIADH), where the hypothalamus continues to secrete ADH despite an adequate circulating blood volume and plasma osmolarity, may be present in patients with small-cell lung cancer.110 These patients may exhibit hyponatremia with low plasma osmolarity, urine osmolarity more than 100 mOsm/kg and high urine sodium concentration. SIADH generally resolves with treatment of the underlying lung cancer, but profound hyponatremia should be treated before a surgical procedure to avoid further fluid shifts and potential brain edema.
In Eaton-Lambert syndrome, an autoimmune syndrome associated with small-cell lung cancer, there are antibodies against the presynaptic voltage-gated calcium channels at the motor end plate.111 The antibodies decrease the calcium influx needed to release acetylcholine. The net effect is less acetylcholine in the motor end plate and muscle weakness. Repeated stimuli typically improve the muscle weakness. Patients with Eaton-Lambert syndrome are profoundly sensitive to both non-depolarizing and depolarizing neuromuscular blockers. The symptoms of Eaton-Lambert syndrome are similar to, and often confused with, the symptoms of myasthenia gravis. Myasthenia gravis is caused by autoimmune-mediated antibodies against the nicotinic acetylcholine receptor.112 Such patients, who may be evaluated before a thymectomy, suffer muscle weakness and fatigue with repeated muscle stimulation. They are also profoundly sensitive to non-depolarizing neuromuscular blockers but are resistant to depolarizing blockers such as succinylcholine. In summary, patients with myasthenia gravis may be resistant to succinylcholine and sensitive to non-depolarizing neuromuscular blockers; patients with Eaton-Lambert syndrome are sensitive to both types of neuromuscular blockers. Plasma cholinesterase activity may decrease in patients with myasthenia gravis after preoperative plasmapheresis or use of an anticholinesterase (eg, pyridostigmine). Thus, succinylcholine may have a prolonged effect in these patients.
Cancer is a well-known risk factor for deep vein thrombosis (DVT) and pulmonary venous thromboembolism and, combined with another risk factor, surgery, makes the perioperative period one of risk for both conditions. In one study, incidence of DVT or pulmonary embolism was 7.4% after pneumonectomy for malignancy.113 Some form of prophylaxis is often used. Lower extremity sequential compression devices are one example. Prophylaxis with heparin or low-molecular-weight heparin may be considered as well, but timing of surgery and epidural catheter placement and removal must be carefully coordinated.
LUNG ISOLATION AND POSTOPERATIVE PAIN CONTROL
Lung isolation is covered extensively in Chapter 5 of this text but is worth consideration in the preoperative period. Lower airway difficulties may be predicted by review of the preoperative chest x-ray, CT scans, or preoperative bronchoscopy for masses that may affect airway management, such as choice of lung isolation or tube size. Similarly, pain control is also discussed in Chapter 24. However, a plan for pain management should be considered before surgery since some techniques (thoracic epidurals) are implemented before the induction of general anesthesia.
CONCLUSION AND RECOMMENDATIONS
Preoperative evaluation of the thoracic surgical patient requires a thorough, multidisciplinary approach. All patients should have spirometry and DLCO measurements. If values are less than 80% of predicted, the predicted postoperative values should be calculated. If values are less than 40% of predicted, exercise testing should be performed to further stratify the patient’s risk. Cardiac evaluation requires a consultant cardiologist to help manage decisions regarding stress or invasive testing, the discontinuation of anticoagulation, and optimization of perioperative cardiac medications. Particular attention should be paid to right heart function, since lung resection adds an additional strain on the pulmonary vasculature. For patients with cancer, a thorough history pertaining to chemotherapeutic agents and radiation is needed. When applicable, the effects of metastases, masses, and metabolism should be considered as well. Finally, patients who are active smokers should be counseled about smoking cessation.
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