Objectives

1. Understand the factors that determine perioperative risk.
2. Understand when perioperative epidural analgesia improves outcomes.
3. Be familiar with factors that increase mortality in lung volume reduction surgery.
4. Know which drugs should be utilized for airway management in patients with asthma and COPD.
5. Understand anesthetic management of patients with pulmonary hypertension.

Key words

anesthesia; lung disease; management; surgery

Abbreviations

CABG = coronary artery bypass grafting; DLCO = carbon monoxide diffusing capacity of the lung; LMA = laryngeal mask airway; PEFR = peak expiratory flow rate; PRF = postoperative respiratory failure

Changes in medical care and insurance have led to preoperative evaluations being performed the day before surgery, even for high-risk surgeries in the thorax and upper abdomen. Physicians involved in preoperative evaluation (anesthesiologists, cardiologists, pulmonologists, and primary care practitioners) need to be knowledgeable about the proposed surgery and anesthetic implications to accurately determine the patient’s perioperative risks. A patient with severe restrictive lung disease is a reasonable candidate for upper or lower extremity surgery with regional or general anesthesia, but is at a significant perioperative risk for thoracic surgery.

The proposed methods to be utilized in the surgery are also important in risk evaluation. Laparoscopic surgery of the upper abdomen is associated with significantly less pulmonary morbidity and can be performed in patients who have significant lung disease without significantly increasing their perioperative risk. In contrast, open abdominal procedures are associated with significant pulmonary morbidity and are poorly tolerated in patients with severe lung disease.

Perioperative risks are decreased when a specialized surgical procedure is performed frequently at a hospital¹ and, conversely, increased when the surgical procedure is performed rarely. Therefore, practitioners involved in perioperative evaluations need to know the risks involved for a specific procedure at the proposed hospital. For high-risk procedures, physicians should consider referring the patient to a center where the procedure is performed frequently.

Perioperative Analgesia

Perioperative epidural analgesia has been shown to be important in decreasing pulmonary complications. A recent meta-analysis² suggested that a significant number of perioperative complications were decreased by the administration of epidural analgesia (epidurals that included local anesthetics alone or in combination with opioids). The incidence of perioperative deaths, myocardial infarctions, pulmonary emboli, and deep venous thromboses was shown to be significantly decreased in this meta-analysis. In a randomized, multicenter, controlled trial of 915 patients undergoing major abdominal surgery with epidural analgesia (utilizing narcotics and local anesthesia) for 72 h, the authors documented that there was no difference between the control group and experimental group in terms of mortality.³ However, there was a significant decrease in the frequency of respiratory failure in the experimental group, which had received epidural analgesia; the authors found that 15 patients would need to have received epidural analgesia to prevent one episode of respiratory failure.³ The investigation also found that pain scores were significantly lower in the epidural group.³

Another randomized, controlled trial of epidural analgesia was recently performed in the Veterans Hospitals.⁴ This investigation involved 1,021 patients who underwent surgery for intra-abdominal aortic, gastric biliary, or colon operations. The patients were elderly with a mean age of about 67 years. Approximately 33% of the patients had the diagnosis of COPD, and almost 40% of the patients were active smokers. In this study, epidural analgesia did not decrease mortality, except in patients who underwent aortic repairs.⁴ The patients who underwent aortic vascular surgery and received epidural analgesia (that included local anesthesia) had a significant decrease in their incidence of myocardial infarctions, respiratory failure, and stroke compared with the group that was treated with parenteral analgesia. Again, the patients who received epidural analgesia had significantly better pain control. Finally, the length of intubation and length of ICU stay was significantly shorter in patients who underwent aortic vascular surgery and received epidural analgesia.⁴ Therefore, it seems prudent to administer epidural analgesia, when possible, to patients undergoing high-risk operations such as aortic, other vascular, abdominal, or thoracic surgeries.

Perioperative Beta-Blockade

Numerous investigations have shown that the administration of perioperative beta-blockade or alpha-blockade significantly decreases the incidence of ischemia, myocardial infarctions, and death.^5-7 Every attempt should be made to administer b-blockers or a-blockers to patients who are at high risk for ischemic events. These patients are those who are scheduled for high-risk surgeries (see above) and have a history of coronary artery disease, stroke or cerebral vascular events, renal failure, or diabetes. There are very few data to suggest that patients with COPD have increased problems with perioperative beta-blockade. One of the original investigations was performed in a Veteran’s hospital population, in which a large percentage of the patients had COPD and smoked.^6,7

COPD

Lung Volume Reduction Surgery

Some of the most important data in the area of perioperative complications have come from the National Emphysema Treatment Trial Research Investigation.⁸ The main goal of the investigation has been to determine the survival and exercise capacity of surgical patients 2 years after lung volume reduction surgery and to compare these findings with those in a control group of similar patients who underwent medical therapy. No previous randomized, controlled investigations had included so many patients or included a medical treatment group. The results of these studies can be generalized when considering perioperative risks in COPD patients, as the data were generated in a trial of thoracic surgery in patients with severe COPD. Patients with severe COPD are often denied elective surgery; however, the results of the National Emphysema Treatment Trial are reassuring in that only the patients with the most severe COPD had a significant increase in their perioperative mortality.

Some of the results of the investigation were reported⁸ when a subgroup of patients were found to exceed the guidelines for perioperative mortality (a 30- day mortality cut-off of > 8% had been adopted as unacceptable). Patients had been included in the investigation if they had an FEV₁ of ≤ 45% of predicted value but ≥ 15% of their predicted value. The patients also had to have a total lung capacity ≥ 100% of predicted value and a residual volume that was ≥ 150% of the predicted value, a PCO2 of ≤ 60 mm Hg while breathing room air, a PaO₂ of ≥ 45 mm Hg while at rest and breathing room air, and an ability to walk > 140 m (459 feet) in 6 min. In addition, patients had to complete a measurement of carbon monoxide diffusing capacity of the lung (DLCO ) but were not excluded on the basis of the value. Cessation of smoking for 6 months was required before extensive preoperative testing that included physiologic tests and quality of wellbeing questionnaires. All patients completed 6 to 10 weeks of pulmonary rehabilitation, after which they were tested again and then randomly assigned to receive either surgery or medical treatment.

The data and safety monitoring board reviewed subgroups of patients every 3 months. In April 2001, these analyses suggested that a low FEV₁ (≤ 20% of predicted value), a homogeneous pattern of emphysema, and a high perfusion ratio predicted an increased risk of mortality. Also, a low FEV₁ (≤ 20% of predicted value) and a low DLCO were associated with an increased risk of 30- day mortality. Additional analyses led to the identification of a high-risk subgroup with a low FEV₁ (≤ 20% of predicted value) and either a low DLCO (≤ 20% of predicted value) or a pattern of homogeneous emphysema. These characteristics were associated with an increased risk of death after lung volume reduction surgery, as patients with all three characteristics had a 30-day mortality rate of 25%.⁸ These patients most frequently died of respiratory complications (90% of the patients), and pneumonia was diagnosed in 30% of these high-risk patients within 30 days of their operations.

These important results suggest there are pulmonary function data that define a group of patients with COPD who should not undergo elective thoracic surgery, as their perioperative mortality is extremely high. These results were generated in a large, multicenter trial and so should be considered applicable to the population of patients with COPD. Similarly, patients with a low FEV₁ (≤ 20% of predicted value) and a low DLCO (≤ 20% of predicted value) might be at high risk for mortality after surgery in the upper abdomen, where perioperative pulmonary function can be compromised. Notably, no single pulmonary function test identified a group at high risk of increased mortality. Although advanced age, low values on the 6-min walk test, and hypercapnia were associated with a slightly increased mortality rate after lung volume reduction surgery, these variables did not identify patients who were at an increased risk when compared with similar patients who received medical treatment.

Noncardiac Surgery

The National Veterans Administration Surgical Quality Improvement Program has recently developed and validated a preoperative risk index for predicting postoperative respiratory failure.^9,10 An index was formulated based on data from 81,719 patients and then validated using 99,390 patients. Postoperative respiratory failure was defined as mechanical ventilation for > 48 h after surgery or the need for reintubation and institution of mechanical ventilation after extubation. The investigation excluded female patients, ventilator-dependent patients, and comatose patients or patients who were not to be resuscitated. The investigation found that postoperative respiratory failure (PRF) developed in 3.4% of postoperative patients. The factors that were associated with PRF included abdominal aortic aneurysm repair, thoracic surgery, neurosurgery, upper abdominal surgery, peripheral vascular surgery, neck surgery, emergency surgery, albumin level < 30 g/L, BUN level > 30 mg/dL, dependent functional status, age, and COPD. Once again, the type of surgery is of the utmost importance in determining a patient’s risk for perioperative problems. The only factor that possibly might be altered preoperatively in the index is the BUN level. The same research group developed a multifactorial risk index for postoperative pneumonia after major noncardiac surgery.⁹ Using the same patients as discussed for the PRF index, patients were defined as having postoperative pneumonia when they met the Centers of Disease Control definition of nosocomial pneumonia. This definition includes rales or dullness to percussion on physical examination and either new purulent sputum, a positive blood culture, or isolation of a pathogen from a pulmonary sample. The definition also includes the patient with a new pulmonary infiltrate or pleural effusion and isolation of a pathogen from a pulmonary sample. However, this definition is not accepted worldwide for the diagnosis of nosocomial pneumonia.¹¹ The investigation did not include patients who had received preoperative assisted ventilation.

The investigators found that 2,466 of the patients investigated (1.5%) developed postoperative pneumonia.⁹ The mean age of patients who developed pneumonia was about 69 years, whereas the patients who did not develop pneumonia averaged about 61 years. Patients in whom pneumonia developed also had respiratory failure, systemic sepsis, cardiac arrest requiring cardiopulmonary resuscitation, prolonged ileus, and myocardial infarctions. The patients who developed pneumonia had a 21% perioperative mortality rate, whereas those who did not develop pneumonia had a 2% mortality.⁹ The Risk Index that predicted postoperative pneumonia includes high-risk surgical procedures (see above), age, poor functional status, and history of COPD. However, history of cerebrovascular accident and transfusions > 4 units also increased the risk of pneumonia. Chronic steroid use, smoking, and drinking alcohol also increased the risk of perioperative pneumonia. Patients may be able to decrease their risk of perioperative pneumonia by abstaining from alcohol and smoking and perhaps by postponing surgery until steroid treatment can be safely discontinued.

Cardiac Surgery

A retrospective investigation from Canada documented that in 1,829 sequential patients, prolonged ventilation after coronary artery bypass grafting (CABG) occurred more frequently when patients had COPD (twofold increased incidence of prolonged ventilation).¹² Other factors that increased the chances of postoperative ventilation included unstable angina, ejection fraction of < 50%, preoperative renal failure, female sex, and age > 70 years. This investigation found that the perioperative mortality rate increased to 18% when patients required prolonged mechanical ventilation.¹²

However, in a prospective investigation of 272 patients who underwent CABG in Greece, mild to moderate COPD did not appear to influence perioperative outcome significantly.¹³ Routine spirometry was performed to diagnose COPD. Among the patients with COPD who underwent CABG, the length of stay was 8 days and the perioperative mortality rate was 1.4%. In comparison, patients who did not have COPD had a 7.5-day hospital stay and a 0.7% perioperative mortality; thus, the results are similar.¹³ Therefore, in patients with COPD, the risk of prolonged intubation or mortality from CABG procedures is not clear. However, if a patient with COPD also has significant cardiac disease, renal failure, or diabetes and is currently smoking,¹⁴ he or she appears to have a significant risk for prolonged intubation and perioperative complications.

Anesthetic Considerations

The drug and anesthetic options for COPD patients and asthma patients are similar and will be discussed below.

Asthma

Stable asthmatics have no significant increased perioperative risk from their disease; however, there are few data regarding perioperative risk in patients with poorly controlled asthma. Therefore, all anesthesiologists attempt to anesthetize patients who have been maximally treated. Asthmatics should be distinguished from patients who smoke and have increased airway reactivity or from patients with COPD, as the airway reactivity is caused by different etiologies and the treatment differs. However, the anesthetic management of all patients with increased airway reactivity and hyperinflated lungs is often similar.

Preoperative Assessment

Patient characteristics associated with poorly controlled asthma include diaphoresis, inability to talk, and silent respirations, as well as the usual symptoms of prolonged expiration, use of accessory muscles, and wheezing.¹⁵

The more objective way to quickly assess the functional status is to compare the patient’s current peak expiratory flow rate (PEFR) to his or her personal best or predicted PEFR. A > 50% reduction in PEFR is indicative of a severe asthma exacerbation. Arterial blood gas sampling is not necessary to determine whether a stable patient is acceptable for surgery. However, arterial blood gas sampling may be useful in the management of severe asthmatics who need emergency surgery.

Poorly Controlled Airway Reactivity: Anesthetic Considerations

Mild sedation before entering the operating room may help extremely anxious patients. The short-acting benzodiazepine midazolam is an excellent agent that can be given IV (0.05 to 0.1 mg/kg IV) or, in small children, orally (0.5 to 1 mg/kg, with a maximum of 15 mg). At appropriate doses, midazolam produces reliable anxiolysis and, frequently, anterograde amnesia. Bronchodilators should be given just prior to induction of anesthesia regardless of the recent course of the disease, as airway manipulation stimulates airway reflexes. Metered-dose inhalers with spacers have been shown to be equally as effective as nebulizers and are, due their ease of use, the preferred choice for preventive preoperative treatment.^16,17 In addition, at most hospitals, patients are advised to bring their inhalers to the hospital on the day of surgery.

If general anesthesia is planned, induction of anesthesia is frequently achieved by IV hypnotics, such as propofol (1 to 2.5 mg/kg), thiopental (3 to 5 mg/kg), etomidate (0.2 to 0.5 mg/kg), or ketamine (1 to 2 mg/kg). Ketamine, because of its bronchodilatory effects in an animal model,¹⁸ may be preferred over thiopental, which can release histamine.19 However, there are no controlled studies in humans confirming this finding.

Similarly, propofol is believed to more profoundly depress airway reflexes than thiopental. Eames et al²⁰ demonstrated that respiratory resistance and wheezing were lower after induction with propofol than with thiopental or high-dose etomidate.

Laryngoscopy and intubation are intensively stimulating, and an inadequate depth of anesthesia can lead to a significant increase in airway resistance. Therefore, the plane of anesthesia achieved prior to laryngoscopy is more important than which induction agent is utilized. Because some of the more elderly patients may not tolerate the hemodynamic changes caused by large doses of IV hypnotic agents (with the exception of etomidate), the administration of potent volatile anesthetics, such as isoflurane, desflurane, or sevoflurane, should be considered to achieve an adequate level of anesthesia before manipulating the airway. This technique cannot be used in patients who have a full stomach or severe gastroesophageal reflux disease.

Other measures that can help blunt airway reflexes stimulated by laryngoscopy include the administration of IV lidocaine, the administration of inhaled lidocaine and salbutamol, or salbutamol inhalation alone.^20-23 The use of the laryngeal mask airway (LMA), instead of laryngoscopy and endotracheal intubation, should be considered in patients undergoing minor surgery, as airway reflexes are stimulated less significantly. After induction of general anesthesia, the LMA is placed (without laryngoscopy) in the posterior pharynx above the vocal cords. Note that the LMA does not protect the airway from aspiration and is not effective in ventilating patients who have a significant elevation in airway pressure.

Maintenance of anesthesia can be achieved by either IV infusion of hypnotic agents, such as propofol (50 to 200 mg/kg/min), or the administration of volatile anesthetics, which induce bronchodilatation in a dose-dependent fashion.²⁴ In addition to volatile anesthetics, opioids and muscle relaxants are frequently administered during surgery. Fentanyl (1 to 3 mg/kg) and its derivatives do not release histamine and therefore are the preferred choices among opioids. Various muscle relaxants, including atracurium and mivacurium, have been associated with histamine release and should be avoided in patients with asthma. Vecuronium (0.08 to 0.12 mg/kg) and rocuronium (0.6 to 1.2 mg/kg) are devoid of histamine release and are the preferred choices for muscle relaxation.^25,26 Asthmatics who are steroid-dependent should be given additional therapy perioperatively in order to avoid adrenal insufficiency during surgery. In addition, these patients are at high risk for myopathy when they receive repeated administration of any muscle relaxants. Therefore, muscle relaxants should be administered only for the duration of surgery.²⁷

With regard to mechanical ventilation, it is important to recognize that intraoperative bronchospasm can lead to dynamic hyperinflation of the lungs, low ventilation-perfusion ratios, increased alveolar-to-arterial oxygen gradients, and hypotension owing to a decreased venous return. Management of dynamic hyperinflation includes the use of low tidal volumes, low respiratory rate, and high inspiratory flows to maximize expiratory time. Positive end-expiratory pressure is associated with increased risk for barotrauma and should be avoided in this setting.^28,29 In severe cases, permissive hypercapnia is employed with low tidal volumes and respiratory rates to avoid barotrauma. Adequate muscle relaxation may be necessary to improve the patient-ventilator synchrony during an operation.

Pulmonary Hypertension

Cardiovascular diseases, including pulmonary hypertension, are a major cause of perioperative morbidity and mortality. The adrenergic response to surgical stimulation and the circulatory effects of anesthetic agents, endotracheal intubation, positive pressure ventilation, blood loss, fluid shifts, and alterations in body temperature impose an additional burden on an already compromised cardiovascular system. Optimal anesthetic management of patients with pulmonary hypertension requires a thorough understanding of the condition’s etiology and severity, the patient’s functional status, and appropriate medical management.

Regardless of the etiology, pulmonary hypertension in perioperative patients has significant impact on postoperative morbidity and mortality. Preoperative pulmonary hypertension has been shown to be a significant and independent predictor of hospital mortality in elderly patients undergoing cardiac procedures.³⁰ Similarly, in pregnant women, pulmonary hypertension carries a high risk of maternal death, often shortly after the delivery of the newborn.^31-33 Finally, in a retrospective study, patients with moderate to severe portopulmonary hypertension (mean pulmonary artery pressure, > 35 mm Hg) undergoing liver transplantation had a mortality up to 50%.³⁴ Appropriate preoperative evaluation—with regard to etiology, severity, reversibility, and discussions regarding whether elective surgery should be undertaken—is essential in patients with pulmonary hypertension.

Preoperative Assessment

The goals of the preoperative assessment are (1) to identify undiagnosed patients at high risk for pulmonary hypertension and (2) to identify the etiology and evaluate the functional status of patients with known pulmonary hypertension. Unlike primary (idiopathic) pulmonary hypertension, which is characterized by progressive dyspnea and a rapid downhill course, secondary pulmonary hypertension can be difficult to recognize clinically when signs are nonspecific and symptoms are primarily those of the underlying disease (ie, dyspnea and fatigue). Dull retrosternal chest pain resembling angina pectoris may be present. Fatigue and syncope on exertion may also occur secondary to decreased cardiac output related to increased pulmonary pressure. The signs of pulmonary hypertension are narrow splitting of the second heart sound, accentuation of the pulmonic component of the second heart sound, and a systolic ejection click. In advanced pulmonary hypertension, tricuspid and pulmonary valve insufficiencies and signs of right ventricular failure are found. In any patient in whom pulmonary hypertension is suspected, appropriate laboratory tests and imaging studies should be performed.

The role of the ECG in pulmonary hypertension is somewhat controversial. While it was demonstrated in one study that ECG may have a prognostic role in primary pulmonary hypertension with regard to survival,³⁵ another study found ECG inadequate as a screening tool to rule out clinically relevant pulmonary hypertension.³⁶ However, ECG changes, when present, are those of right-axis deviation, right ventricular strain or hypertrophy, and right atrial enlargement. Echocardiography is particularly helpful in evaluating patients with underlying valvular disease and, despite potential limitations in patients with severe COPD, the procedure is a feasible, noninvasive tool that can identify patients who have cor pulmonale.^37,38 Doppler ultrasonography is a noninvasive means of estimating pulmonary systolic artery pressure, but precise hemodynamic measurements can be obtained only with right heart catherization. Routine pulmonary function tests reveal no findings diagnostic of pulmonary hypertension. In chronic disease, there is often dilation of the central pulmonary arteries radiographically. In advanced pulmonary hypertension, right ventricular and right atrial enlargement may be present.

Once the diagnosis of pulmonary hypertension is confirmed, its etiology should be sought. With the diagnosis confirmed and etiology (primary vs secondary hypertension) established,^39,40 the patient’s functional status must be assessed and medical management optimized before the patient can be cleared for surgery.

Anesthetic Considerations

The major perioperative concern with pulmonary hypertension is circulatory compromise or failure. Significant increases in pulmonary hypertension lead to elevation of right ventricular afterload, myocardial wall tension, and increased oxygen consumption.^41,42 Subsequent depressed right ventricular function results in decreased cardiac output and potentially shock. Therapy for elevated pulmonary pressures is directed at optimizing preload, maintaining or increasing right ventricular coronary perfusion pressures and contractility, lowering pulmonary vascular resistance, and unloading the right ventricle.⁴³ Consequently, volume loading/replacement, inotropes, vasopressors, and vasodilators appear to be the therapy of choice. However, different hemodynamic constellations may exist in patients with pulmonary hypertension. A normotensive patient with elevated right ventricular preload is likely to benefit from vasodilators or inotropes but not volume loading. On the converse, a hypotensive patient with low right ventricular preload would benefit from volume loading and vasopressors but not from vasodilators or inotropes. To facilitate the management of these patients, invasive blood pressure monitoring, central venous catheters, pulmonary artery catheters, and/or transesophageal echocardiography are often used.

Given the hemodynamic sensitivity of patients with pulmonary hypertension, the potential hemodynamic consequences of sedating and anesthetizing patients must be appreciated. Induction of anesthesia with most IV hypnotics (ie, thiopenthal or propofol) frequently results in decreased preload and cardiac output. One exception is etomidate, which only minimally alters hemodynamics and may be the preferred agent. Because the sympathetic response to laryngoscopy can acutely increase right ventricular afterload with subsequent right ventricular dysfunction, a deep level of anesthesia and full paralysis should be assured before intubation is attempted. This can be accomplished with opioid supplementation or additional careful titration of volatile anesthetics via mask ventilation. However, in a dose-dependent fashion, volatile anesthetics exhibit negative inotropy, which, similar to hypoxia and hypercapnia, can worsen the symptoms of pulmonary hypertension.^44-47 Therefore, maintenance of anesthesia can best be accomplished with small to moderate doses of volatile anesthetics in combination with opioids that have minimal hemodynamic effect. The combination of various different agents in anesthesia is additive and the goals of anesthesia—namely sedation/amnesia, analgesia, and muscle relaxation—can be achieved by different means. Thus, in patients with moderate to severe pulmonary hypertension, high concentrations of volatile anesthetics ideally should be avoided.

Intraoperatively, a reduction of pulmonary vascular resistance can be achieved by altering ventilation patterns, inspired oxygen concentrations, and blood pH. Specifically, manipulation of the pulmonary vascular bed is a matter of regulating PaCO₂, pH, PaO₂, alveolar partial pressure of oxygen, and ventilatory mechanics. PaCO₂ is a potent mediator of pulmonary vascular resistance. Reducing PaCO₂ and increasing pH produces a consistent and reproducible reduction in pulmonary vascular resistance. Similarly, increases in PaO₂ and the alveolar partial pressure of oxygen also decrease pulmonary vascular resistance.^45-47

Because pain with increased sympathetic activity, subsequent hypoventilation secondary to opioid administration (in the patient breathing spontaneously), and ongoing fluid shifts may aggravate pulmonary hypertension, patients should be admitted to the ICU after major surgery for close monitoring.

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