Chronic Obstructive Pulmonary Disease

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Chapter 74

Chronic Obstructive Pulmonary Disease

Stuart P. Swadron and Phillip F. Gruber

Perspective

Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death worldwide. Although prevalence estimates vary by measurement methods and by population studied, there is general agreement that COPD is underdiagnosed and under-reported. Regardless of the success of smoking cessation programs, smoking behavior in the past several decades and the delay of the appearance of symptoms in an aging population virtually guarantee an increase in prevalence, especially in developed nations. In addition, it is becoming increasingly clear that other risk factors besides cigarette smoking contribute significantly to the worldwide burden of COPD.¹

It is estimated that COPD will be the fifth leading cause of lost disability-adjusted life years worldwide by 2030.² The financial burden of COPD is enormous, accounting for billions of dollars every year for treatment and lost productivity. The majority of these costs are related to hospitalization for acute exacerbations.³ Despite its enormous effects, COPD has received relatively less attention from basic medical researchers and clinicians than other diseases. Large multinational collaborations, such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD), sponsored jointly by the National Heart, Lung, and Blood Institute and the World Health Organization, have reinvigorated the scientific and medical communities frustrated by the unrelenting progressive nature of COPD and its poor response to existing therapies.

The definition of COPD is imprecise and incorporates advances in our understanding of its underlying mechanisms and natural history. In their consensus statement, the GOLD collaborators define COPD as “a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible.” They also state that “the airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.”⁴ This definition reflects new data underscoring the systemic nature of the disease, as well as a deliberate optimism with respect to new prevention and treatment strategies. It specifically avoids mention of chronic bronchitis and emphysema, two entities that have been traditionally included in the definition of COPD. Chronic bronchitis, defined as the presence of cough and sputum production for at least 3 months in each of 2 consecutive years, can occur without airflow limitation. Emphysema, the destruction of alveoli, is a pathologic term, not one that pertains to clinical diagnosis. Unlike with many earlier definitions of COPD, the GOLD collaborators also specifically exclude asthma, which is reversible airflow limitation. Whether reversible airflow limitation is considered to be part of COPD itself or caused by coexisting asthma is of limited significance to the emergency physician, who will continue to make every attempt to identify and reverse airflow limitation.

As many as 50% of all acute COPD exacerbations are not reported to physicians. In addition, not all reported exacerbations necessitate hospitalization.⁵ Nonetheless, in 2007 almost 2% of all hospital admissions in the United States were directly attributed to COPD, and it was considered a contributory factor in another 9%. In patients older than 65 years, the percentage of all hospitalizations related to COPD approaches 20%.⁶ As the severity of the underlying disease progresses, so does the frequency of exacerbations.⁷ Moreover, in a subset of patients, incomplete recovery from acute exacerbations may reflect a contribution of exacerbations to the pathophysiology of relentless disease progression.

Principles of Disease

Pathophysiology

In the past several decades the discovery that chronic airway inflammation plays a central role in the pathophysiology of asthma has led to an important change in its management, specifically, the liberal use of corticosteroids for treating moderate to severe disease. Airway inflammation is also at the center of the pathophysiology of COPD, but the inflammatory process of COPD differs from that of asthma. In COPD, neutrophils, CD8+ lymphocytes, and macrophages predominate in bronchial washings, whereas in asthma the cellular response is characterized by the presence of eosinophils.⁸ The inflammatory mediators differ in COPD, and several mediators, such as tumor necrosis factor, leukotriene B4, and interleukin-8, are linked to the destruction of parenchyma. These differences in the nature of the inflammatory response in COPD may account for its relatively poor response to current anti-inflammatory treatment compared with asthma.

Pathologically, the abnormalities in COPD are found throughout the lungs. Although certain changes may be more or less prominent in a given patient, most patients have at least some component of the two main pathologic entities: chronic obstructive bronchitis and emphysema. Evidence of airway inflammation is found from the trachea down to the smallest peripheral airways, which become progressively scarred and narrowed. An increase in both the number and size of mucus-secreting goblet cells results in the formation of mucous plugs, which further contributes to airflow obstruction. Damage to the endothelium impairs the mucociliary response that clears bacteria and mucus. The lung parenchyma is progressively destroyed over time, usually in a pattern of centrilobular emphysema. This consists of a destruction of alveoli, loss of lung elasticity, and the closure of small airways, which rely on the radial support of surrounding connective tissues to maintain their patency during expiration.

The combination of airway obstruction and obliteration of the pulmonary vascular bed results in a failure of gas exchange. Thus arterial blood gases (ABGs) may reveal both hypoxemia and hypercapnia. As the overall size of the pulmonary vascular bed decreases with time, chronic hypoxia induces a thickening of the vessel walls. Both of these factors contribute to the development of pulmonary hypertension, polycythemia and, eventually, right-sided heart failure (cor pulmonale).

The pathophysiology of COPD reflects the apparent imbalance between proteases and antiproteases that favors the destruction of connective tissue in the lungs. In one small subset of COPD patients with congenital α₁-antitrypsin deficiency, a lack of α₁-antitrypsin, an enzyme that inhibits neutrophil elastase, leads to the pathology of severe panacinar emphysema. In the majority of patients, however, the specific genetic factors are less well elucidated. Oxidative stress, the imbalance of oxidant to antioxidant activity in favor of oxidants, is another important facet of the pathophysiology of COPD. External oxidants are found in cigarette smoke, whereas the products of the inflammatory process result in intrinsic oxidants. Not only may oxidants cause direct parenchymal damage, but oxidative stress indirectly fuels further inflammation and protease activity.

Cigarette smoking, the most significant risk factor for the development of COPD, exerts its effects at multiple points in the inflammatory cascade of COPD, negatively affecting both the protease to antiprotease and oxidant to antioxidant balances. Although smoking cessation slows the progression of the disease, it does not end the chronic inflammatory process within the airways, indicating that mechanisms independent of smoking are involved.⁹ Moreover, although a majority of COPD patients have a significant smoking history, only a minority of smokers ever develop airflow limitation. This suggests the importance of other factors, both environmental and genetic.¹ Other identified causative factors include heavy occupational exposure to dusts and air pollution from indoor cooking, particularly in the developing world.^10–12 Long-term passive exposure to tobacco smoke and urban air pollution also appear to be contributory.^13,14 Although there is an association between early childhood lower respiratory tract infections and later development of COPD, a causal relationship is less certain.

Compensatory physiologic responses in COPD vary according to the balance of underlying pathologic derangements seen in individual patients. In a minority of patients, ventilatory drive is increased to maintain a near normal partial pressure of oxygen (PO₂), preventing any cyanosis. The resultant tachypnea may also cause a slightly low partial pressure of carbon dioxide (PCO₂). In patients with relatively normal blood gases, pulmonary hypertension and cor pulmonale may not occur until very late in the course of the disease.

Although the precise mechanisms are ill-defined, the pathologic processes of COPD extend beyond the cardiac and pulmonary systems. The effects of circulating inflammatory mediators, oxidative stress, and protease-antiprotease imbalance may be responsible for the weight loss, muscular wasting, metabolic derangements, and depression often seen in the later stages of disease. These features of COPD are partly responsible for the influence of COPD as a comorbid illness, even when the presenting complaint is nonpulmonary. COPD influences a variety of management decisions in the emergency department (ED), ranging from the choice of agents for procedural sedation and rapid sequence intubation to the appropriate disposition of patients with nonpulmonary diagnoses.

Staging the Severity of Disease

Most classifications of disease severity are based on quantitative measurements of airflow limitation, such as the forced expiratory volume in 1 second (FEV₁) and FEV₁/forced vital capacity (FVC) ratio. These indices are measured after any reversible airflow limitation is addressed by treatment with bronchodilator medications. The GOLD collaborators define four stages, beginning with a mild stage (stage I), when spirometry is abnormal but symptoms may not yet be apparent, and ending in very severe COPD (stage IV), when FEV₁ is less than 30% of predicted (Table 74-1). Frequent exacerbations are usually seen when the FEV₁ falls below 50% predicted (stages III and IV).^4,15,16

Table 74-1

The GOLD Classification of Severity of Chronic Obstructive Pulmonary Disease (COPD)

FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; PaCO₂, arterial partial pressure of carbon dioxide; PaO₂, arterial partial pressure of oxygen; SOB, shortness of breath.

Acute Exacerbations

Unlike asthma exacerbations, COPD exacerbations are not necessarily associated with major reductions in peak flow and FEV₁ measurements. As with COPD itself, the definition of an acute exacerbation is imprecise and relies on clinical parameters that are often subjective. The definition adopted by the GOLD collaborators is “an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant change in regular medication in a patient with underlying COPD.”

As with asthma, viral infection appears to be a frequent inciting agent in COPD exacerbations. Commonly implicated viruses include rhinovirus, respiratory syncytial virus, coronavirus, and influenza virus.17–19 Exacerbations associated with a viral cause are longer and more severe than those without an apparent inciting agent.^18,20

Controversy remains regarding the role of bacterial pathogens in acute exacerbations of COPD, because the evidence for the role of bacteria in the pathogenesis remains indirect. Almost half of all exacerbations are associated with negative cultures for the typical respiratory pathogens, such as Haemophilus influenzae, Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and Pseudomonas aeruginosa. In addition, these organisms are recovered from the tracheobronchial tree of patients in their chronic, steady state, suggesting that bacteria may play a more important role in the pathogenesis of chronic COPD than in acute exacerbations.²¹ Although molecular typing shows that recent colonization with new serotypes of the common pathogens is associated with an exacerbation, there is a possibility that this relationship is not causal. Experimental evidence of specific immunologic responses to bacteria in exacerbations suggests, however, that they do play a significant role.^22,23

Environmental factors, such as air pollution, are also implicated in COPD exacerbations. Indirect evidence for this relationship is largely derived from hospitalization rates for exacerbations during periods of increased air pollution.²⁴ Finally, in as many as one third of all COPD exacerbations, no specific cause can be identified.

In addition to having acute exacerbations, patients with COPD may experience worsening symptoms because of comorbid conditions, such as pneumonia, congestive heart failure (CHF), pneumothorax, pulmonary embolism (PE), lobar atelectasis, pleural effusion, or dysrhythmias. All of these are associated with COPD and may mimic or coexist with an acute exacerbation.

Clinical Features

Symptoms and Natural History

COPD patients have a long premorbid course during which decreases in air flow indices can be measured in the absence of symptoms. Intermittent cough or shortness of breath on exertion may be easily misattributed to poor physical conditioning. Moreover, patients may remain asymptomatic for many years by gradually limiting their activities in proportion to their pulmonary reserve. After several years, a daily productive cough frequently develops, and periods of dyspnea, the cardinal symptom of airflow limitation, increase. The clinical progression of COPD is slow and insidious, with gradual decreases in airflow punctuated by increasingly frequent and debilitating exacerbations. Eventually the patient becomes truly incapacitated by dyspnea on minimal or no exertion. Profound muscle wasting and weight loss and the emergence of cor pulmonale or chronic ventilatory failure are characteristic of end-stage disease. Figure 74-1 depicts the progression of COPD over time.

Figure 74-1 The progression of chronic obstructive pulmonary disease (COPD) over time. Natural history of COPD as measured by forced expiratory volume in 1 second (FEV₁) as a percentage of the baseline value at age 25. Normal nonsmoking individuals (A) have a progressive loss of FEV₁ but never become symptomatic with airway obstruction. Patients with COPD who quit smoking (B) experience an FEV₁ decline that parallels a nonsmoking, age-matched person. Patients with progressive COPD (C) can develop a loss of FEV₁ that may eventually produce symptoms, disability, and death. Some COPD patients (D) have steep declines in lung function during discrete clinical episodes. (From Heffner JE: Chronic obstructive pulmonary disease on an exponential curve of progress. Respir Care 47:586, 2002.)

Physical Examination

The division of patients with COPD into two phenotypes, the “blue bloater” (for the patient with chronic obstructive bronchitis) and the “pink puffer” (for the patient with emphysema), is outdated because many patients with COPD do not conform to these descriptions. Nonetheless, these classic images do highlight some of the important clinical features that may be encountered in the patient with COPD and have implications for management. Most patients have some combination of chronic obstructive bronchitis and emphysema and appear with a mixture of the syndromes described later. The precise identification of which process is predominant is less important than the evaluation of each patient and formulation of a specific treatment plan based on the individual clinical findings. In particular, the degree of chronic hypoxemia and dependence on home oxygen therapy, the presence of cor pulmonale, and evidence of comorbid illness, such as ischemic heart disease, should be determined.

In patients in whom chronic obstructive bronchitis predominates, the findings are those of chronic respiratory failure and cor pulmonale. Little air hunger or anxiety is present, and the combination of polycythemia and hypoxemia creates a plethoric, cyanotic appearance. Cough, as the clinical hallmark of bronchitis, is prominent and, when vigorous, causes expectoration. If acute ventilatory failure is present, the patient’s consciousness is clouded. This often is described as “irritable somnolence,” and asterixis may be present. Chronic ventilatory failure and cor pulmonale account for the prominent peripheral edema and chronic jugular venous distention. If there is relatively little emphysema, the thoracic anteroposterior diameter is normal, and the diaphragm is not abnormally low. The presence of severe bronchopulmonary secretions is evidenced by scattered rhonchi and rales, especially at both lung bases posterolaterally. These patients often have chronic carbon dioxide (CO₂) retention, requiring close monitoring of oxygen therapy because of their relative dependency on hypoxemic drive for ventilation.

When emphysema predominates, the patient is often thin, anxious, alert and oriented, dyspneic, and tachypneic and uses accessory muscles of breathing. The patient often self-administers positive end-expiratory pressure (PEEP) by using a pursed lip exhalation pattern to increase intraluminal bronchial pressure and provide internal support for bronchial walls that have lost their external support. Such patients usually assume a sedentary existence, chronically hunched forward. Gross lung overinflation occurs, with a low immobile diaphragm and an increased anteroposterior diameter of the thorax. Percussion of the chest reveals hyper-resonance, and auscultation demonstrates diminished breath sounds with faint end-expiratory rhonchi. Despite air hunger caused by the extensive lung parenchyma destruction, the patient maintains adequate oxygen saturation and often has near-normal ABG levels. The heart is small and hypodynamic, and the blood pressure is usually low.

Cardiac examination in a patient with suspected COPD is crucial in the diagnosis of cor pulmonale and coexisting left ventricular failure. A subxiphoid or retrosternal heave suggests chronic right ventricular hypertrophy (RVH), an S₄ suggests decreased left ventricular compliance, an S₃ indicates left ventricular failure, and a holosystolic blowing murmur of tricuspid insufficiency is secondary to right ventricular and tricuspid ring dilation. Accentuation of the pulmonic component of the secondary sound reflects pulmonary hypertension. Chronic visceral congestion causes hepatomegaly, hepatojugular reflux, and sometimes prominent abnormalities of liver function.

Diagnostic Strategies

Pulse Oximetry, Arterial Blood Gas Analysis, and Waveform Capnography

Pulse oximetry is part of the evaluation and monitoring of every patient with a COPD exacerbation. Comparison with prior values, both in crisis and in baseline state, helps to interpret measurements obtained during an acute exacerbation. The change in pulse oximetry from baseline or in response to emergency therapy is generally more important than absolute levels.

The stages of COPD severity correlate with arterial gas tensions. Abnormal ventilation-perfusion relationships of COPD produce only modest decrements in arterial partial pressure of oxygen (PaO₂) in its early stages (80-100 mm Hg). Later in the course of the disease, hypoxemia below 60 mm Hg stimulates respiratory centers, producing hyperventilation (PCO₂ over 35) and acute respiratory alkalosis. As pulmonary dysfunction progresses, the work of hyperventilation becomes cost-ineffective—that is, more CO₂ is produced by the effort than is cleared by the increased ventilation. Eventually, alveolar hypoventilation impairs gas exchange, leading to CO₂ retention and acute respiratory acidosis. With renal compensation through bicarbonate retention, the pH normalizes. Finally, when acute ventilatory failure is superimposed at this stage of the disease, an elevated PCO₂, lowered pH, and elevated bicarbonate are found.

ABG values, once a mainstay of ED evaluation of COPD patients, are of limited value in management of acute COPD episodes. Status and response to therapy often are monitored noninvasively by capnography and pulse oximetry. The presence of respiratory failure unresponsive to therapy (defined as PaO₂ <40 mm Hg, PaCO₂ >60 mm Hg, and pH <7.25 mm Hg) warrants consideration of admission to an intensive care unit, but clinical evaluation is much more important than any particular blood gas values.⁴ When baseline blood gas levels are not available, the usefulness of ABGs is even more limited, and interpretation should be based on the degree of acidemia present, which likely represents the extent of acute CO₂ retention. ABGs should not be used to determine whether a patient requires intubation or noninvasive ventilatory support (NIVS). These decisions should rather be guided by the overall state of the patient, progression of fatigue, comorbid illness, and response to therapy. Patients with very poor blood gas values may do well without intubation or NIVS, but others with mildly disturbed values may require urgent airway intervention. Thus measurement of ABGs should not be performed routinely in the ED and should be undertaken only in response to specific circumstances, such as irregular or apparently unreliable pulse oximetry values or when a single baseline correlation with end-tidal carbon dioxide (ETCO₂) is desired.

Waveform capnography represents the continuous quantitative measurement of exhaled CO₂. It has emerged as a potential diagnostic and monitoring tool in patients with acute respiratory distress. The appearance of the waveform may assist the clinician in differentiating acute exacerbation of COPD from other causes of acute dyspnea, such as CHF. In patients with obstructed airways, the plateau phase of the waveform typically steepens in proportion to the severity of the obstruction, as depicted in Figure 74-2. Unfortunately, in patients with COPD, the actual end-tidal PCO₂ measurements obtained from capnography do not correlate well with arterial PCO₂ measurements, especially in more severe disease. Nonetheless, the patterns and trends from capnography may be helpful in guiding management and assessing response to therapy.²⁵

Figure 74-2 Capnography tracing in bronchospasm and obstruction. The upslope at the beginning of the expiratory phase is blunted because of expiratory airflow limitation.

Despite the sensitivity of BNP in detecting the physiologic presence of heart failure, its utility as a routine test in the assessment of dyspneic patient is debated. Some data indicate that routine use reduces evaluation times, total costs, and diagnostic accuracy.31–33 Data on the clinical usefulness of BNP, however, are derived from studies that include patients with clear clinical features of either pulmonary or cardiac disease, casting doubt on its usefulness in the subset of patients who present a true diagnostic dilemma.^34,35 BNP measurements may be helpful in revealing patients with unsuspected CHF, but caution should be exercised to prevent over-reliance on this test (see the discussion of differential considerations).

Differential Considerations

The differential diagnosis of the acutely dyspneic and hypoxic patient is broad. The condition that is most commonly mistaken for COPD is cardiogenic pulmonary edema, which may manifest with dyspnea and wheezing (“cardiac asthma”). Other serious cardiac causes include myocardial ischemia and pericardial effusion. Important pulmonary diagnoses include pneumothorax, PE, pneumonia, asthma, acute respiratory distress syndrome, bronchiectasis, pulmonary fibrosis, pleural effusions, and tuberculosis. In addition, metabolic acidosis and shock may manifest as dyspnea and ventilatory failure.

In most cases, differentiation of COPD exacerbation from acute CHF can be made on clinical grounds. Nonetheless, a significant percentage of patients who come to the ED with acute dyspnea and an established diagnosis of COPD are ultimately diagnosed with acute CHF despite having no prior history of heart failure. The addition of a BNP assay to the ED evaluation of such patients identifies some in whom a new diagnosis of CHF is not suspected.³³

Because BNP can be elevated in association with right ventricular stretch, incautious interpretation of an elevated BNP may lead the clinician to favor the diagnosis of acute left-sided CHF and overlook cor pulmonale and PE, both critical considerations in the patient with COPD.³⁶ Moreover, acute CHF and COPD often coexist, and even severe elevations in BNP do not obviate the identification and treatment of acute pulmonary pathology. Thus, although BNP measurement may be helpful in the evaluation of the acutely dyspneic patient, it cannot be interpreted in isolation and must not supplant clinical judgment.

Acute pneumothorax can occur with COPD. This diagnosis should be actively pursued in patients with worsening respiratory status, especially when its onset is abrupt. In older patients with COPD, chest pain is often absent. A small pneumothorax cannot be excluded by physical examination and can be very difficult to detect on inspiratory chest films, especially in patients with bullous emphysema. Bedside ultrasound is a useful modality for diagnosing pneumothorax in the ED, particularly in major trauma, and may have a future role in diagnosing pulmonary edema.37,38 In assessing for pneumothorax, however, the presence of COPD may result in false-positive results, and data in this setting are limited.³⁹ Ultimately, it is appropriate to perform chest computed tomography (CT) when clinical suggestion of a pneumothorax remains high and results of plain films and ultrasound are nondiagnostic.

Patients with COPD are often sedentary and consequently at increased risk for venous thromboembolic disease.⁴⁰ The patient with cor pulmonale is at even higher risk because of increased blood viscosity, high peripheral venous pressure, and venous stasis. PE should be considered when an acute exacerbation is more severe than prior episodes, particularly if deterioration occurs quickly with no other apparent cause.⁴¹ Unfortunately, because there is significant overlap in their patterns of presentation, differentiating PE from a COPD exacerbation can be extremely difficult. Prophylactic measures to prevent venous thromboembolic disease are important considerations in the inpatient management of an acute exacerbation of COPD.

A negative screening with a sufficiently sensitive D-dimer assay (enzyme-linked immunosorbent assay [ELISA] or whole-blood agglutination) excludes venous thromboembolic disease in all but high pretest likelihood situations.42,43 Pretest probability can be assessed via any one of several structured, validated scoring systems. If either the D-dimer is elevated or the pretest probability for PE is high, CT pulmonary angiography should be performed.⁴⁴ This requires multislice CT capability and may include indirect CT venography to evaluate the lower extremities for deep vein thrombosis or lower limb duplex ultrasonography.^45–48 A more detailed discussion of the diagnostic evaluation and treatment of PE can be found in Chapter 88.

Lobar atelectasis occurs as a result of mucous plugging of bronchi and can be lethal. Similar to pneumothorax and PE, it may manifest abruptly. The chest film may show linear horizontal streaking or small flarelike shadows; more often, it is normal. Hypoxemic reactive airway patients with a protracted course unresponsive to bronchodilators should be presumed to have either PE or atelectasis. If PE is excluded, such patients often require endotracheal intubation and aggressive interventional pulmonary toilet.

Pneumonia is a common, devastating complication of COPD that leads to mortality in many patients. Its clinical appearance is more muted than the classically described lobar pneumonia of young adults. Classic symptoms of cough, fever, and toxicity are seen less often than the more nonspecific and subtle symptoms of malaise, weakness, decreased activity, and anorexia. Leukocytosis may or may not be present, and its presence should not be taken as indicative of infection because of its low specificity. Radiographic infiltrates may be subtle or absent, especially in patients whose lung parenchyma has been distorted or obliterated by emphysema, and correlation with previous radiographic studies may be necessary.

Rib fractures occur in patients with COPD secondary to trauma, but in patients receiving steroid therapy, they can be caused by vigorous cough alone. When rib fractures are identified, secondary pulmonary contusion and pneumothorax also are considered. An intercostal nerve block may relieve enough discomfort to restore baseline pulmonary function.

Electrolyte disturbances, such as hypokalemia, hypomagnesemia, hypocalcemia, or hypophosphatemia, may impair the contractility of muscles.

There are other treatable chronic, nonobstructive pulmonary diseases. For example, bronchiectasis is an often overlooked cause of purulent expectoration. It may accompany and contribute to COPD exacerbations. Although its pathologic characteristic is dilation, not constriction, of airways, the secretions that accompany it may result in an obstructive component. Active tuberculosis is considered in patients with infiltrates (not only apical), a chronic wasting course, and risk factors for active disease, such as human immunodeficiency virus (HIV) disease and homelessness. Sarcoidosis, which can manifest with chronic cough and constitutional symptoms, usually causes a dry cough and may be suggested on the basis of the chest film appearance.

Finally, there are some iatrogenic causes of acute decompensation in COPD. Many agents, such as beta-blockers and cholinergic agents, may directly or indirectly produce bronchospasm. A second group of potentially deleterious drugs is sedatives. It is important not to confuse hypoxic agitation with anxiety because patients with chronic respiratory failure are abnormally sensitive to the respiratory depressant effect of sedatives, and even small doses may significantly worsen hypoventilation.

Box 74-1 summarizes the causes of acute decompensation in the patient with COPD.

BOX 74-1 Causes of Acute Decompensation in the Patient with Chronic Obstructive Pulmonary Disease

Acute Exacerbations

Infectious

1. Viral

Rhinovirus, respiratory syncytial virus, coronavirus, influenza virus

2. Bacterial

Haemophilus influenzae, Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, Pseudomonas aeruginosa

3. Atypical bacteria

Chlamydia pneumoniae, Legionella

Air Pollution

1. Nitrogen dioxide

2. Ozone

3. Particulates, dust

Other Critical Events

1. Pneumothorax

2. Pulmonary embolism

3. Lobar atelectasis

4. Congestive heart failure

5. Pneumonia

6. Pulmonary compression (e.g., obesity, ascites, gastric distention, pleural effusion)

7. Trauma (e.g., rib fractures, pulmonary contusion)

8. Neuromuscular and metabolic disorders

10. Noncompliance with prescribed treatment regimens

11. Iatrogenic

a. Inadequate therapy

b. Inappropriate therapy (e.g., deleterious drugs)

Management

Until recently, the only modalities found to alter the progression of COPD and reduce mortality rates were smoking cessation and, for those with severe disease, chronic oxygen therapy.49,50 Outpatient therapy with long-acting bronchodilators and inhaled steroids may slow the progression of COPD⁵¹ and reduce exacerbation frequency,⁵² although the effects are modest. Vaccines are another important aspect of ongoing outpatient care. Although only influenza vaccines reduce mortality,⁵³ both influenza and pneumococcal vaccinations are recommended for COPD patients.⁴ An overview of the emergency assessment and management of COPD exacerbations is provided in Table 74-2.

Table 74-2

General Therapeutic Guidelines for Chronic Obstructive Pulmonary Disease Exacerbations

LIFE-THREATENING	MODERATE OR SEVERE	MILD
Address ABCs	Oxygen to maintain O₂ saturation near 90%	Oxygen to maintain O₂ saturation near 90%
Bag-valve ventilation, preoxygenation	Nebulized beta-agonist, anticholinergic	MDI or nebulized beta-agonist, anticholinergic
Intubation with or without rapid sequence technique	Noninvasive ventilation if severe	Consider oral or intravenous corticosteroid
In-line beta-agonist, anticholinergic	Intravenous corticosteroid	Consider oral antibiotic on discharge
Intravenous corticosteroid	Intravenous antibiotic
Intravenous antibiotic

ABC, airway, breathing, and circulation; MDI, metered dose inhaler.

It is important to consider an inciting or aggravating factor and provide specific therapy as discussed in text.

Oxygenation and Ventilation

All COPD patients in acute respiratory distress need continuous ECG and pulse oximetry monitoring. Patients who are hypoxemic should receive controlled oxygen therapy, with a goal of oxygen saturation as measured by pulse oximetry (SpO₂) of 88 to 92% or PaO₂ above 60 mm Hg.⁵⁴ The method of administration should be tailored to the clinical circumstances: nasal cannulae are well tolerated but are less useful for patients who are markedly tachypneic or mouth-breathing. Venturi masks are excellent for delivering a more reliable, high-flow, and adjustable concentration of supplemental oxygen but may be difficult for a distressed patient to tolerate.

Some patients with moderate to severe COPD and other chronic pulmonary diseases will respond to high-flow supplemental oxygen by developing hypercapnic respiratory failure. The mechanism for this response is debated but may be a result of several factors, including the suppression of hypoxic respiratory drive in patients accustomed to hypercapnia and the release of hypoxic vasoconstriction in poorly oxygenated areas of the lung, worsening ventilation-perfusion mismatch.55,56 Data from a prospective, randomized clinical trial clearly support setting a specific target of 88 to 92% and avoiding uncontrolled high-flow oxygen in dyspneic COPD patients, including in the prehospital environment.⁵⁷

The patient in terminal ventilatory failure is cyanotic, speechless, lethargic, usually and confused and has gasping, ineffective respirations. Such patients require immediate endotracheal intubation and mechanical ventilation. Because these patients have exhausted all pulmonary reserve, rapid sequence intubation should be performed with the goal of rapid paralysis and unconsciousness (see Chapter 1). For induction and paralysis, a combination of a hemodynamically stable sedative-hypnotic such as etomidate and a rapidly acting paralytic such as succinylcholine is an appropriate regimen.

Initial ventilator settings should include a fraction of inspired oxygen (FIO₂) of 100%, tidal volume in the 6- to 8-mL/kg range, and respiratory rate of 8 to 10 breaths/min in an assist-control mode with an inspiratory flow rate of 80 to 100 L/min. Sedation and analgesia are indicated to facilitate ventilation. Neuromuscular blockade is not routinely required and should be avoided when possible (see Chapter 1). Increased air trapping and resultant high intra-alveolar pressures induce intrinsic positive end-expiratory pressure (iPEEP) that can cause barotrauma. In addition, increased intrathoracic pressure decreases cardiac filling and output; therefore peak flow pressures and systemic blood pressures must be carefully monitored. If continuous capnography is not available, ABGs should be drawn after 15 to 20 minutes to ensure that ventilation is appropriate. In some settings, placement of an arterial line is helpful for monitoring blood pressure and ABG tensions. After intubation, permissive hypercapnia is essential to the ventilatory treatment of these patients, and subsequent normalization of pH and PCO₂ should be gradual over many hours. Low volume and rate settings will result in hypercapnia and respiratory acidosis, but this approach helps prevent associated barotrauma often seen in treating these patients. Moreover, hyperventilation alkalosis must be scrupulously avoided, particularly because patients may have preexisting chronic metabolic alkalosis. This alkalosis can result in seizures and dysrhythmias, especially with coexisting hypokalemia.

NIVS is an accepted alternative to invasive ventilation in many patients with ventilatory failure (see Chapter 2). NIVS can be highly effective in avoiding intubation, increasing pH, reducing PCO₂ and dyspnea in the first 4 hours of treatment, and reducing mortality rates.^58,59 If the patient fails NIVS and requires intubation, NIVS, at the least, optimizes preoxygenation for the intubation. Patients likely to benefit from NIVS are those with moderate to severe ventilatory failure and elevated PCO₂, but without marked hypoxemia.⁶⁰ NIVS cannot substitute for invasive ventilation in patients who are hemodynamically unstable or in whom respiratory arrest appears inevitable. On the opposite end of the spectrum, it remains unclear whether NIVS should be instituted in patients with mild to moderate exacerbations. Although the Cochrane systematic review stresses early NIVS therapy to prevent the development of worsening acidosis and need for intubation, there is insufficient evidence to recommend the routine use of NIVS in mild exacerbations.^59,61 Table 74-3 outlines inclusion and exclusion criteria for the use of NIVS.

Table 74-3

PaCO₂, arterial partial pressure of carbon dioxide.

Adapted from Rabe K, 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 176:532, 2007; and Soto F, Varkey B: Evidence-based approach to acute exacerbations of COPD. Curr Opin Pulm Med 9:117, 2003.

NIVS can be delivered by either nasal or full-face mask. It is not uncommon for patients to experience claustrophobia and panic with either type of mask. Coaching and reassurance may help some of these patients tolerate NIVS long enough to feel some relief of their dyspnea and anxiety. Moreover, some patients who do not tolerate nasal masks will tolerate full-face masks, and vice versa. Repeated and prolonged attempts at NIVS, however, in a patient who is panicked and in obvious respiratory failure should not delay definitive airway intervention if necessary.

Modes of ventilation include continuous positive airway pressure (CPAP) and biphasic positive airway pressure (BPAP). Patients with COPD and respiratory distress have significant iPEEP, and this acts as an inspiratory threshold for the patient and increases the work of breathing. Both modes of NIVS help to counteract this iPEEP and thereby decrease the work of breathing. Nasal CPAP is a simple technique, and 5 to 10 cm H₂O pressure is required. When bilevel positive airway pressure (BL-PAP, often referred to as “BiPAP”) ventilation, is used, expiratory positive airway pressures are typically set at 2.5 to 5 cm H₂O, whereas inspiratory pressures range from 7.5 to 15 cm H₂O.

If the patient experiences relief of dyspnea, has stronger respirations, and becomes more alert, intubation may be averted, but the patient must be diligently observed for deterioration. Increasing respiratory rate, lethargy, exhaustion, speechlessness, paradoxical abdominal breathing movements, and falling oxygen saturation despite therapy necessitate invasive ventilation.

The most important factor in the decision to intubate is the patient’s clinical status, not ABG measurements. Even in the face of a significant rise in PCO₂ with oxygen administration, intubation may be unnecessary if the patient’s clinical status has stabilized. Similarly, improving ABG values should not overrule the clinical impression of deterioration. Temporary improvement may be followed by exhaustion and respiratory failure. Box 74-2 outlines indications for invasive mechanical ventilation. Several of these criteria, adapted from the GOLD collaborators, are subject to interpretation, underscoring the critical role of clinical judgment in airway management decisions.

BOX 74-2

Proposed Indications for Mechanical Ventilation

Respiratory arrest

Worsening level of consciousness despite maximal therapy *

Cardiovascular instability (shock, heart failure)*

NIPPV failure or exclusion criteria (see Table 74-3)

Severe dyspnea with use of accessory muscles and paradoxical abdominal motion *

Severe tachypnea *

Life-threatening hypoxia

Severe acidosis and hypercapnia *

Other complications (metabolic abnormalities, sepsis, pneumonia, pulmonary embolism, barotraumas, massive pleural effusion)*

NIPPV, nasal intermittent positive-pressure ventilation.

^*For several of these parameters, criteria are deliberately imprecise; clinical decisions must be individualized in each case.

General Drug Therapy

Bronchodilators

Although bronchospasm is not the primary inciting event in acute COPD exacerbation, both beta-agonists and anticholinergic agents are considered first-line agents. The choice of agent for treating a given patient may depend on the respective side effect profiles of these two classes of drugs.62,63

Although many choices are available, inhaled albuterol, which is short acting with selective beta₂-receptor action, is the beta-agonist of choice. The nebulization dose of albuterol is 2.5 to 5.0 mg (0.5-1.0 mL of 0.5% solution). Most patients tolerate two to three rapid successive doses of oxygen-nebulized beta-agonist with little difficulty. Therapy must occasionally be titrated if the side effects of tremor, tachycardia, or ventricular ectopy are significant.

Anticholinergic agents block muscarinic receptors and prevent smooth muscle contraction while decreasing the release of secretions from submucosal glands. Inhaled anticholinergic agents are as effective as beta₂-agonists in COPD and can be used alone or in conjunction with beta₂-agonists as first-line therapy in acute exacerbations.⁶⁴ Although evidence regarding the efficacy of their coadministration is controversial, for moderate to severe exacerbations in the ED, these drugs should be given together for their possible synergistic effects.⁴ Anticholinergics can be administered by nebulization or metered dose inhaler (MDI) and are also effective for intubated patients. Ipratropium bromide, a quaternary ammonium compound, has been extensively studied in COPD. It has few systemic effects, yet has powerful bronchodilating properties. The nebulization dose is 0.5 mg, which may be repeated every half hour for a total of three doses and subsequently every 4 hours.

Long-acting bronchodilator agents, such as salmeterol (beta₂-agonist) and tiotropium (anticholinergic), are added to treatment recommendations for chronic stable COPD.⁴ Although these agents may reduce the frequency of COPD exacerbations, no role for their use in ED management of acute exacerbation has been defined.

The COPD patient with a mild to moderate exacerbation may be able to self-administer bronchodilator agents through use of an MDI with a spacer device, which is equally effective as nebulized treatment. Studies also demonstrate the efficacy and cost benefit of MDI therapy over nebulization in acutely hospitalized patients. Because of the smaller dose delivered with single MDI puffs, MDI protocols often involve multiple puffs at each administration interval. This mode of therapy should be considered only for stable, cooperative emergency patients. The intubated patient should receive bronchodilator therapy via in-line nebulization.

Methylxanthines, principally aminophylline, were once commonly used in COPD exacerbations. Evidence is not supportive of their use, however, because they do not improve outcomes, even when combined with beta-agonists and anticholinergic agents. Recommendations that include methylxanthines as a second-line therapy when other modalities have failed are tempered by concerns about toxicity, which may outweigh the positive effects of these agents.⁶⁵ If a rare patient is encountered who is taking methylxanthines on a chronic, ambulatory basis, additional methylxanthines should not be used in the course of treatment in the ED.

Corticosteroids

The anti-inflammatory effects of steroids provide a strong rationale for their use in acutely ill patients with COPD. Although steroids may not alter the immediate ED course, evidence points to a modest decrease in the relapse rate of acute exacerbations and improvement of dyspnea.66–68 For severe exacerbations necessitating admission, intravenous methylprednisolone or oral prednisone (1-2 mg/kg) is given early in treatment and continued daily.⁶⁹ Oral prednisone (40 mg once daily) is appropriate for discharged patients. Recommended doses of corticosteroids vary widely in the published studies. Consensus guidelines emphasize use of doses on the lower end of the accepted range to minimize common adverse effects, such as hyperglycemia, myopathy, and immunosuppression.^4,70

Antibiotics

In contrast to asthma exacerbation and acute bronchitis in the setting of normal lung function, in which antibiotics are of no benefit, some COPD patients with an acute exacerbation appear to benefit from antibiotic therapy.71–73 The GOLD collaborators recommend administering antibiotics to patients with an increase in sputum purulence and either increased dyspnea or increased sputum volume, as well as to any patients requiring invasive or noninvasive ventilation (see later discussion of pneumonia).⁴ Furthermore, some patients may have clinical pneumonia without radiographic evidence, which may also warrant antibiotic therapy. Because the potential benefits of antibiotics outweigh their adverse effects in most patients with acute exacerbations, these agents should be considered in patients in the ED.

Most of the randomized, controlled trials suggesting a treatment benefit with antibiotics were conducted before the emergence of widespread resistance. Amoxicillin, tetracycline, and trimethoprim-sulfamethoxazole were the most common antibiotics used in these studies. Although antibiotics with broader-spectrum coverage, such as the fluoroquinolones and third-generation cephalosporins, are commonly prescribed, the evidence for the superiority of these newer agents is indirect. The GOLD collaborators recommend use of antibiotics that reflect local patterns of antibiotic sensitivity to S. pneumoniae, H. influenzae, and M. catarrhalis.⁴ Studies suggest that short (3- to 5-day) courses of antibiotics, such as respiratory fluoroquinolones or macrolides, may be as effective as more traditional, longer (7- to 14-day) courses of β-lactams and tetracyclines.^74–76