Acute exacerbations of COPD are characterized by worsening of respiratory symptoms beyond normal day-to-day variations20 and are usually triggered by an infection or respiratory irritant. More than 75% of patients with acute exacerbations have evidence of viral or bacterial infection, with up to half specifically due to bacteria.21,22 Other important triggers for exacerbations are hypoxia, cold weather,23 β-blockers, narcotics, or sedative-hypnotic agents. The final common pathway for an exacerbation is the release of inflammatory mediators that result in bronchoconstriction, pulmonary vasoconstriction, and mucus hypersecretion. The work of breathing increases due to higher airway resistance and lung hyperinflation. The oxygen demand of respiratory muscles increases, generating additional carbon dioxide and causing hypercapnia, resulting in further physiologic stress.23 Acute exacerbations of COPD are primarily due to ventilation–perfusion mismatch rather than the expiratory airflow limitation seen with asthma exacerbations.24 Supplemental oxygen increases blood oxygen concentrations and can help reverse pulmonary vasoconstriction.
The most life-threatening feature of an acute exacerbation is hypoxemia (arterial saturation <90%). Signs of hypoxemia include tachypnea, tachycardia, systemic hypertension, cyanosis, and a change in mental status. With increased work of breathing, carbon dioxide production increases; alveolar hypoventilation creates arterial carbon dioxide retention and respiratory acidosis.
The patient tries to overcome severe dyspnea and orthopnea by sitting in an up-and-forward position, using pursed-lip exhalation, and engaging accessory muscles to breathe. Pulsus paradoxus (a drop of >10 mm Hg in systolic blood pressure during respiratory cycles) may be noted during palpation of the pulse or during blood pressure recording. Complications, such as pneumonia, pneumothorax, pulmonary embolism, or an acute abdomen, may exacerbate COPD. Other acute triggers include asthma, congestive heart failure, pneumonia, pulmonary embolism, tuberculosis, and metabolic disturbances.
With the history, seek causes for exacerbation and triggers plus sputum changes; then assess oxygenation and acid-base status, and perform a physical examination.
Pulse oximetry may identify hypoxemia, and capnography may identify hypercarbia. Arterial blood gas analysis is the best tool in acute evaluation for assessing oxygenation, ventilation, and acid-base disturbances. Arterial blood gases clarify the severity of exacerbation and the probable clinical course. Respiratory failure is characterized by an arterial PaO2 of <60 mm Hg or an arterial SaO2 <90% in room air. Respiratory acidosis is present if the partial pressure of carbon dioxide (Pco2) is >44 mm Hg. If the pH is <7.35, there is an acute and uncompensated component of respiratory or metabolic acidosis present.
In acute respiratory acidosis, the serum bicarbonate rises by 1 mEq/L for each 10-mm Hg increase in Pco2, and the pH will change by 0.008 × (40 – Pco2). In chronic respiratory acidosis, the bicarbonate rises by 3.5 mEq/L for each 10-mm Hg increase in Pco2, and the pH will change by 0.03 × (40 – Pco2) (Formulas 1 and 2). Changes outside of these ranges suggest an accompanying metabolic disorder (see chapters 15, "Acid-Base Disorders" and 62, "Respiratory Distress").
Frequently, patients with an acute COPD exacerbation are too dyspneic to perform bedside pulmonary function tests, and measurements are often inaccurate.2,3,4,5,6 Similarly, physical examination and physician estimates of pulmonary function are inaccurate.25
Assessment of sputum includes questions about changes in volume and color, especially an increase in purulence. An increase in sputum volume and change in sputum color suggest a bacterial infection and the need for antibiotic therapy.24,26 Sputum cultures usually contain mixed flora and do not help guide ED antibiotic selection.2,3,4,5,6
Radiographic abnormalities are common in COPD exacerbation and may identify the underlying cause of the exacerbation, such as pneumonia, or may identify an alternative diagnosis such as acute heart failure.27
The ECG can identify ischemia, acute myocardial infarction, cor pulmonale, and dysrhythmias. Measure levels in patients who take theophylline. Other tests, such as CBC, electrolytes, B-type natriuretic peptide, d-dimers, and CT angiography of the chest, are chosen based on clinical findings.
The goals of treatment are to correct tissue oxygenation, alleviate reversible bronchospasm, and treat the underlying cause (Table 70-2). Factors that influence therapy in the ED include a patient's mental status changes; the degree of reversible bronchospasm; recent medication usage and assessment for drug toxicity; prior history of exacerbation courses, hospitalization, and intubation; presence of contraindications to any drug or drug class; and specific causes or complications from the exacerbation. Patients who do not respond as expected to standard therapy should prompt a reevaluation for other potentially life-threatening issues. See Table 70-3 for an overview of the differential diagnosis of COPD exacerbations.
TABLE 70-2ED Management of COPD Exacerbations2,3,4,5,6 ||Download (.pdf) TABLE 70-2 ED Management of COPD Exacerbations2,3,4,5,6
Assess severity of symptoms
Administer controlled oxygen
Continuous cardiovascular status monitoring
Perform arterial blood gas measurement after 20–30 min if arterial oxygen saturation remains <90% or if concerned about symptomatic hypercapnia
β2-Agonists and/or anticholinergic agents by nebulization or metered-dose inhaler with spacer
Add oral or IV corticosteroids
Consider antibiotics if increased sputum volume, change in sputum color, fever, or suspicion of infectious etiology of exacerbation
Consider adding IV methylxanthine if above treatments do not improve symptoms
Consider noninvasive mechanical ventilation
Evaluation may include chest radiograph, CBC with differential, basic metabolic panel, ECG
Address associated comorbidities
TABLE 70-3Critical Differential Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations2,3,4,5,6 ||Download (.pdf) TABLE 70-3 Critical Differential Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations2,3,4,5,6
|Diagnosis ||Clinical Features ||Caveats |
|Asthma || |
Can coexist with COPD.
Many patients diagnosed with asthma actually have COPD or mixed asthma-COPD
|CHF || |
Presence of orthopnea (LR, 2.0) and dyspnea with exertion (LR, 1.3) slightly favors CHF
Jugular venous distention, hepatojugular reflux, bibasilar rales
Chest x-ray may show cardiomegaly or interstitial edema
BNP <100 picograms/mL not likely to be CHF; BNP >500 picograms/mL more likely to be CHF
Can coexist with COPD.
Shares some historical elements also found in COPD.
Multiple conditions can falsely elevate or decrease the BNP level.
|PE || |
Risk factors include older age, recent surgery or trauma, prior venous thromboembolic disease, hereditary thrombophilia, malignancy, smoking, and use of medications containing estrogen
Patients with intermediate to high pretest probability may require further testing, such as CT angiography; d-dimer may be useful in ruling out PE in low-risk patients
20%–25% of patients with a severe COPD exacerbation with an unclear trigger have a PE.
Triad of PE (pleuritic chest pain, dyspnea, tachycardia, and hypoxemia) unusual.
|ACS ||Obtain ECG or troponin in those with chest pain or dyspnea and risk factors for ACS ||Dyspnea may be the primary complaint in patients with ACS. |
|Pneumothorax ||Obtain chest x-ray, US, or CT ||COPD is a risk factor for spontaneous pneumothorax. |
|Pneumonia ||Obtain chest x-ray ||Frequently coexists with a COPD exacerbation. |
Administer oxygen to raise the PaO2 above 60 mm Hg or the SaO2 above 90%. Use any of the following devices: standard dual-prong nasal cannula, simple facemask, Venturi mask, or nonrebreathing mask with reservoir and one-way valve. Because oxygen administration may produce hypercapnia, arterial blood gases and/or continuous end-tidal carbon dioxide and oxygen saturation monitoring with venous blood gases will allow optimal assessment of the Pco2 and acid-base status. It may take 20 to 30 minutes from administration of supplemental oxygen for improvement to occur. If adequate oxygenation is not achieved or respiratory acidosis develops, assisted ventilation may be required.
Short-acting β2-agonists and anticholinergic agents are first-line therapies in the management of acute, severe COPD.2,3,4,5,6 Both lead to improved clinical outcomes and shorter ED lengths of stay, especially when used together.2,3,4,5,6 Aerosolized forms, using nebulizer or metered-dose inhalers, deliver drug to the target area optimally and minimize systemic toxicity. β2-Agonists are best given every 30 to 60 minutes if tolerated.2,3,4,5,6 Nebulized aerosols every 20 minutes may result in more rapid improvement of FEV1, but more frequent side effects,28 including tremor, anxiety, and palpitations. Continuous cardiac monitoring is helpful, especially for patients with heart disease.
Some guidelines favor β2-agonists as a first-line therapy, whereas others favor anticholinergic agents. Ipratropium bromide given as a single dose by metered-dose inhaler with a spacer or as an inhalant solution by nebulization (0.5 milligram or 2.5 mL of the 0.02% inhalant solution) is the usual agent of choice, although aerosolized glycopyrrolate (2 milligrams in 10 mL of saline) is also effective. Side effects are minimal and appear to be limited to dry mouth and an occasional metallic taste.
Evidence regarding the efficacy of the combination of a β2-adrenergic agent and an anticholinergic agent compared with a single agent alone is conflicting, although many physicians favor using this combination initially and some favor using it if the response to maximal doses of a single bronchodilator is poor. Long-acting inhaled anticholinergics, such as tiotropium, aclidinium, and glycopyrronium, are not used for the acute management of COPD.2,3,4,5,6
The use of a short course (5 to 7 days) of systemic steroids improves lung function and hypoxemia and shortens recovery time in acute COPD exacerbations.29 Use of corticosteroids in the ED does not affect the rate of hospitalization but does decrease the rate of return visits. The lack of effect on hospitalization rates is likely due to the approximately 6-hour delay before onset of action. There appears to be no clear benefit from a dose >40 to 60 milligrams of oral prednisone daily.29 Hyperglycemia is the most common adverse effect.
Prescribe antibiotics if there is evidence of infection, such as change in volume of sputum and increased purulence of sputum.26 Choose agents directed at the most common pathogens associated with COPD exacerbation: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. There is no specific agent shown to be superior.24,26 Initial antibiotics include macrolides (azithromycin), tetracyclines (doxycycline), or amoxicillin with or without clavulanic acid. There is little evidence regarding the duration of treatment, which ranges from 3 to 14 days.
Methylxanthines, such as theophylline (oral) and aminophylline (parenteral), inhibit phosphodiesterases and may enhance respiration in two ways: by improving the mechanics of breathing (at the smooth muscle and diaphragm) and through an anti-inflammatory effect that happens at lower doses than used previously for bronchodilation and potentiating exogenous steroid effects. Data are conflicting on the value in acute COPD care, and these agents may induce nausea and vomiting.30,31 The therapeutic index is narrow, so drug levels must be monitored. Methylxanthines (aminophylline 3 to 5 milligrams/kg IV over 20 minutes) are third-line options after inhaled therapies and steroids and when first-line therapies fail.
Indications and relative contraindications of noninvasive ventilation are listed in Table 70-4 Noninvasive ventilation can be delivered by nasal mask, full facemask, or mouthpiece. Patients with respiratory failure who receive noninvasive ventilation have better outcomes in terms of intubation rates, short-term mortality rates, symptomatic improvement, and length of hospitalization.32 Disadvantages of noninvasive positive-pressure ventilation include slower correction of gas exchange abnormalities, risk of aspiration, inability to control airway secretions directly, and possible complications of gastric distention and skin necrosis. Contraindications to noninvasive ventilation include an uncooperative or obtunded patient, inability of the patient to clear airway secretions, hemodynamic instability, respiratory arrest, recent facial or gastroesophageal surgery, burns, poor mask fit, or extreme obesity. Noninvasive ventilation methods are discussed in detail elsewhere (see chapter 28, Noninvasive Airway Management).
TABLE 70-4Indications and Relative Contraindications for Noninvasive Ventilation2,3,4,5,6 ||Download (.pdf) TABLE 70-4 Indications and Relative Contraindications for Noninvasive Ventilation2,3,4,5,6
|Selection criteria || |
Acidosis (pH <7.36)/hypercapnia (Paco2 >50 mm Hg)/oxygenation deficit (Pao2 <60 mm Hg or Sao2 <90%)
Severe dyspnea with clinical signs like respiratory muscle fatigue or increased work of breathing
|Exclusion criteria (any) || |
Cardiovascular instability (hypotension, arrhythmias, myocardial infarction)
Change in mental status; uncooperative patient
High aspiration risk
Viscous or copious secretions
Recent facial or gastroesophageal surgery
Fixed nasopharyngeal abnormalities
All patients receiving noninvasive positive-pressure ventilation require continuous cardiorespiratory monitoring and frequent reassessment for setting changes and for tolerance of therapy.
Mechanical ventilation is indicated if there is evidence of respiratory muscle fatigue, worsening respiratory acidosis, deteriorating mental status, or refractory hypoxemia (Table 70-5). The goals of assisted ventilation are to rest ventilatory muscles and to restore adequate gas exchange. After endotracheal intubation, the methods most commonly used are assist control ventilation, pressure support ventilation, or pressure support ventilation in combination with intermittent mandatory ventilation. Adverse events associated with invasive ventilation include pneumonia, barotrauma, and inability to wean the COPD patient from the ventilator.
TABLE 70-5Indications for Intubation with Mechanical Ventilation2,3,4,5,6 ||Download (.pdf) TABLE 70-5 Indications for Intubation with Mechanical Ventilation2,3,4,5,6
Unable to tolerate noninvasive ventilation (NIV) or NIV failure
Respiratory or cardiac arrest
Decreased consciousness or increased agitation
Persistent inability to remove respiratory secretions
Persistent hypoxemia despite optimal respiratory treatment
Current evidence does not support the use of a mixture of helium and oxygen or magnesium in the treatment of an acute COPD exacerbation.
DISPOSITION AND FOLLOW-UP
Patients who fail to improve, those who deteriorate despite medical therapy, those with significant comorbidity, or those without an intact social support system are admitted. Objective criteria regarding hospital admission, observation unit stay, and ED discharge are lacking. The Global Initiative for Chronic Obstructive Lung Disease guidelines help guide the ED disposition decision-making process (Tables 70-6 and 70-7). Select patients without respiratory failure may avoid hospitalization with nurse-administered home care ("hospital at home care").33 After ED discharge, 25% to 43% of patients with COPD exacerbation show ongoing or relapse of symptoms.34,35,36
TABLE 70-6Indications for Hospital Admission2,3,4,5,6 ||Download (.pdf) TABLE 70-6 Indications for Hospital Admission2,3,4,5,6
Marked increase in intensity of symptoms, such as sudden development of resting dyspnea or inability to walk from room to room
Failure of exacerbation to respond to initial medical management
Newly occurring dysrhythmias, heart failure
Frequent exacerbations and/or frequent relapse after ED treatment
Insufficient home support
TABLE 70-7Indications for Intensive Care Admission2,3,4,5,6 ||Download (.pdf) TABLE 70-7 Indications for Intensive Care Admission2,3,4,5,6
Severe dyspnea that responds inadequately to initial emergency therapy
Respiratory or ventilatory failure (current or impending) despite supplemental oxygen and noninvasive positive-pressure ventilation
Decreasing level of consciousness or increasing confusion or agitation
Presence of comorbidities leading to end-organ failure
The following are associated with a higher risk for relapse within 2 weeks after an ED visit: five or more ED or clinic visits in the past year, the amount of activity limitation (based on a 4-point scale), the initial respiratory rate (for each 5 breaths/min over 16 breaths/min), and use of oral corticosteroids before arrival in the ED.34,35,36
If discharging from the ED or observation unit, arrange the following: (1) a supply of home oxygen, if needed; (2) adequate and appropriate bronchodilator treatment (usually a metered-dose inhaler with a spacer and teaching; nebulized therapies are reserved for those who cannot use the metered-dose inhaler); (3) short course of oral corticosteroids2,3,4,5,6; and (4) a follow-up appointment with the primary care physician or pulmonologist, preferably within a week. Reassess inhaler technique, reinforce importance of completion of steroid therapy and antibiotics, if prescribed, and review management plan.