|
Assessing and Managing Exacerbations of COPD
The authors review the signs and symptoms of a flare-up of COPD, the keys to gauging severity, and the interventions most likely to succeed in restoring baseline function.
By John L. Alexander, MD, FACEP, and Joshua P. Morrison, DO
Despite the decline in mortality seen with other major health conditions, including coronary artery disease and stroke (down 45% and 58%, respectively), mortality associated with chronic obstructive pulmonary disease (COPD) increased 71% in the United States from 1966 to 1996. During that period of time, the 16 million people with COPD accounted for 1 million visits to emergency departments, with almost half of them requiring hospitalization, resulting in $18 billion in direct health care costs.
This article will present an overview of COPD and what constitutes an exacerbation. It will also discuss different assessment measures to determine the severity of a COPD exacerbation and review the role of various treatment strategies for exacerbations in the emergency department setting.
several conditions involved
The term “chronic obstructive pulmonary disease” is used to describe several conditions that lead to airway outflow obstruction. Two acquired conditions that can result in COPD are emphysema and chronic bronchitis. Emphysema is characterized by abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls without obvious fibrosis. Chronic bronchitis is defined as a chronic cough or mucus production lasting at least three months during at least two successive years when other causes of chronic cough have been excluded. Emphysema and chronic bronchitis may exist in a patient with both alveolar destruction and mucous production. In addition, patients with COPD may have some degree of airway inflammation, reactive airway disease, or asthma. When considering the treatment options for the patient with COPD, the underlying pathophysiologic changes must be taken into account.
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) is an international panel of experts with the mission of decreasing morbidity and mortality from COPD through educational outreach and scientific inquiry. The GOLD classification system develops a framework for determining the best treatment options based on the severity of the disease (see table below). Treatment considerations for each successive stage are additive and serve as a useful means of quickly assessing a patient’s underlying lung function.
 |
Exacerbations of COPD are associated with an acute worsening of chronic symptoms and tend to occur more frequently as the disease progresses (see table below). The symptoms of an exacerbation are variable but may include cough, wheezing, dyspnea (either exertional or at rest), increased sputum volume and purulence, and occasional fever. A history of the patient presenting with a COPD exacerbation should be problem-focused and should seek to determine the duration of symptoms, medication use and compliance, use of home oxygen therapy, incidence of other illnesses or infections, and other comorbidities limiting therapy. In addition, an inquiry into the number and frequency of exacerbations can provide useful information.
During the physical examination, signs of severe obstruction should be identified. These include inability to speak, altered mental status, diaphoresis, and absent or diminished breath sounds bilaterally.
evaluative measurements
Limited data exist as to the utility of evaluative measurements to determine the severity of COPD exacerbations. Most clinicians rely on their clinical judgment to organize a diagnostic strategy for the patient with an exacerbation.
Peak expiratory flow rate (PEFR) is an objective measure of outflow obstruction that has been shown to correlate well with forced expiratory volume in one second (FEV1). Many patients with COPD have some degree of airway reactivity, and PEFR is most useful in these patients. More often, though, PEFR is difficult for patients with COPD to perform and may result in worsened dyspnea in the patient with a severe exacerbation.
Pulse oximetry is a commonly used tool in the assessment of the patient with an acute exacerbation of COPD. While the SaO2 measurement is an easy, noninvasive means of assessment, it is important to remember that no single value can reliably predict patient outcome. In addition, patients with severe or very severe COPD may have chronic hypoxia, making SaO2 values unreliable correlates of the severity of an exacerbation.
Arterial blood gas (ABG) analysis may play a role in the emergent assessment of a patient with an acute COPD exacerbation. It can help to determine impending respiratory failure in the patient with chronically severe COPD, and can indicate the need for intervention with bilevel positive airway pressure (BiPAP) or consideration of intubation. The most common finding on ABG analysis is a respiratory acidosis and a metabolic alkalosis, together with some degree of hypoxia. While there are limited outcome data to support its routine use, an ABG analysis may also be beneficial in the setting of an unclear diagnosis, a patient refractory to therapy, a patient with prior ABG values available for comparison, or in the postintubation patient.
Chest x-rays may be helpful to the clinician in the emergent evaluation of the COPD patient. Abnormal findings occur commonly, especially in a patient with emphysema or asthma. The most frequently seen abnormalities include hyperinflation, flattening of the diaphragm, atelectasis, loss of interstitial markings, and bullous formation. When a chest x-ray is obtained, the clinician may be seeking alternative or contributing diagnoses, such as congestive heart failure, pneumothorax, or pneumonia. Therefore, a chest x-ray should be considered for patients presenting with an unclear diagnosis, fever, or significant sputum production, and those who are refractory to therapy or exhibit evidence of respiratory failure.
treatment with brochodilators
Aside from improving oxygenation via oxygen delivery, treatment of the patient with an acute exacerbation of COPD revolves around relieving airway obstruction to increase ventilation (with bronchodilators), decreasing inflammation (with corticosteroids), and eliminating bacterial invasion of damaged airspace (with antibiotics). In a study conducted by the Multicenter Airway Research Collaboration (MARC) reviewing treatment strategies used in 397 COPD patients presenting to 29 different emergency departments with exacerbations, it was noted that significant variability in the use of different pharmacologic agents resulted in a significant trend toward hospitalization and relapse (see graph below). Beta-agonist medications are considered first-line bronchodilator therapy for both stable COPD and acute exacerbations. Numerous studies have demonstrated improvements in FEV1 and dyspnea scores with these medications, as well as decreases in hospitalization rate, length of stay, and recurrent exacerbations and hospitalizations. Use of beta-agonists results primarily in bronchodilation of small airways. The mechanism involves conversion of adenosine triphosphate to cyclic adenosine monophosphate via a beta-2 receptor, leading to smooth muscle dilation in small airways.
|
The Multicenter Airway Research Collaboration (MARC) trial was conducted at 29 emergency departments in 15 U.S. states and three Canadian provinces, and involved 397 patients, age 55 and older, presenting with COPD exacerbation. Of the total, 224 (56%) had COPD only and 173 (44%) had asthma and COPD. The average age was 70.
Source: Cydulka RK, 2003 (see Suggested Reading)
|
|
Several beta-agonists are available, including short-acting agents, such as albuterol and levalbuterol, and long-acting preparations, such as formoterol and salmeterol. There have been limited data to support the use of levalbuterol over albuterol in the setting of an acute exacerbation of COPD. In one study evaluating the use of formoterol versus albuterol in patients with stable COPD, both drugs produced similar improvements in FEV1 and forced vital capacity after 25 minutes. In the setting of an acute exacerbation of COPD, use of any of the short-acting beta-agonists should be the mainstay of therapy.
Metered-dose-inhaler (MDI) therapy for patients with a COPD exacerbation has been shown to be equivalent to nebulizer therapy in improving FEV1 and dyspnea scores when combined with the use of a spacer. A study of 1420 adults with asthma found that MDI therapy outperformed nebulizer therapy in improving PEFR and length of stay in the emergency department with one sixth the dose of albuterol administered. The rate of hospitalization in both groups was similar.
Numerous studies support the use of anticholinergics in the setting of an acute COPD exacerbation. These medications, including ipratropium and tiotropium, are effective bronchodilators of large airways. They have a delayed onset of action but are beneficial due to their long duration of action and the absence of significant side effects. Anticholinergic medications act at muscarinic receptors M1, M2, and M3 to block cholinergic transmission, acetylcholine release, and acetylcholine activation, respectively, on airway smooth muscle and submucosal glands. Inhaled anticholinergic medications act at all three muscarinic receptors, with greatest affinity at the M3 site. Combination therapy with a short-acting beta-agonist has been found to improve pulmonary function and shorten length of stay in the emergency department.
Tiotropium is the first long-acting inhaled anticholinergic available for treatment of stable COPD, but it is not indicated in the treatment of an acute exacerbation. A study evaluating the time-response of formoterol and tiotropium demonstrated a 12% improvement in FEV1 after 38 and 79 minutes, respectively. Tiotropium had a slower onset and lower peak bronchodilation but resulted in a longer therapeutic duration of action.
Methylxanthines are no longer recommended for the treatment of acute exacerbations of COPD. Their mechanism of action is not fully understood, although they are known to inhibit phosphodiesterase at high doses, which results in a decrease in airway smooth muscle constriction. Their side effect profile includes nausea and vomiting, tremor, and palpitations. Studies of methylxanthines have shown some improvement of pulmonary function testing in stable COPD patients. However, because their narrow therapeutic range, potential toxicity, and variable pharmacokinetics can be problematic, these medications are used less frequently than the newer agents.
using corticosteroids and antibiotics
Treatment with corticosteroids results in decreased airway inflammation, which enhances ventilation. Several studies have demonstrated improvement in pulmonary function, admission rates, and relapse rates with the use of corticosteroids. One placebo-controlled study of 27 patients with COPD exacerbations demonstrated significant improvements in PaO2 after 3 and 10 days of therapy, a one third increase in FEV1 at day 10 after onset, and a positive trend in dyspnea score improvement. A randomized study of 147 emergency department patients with COPD exacerbations showed a significant improvement in FEV1 and a decrease in the risk of relapse at 30 days with steroid therapy. A review of 10 studies reported an improvement in treatment failure and relapse rate with steroid therapy, but it found no difference in rehospitalization or mortality and a doubling of the risk of adverse drug reactions.
Corticosteroid use is recommended for treatment of acute exacerbations of COPD. However, there is no consensus regarding optimal dosing for adults. Studies comparing routes of delivery for systemic corticoster-oids have demonstrated no benefit of either IV or IM parenteral over oral delivery.
Patients with COPD, especially those with chronic bronchitis, are prone to lower respiratory tract infections due to inflammation and damage of epithelial cells and interstitial tissues. Infection is the most common identifiable cause of COPD exacerbations. Although the majority of causative agents are viral, 50% of sputum samples collected during exacerbations reveal pathogenic bacteria. Any patient with symptoms or signs of an infection should have antibiotic therapy initiated in the emergency department.
Studies assessing the routine use of antibiotics in patients with COPD exacerbations have yielded mixed results. In one meta-analysis, treatment with antibiotics resulted in a modest overall improvement in clinical outcome. A recent systematic review, including 11 trials utilizing 857 patients, found a 77% reduction in the risk of short-term mortality with the use of antibiotics following a COPD exacerbation associated with increased cough and sputum purulence. One study suggested the use of three indicators to determine the likelihood of a positive sputum culture: the presence of bacteria on a sputum Gram stain, a clinically relevant decrease in pulmonary function from baseline, and more than one other episode of an exacerbation in the past year. The presence of these indicators yielded a 100% negative predictive value.
The choice of antibiotic therapy should be based on the severity of the patient’s illness (see table below). Patients with mild or moderate illness are more likely to be infected with common respiratory tract pathogens, including Streptococcus pneumococcus, nontypeable Haemophilus influenzae, and Moraxella catarrhalis. These patients should be treated with narrow-spectrum antibiotics such as amoxicillin, trimethoprim-sulfamethoxazole, or doxycycline. Patients with severe illness are more likely to have gram-negative bacteria as their source of infection and require broad-spectrum antibiotic therapy with a fluoroquinolone, macrolide, or cephalosporin.
noninvasive positive pressure ventilation
Noninvasive positive pressure ventilation (NPPV) is recommended as a first-line intervention for the management of respiratory failure secondary to an acute exacerbation of COPD. It should be considered early in the course of respiratory failure and before severe acidosis ensues. A review of 14 studies involving patients admitted with respiratory failure secondary to a COPD exacerbation demonstrated significant improvements in mortality; need for intubation; treatment failure; first-hour change in pH, PaCO2, and respiratory rate; treatment complications; and length of hospital stay.
Noninvasive ventilation, such as BiPAP, is useful in the patient with hypercapnic respiratory failure for a number of reasons. It augments inspiratory pressure or volume, allowing respiratory muscles to rest, while improving expiratory airflow through dynamic airway compression or collapse (that is, splinting). In addition, the timing of breaths compensates for diminished central respiratory drive, and greater levels of FiO2 may be administered. Studies have demonstrated a reduction in the need for endotracheal intubation of patients with acute exacerbations of COPD when NPPV treatment is used early.
This intervention should be avoided or used cautiously, however, in the patient with poor or absent spontaneous respirations, the inability to form a sufficient seal with the face mask, a history of facial trauma, or severe anxiety or claustrophobia. In these patients, endotracheal intubation may be necessary.
patient disposition
Several recent studies have evaluated the utility of different variables to determine which can best predict the need for hospital admission. In one study evaluating the correlation between existing criteria for measuring the severity of COPD exacerbation and frequency of hospital admissions, the GOLD classification system outperformed those developed by the American Thoracic Society, British Thoracic Society, and European Respiratory Society. In a different study, Ong found the combination of four variables (body mass index, airflow obstruction, dyspnea, and exercise capacity) to be a better predictor of the need for hospital admission than FEV1 in patients with acute exacerbations of COPD.
The MARC investigators published their findings on risk of relapse following an exacerbation of COPD in 29 emergency departments. They found a significant correlation between relapse within two weeks and frequent urgent care or emergency department visits (five or more) in the previous 12 months, limitation of activity within the previous 24 hours, and increased respiratory rate (more than 20) on admission.
Criteria for hospitalization of the patient in ADHF are listed in the table below. Some patients who respond promptly to diuretics and have an identifiable, nonurgent cause for decompensation (for example, excessive salt intake) may not require hospitalization. Inpatient management of ADHF focuses on reversing the acute illness, determining the cause of the exacerbation in order to prevent recurrence, adjusting medications, and educating the patient in self-management.
Most practitioners base their decision to admit patients with an acute exacerbation of COPD on a combination of historical and presenting factors. Important elements from the history include the number of COPD exacerbations and hospitalizations in the previous year, previous endotracheal intubation, and recent or frequent steroid use. Factors used to determine severity and the need for admission on presentation include oxygen saturation at rest and with exertion, use of home oxygen, presence of concurrent infection, and subjective symptomatic improvement, along with objective measurement of improvement in airflow obstruction (using PEFR, for example). In addition, the decision to admit the patient with an acute exacerbation of COPD should take into consideration the patient’s home environment, social support network, and ability to access health care resources.
Suggested Reading
Aaron SD, et al.: Outpatient oral prednisone after emergency treatment of chronic obstructive pulmonary disease. N Engl J Med 348(26):2618, 2003.
Bellia V, et al.: The use of bronchodilators in the treatment of airway obstruction in elderly patients. Pulm Pharmacol Ther 19(5): 311, 2005.
Berry RB, et al.: Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD. Chest 96(6):1241, 1989.
Braun SR, et al.: Comparison of ipratropium bromide and albuterol in chronic obstructive pulmonary disease: a three-center study. Am J Med 91(4A):28S, 1991.
Brochard L, et al.: Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Eng J Med 333(13):817, 1995.
Cazzola M, et al.: Formoterol as dry powder oral inhalation compared with salbutamol metered-dose inhaler in acute exacerbations of chronic obstructive pulmonary disease. Clin Ther 24(4):595, 2002.
Cazzola M, et al.: The pharmacodynamic effects of single inhaled doses of formoterol, tiotropium and their combination in patients with COPD. Pulm Pharmacol Ther 17(1):35, 2004.
Cydulka RK and Emerman CL: Effects of combined treatment with glycopyrrolate and albuterol in acute exacerbation of chronic obstructive pulmonary disease. Ann Emerg Med 25(4):470, 1995.
Cydulka RK, et al.: Emergency department management of acute exacerbations of chronic obstructive pulmonary disease in the elderly: the Multicenter Airway Research Collaboration. J Am Geriatric Soc 51(7):908, 2003.
FASTATS on COPD. National Center for Health Statistics (Web site). Available at http://www.cdc.gov/nchs/fastats/copd.htm. Accessed on January 31, 2007.
Kim S, et al.: Prospective multicenter study of relapse following emergency department treatment of COPD exacerbation. Chest 125(2):473, 2004.
Lightowler JV, et al.: Noninvasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ 326(7382):185, 2003.
Newman KB, et al.: A comparison of albuterol administered by metered-dose inhaler and spacer with albuterol by nebulizer in adults presenting to an urban emergency department with acute asthma. Chest 121(4):1036, 2002.
Ong KC, et al.: A multidimensional grading system (BODE Index) as predictor of hospitalization for COPD. Chest 128(6):3810, 2005.
Ram FS, et al.: Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev (2):CD004403, 2006.
Ram FS, et al.: Noninvasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev (3):CD004104, 2004.
Saint S, et al.: Antibiotics in chronic obstructive pulmonary disease exacerbations: a meta-analysis. JAMA 273(12):957, 1995.
Shrestha M, et al.: Decreased duration of emergency department treatment of chronic obstructive pulmonary disease exacerbations with the addition of ipratropium bromide to beta-agonist therapy. Ann Emerg Med 20(11):1206, 1991.
Thompson WH, et al.: Controlled trial of oral prednisone in outpatients with acute COPD exacerbation. Am J Respir Crit Care Med 154(2 Pt 1):407, 1996.
Tsoumakidou M, et al.: Is there any correlation between the ATS, BTS, ERS and GOLD COPD severity scales and the frequency of hospital admissions? Respir Med 98(2):178, 2004.
Van der Valk P, et al.: Clinical predictors of bacterial involvement in exacerbations of chronic obstructive pulmonary disease. Clin Infect Diseases 39(7):980, 2004.
Wood-Baker RR, et al.: Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev (1):CD001288, 2005. |
|
