The overall goals of therapy are to alleviate the patient's symptoms of dyspnea, to stabilize and improve respiratory status, and where possible, to remove the ongoing trigger. Short-acting beta-2 agonists and anticholinergic medications are considered first-line therapy, and may provide benefit within 15 and 30 minutes, respectively. If the patient remains symptomatic, repeat doses may be given. There are as yet no clinical trials to guide whether long-acting bronchodilators should be continued during acute COPD exacerbation. Although discontinuation of a maintenance therapy might potentially contribute to worsening symptoms and/or lung function, regular frequent administration of short-acting bronchodilators in addition to long-acting bronchodilators of the same class has the potential to increase the risk of medication-related adverse effects. Supplemental oxygen may be needed if the patient is hypoxic, although oxygen should be applied with caution to prevent further hypercarbia. Careful titration of supplemental oxygen even in the pre-hospital setting (e.g., en route to the hospital) is important to prevent worsening respiratory acidosis, which may increase mortality.[197]

Systemic corticosteroids decrease airway inflammation and have been shown to be beneficial for patients with acute exacerbation of COPD.[125][198][199][200][201] They enhance early (within 3 days) improvements in symptoms and lung function, reduce treatment failures and early (within 1 month) relapses, and reduce hospital length of stay.[199] Systemic corticosteroids should be initiated after the first treatment of short-acting inhaled bronchodilators. However, studies examining the role of systemic corticosteroids have been primarily performed among people presenting to emergency rooms and those who are hospitalized. The shortest duration of systemic corticosteroids that confers clinical benefit while minimising adverse effects remains unclear.[202] [ Cochrane Clinical Answers logo ] The balance of risks and benefits of corticosteroids for people with milder exacerbations is uncertain. Moreover, the benefit of systemic corticosteroid therapy for people with acute exacerbations of COPD with associated respiratory failure requiring mechanical ventilatory support is also unclear. One randomized controlled trial found no difference in ICU mortality, duration of mechanical ventilation, or ICU length of stay between patients who received prednisone versus the control group who did not, yet those who received prednisone had a higher risk of hyperglycemia.[203]

The presence of pneumonia as a cause of respiratory decompensation in a patient with COPD does not necessarily imply the presence of a COPD exacerbation per se (i.e., the presence of worsened airflow limitation related to airways inflammation and/or bronchoconstriction), and as such careful consideration should be given as to whether systemic corticosteroids are warranted in such patients.

Nebulized corticosteroids have been used with some success, but their utility in acute exacerbations of COPD and relative efficacy compared with systemic corticosteroids is not fully clear.[1][204]

While methylxanthine medications may provide benefit to some people with COPD,[205][206] this class of medications has a narrow therapeutic window and there does not appear to be a role for use in patients with acute exacerbations.[207]

The use of mucolytics, expectorants, and/or physical mucus-clearing techniques does not appear to provide any clear proven benefit,[208][209] although some patients do experience symptomatic relief.

COPD patients and their exacerbations are highly heterogeneous. While many aspects of their care are amenable to protocols, those who may require hospitalization, those who may benefit from pulmonary rehabilitation, or those who have a less- versus more-severe acute exacerbation vary greatly according to the comorbidities and other characteristics of the individual patient.

Hospitalization should be considered for people with marked or sudden increase in symptom severity, severe underlying COPD, or new physical signs (such as peripheral edema or cyanosis); those who have a history of frequent exacerbations or comorbid illness; those who are of older age; or those who fail to respond to initial outpatient management or have suboptimal home support.[1]

Exacerbations with suspected bacterial etiology

Bacterial infections are thought to be a common trigger.[61] Multiple randomized placebo-controlled trials have shown that antibiotics are beneficial for the treatment of patients with acute exacerbation of COPD.[62][210][211] Antibiotics should be given to patients suspected of having a bacterial trigger.[12] A bacterial trigger may be present in people with two or more of the following: increased sputum purulence, increased sputum volume, or worsening dyspnea.[45][176][194] The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend antibiotics for people with a combination of increased dyspnea, increased sputum volume, and increased sputum purulence, or for those with increased sputum purulence combined with one of the other two criteria noted above.[1] Patients with more severe exacerbations, particularly those requiring treatment in the intensive care unit (ICU), have been shown to derive greater benefit from antibiotic therapy;[62][212] [ Cochrane Clinical Answers logo ] antibiotics should be given to patients with severe exacerbations requiring mechanical ventilation (invasive or noninvasive).[1] However, patients who receive antibiotics are at increased risk for antibiotic-associated diarrhea.[212] Antibiotic choice and duration of therapy is an unresolved issue, but in general should be based on local resistance patterns and patient characteristics.[194] The NHLBI/WHO (National Heart, Lung and Blood Institute/World Health Organization) workshop recommended choosing specific antibiotics based on local susceptibility patterns of common bacteria associated with exacerbations: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.[45] It has been recommended that more narrow-spectrum antibiotics (e.g., amoxicillin, amoxicillin/clavulanate, doxycycline, tetracycline, second-generation cephalosporins, macrolides, trimethoprim/sulfamethoxazole) be considered for patients at less risk for a poor outcome and with an exacerbation of lesser severity. Patients with more severe underlying COPD and those with greater exacerbation severity are more often colonized with gram-negative bacteria such as Pseudomonas aeruginosa or other enteric gram-negative organisms and/or Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus).[60] Therefore, extended-spectrum beta-lactam combination drugs, fluoroquinolones, and vancomycin are considered for patients at greater risk for a poor outcome or with an episode of greater severity, such as people with recent history of antibiotic use, treatment failure, prior antibiotic resistance, or risk factors for healthcare-associated infections, or critically ill patients in the ICU.[194] Studies have suggested that the use of a respiratory fluoroquinolone, amoxicillin/clavulanate, second- or third-generation cephalosporins, or macrolides may be associated with fewer treatment failures or recurrent exacerbations.[213][214][215][216][217][218] There is currently insufficient evidence to guide use of antibiotics based on serum procalcitonin levels in patients with COPD.[194]

Severe exacerbations of COPD

Severity depends on patient's prior status and any changes to previous baseline investigation (based on symptoms, examination, lung function, ABG). Use of accessory respiratory muscles, paradoxical respirations, cyanosis, new peripheral edema, hemodynamic instability, and worsened mental status (e.g., confusion, lethargy, coma) are important indicators of severity of exacerbation.[1]

In addition to the general measures, patients with severe exacerbations who do not appear to respond sufficiently to the initial interventions should be considered for noninvasive positive-pressure ventilation (NPPV). The use of NPPV for patients with acute exacerbations of COPD and respiratory failure has been shown to decrease the rate of invasive mechanical ventilation and mortality.[219][220][221][222][223][224] [ Cochrane Clinical Answers logo ] NPPV use should be considered for patients with one or more of the following:[1]

  • Respiratory acidosis (PaCO2 ≥ 6.0 kPa or 45 mmHg and arterial pH ≤ 7.35)

  • Severe dyspnea with clinical signs suggestive of respiratory muscle fatigue, increased work or breathing, or both, such as use of respiratory accessory muscles, paradoxical motion of the abdomen, or retraction of the intercostal spaces

  • Persistent hypoxemia despite supplemental oxygen therapy.

In some patients, NPPV may fail. Invasive mechanical ventilation via endotracheal intubation should be considered for patients who have outright respiratory or cardiac arrest, are in or have signs of impending acute respiratory failure despite NPPV, have impaired mental status or cardiovascular instability, are at high risk for aspiration, or for whom NPPV cannot be appropriately applied (e.g., craniofacial trauma, recent gastroesophageal surgery, copious secretions, anxiety disorder, facial discomfort, or severe skin breakdown).[225] Physiologic criteria for invasive mechanical ventilation include the following: severe hypoxia, inability to tolerate NPPV or failure of NPPV, respiratory or cardiac arrest, irregular breathing with gasping or loss of consciousness, massive aspiration or persistent vomiting, inability to clear respiratory secretions, heart rate <50 beats per minute with diminished alertness, severe hemodynamic instability not responsive to medical treatment, or severe ventricular or supraventricular arrhythmias.[1][226] The risk for mortality is significant (11% to 49%) for people with severe disease in whom invasive mechanical ventilation is indicated.[12][227] Complications of mechanical ventilation include ventilator-associated pneumonia and barotrauma. Weaning patients with severe COPD from mechanical ventilation can be difficult.[225] Use of NPPV to assist weaning from mechanical ventilation can reduce weaning failure and nosocomial pneumonia, and may reduce mortality.[224][228]

Tracheal intubation: animated demonstrationTracheal intubation: animated demonstration

Bag-valve-mask ventilation: animated demonstrationBag-valve-mask ventilation: animated demonstration

Pulmonary rehabilitation

Pulmonary rehabilitation is a multidisciplinary program of care that involves physical rehabilitation as well as guidance on disease management, nutrition, and other lifestyle issues (e.g., smoking cessation, medication compliance and inhaler technique, supplemental oxygen, and maintenance of physical activity).[232][233][234]

  • Selected forms of exercise rehabilitation initiated during a hospitalization for COPD exacerbation, including resistance strength training and transcutaneous electrical muscle stimulation, are well tolerated and can prevent muscle function decline and hasten functional status recovery.[235][236][237]

  • Pulmonary rehabilitation initiated early during the recovery phase of an exacerbation is safe and effective, and leads to improvements in exercise tolerance, physical abilities, the degree of symptoms due to COPD, and quality of life.[238][239][240][241][242]

  • Comprehensive supervised pulmonary rehabilitation in the outpatient setting in the post-exacerbation period decreases the risk for future hospitalization and may reduce mortality.[233][241][242][243] Unsupervised home-based exercise training following exacerbations does not appear to confer the same benefits.[244]

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