Acute exacerbations of COPD are common. When a patient with known COPD presents with respiratory failure, the first step is to differentiate it from other causes that may present similarly. Exacerbations of COPD must be distinguished from pneumonia, pneumothorax, pulmonary embolism (PE), and congestive heart failure (CHF). Pneumonia and pneumothorax usually can be diagnosed by the chest radiograph. PE can be difficult to diagnose in patients with COPD, and spiral CT angiography should be used if embolic disease is suspected. Your suspicion of PE should be high in those patients who have risk factors such as prolonged immobilization, a history of cancer, recent trauma, or a history of clotting disorders. PE should also be expected if the patient is in hypoxic respiratory failure rather than hypercarbic respiratory failure and in those patients who do not respond to appropriate treatment for COPD exacerbation. Patients with respiratory failure due to heart failure usually have a history of systolic or diastolic heart failure. On physical examination, they have bibasilar crackles, elevated JVD, and peripheral edema of their lower extremities. Their CXRs will show pulmonary vascular congestion and sometimes pulmonary edema. Elevated beta-natriuretic peptide (BNP) will further support this diagnosis.

Now if we look back at our patient, neither he has signs of heart failure nor does his CXR show any pulmonary vascular congestion or pulmonary edema. Pneumonia and pneumothorax can be excluded based on findings of chest auscultation and CXR. The patient does not have any risk factors for PE and his ABGs are consistent with a COPD exacerbation. Although PE cannot be fully excluded without a spiral CT scan of the chest, we should see the patient respond to initial treatment over the next couple of days.

COPD Exacerbations

An acute exacerbation of COPD is defined as an acute increase in symptoms beyond normal day-to-day variation. This generally includes an acute increase in 1 or more of the following cardinal symptoms:

  • Cough increases in frequency and severity.

  • Sputum production increases.

  • Dyspnea increases.

It is estimated that 70% to 80% of COPD exacerbations are due to respiratory infections. Viral and bacterial infections cause most exacerbations, whereas atypical bacteria are a relatively uncommon cause. The remaining 20% to 30% are due to environmental pollution or have an unknown etiology.


Initial evaluation of a patient with a suspected exacerbation of COPD includes a medical history, physical examination, chest radiograph, and routine laboratory studies. ABG analysis should be performed in most patients to assess the severity of the exacerbation and to establish a baseline from which improvement or deterioration can be measured.

The first step is to triage the patient to inpatient or outpatient management following the initial evaluation. Patients having any of the following should be hospitalized:

  • Inadequate response of symptoms to outpatient management

  • Marked increase in dyspnea

  • Inability to eat or sleep due to symptoms

  • Worsening hypoxemia

  • Worsening hypercapnia

  • Changes in mental status

  • Inability to care for oneself (ie, lack of home support)

  • Uncertain diagnosis

  • High-risk comorbidities including pneumonia, cardiac arrhythmia, heart failure, diabetes mellitus, renal failure, or liver failure

In addition, there is general consensus that acute respiratory acidosis justifies hospitalization.


Successful management of acute exacerbations of COPD in either the inpatient or outpatient setting requires attention to a number of key issues:

  1. Identifying and ameliorating the cause of the acute exacerbation

  2. Assuring adequate oxygenation and secretion clearance

  3. Optimizing lung function by administering bronchodilators and other pharmacologic agents

  4. Averting the need for intubation, if possible

  5. Preventing complications of immobility, such as thromboemboli and deconditioning

  6. Addressing nutritional needs

Oxygen Therapy

Supplemental oxygen is a critical component of acute therapy. A target of an arterial oxygen tension (PaO2) of 60 to 70 mm Hg, with an SaO2 of 90% to 94%, is optimal. There are numerous devices available to deliver supplemental oxygen during an acute exacerbation of COPD including nasal cannula, venturi masks, face masks, and non-rebreathing masks.

Adequate oxygenation must be assured, even if it leads to acute hypercapnia. Hypercapnia is generally well tolerated in patients whose arterial carbon dioxide tension (PaCO2) is chronically elevated. However, mechanical ventilation may be required if hypercapnia is associated with depressed mental status, profound acidemia, or cardiac dysrhythmias.

Pharmacologic Treatment

The major components of managing an acute exacerbation of COPD include the use of inhaled short-acting bronchodilators (beta-adrenergic agonists and anticholinergic agents), glucocorticoids, and antibiotics.

Beta-Adrenergic Agonists

Inhaled short-acting beta-adrenergic agonists (eg, albuterol) are the mainstay of therapy for an acute exacerbation of COPD because of their rapid onset of action and efficacy in producing bronchodilation. These medications may be administered via a nebulizer or a metered dose inhaler (MDI) with a spacer device. Typical doses of albuterol for this indication are 2.5 mg (diluted to a total of 3 mL) by nebulizer every 4 hours and as needed, or 4 to 8 puffs (90 μg per puff) by MDI with a spacer every 1 to 4 hours and as needed.

Anticholinergic Agents

Inhaled short-acting anticholinergic agents (eg, ipratropium) are used with inhaled short-acting beta-adrenergic agonists to treat exacerbations of COPD. Typical doses of ipratropium for this indication are 500 μg by nebulizer every 4 hours and as needed. Alternatively, 2 puffs (18 μg per puff) by MDI with a spacer every 4 hours and as needed may be used.


Systemic glucocorticoids, when added to the bronchodilator therapies described above, improve symptoms and lung function, and decrease the length of hospital stay. Oral glucocorticoids are rapidly absorbed (peak serum levels achieved at 1 hour after ingestion) with virtually complete bioavailability and appear as equally efficacious as intravenous glucocorticoids for treating most exacerbations of COPD. However, intravenous glucocorticoids are typically administered to patients who present with a severe exacerbation, who respond poorly to oral glucocorticoids, who are unable to take oral medication, or who may have impaired absorption due to decreased splanchnic perfusion. Frequently used regimens range from prednisone 30 to 60 mg, once daily, to methylprednisolone 60 to 125 mg, 2 to 4 times daily. The optimal duration of systemic glucocorticoid therapy is not clearly established and often depends on the severity of the exacerbation and the observed response to therapy. As a rough guide, most exacerbations are treated with full-dose therapy (eg, prednisone 30–40 mg daily) for 7 to 10 days. After this time, glucocorticoid therapy may be discontinued if the patient has substantially recovered. Alternatively, the dose is tapered over another 7 days, as a trial to determine whether continued glucocorticoid therapy is required. Tapering solely because of concerns about adrenal suppression is not necessary if the duration of therapy is less than 3 weeks (a duration too brief to cause adrenal atrophy).


A “risk stratification” approach should be used when selecting initial antibiotic therapy. Specifically, prescribe a broader antibiotic regimen for patients who have risk factors for a poor outcome. Risk factors include older age (>65 years), comorbid conditions (especially cardiac disease), severe underlying COPD (defined as FEV1 <50%), frequent exacerbations (3 or more per year), and antimicrobial therapy within the past 3 months. Commonly used antibiotics include levofloxacinazithromycin, and amoxicillin. In patients who are at high risk for Pseudomonas infection, antibiotic coverage should be broadened. These risk factors include recent hospitalization (≥2 days duration during the past 90 days), frequent administration of antibiotics (≥4 courses within the past year), severe COPD (FEV1 <50% of predicted), isolation of P. aeruginosa during a previous exacerbation, colonization during a stable period, and systemic glucocorticoid use. The duration of antibiotic therapy for patients with a COPD exacerbation is usually 3 to 7 days, depending on the response to therapy.

Mechanical Ventilation

Noninvasive Positive-Pressure Ventilation

Use of NPPV decreases the risk of endotracheal intubation and decreases intensive care unit (ICU) admission rates.

Indications for NPPV include severe dyspnea, acidosis (pH ≤7.35) and/or hypercapnia (PCO2 >45 mm Hg), and respiratory rate >25 breaths/min. Contraindications to its use are an uncooperative patient, decreased level of consciousness, hemodynamic instability, inadequate mask fit, and severe respiratory acidosis. Increased airway pressure can be delivered by using inspiratory positive airway pressure, continuous positive airway pressure, or bilevel positive airway pressure (BiPAP), which combines the other modalities. When using NPPV, the nasal mask is usually tolerated the best, but patients must be instructed to keep their mouths closed while breathing with the nasal apparatus. A chin strap can be employed to help with this problem. Oxygen can be delivered at 10 to 15 L/min and started in spontaneous ventilation mode with an initial expiratory positive airway pressure setting of 3 to 5 cm H2O and an inspiratory positive airway pressure setting of 8 to 10 cm H2O. Adjustments in these settings should be made in 2 cm H2O increments. It is important to monitor patients with frequent vital sign measurements, ABGs, or pulse oximetry.

Invasive Ventilation

Invasive mechanical ventilation should be administered when patients fail NPPV, do not tolerate NPPV, or have contraindications to NPPV. Other indications include severe dyspnea with evidence of increased work of breathing, acute respiratory acidosis with pH <7.25 and/or PaCO2 >60 mm Hg and PaO2 <40 mm Hg, respiratory rate >35/min, or hemodynamic instability.

Follow-up After Resolution of Acute COPD Exacerbation

Once patients have recovered from an acute exacerbation of COPD and have completed a course of antibiotics and steroids, they should be managed according to the severity of their diseases as measured by the GOLD classification of COPD severity.

  • Stage I: Mild COPD, FEV1/FVC <0.70, FEV1 ≥80%.

  • Stage II: Moderate COPD, FEV1/FVC <0.70, FEV1 50% to 79%.

  • Stage III: Severe COPD, FEV1/FVC <0.70, FEV1 30% to 49%.

  • Stage IV: Very severe COPD, FEV1/FVC <0.70, FEV1 <30% or <50% with chronic respiratory failure present. Chronic respiratory failure is defined as PaO2 <60 mm Hg or PaCO2 >50 mm Hg while breathing air at sea level.

  • The patient should be managed as follows:

    • Stage I: Smoking cessation:

      • Vaccinations (influenza and pneumococcal)

      • Short-acting beta-agonist prn

  • Stage II: All of the above plus:

  • Stage III: All of the above plus:

    • Inhaled corticosteroids

    • Oxygen if needed (PaO2 <55 mm Hg or SaO2 <88%)

  • Stage IV: All of the above plus:

    • Consider surgical treatment.