Treatment of COPD Exacerbation
For acute COPD exacerbations, initiate treatment with short-acting bronchodilators (beta-agonists with or without anticholinergics), systemic corticosteroids (40 mg prednisone daily for 5 days), and antibiotics when indicated by increased sputum purulence plus either increased dyspnea or sputum volume. 1, 2, 3
Initial Bronchodilator Therapy
Administer short-acting beta-agonists (SABAs) combined with short-acting anticholinergics as first-line treatment, as this combination provides superior bronchodilation compared to either agent alone 1, 2, 3. The effects last 4-6 hours and require regular administration during the acute phase 2.
- For mild exacerbations (outpatient): Use SABA and/or ipratropium via metered-dose inhaler (MDI) with spacer or hand-held nebulizer as needed 1
- For moderate exacerbations: Administer either a beta-agonist or anticholinergic via nebulizer 3
- For severe exacerbations (hospitalized): Give both SABA and short-acting anticholinergics together, preferably via nebulizer 1, 2, 3
Nebulizers are preferred over MDIs in sicker hospitalized patients because they are easier to use and don't require the coordination of 20+ inhalations needed to match nebulizer efficacy 2. Either delivery method is acceptable for less severe cases 1, 3.
Do not use intravenous methylxanthines (theophylline) due to their unfavorable side effect profile without added benefit 1, 3.
Systemic Corticosteroid Protocol
Administer 40 mg prednisone orally once daily for exactly 5 days 1, 2, 3, 4. This regimen is supported by high-quality evidence showing it reduces treatment failure by over half (OR 0.48) and decreases relapse rates by one month 5. The REDUCE trial demonstrated that 5-day treatment was non-inferior to 14-day treatment for preventing reexacerbation within 6 months while significantly reducing glucocorticoid exposure 4.
Oral administration is equally effective to intravenous and should be the default route unless the patient cannot tolerate oral intake 1, 2, 6. A randomized controlled trial of 210 hospitalized patients found no difference in treatment failure rates between oral and IV prednisolone (56.3% vs 61.7%) 6.
For patients unable to take oral medications, administer the equivalent IV dose (typically 30-40 mg prednisone equivalent) for up to 14 days 1.
Common pitfall: Avoid extending corticosteroid treatment beyond 5-7 days, as this increases adverse effects without additional benefit 1, 2. Corticosteroids reduce recurrent exacerbations within the first 30 days but provide no benefit beyond this window 2.
Antibiotic Therapy
Prescribe antibiotics when patients present with increased sputum purulence PLUS either increased dyspnea OR increased sputum volume 1, 3. This approach reduces short-term mortality by 77%, treatment failure by 53%, and sputum purulence by 44% 3.
Recommended duration is 5-7 days 2, 3.
Antibiotic selection based on severity:
- Mild exacerbations (outpatient): Amoxicillin/ampicillin, cephalosporins, doxycycline, or macrolides 1
- Failed prior antibiotic therapy: Amoxicillin/clavulanate or respiratory fluoroquinolones 1
- Choice should be guided by local bacterial resistance patterns 1, 2
The FDA label for azithromycin shows clinical cure rates of 85% at Day 21-24 for acute bacterial exacerbations of COPD when given as 500 mg daily for 3 days 7.
Oxygen Therapy
Target oxygen saturation of 90-93% using controlled oxygen delivery to avoid CO2 retention 2. The goal is to maintain PaO2 ≥60 mmHg (8 kPa) or SpO2 ≥90% 1, 3.
For patients with known COPD aged 50 years or older, initial FiO2 should not exceed 28% via Venturi mask or 2 L/min via nasal cannulae until arterial blood gases are obtained 3.
Obtain arterial blood gas measurement within 1 hour of initiating oxygen to assess for worsening hypercapnia 2. Monitor ABGs for PaO2, PaCO2, and pH during severe exacerbations 1.
Critical pitfall: Increasing PaO2 much greater than 60 mmHg confers little added benefit (1-2 vol%) and may increase the risk of CO2 retention leading to respiratory acidosis 1.
Respiratory Support for Severe Exacerbations
Initiate noninvasive ventilation (NIV) immediately as first-line therapy for patients with acute hypercapnic respiratory failure who have no absolute contraindications 1, 2, 3. NIV improves gas exchange, reduces work of breathing, decreases need for intubation, shortens hospitalization duration, and improves survival 3.
Indications for ICU or special care unit admission include: impending or actual respiratory failure, presence of other end-organ dysfunction (shock, renal, liver, or neurological disturbance), and/or hemodynamic instability 1.
Criteria for Hospitalization
Hospitalize patients with any of the following: 1
- Marked increase in intensity of symptoms (sudden onset of resting dyspnea)
- Severe underlying COPD
- Onset of new physical signs (cyanosis, peripheral edema)
- Failure of exacerbation to respond to initial medical management
- Significant comorbidities
- Frequent exacerbations
- Newly occurring arrhythmias
- Diagnostic uncertainty
- Older age
- Insufficient home support
More than 80% of exacerbations can be managed on an outpatient basis 2, 3.
Discharge Planning and Follow-Up
Initiate maintenance therapy with long-acting bronchodilators as soon as possible before hospital discharge 1, 3. Consider LAMA monotherapy, ICS/LABA combination, or LAMA/LABA combination based on exacerbation frequency and symptom burden 2.
Schedule pulmonary rehabilitation within 3 weeks after discharge to reduce hospital readmissions and improve quality of life 2. Starting rehabilitation during hospitalization increases mortality, while post-discharge timing reduces admissions 2.
Important caveat: At 8 weeks after an exacerbation, 20% of patients have not recovered to their pre-exacerbation state, highlighting the critical importance of structured follow-up care 2, 3.
Additional Monitoring
Monitor fluid balance and nutrition status during hospitalization 2. Ensure proper inhaler technique when prescribing bronchodilators 1, 3. Consider use of spacer devices for MDI administration 1.
Adverse effects of corticosteroids: Overall, one extra adverse effect occurs for every six people treated, with significantly increased risk of hyperglycemia (OR 2.79) 5. The incidence of treatment-related adverse events is higher with parenteral administration compared with oral treatment 5.