What are the common drugs and doses used in the management of Chronic Obstructive Pulmonary Disease (COPD) exacerbations in Canada?

COPD Exacerbation Management in Canada: Common Drugs and Doses

Systemic Corticosteroids

For acute COPD exacerbations, use prednisone 30-40 mg orally daily for 5 days as first-line therapy. 1, 2

• Prednisone 30-40 mg PO daily for 5 days is the standard recommended regimen by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and American Thoracic Society 1, 2
• Do not extend treatment beyond 5-7 days - longer courses increase adverse effects (hyperglycemia, weight gain, insomnia) without additional benefit 1, 3
• Oral administration is preferred over IV when the patient can tolerate oral medications 1
• If oral route is not possible, use methylprednisolone 100 mg IV or hydrocortisone 100 mg IV 1, 2
• Alternative: Nebulized budesonide 4 mg twice daily (8 mg/day total) can be considered for patients who cannot tolerate oral medications, have significant hyperglycemia concerns, or are already receiving nebulized bronchodilators 1

Clinical benefits: Corticosteroids reduce treatment failure by over 50%, prevent hospitalization for subsequent exacerbations within the first 30 days, improve lung function and oxygenation, and shorten recovery time 4, 1, 2

Critical limitation: Systemic corticosteroids should NOT be used beyond 30 days after the initial exacerbation - long-term use carries risks of infection, osteoporosis, and adrenal suppression that far outweigh any benefits 4, 1

Short-Acting Bronchodilators

Start with short-acting beta2-agonists (SABA) with or without short-acting anticholinergics (SAMA) as initial bronchodilator therapy. 2

Beta2-Agonists (SABA)

• Salbutamol (albuterol) 2.5-5 mg via nebulizer every 4-6 hours, or more frequently if required 2
• Can be administered via nebulizer, pressurized metered-dose inhaler (pMDI), pMDI with spacer, or soft mist inhaler 5

Anticholinergics (SAMA)

• Ipratropium bromide 500 mcg via nebulizer three times daily 2, 6
• For severe exacerbations or poor response to either agent alone, combine SABA + SAMA together 2
• Nebulized bronchodilators should be given upon arrival and at 4-6 hourly intervals thereafter 2

Antibiotics

Prescribe antibiotics for patients with three cardinal symptoms: increased dyspnea, increased sputum volume, AND increased sputum purulence. 2

First-Line Antibiotics

• Amoxicillin (dose not specified in guidelines, but standard is 500 mg PO three times daily or 875 mg PO twice daily) 2
• Tetracycline/Doxycycline (standard doxycycline dose: 100 mg PO twice daily) 2
• Duration: 5-7 days 2

Macrolide Option for Acute Exacerbations

• Azithromycin 500 mg PO daily for 3 days OR 500 mg as single dose on Day 1, followed by 250 mg daily on Days 2-5 7
• This is FDA-approved for acute bacterial exacerbations of COPD 7

Long-Term Macrolide for Prevention (Not Acute Treatment)

• For patients with moderate to severe COPD who have ≥1 moderate or severe exacerbation in the previous year despite optimal maintenance therapy, consider long-term macrolide therapy to prevent future exacerbations 4
• Important caveat: Clinicians must consider risks of QT prolongation, hearing loss, and bacterial resistance 4

Oxygen Therapy

Target SpO₂ of 88-92% (or PaO₂ ≥6.6 kPa [≈50 mmHg]) without causing respiratory acidosis. 2, 5

• In patients with known COPD aged ≥50 years, initial FiO₂ should not exceed 28% via Venturi mask or 2 L/min via nasal cannulae until arterial blood gases are known 2
• Titrate oxygen to maintain SpO₂ 88-92% 2, 5
• Arterial blood gases remain the standard for assessing gas exchange 5

Treatment Algorithm for Acute Exacerbations

Step 1: Initial Assessment and Bronchodilators

• Start SABA (salbutamol 2.5-5 mg nebulized) every 4-6 hours 2
• For moderate-to-severe exacerbations, add SAMA (ipratropium 500 mcg nebulized) three times daily 2

Step 2: Add Systemic Corticosteroids

• Prednisone 30-40 mg PO daily for 5 days for all exacerbations requiring emergent care 1, 2
• Blood eosinophil count ≥2% predicts better response, but treat all exacerbations regardless of eosinophil levels 1

Step 3: Antibiotics (If Indicated)

• Give antibiotics if patient has all three cardinal symptoms: increased dyspnea, increased sputum volume, AND increased sputum purulence 2
• Amoxicillin or doxycycline for 5-7 days (or azithromycin 500 mg daily for 3 days) 2, 7

Step 4: Oxygen Therapy (If Hypoxemic)

• Add controlled oxygen to maintain SpO₂ 88-92% 2, 5
• Start with FiO₂ ≤28% or 2 L/min nasal cannula in known COPD patients until ABG results available 2

Step 5: Consider Noninvasive Ventilation

• For patients with acute respiratory failure, NIV improves gas exchange, reduces work of breathing, decreases hospitalization duration, and improves survival 2, 5

Common Pitfalls to Avoid

• Never extend corticosteroid therapy beyond 5-7 days - this increases adverse effects without benefit 1, 3
• Do not use systemic corticosteroids for prevention beyond 30 days after the initial exacerbation 4, 1
• Do not use methylxanthines (theophylline) - they have increased side effect profiles without clear benefit 1
• Do not prescribe antibiotics without purulent sputum or other clear signs of bacterial infection 2
• Avoid excessive oxygen - target SpO₂ 88-92%, not normalization, to prevent CO₂ retention 2, 5

Maintenance Therapy After Exacerbation

After treating the acute exacerbation, optimize maintenance therapy to prevent future exacerbations:

• Long-acting muscarinic antagonist (LAMA) + long-acting beta2-agonist (LABA) combination as initial strategy for frequent exacerbators (>1 exacerbation/year) 4, 8
• For patients who continue to exacerbate despite LAMA/LABA, add inhaled corticosteroid (ICS) to LABA/LAMA in patients with asthma-COPD overlap or high blood eosinophil counts 4, 8
• For exacerbators with chronic bronchitis, consider roflumilast (PDE-4 inhibitor) or high-dose mucolytic agents 8
• For patients with frequent bacterial exacerbations and/or bronchiectasis, consider long-term macrolide (e.g., azithromycin) or mucolytic agents 4, 8