Management of COPD Exacerbation
For acute COPD exacerbations, immediately initiate short-acting beta-2 agonists combined with short-acting anticholinergics (salbutamol 2.5-5 mg plus ipratropium 0.25-0.5 mg via nebulizer every 4-6 hours), oral prednisone 40 mg daily for exactly 5 days, and antibiotics for 5-7 days if the patient has increased sputum purulence plus either increased dyspnea or increased sputum volume. 1, 2
Severity Classification and Treatment Setting
COPD exacerbations are classified into three categories that determine treatment location 3, 1:
- Mild exacerbations: Treated with short-acting bronchodilators only in the outpatient setting 3, 1
- Moderate exacerbations: Require short-acting bronchodilators plus antibiotics and/or oral corticosteroids, typically managed outpatient 3, 1
- Severe exacerbations: Require hospitalization or emergency department evaluation, often associated with acute respiratory failure 3, 1
Hospitalization is mandatory when patients present with marked increase in symptom intensity, severe underlying COPD, new physical signs (cyanosis, peripheral edema, confusion), failure to respond to initial outpatient management, significant comorbidities, or inability to care for themselves at home 1, 2.
Immediate Bronchodilator Therapy
The combination of short-acting beta-2 agonists with short-acting anticholinergics provides superior bronchodilation lasting 4-6 hours compared to either agent alone 1, 2. Administer salbutamol 2.5-5 mg plus ipratropium bromide 0.25-0.5 mg via nebulizer initially, then repeat every 4-6 hours during the acute phase (typically 24-48 hours) until clinical improvement occurs 1, 2.
Nebulizers are preferred over metered-dose inhalers in hospitalized patients because they are easier to use and do not require coordination of 20+ inhalations needed to match nebulizer efficacy 2. However, metered-dose inhalers with spacers are acceptable for less severe exacerbations or outpatient management 1, 2.
Critical Pitfall to Avoid
Do NOT use intravenous methylxanthines (theophylline/aminophylline) - they increase side effects without added benefit and are explicitly not recommended 3, 1, 2. The FDA label for ipratropium also notes that combination therapy has not been shown to be more effective than either drug alone in reversing bronchospasm in acute COPD exacerbations, though clinical guidelines still recommend combination therapy based on mechanistic rationale 4.
Systemic Corticosteroid Protocol
Administer oral prednisone 30-40 mg once daily for exactly 5 days - this duration is equally effective as 14-day courses but reduces cumulative steroid exposure by over 50% 1, 2. Oral administration is equally effective to intravenous and should be the default route unless the patient cannot tolerate oral intake 1, 2.
Systemic corticosteroids improve lung function (FEV1), oxygenation, shorten recovery time and hospitalization duration, and reduce treatment failure by over 50% 3, 1, 2. Do not continue corticosteroids beyond 5-7 days after the acute episode unless there is a separate indication for long-term treatment 2.
Corticosteroids may be less efficacious in patients with lower blood eosinophil levels 2.
Antibiotic Therapy
Prescribe antibiotics for 5-7 days when the patient has increased sputum purulence plus either increased dyspnea or increased sputum volume (at least two of three cardinal symptoms) 3, 1, 2. Antibiotics reduce the risk of short-term mortality by 77%, treatment failure by 53%, and sputum purulence by 44% 2.
First-line antibiotic choices include amoxicillin, tetracycline derivatives (doxycycline), or amoxicillin/clavulanic acid based on local bacterial resistance patterns 1, 2. Alternative treatments include newer cephalosporins, macrolides (azithromycin), or quinolone antibiotics for patients with risk factors for resistant organisms 1, 2.
The most common organisms causing COPD exacerbations are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and viruses 1, 2.
Oxygen Therapy and Respiratory Support
Controlled Oxygen Delivery
Target oxygen saturation of 88-92% using controlled oxygen delivery to prevent CO2 retention and worsening respiratory acidosis 1, 2. In patients over 50 years old with a history of COPD, oxygen should not be administered at a FiO2 greater than 28% via Venturi mask or 2 L/min via nasal cannulae until arterial blood gases are known 1.
Mandatory arterial blood gas measurement within 60 minutes of initiating oxygen therapy and within 60 minutes of any change in oxygen concentration to assess for worsening hypercapnia or acidosis 1, 2. A pH below 7.26 is predictive of poor prognosis 1.
Noninvasive Ventilation (NIV)
For patients with acute hypercapnic respiratory failure, persistent hypoxemia despite oxygen, or severe dyspnea with respiratory muscle fatigue, initiate noninvasive ventilation immediately as first-line therapy 3, 1, 2. NIV improves gas exchange, reduces work of breathing, decreases intubation rates by approximately 50%, shortens hospitalization duration, and improves survival 3, 1, 2.
Absolute contraindications to NIV include respiratory arrest, cardiovascular instability, inability to protect airway, excessive secretions, and altered mental status preventing cooperation 1, 2. Consider invasive mechanical ventilation if NIV fails, particularly in patients with a first episode of respiratory failure, demonstrable remedial cause, or acceptable baseline quality of life 2.
Initial Diagnostic Evaluation
Urgent investigations should include 1, 2:
- Arterial blood gases - mandatory for all hospitalized patients and those with SpO2 <90% 1, 2
- Chest radiography - changes management in 7-21% of cases by identifying pneumonia, pneumothorax, or pulmonary edema 2
- Full blood count, urea, electrolytes 1
- Electrocardiogram - if resting heart rate <60/min or >110/min, or if cardiac symptoms present 2
- Sputum culture - if purulent sputum is present 1
- Blood cultures - if pneumonia is suspected 1
Exacerbations must be differentiated from acute coronary syndrome, worsening congestive heart failure, pulmonary embolism, and pneumonia 3.
Maintenance Therapy Before Discharge
Initiate or optimize long-acting bronchodilator therapy before hospital discharge 3, 1, 2. Maintenance therapy with long-acting bronchodilators (LAMA, LABA, or combinations) should be started as soon as possible 3, 1, 2.
Do not step down from triple therapy (LAMA/LABA/ICS) during or immediately after an exacerbation - ICS withdrawal increases the risk of recurrent moderate-severe exacerbations, particularly in patients with eosinophils ≥300 cells/μL 2.
Post-Exacerbation Management and Prevention
Schedule pulmonary rehabilitation within 3 weeks after discharge - this reduces hospital readmissions and improves quality of life 1, 2. Do NOT initiate pulmonary rehabilitation during hospitalization - this increases mortality; wait until post-discharge 2.
Additional Preventive Strategies
For patients with ≥2 moderate-to-severe exacerbations per year despite optimal inhaled therapy 1, 2:
- Consider long-term macrolide therapy (azithromycin 250-500 mg three times weekly) for former smokers with frequent exacerbations, though this requires consideration of potential QT prolongation, hearing loss, and bacterial resistance 2
- Consider roflumilast (PDE-4 inhibitor) for patients with severe COPD associated with chronic bronchitis and exacerbation history - reduces exacerbation rate by 15-18% 2, 5
- Consider N-acetylcysteine for patients with chronic bronchitic phenotype (chronic cough and sputum production) 2
Follow-Up Care
Schedule follow-up within 3-7 days to assess response to treatment 2. At 8 weeks after an exacerbation, 20% of patients have not recovered to their pre-exacerbation state, highlighting the importance of follow-up care 2.
- Provide intensive smoking cessation counseling with nicotine replacement therapy and behavioral intervention for current smokers
- Review and correct inhaler technique
- Ensure annual influenza vaccination and pneumococcal vaccination as indicated
Additional Supportive Measures for Hospitalized Patients
- Administer prophylactic subcutaneous heparin for venous thromboembolism prevention in patients with acute-on-chronic respiratory failure 2
- Use diuretics only if there is peripheral edema and raised jugular venous pressure 2
- Do NOT use chest physiotherapy in acute COPD exacerbations - there is no evidence of benefit 2
- Monitor fluid balance and nutrition status 2