What is the recommended management of an acute exacerbation of chronic obstructive pulmonary disease?

Management of Acute Exacerbation of COPD

For acute COPD exacerbations, immediately initiate combined short-acting bronchodilators (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, controlled oxygen targeting SpO₂ 88–92%, and antibiotics for 5–7 days only when sputum purulence is present with either increased dyspnea or increased sputum volume. 1, 2, 3

Initial Assessment and Severity Classification

Classify the exacerbation severity to determine treatment location: 1

• Mild exacerbation: Treat outpatient with short-acting bronchodilators alone 1
• Moderate exacerbation: Treat outpatient with bronchodilators plus antibiotics and/or oral corticosteroids 1
• Severe exacerbation: Requires hospitalization or emergency department evaluation, often with acute respiratory failure 1

Hospitalization criteria include any of the following: 1, 3

• Marked increase in dyspnea unresponsive to outpatient therapy
• Respiratory rate >30 breaths/min
• Inability to eat or sleep due to respiratory symptoms
• New or worsening hypoxemia (SpO₂ <90% on room air)
• New or worsening hypercapnia (PaCO₂ >45 mmHg)
• Altered mental status or loss of alertness
• Persistent rhonchi after initial treatment requiring continued nebulization
• High-risk comorbidities (pneumonia, cardiac arrhythmia, heart failure, diabetes, renal/liver failure)
• Inability to care for self at home

Immediate Pharmacological Management

Bronchodilator Therapy

Administer combined salbutamol 2.5–5 mg plus ipratropium 0.25–0.5 mg via nebulizer every 4–6 hours during the acute phase; this combination provides superior bronchodilation lasting 4–6 hours compared with either agent alone. 1, 2, 3 For outpatients who can coordinate inhalation, metered-dose inhalers with a spacer are equally effective. 1

Power nebulizers with compressed air (not oxygen) when hypercapnia or respiratory acidosis is present, and provide supplemental oxygen separately via nasal cannula at 1–2 L/min. 1, 2 Continue nebulized bronchodilators for 24–48 hours until clinical improvement, then transition to metered-dose inhalers 24–48 hours before discharge. 3

Never use intravenous methylxanthines (theophylline/aminophylline) because they increase adverse effects without clinical benefit. 1, 2, 3

Systemic Corticosteroid Protocol

Give oral prednisone 30–40 mg once daily for exactly 5 days starting immediately at presentation. 1, 2, 3 This short course is as effective as a 14-day regimen while reducing cumulative steroid exposure by more than 50%. 1, 3 Oral administration is equally effective to intravenous and should be the default route unless oral intake is impossible. 1, 3

The 5-day regimen improves lung function and oxygenation, shortens recovery time and hospital stay, reduces treatment failure by over 50%, and lowers the risk of rehospitalization within the first 30 days. 1, 3

Do not extend systemic corticosteroids beyond 5–7 days for a single exacerbation unless another indication exists, as longer courses increase adverse effects without added benefit. 1, 2, 3

Antibiotic Therapy

Prescribe antibiotics for 5–7 days only when sputum purulence is present together with either increased dyspnea or increased sputum volume (two of three cardinal symptoms, with purulence required). 1, 2, 3 This strategy reduces short-term mortality by approximately 77%, treatment failure by 53%, and sputum purulence by 44%. 1

First-line antibiotic choices (selected according to local resistance patterns) include: 1, 3, 4

• Amoxicillin-clavulanate 875/125 mg orally twice daily for 5–7 days
• Doxycycline 100 mg orally twice daily for 5–7 days
• Azithromycin 500 mg daily for 3 days (or 500 mg on Day 1, then 250 mg daily for Days 2–5) 4

The most common causative organisms are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 1, 3

Do not prescribe antibiotics empirically without meeting the criteria of purulent sputum plus either increased dyspnea or sputum volume. 2, 3

Oxygen Therapy and Respiratory Support

Controlled Oxygen Delivery

Target oxygen saturation of 88–92% using controlled-delivery devices (Venturi mask 24–28% FiO₂ or nasal cannula 1–2 L/min) to correct life-threatening hypoxemia while minimizing CO₂ retention and respiratory acidosis. 1, 2, 3 Higher oxygen concentrations can worsen hypercapnic respiratory failure and increase mortality by approximately 78%. 1

Obtain an arterial blood gas within 60 minutes of initiating oxygen to identify hypercapnia (PaCO₂ >45 mmHg) or acidosis (pH <7.35). 1, 3 If the patient deteriorates clinically or the initial pH is <7.35, repeat the arterial blood gas 30–60 minutes later. 1

Never administer high-flow oxygen (>28% FiO₂ or >4 L/min) without arterial blood-gas monitoring, as this can precipitate respiratory acidosis and increase mortality. 1, 2

Non-Invasive Ventilation (NIV)

Initiate NIV immediately as first-line therapy when acute hypercapnic respiratory failure (PaCO₂ >45 mmHg) with acidosis (pH <7.35) persists for more than 30 minutes after standard medical treatment. 1, 2, 3 NIV improves gas exchange, reduces work of breathing, decreases intubation rates by approximately 50%, shortens hospital stay, and improves survival; success rates in appropriately selected patients are 80–85%. 1, 3

Transfer to ICU if pH remains <7.26 despite NIV. 1

Contraindications to NIV include altered mental status with inability to protect the airway, large-volume secretions, hemodynamic instability, or recent facial/upper-airway surgery. 1

Additional Supportive Measures

Administer diuretics only if peripheral edema and elevated jugular venous pressure are present; avoid aggressive diuresis that could compromise cardiac output. 5, 3

Give prophylactic subcutaneous heparin for venous thromboembolism prevention in patients with acute-on-chronic respiratory failure. 5, 3

Do not use chest physiotherapy in acute COPD exacerbations, as there is no evidence of benefit. 5, 3

Avoid sedatives, which worsen respiratory depression. 3

Discharge Planning and Follow-Up

Schedule pulmonary rehabilitation within 3 weeks after discharge to reduce hospital readmissions and improve quality of life; initiating rehabilitation during hospitalization increases mortality. 1, 2, 3

Initiate or optimize long-acting bronchodilator therapy (LAMA, LABA, or LAMA/LABA/ICS triple therapy) before hospital discharge. 1, 2, 3 Do not step down from triple therapy during or immediately after an exacerbation, as inhaled corticosteroid withdrawal raises the risk of recurrent exacerbations. 1

Verify proper inhaler technique at discharge and provide smoking cessation counseling with nicotine replacement therapy and behavioral support for current smokers. 1, 3

Measure FEV₁ before discharge to establish new baseline, and check arterial blood gases on room air in patients who presented with respiratory failure. 3

Schedule follow-up within 3–7 days to assess treatment response and prevent subsequent exacerbations. 1

Common Pitfalls to Avoid

• Never power nebulizers with oxygen in hypercapnic patients; use compressed air and provide supplemental oxygen via a separate nasal cannula 1, 2
• Never delay NIV when criteria for acute hypercapnic respiratory failure are met (pH <7.35, PaCO₂ >45 mmHg persisting >30 minutes) 1, 2
• Never use methylxanthines (theophylline/aminophylline) in acute exacerbations—they add toxicity without benefit 1, 2, 3
• Never continue systemic corticosteroids beyond 5–7 days for a single exacerbation unless another indication exists 1, 2, 3
• Never administer high-flow oxygen without arterial blood-gas monitoring 1, 2
• Never prescribe antibiotics without meeting criteria (purulent sputum plus increased dyspnea or sputum volume) 2, 3
• Do not delay hospital evaluation when severity is uncertain—err on the side of caution 3