What are the first‑line medications, dosages, and administration schedule for treating an adult with an acute exacerbation of chronic obstructive pulmonary disease?

First-Line Medications for Acute COPD Exacerbation

For an adult with acute COPD exacerbation, immediately initiate combined short-acting bronchodilators (albuterol 2.5–5 mg plus ipratropium 0.25–0.5 mg via nebulizer every 4–6 hours), oral prednisone 30–40 mg once daily for exactly 5 days, and antibiotics for 5–7 days when sputum purulence is present with either increased dyspnea or increased sputum volume. 1

Bronchodilator Therapy

Combination Short-Acting Agents

• Administer albuterol (salbutamol) 2.5–5 mg combined with ipratropium bromide 0.25–0.5 mg via nebulizer or metered-dose inhaler with spacer every 4–6 hours during the acute phase. 1
• This combination provides superior bronchodilation lasting 4–6 hours compared with either agent alone, with peak improvement occurring within the first 4 hours. 1, 2
• Continue regular dosing every 4–6 hours for 24–48 hours or until clinical improvement occurs, then transition to metered-dose inhalers with spacer. 1

Delivery Method Selection

• Metered-dose inhalers with spacer are equally effective as nebulizers for most patients and should be the preferred delivery device. 1
• Nebulizers may be easier for sicker patients who cannot coordinate multiple inhalations or require more than 20 inhalations to match nebulizer efficacy. 1
• When hypercapnia (PaCO₂ > 45 mmHg) or respiratory acidosis is present, power nebulizers with compressed air rather than oxygen; provide supplemental oxygen separately via nasal cannula at 1–2 L/min. 1

Agents to Avoid

• Do not use intravenous methylxanthines (theophylline or aminophylline) because they increase adverse effects without providing clinical benefit. 1, 3

Systemic Corticosteroid Protocol

Standard Regimen

• Give oral prednisone 30–40 mg once daily for exactly 5 days starting immediately at presentation. 1, 4
• This 5-day course is as effective as a 14-day regimen while reducing cumulative steroid exposure by more than 50%. 1, 4
• Oral administration is equally effective to intravenous and should be the default route unless the patient cannot tolerate oral intake. 1, 4

Clinical Benefits

• The 5-day regimen improves lung function and oxygenation, shortens recovery time, reduces treatment failure by over 50%, and lowers the risk of rehospitalization within the first 30 days. 1, 4
• Systemic corticosteroids prevent hospitalization for subsequent exacerbations within the first 30 days following the initial event. 4

Duration Limits

• Do not extend systemic corticosteroids beyond 5–7 days for a single exacerbation unless another indication exists, as longer courses increase adverse effects (hyperglycemia, weight gain, insomnia, infection, osteoporosis) without additional benefit. 1, 4
• No tapering is required after a 5-day course. 4

Intravenous Alternative

• For patients unable to take oral medications due to vomiting, inability to swallow, or impaired gastrointestinal function, use intravenous hydrocortisone 100 mg (equivalent to oral prednisolone 30 mg daily). 3
• Intravenous methylprednisolone 40 mg IV every 6–8 hours is an alternative for patients requiring IV therapy. 4
• Switch to oral corticosteroids as soon as the patient can tolerate oral intake, as IV administration may increase adverse effects without improving outcomes. 3

Antibiotic Therapy

Indications

• Prescribe antibiotics for 5–7 days when sputum purulence is present together with either increased dyspnea or increased sputum volume (two of three cardinal symptoms, with purulence required). 1
• Antibiotics are also indicated when all three cardinal symptoms are present or when mechanical ventilation is required. 1

Clinical Impact

• Antibiotic treatment reduces short-term mortality by approximately 77%, treatment failure by 53%, and sputum purulence by 44%. 1

First-Line Agents

• Amoxicillin-clavulanate 875/125 mg orally twice daily for 5–7 days (preferred for broader coverage). 1
• Doxycycline 100 mg orally twice daily for 5–7 days (acceptable alternative). 1
• Azithromycin 500 mg on day 1, then 250 mg daily for 4 days (macrolide alternative). 1
• Selection should be based on local bacterial resistance patterns. 1

Target Pathogens

• The most common bacterial organisms are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. 1

Oxygen Therapy

Target Saturation

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

Monitoring Requirements

• Obtain an arterial blood gas within 60 minutes of initiating oxygen to detect hypercapnia (PaCO₂ > 45 mmHg) or acidosis (pH < 7.35). 1
• Repeat arterial blood gas at 30–60 minutes (or sooner if clinical deterioration occurs) to detect rising PaCO₂ or falling pH. 1
• If pH falls below 7.26 with rising PaCO₂, prepare for immediate non-invasive ventilation. 1

Non-Invasive Ventilation (NIV)

Indications

• 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
• Additional indications include persistent hypoxemia despite oxygen, severe dyspnea with respiratory muscle fatigue, or respiratory rate ≥25–30 breaths/min. 1

Clinical Benefits

• 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

Contraindications

• Altered mental status with inability to protect the airway, large-volume secretions, hemodynamic instability, or recent facial/upper-airway surgery. 1

Hospitalization Criteria

Admit or evaluate in the emergency department if any of the following are present: 1

• Marked increase in dyspnea unresponsive to outpatient therapy
• Respiratory rate > 30 breaths/min
• Inability to eat or sleep because of 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 or liver failure)
• Inability to care for self at home

Common Pitfalls to Avoid

• Never power nebulizers with oxygen in hypercapnic patients; use compressed air and provide supplemental oxygen separately via nasal cannula. 1
• Never delay NIV when criteria for acute hypercapnic respiratory failure are met (pH < 7.35, PaCO₂ > 45 mmHg persisting >30 minutes). 1
• Never use methylxanthines (theophylline/aminophylline) in acute exacerbations—they add toxicity without benefit. 1
• Never continue systemic corticosteroids beyond 5–7 days for a single exacerbation unless another indication exists. 1, 4
• Never administer high-flow oxygen (>28% FiO₂ or >4 L/min) without arterial blood-gas monitoring, as this can worsen hypercapnic respiratory failure and increase mortality. 1
• Do not prescribe antibiotics routinely; limit use to cases meeting the purulent-sputum plus one additional cardinal symptom criterion. 1

Discharge Planning

• Arrange pulmonary rehabilitation within 3 weeks after discharge to reduce readmissions and improve quality of life; initiating rehabilitation during the hospital stay is associated with increased mortality. 1
• Optimize long-acting bronchodilator therapy (LAMA, LABA, or combinations) before discharge. 1
• Do not step down from triple therapy (LAMA + LABA + ICS) during or immediately after an exacerbation, as inhaled corticosteroid withdrawal raises the risk of recurrent exacerbations. 1
• Verify correct inhaler technique at discharge and provide smoking-cessation counseling with nicotine replacement and behavioral support. 1