Acute Exacerbation of COPD

Acute worsening of respiratory symptoms (breathlessness, cough, sputum volume or purulence) beyond day-to-day variation that leads to a change in treatment, in a patient with COPD (post-bronchodilator FEV1/FVC less than 0.70).

• Causes: respiratory viruses (about 30 to 50%), bacteria (about 40 to 50%; Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa in advanced disease), air pollution, and non-infective triggers (pulmonary embolism, heart failure, pneumothorax, arrhythmia, drugs, sedatives, poor adherence). No cause is found in about 30%.
• Severity: mild (treated with bronchodilators alone), moderate (bronchodilators plus corticosteroid and, or, antibiotic), severe (needs hospital admission or emergency visit; acute respiratory failure with pH less than 7.35 and PaCO2 greater than 6.5 kPa is the most severe).
• In hospital mortality is about 4 to 10%, about 15 to 25% in patients needing intensive care, and about 30 to 40% at 1 year after a hypercapnic admission. Each exacerbation accelerates decline in lung function and increases the risk of further exacerbations, cardiovascular events and death.

• Increased dyspnoea, cough, wheeze, increased sputum volume or purulence, chest tightness, fatigue, sometimes fever, confusion or drowsiness (hypercapnia), peripheral oedema (cor pulmonale).
• Signs: tachypnoea, accessory muscle use, pursed lip breathing, wheeze, reduced air entry, cyanosis, flapping tremor and bounding pulse (hypercapnia), raised jugular venous pressure and oedema.
• Differential diagnosis: pneumonia, pneumothorax, pulmonary embolism, acute heart failure, arrhythmia (atrial fibrillation), myocardial infarction, pleural effusion, lung cancer, upper airway obstruction, sedative or opioid overdose.
• Complications: acute respiratory failure, respiratory acidosis, cor pulmonale, arrhythmia, pneumothorax, venous thromboembolism, pneumonia, muscle wasting and prolonged weakness.

• Pulse oximetry (target 88 to 92%), arterial blood gas for all admitted patients (pH, PaCO2, PaO2, bicarbonate), and repeat 30 to 60 minutes after oxygen is started or changed.
• Chest X-ray (pneumonia, pneumothorax, effusion, oedema), ECG (arrhythmia, ischaemia, right heart strain), full blood count (polycythaemia, eosinophils), urea and electrolytes, glucose, CRP, troponin and natriuretic peptide when indicated, theophylline level if taking it.
• Sputum culture if purulent and the patient is admitted, has had recent antibiotics or frequent exacerbations; respiratory viral PCR; blood cultures if febrile or septic.
• CT pulmonary angiography when pulmonary embolism is suspected (breathlessness without clear infective trigger, pleuritic pain, leg swelling). Echocardiography for suspected heart failure or pulmonary hypertension.
• Spirometry when stable (not during an exacerbation) to confirm the diagnosis.

• Controlled oxygen: target SpO2 88 to 92% with a Venturi mask (24% or 28%) or nasal cannulae at 1 to 2 L/min; repeat blood gas at 30 to 60 minutes. Avoid hyperoxia, which worsens carbon dioxide retention.
• Bronchodilators:
  • Salbutamol 2.5 to 5 mg nebulised (or 4 to 8 puffs of 100 micrograms via spacer) every 4 to 6 hours, more often initially; ipratropium 500 micrograms nebulised every 4 to 6 hours. Use air driven nebulisers with supplemental oxygen by nasal cannulae in hypercapnic patients.
• Systemic corticosteroid: prednisolone 30 to 40 mg orally once daily for 5 days (no taper; longer courses add side effects without benefit); hydrocortisone 100 mg IV every 6 hours if oral therapy is not possible. Blood eosinophil count less than 100 per microlitre suggests lower benefit and higher infection risk.
• Antibiotics when sputum purulence is present with increased dyspnoea or sputum volume, or when ventilation is needed (5 days):
  • Amoxicillin 500 mg to 1 g orally three times daily, or doxycycline 200 mg on day 1 then 100 mg daily, or clarithromycin 500 mg twice daily.
  • Co-amoxiclav 625 mg orally three times daily (or 1.2 g IV three times daily) for patients with severe disease, frequent exacerbations or recent antibiotics.
  • Pseudomonas risk (previous isolation, severe airflow limitation, bronchiectasis): ciprofloxacin 500 to 750 mg orally twice daily (400 mg IV every 8 to 12 hours), or levofloxacin 750 mg daily, or piperacillin tazobactam 4.5 g IV every 6 hours.
  • Tailor to sputum culture; avoid antibiotics for mild exacerbations without purulence.
• Non-invasive ventilation is the treatment of choice for acute hypercapnic respiratory failure (pH less than 7.35 with PaCO2 greater than 6.5 kPa persisting after 1 hour of optimal medical treatment):
  • Initial settings: inspiratory pressure 10 cmH2O and expiratory pressure 4 to 5 cmH2O, raising inspiratory pressure by 2 to 5 cmH2O every 10 to 30 minutes toward 20 cmH2O as tolerated, with a respiratory rate 12 to 16 per minute and humidification; oxygen titrated to 88 to 92%.
  • Reassess at 1 to 2 hours: improvement is a fall in PaCO2, rise in pH and fall in respiratory rate. Continue for at least 6 hours, ideally 16 to 24 hours in the first day, then wean over days.
  • Reduces intubation, mortality and length of stay.
• Intubation and invasive ventilation for non-invasive ventilation failure (pH falling, exhaustion, coma, aspiration, haemodynamic instability), respiratory arrest, or pH less than 7.25 with deteriorating condition: use low tidal volumes (6 to 8 mL/kg), long expiratory time, accept permissive hypercapnia, and plan early weaning and extubation to non-invasive ventilation. Doxapram 1.5 to 4 mg/min IV is used only when non-invasive ventilation is unavailable (evidence is limited).
• Theophylline or aminophylline: 5 mg/kg IV over 20 minutes (omit if already on theophylline) then 0.5 mg/kg/h, target level 10 to 20 mg/L; second line only (arrhythmia, seizures, interactions).
• Other measures: IV fluids for dehydration, diuretics (furosemide 20 to 40 mg IV) for oedema, enoxaparin 40 mg SC daily, nutrition, treatment of arrhythmia and heart failure, chest physiotherapy for sputum retention, and early mobilisation.
• Discharge criteria: stable on bronchodilators every 4 hours, able to eat, sleep and walk, SpO2 and blood gas stable, understanding of the inhaled regimen, and follow up arranged. Early supported discharge or hospital at home for selected patients.
• After discharge:
  • Check inhaler technique; give long acting muscarinic and beta agonist combination (for example indacaterol/glycopyrronium 110/50 micrograms once daily), adding an inhaled corticosteroid for frequent exacerbations and eosinophils of 300 per microlitre or more (triple therapy: fluticasone furoate/umeclidinium/vilanterol 100/62.5/25 micrograms once daily, or beclometasone/formoterol/glycopyrronium 87/5/9 micrograms 2 puffs twice daily).
  • Pulmonary rehabilitation started within 4 weeks of discharge (reduces readmission and mortality).
  • Smoking cessation: varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks, plus nicotine patch 21 mg/24 h; or bupropion 150 mg daily for 3 days then twice daily.
  • Vaccination (influenza yearly, pneumococcal conjugate, COVID-19, respiratory syncytial virus in older adults); self-management plan with a rescue pack (prednisolone 30 mg daily for 5 days and an antibiotic) for selected patients.
  • Roflumilast 500 micrograms daily for chronic bronchitis with FEV1 less than 50% and a hospital admission or two or more exacerbations a year (avoid in depression, low body weight; monitor weight and mood).
  • Azithromycin 250 mg daily (or 500 mg three times weekly) for frequent exacerbators who are ex smokers, after excluding non-tuberculous mycobacteria and checking the QT interval and hearing.
  • Dupilumab 300 mg SC every 2 weeks for chronic bronchitis with blood eosinophils of 300 per microlitre or more and exacerbations despite triple therapy.
  • Long term oxygen therapy for PaO2 7.3 kPa or less (or 8.0 kPa or less with cor pulmonale, haematocrit greater than 55% or nocturnal hypoxaemia) for at least 15 hours daily; home non-invasive ventilation for persistent hypercapnia (PaCO2 greater than 7 kPa) after an acidotic admission.
• Special groups:
  • Pregnancy: rare; use salbutamol, ipratropium and prednisolone; avoid tetracyclines and fluoroquinolones.
  • Elderly: assess for frailty, delirium, malnutrition, and polypharmacy; discuss goals of care and advance care planning.
  • Renal impairment: adjust antibiotic doses; avoid nephrotoxic combinations.
  • Low resource settings: where biomass smoke or tuberculosis damage cause airflow limitation, treat with inhaled bronchodilators and prednisolone 30 to 40 mg daily for 5 days during exacerbations, and exclude tuberculosis with sputum Xpert MTB/RIF.
• Red flags: pH less than 7.35, drowsiness or confusion, SpO2 less than 88% on oxygen, hypotension, new arrhythmia, chest pain, haemoptysis, failure to improve at 48 to 72 hours.
• Follow up: telephone review at 48 to 72 hours, clinic review at 4 to 6 weeks with spirometry, inhaler technique, oxygen assessment and exacerbation plan; review every 3 to 6 months thereafter.