COPD exacerbation

Etiology

• infections (most common)
  • bacterial
    • Streptococcus pneumonia
    • Haemophilus influenza, Haemophilus parainfluenza
    • Moraxella catarrhalis
    • Mycoplasma pneumonia
  • viral
    • influenza virus
    • adenovirus
    • respiratory syncytial virus (RSV) 9%
• heart failure, cor pulmonale
• myocardial infarction
• cardiac arrhythmias
• pneumothorax
• pulmonary embolism (as high as 25%); up to 6%
• bronchogenic carcinoma
• environmental exposure to bronchospastic agents
  • each 1 degree C increment in outdoor temperature associated with a 2% increased risk of COPD exacerbation
• oversedation
• non-compliance with medications
• excessive oxygen use (suppression of respiratory drive)
• tachyphylaxis to beta-2 adrenergic agonists
• mucus plugging
• emotional factors
• vitamin D status is not a risk factor
• risk factors for early hospital readmission
  • multiple comorbidities (most significant)
    • heart failure, lung cancer, depression. anxiety, osteoporosis, alcoholism
    • rate of early hospital readmission increases as the number of comorbidities increases
  • inadequate hospital discharge medications
  • length of hospital stay < 2 days or > 5 days
  • male gender
• gabapentinoid use increases risk for severe COPD exacerbation

Pathology

• persistent or recurrent COPD exacerbations are driven mostly by residual airway inflammation, not by infection
• auto-PEEP contributes to increased work of breathing during exacerbations of obstructive lung disease

Clinical manifestations

• increase in severity of cough
• dyspnea, respiratory failure may occur
• sputum may be increased or changed in character with exacerbations
• fatigue
• purulent sputum predicts need for antibiotics in patients with mild-to-moderate COPD*

* mild-to-moderate COPD defined as FEV1 > 50% of predicted

* severity of exacerbationis determined by dyspnea intensity, respiratory rate, heart rate, & oxygen saturation

Laboratory

• SaO2
• arterial blood gas (ABG)
  • hypercarbia over baseline
    • a decrease in pCO2 of over baseline suggests pulmonary embolism
  • pH < 7.30
  • carboxyhemoglobin level to identify continued smoking
• D-dimer in plasma: rule out pulmonary embolism
• complete blood count
  • eosinophilia: blood eosinophils > 2% predicts favorable response to glucocorticoids
  • patients with eosinophil count < 300/mL may not need oral glucocorticoids
• basic metabolic panel
• serum C-reactive protein patients with mild-to-moderate COPD*
  • < 20 ng/mL unlikely to benefit from antibiotics
  • 20-40 ng/mL possible benefit of antibiotics
  • > 40 mg/dL predicts need for antibiotics
• low serum procalcitonin may identify patients hospitalized with COPD exacerbation for which antibiotic therapy > 24 hours does not reduce readmission rates
• sputum culture not indicated (rarely affects management)
• for mild COPD exacerbations, clinical assessment is sufficient
  • if physical examination is unremarkable, laboratory testing &/or imaging is unlikely to beneficially alter management

* mild-to-moderate COPD defined as FEV1 > 50% of predicted

Diagnostic procedures

• electrocardiogram (see Complications: below)
• pulmonary angiography if pulmonary embolism suspected

Radiology

• chest X-ray
• rule out pulmonary embolism
  • CT angiography or ventilation perfusion scan
• computed tomography (CT):
  • pulmonary artery enlargement predicts COPD exacerbation

Complications

• pulmonary embolism in 17%
  • patients with purulent sputum at lower risk (RR=0.43)

Differential diagnosis

• need for large amounts of supplemental oxygen suggests diagnosis other than obstructive lung disease (asthma, COPD)
• pulmonary embolism
• unstable angina
  • deep symmetric T-waves with flat ST segment in leads V2 & V3 suggest stenosis of the proximal left anterior descending coronary artery
• heart failure, cor pulmonale

Management

• observation units may reduce need for hospitalization (63% vs 78%)
• combination therapy
  • glucocorticoids plus antibiotics
    • for hospitalized patients
    • beneficial regardless of severity
    • antibiotics for patients with purulent sputum (GOLD)
  • short-acting inhaled beta-2 adrenergic receptor agonist
    • albuterol MDI &/or nebulizer
  • anticholinergic agent: ipratropium (Atrovent) MDI &/or nebulizer
  • continue maintenance theophylline
• glucocorticoids may preferentially benefit patients with eosinophilia
  • prednisone 40 mg/day for 5 days sufficient (ACP)
    • equivalent to higher &/or longer doses &/or IV administration
  • personalized prednisone dosing better than standard dosing 40 mg/day
    • based on 5 factors including symptom scales, previous steroid dosing, inflammatory markers, & blood gas results
    • optimal dose 40-60 mg prednisone/day for 5 days
  • avoid glucocorticoid therapy for > 2 weeks
  • NNT = 10, NNH = 7 (adverse effects)
  • reserve intravenous glucocorticoids for patients that cannot tolerate oral therapy
  • methylprednisolone 2 mg/kg/day in divided doses
    • 80-160 mg/day may be sufficient in ICU patients
  • manage glucocorticoid-induced hyperglycemia in patients who are eating with basal, prandial & correctional insulin
• antimicrobial therapy:
  • for severe exaberbations
    • all hospitalized patients with COPD exacerbation
    • limited to patients with purulent sputum or mechanical ventilation (GOLD)
    • see pneumonia for empiric antibiotic therapy
  • for mild-moderate exacerbations with:
    • increased dyspnea
    • increased sputum volume
    • increased sputum purulence
    • increased cough & sputum purulence
  • 5 day course of oral antibiotics (previously 7-10 days)
  • complicated exacerbation
    • older age > 65 years, FEV1 < 50%, heart disease, >= 2 COPD exacerbations/year
    • amoxicillin/clavulanate or
    • respiratory fluoroquinolone:
      • 2 days of levofloxacin non inferior to 7 days
  • amoxicillin 250 mg PO TID
  • Bactrim DS 1 PO BID (works as well as Cipro)
  • doxycycline 100 mg PO BID
  • azithromycin (Zithropac) 250 mg, 2 tabs day 1, then 1 tab PO QD
    • 500 mg QD for 3 days, then 250 mg QOD
  • increased cardiovascular mortality noted 1 year after treatment of COPD exacerbation with clarithromycin
• chest physiotherapy
  • may improve clearance of secretions
  • increased hypoxia may occur during chest percussion or postural drainage
• supplemental oxygen
  • maintain an oxygen saturation (of hemoglobin) of 88-90%, even in the face of increasing hypercapnia
    • higher oxygen flow rates associated with increased mortality
  • a Venturi mask provides good control over oxygen delivery
• criteria for ICU admission
  • PaO2 < 40 mm Hg
  • respiratory acidosis, pH < 7.25 requiring enndotracheal intubation
  • mental status changes
  • hemodynamic instability
• ventilatory support
  • non-invasive positive pressure ventilation (NPPV) is needed in 10-20% of patients
    • reduces mortality (relative risk 0.41)
      • is associated with lower in-hospital mortality (NNT=12), length of stay (3.4 days shorter), & cost compared with mechanical ventilation
    • reduces need for endotracheal intubation (RR 0.42)
    • BiPAP is NPPV of choice
      • acute on chronic hypercapneic respiratory failure
      • high inspiratory flow rates (80-100 L/min)
    • high-pressure NPPV may result in the need for fewer intubations than standard low-pressure NPPV
    • CPAP can open the upper airway to treat obstructive sleep apnea, but will not help patients ventilate & clear carbon dioxide
    • superior to high-flow nasal cannula in patients with moderate hypercapnic respiratory failure during COPD exacerbation
  • mechanical ventilation
    • obtundation, delirium, or other mental status changes preclude cooperation necessary for NPPV
    • inability to protect airway
      • loss of gag reflex
      • vomiting, excessive secretions, upper GI bleed
    • failure of CPAP/BiPAP trial
    • hypoxemic respiratory failure, acute respiratory distress syndrome (ARDS)
    • complications: auto-PEEP, use low tidal-volume ventilation (see ARDS)
• pulmonary rehabilitation after hospital discharge
  • may be helpful
  • reduces rate of rehospitalizations after COPD exacerbation
  • reduces 1 year mortality when pulmonary rehabilitation started within 90 days of hospitalization for COPD
  • progressive exercise rehabilitation should not be started during the early stages of recovery
• see chronic obstructive pulmonary disease for outpatient supplemental oxygen
  • no mortality benefit if oxygen desaturation with exercise between 80-89%
• prevention of COPD exacerbation
  • smoking cessation, ensure pneumococcal vaccination & influenza vaccination, ensure proper inhaler technique
  • see COPD
• home care for COPD exacerbation is increasingly common
  • reasonable for mild-moderate exacerbation in patients without significant comorbidities
  • home non-invasive positive pressure ventilation (NPPV) reduces hospital readmissions 4.3 months vs 1.4 months for oxygen alone in patients with persistent hypercapnia (PaCO2 >53 mm Hg)
• risk factors for early hospital readmission (see etiology above)
• surgery:
  • delay elective surgery until resolution of exacerbation

More general terms

• chronic obstructive pulmonary disease (COPD)
• exacerbation

Patient information

COPD exacerbation patient information