COPD exacerbation resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]

Overview

COPD exacerbation is an acute event characterized by a worsening of the patient’s respiratory symptoms (baseline dyspnea, cough, and/or sputum production) that is beyond normal day-to-day variations and leads to a change in medication.

Causes

Life-Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Arrhythmia
• Congestive heart failure
• Pleural effusion
• Pneumonia
• Pneumothorax
• Pulmonary embolism

Common Causes

• Respiratory tract infections (~½)
• Unknown (~⅓)
• Air pollutants

Management

Characterize the symptoms: ❑ Increased cough ❑ Increased dyspnea ❑ Increased sputum production

Examine the patient: ❑ Pulse oximetry ❑ Arterial blood gas

Consider alternative dagnosis: ❑ Pulmonary embolism ❑ Heart failure ❑ Asthma exacerbation ❑ Bronchiectasis ❑ Broncholitis obliterans

Supplement Oxygen: (Urgent) ❑ Maintain SaO2 ≥ 88-92% )

Need for ICU admission? ❑ Hemodynamic instability AND/OR ❑ Changes in mental status (confusion, lethargy, coma) AND/OR ❑ Severe dyspnea that responds inadequately to initial emergency therapy AND/OR ❑ Worsening hypoxemia (PaO2 <40 mm Hg) and/or respiratory acidosis (pH <7.25)

No

Yes

Indications for Hospitalization: ❑ Marked increase in intensity of symptoms (eg, sudden development of resting dyspnea) ❑ Presence of serious comorbidities (eg, heart failure or newly occurring arrhythmias) ❑ Failure of an exacerbation to respond to initial medical management ❑ Onset of new physical signs (eg, cyanosis, peripheral edema) ❑ Severe underlying COPD (GOLD 3—4 categories) ❑ Frequent exacerbations (≥2 events per year) ❑ Insufficient home support ❑ Older age (>65 years)

Assessment of Exacerbation: ❑ Cardinal symptoms (↑ dyspnea, ↑ sputum volume, and ↑ sputum purulence) ❑ ECG (identify coexisting cardiac problems) ❑ Chest radiograph (exclude alternative diagnoses) ❑ Whole-blood count (identify polycythemia, anemia, or leukocytosis) ❑ Electrolytes and glucose (identify electrolyte disturbances or hyperglycemia)

❑ Admit patient to ICU ❑ Classify as Life-threatening COPD exacerbation ❑ Assess patients need for mechanical ventilation

Indications for Noninvasive Mechanical Ventilation ❑ Respiratory acidosis (arterial pH < 7.35 or PaCO2 >45 mm Hg) ❑ Severe dyspnea with signs of respiratory muscle fatigue ❑ Increased work of breathing

Indications for Invasive Mechanical Ventilation ❑ Diminished consciousness, psychomotor agitation inadequately controlled by sedation ❑ Severe hemodynamic instability without response to fluids and vasoactive drugs ❑ Respiratory pauses with loss of consciousness or gasping for air ❑ Life-threatening hypoxemia in patients unable to tolerate NIV ❑ Persistent inability to remove respiratory secretions ❑ Heart rate <50/min with loss of alertness ❑ Severe ventricular arrhythmias ❑ Respiratory or cardiac arrest ❑ Failure of initial trial of NIV ❑ Massive aspiration

Mild Exacerbation (⊕ 1 cardinal symptom) ❑ Consider outpatient management ❑ Require change of inhaled treatment by the patient

Moderate Exacerbation (⊕ 2 cardinal symptoms) ❑ Consider outpatient management ❑ Require a short course of antibiotics and/or oral corticosteroids

Severe Exacerbation (⊕ 3 cardinal symptoms) ❑ Consider inpatient management ❑ Assess symptoms, ABG, and CXR ❑ Monitor fluid balance and nutrition ❑ Identify and treat associated conditions ❑ Consider subcutaneous heparin or LMWH ❑ Controlled oxygen therapy (consider NIV if indicated) ❑ Antibiotics (if ↑ sputum purulence or ⊕ bacterial infection) ❑ Corticosteroids ❑ Bronchodilators ▸ Increase doses/frequency of short-acting bronchodilators ▸ Combine short-acting β2-agonists and anticholinergics ▸ Use spacers or air-driven nebulizers

Pharmacologic Treatment

β2-adrenergic agonists ▸ Albuterol MDI 4—8 puffs IH q1—2h OR Nebulizer 2.5—5 mg IH q1—2h Anticholinergics ▸ Ipratropium MDI 4—8 puffs IH q1—2h OR Nebulizer 0.5 mg IH q1—2h Methylxanthines ▸ Aminophylline 0.9 mg/kg/hr IV ▸ Theophylline 150—450 mg PO bid Treatment Notes ❑ Short-acting β2-agonists with or without short-acting anticholinergics are generally preferred ❑ Consider methylxanthine as an adjunct if inadequate response to bronchodilators

Corticosteroids ▸ Prednisolone 30—40 mg PO q24h for 10—14 days (for mild/moderate exacerbation) ▸ Methylprednisolone 125 mg IV q6h for 3 days (for severe exacerbation) Treatment Notes ❑ Budesonide 400 mcg IH bid may be an alternative to oral corticosteroids ❑ Corticosteroids should be tapered over 2 weeks

Indications for Antibiotics ❑ Mechanical ventilation required ❑ Severe exacerbation (⊕ 3 cardinal symptoms) ❑ Moderate exacerbation with ↑ sputum purulence Complicated COPD (⊕ Risk Factors) ❑ Age ≥65 years ❑ FEV1 ≤50% predicted ❑ ≥3 exacerbations per year ❑ Cardiac disease ▸ Moxifloxacin 400 mg PO q24h ▸ Gemifloxacin 320 mg PO q24h ▸ Levofloxacin 500 mg PO q24h ▸ Amoxicillin-Clavulanate 875/125 mg PO bid or 2000/125 mg PO bid or 500/125 mg PO q8h ▸ Ciprofloxacin 750 mg PO q12h with sputum culture (if at risk for Pseudomonas) Uncomplicated COPD (⌀ Risk Factors) ▸ Azithromycin 500 mg PO q24h or 500 mg PO x1 dose followed by 250 mg PO q24h ▸ Clarithromycinextended-release 1000 mg PO q24h ▸ Cefuroxime axetil 250 or 500 mg PO q12h ▸ Cefpodoxime 200 mg PO q12h ▸ Cefdinir 300 mg PO q12h or 600 mg PO q24h ▸ Doxycycline 100 mg PO bid ▸ Trimethoprim-Sulfamethoxazole 160/800 mg PO bid Treatment Notes ❑ Antibiotic choice should reflect local resistance pattern ❑ Use alternative class if antibiotic exposure within 3 months ❑ Re-evaluate and consider sputum culture if failed to respond in 72 hours ❑ The recommended length of antibiotic therapy is usually 5—10 days

Checklist at Time of Discharge From Hospital

Action Items at Discharge ❑ Reinforce smoking cessation measures ❑ Assure effective home maintenance of pharmacotherapy regimen ❑ Reassess inhaler technique ❑ Educate about maintenance regimen ❑ Give instruction regarding completion of steroid therapy and antibiotics ❑ Assess need for long-term oxygen therapy ❑ Assure follow-up visit in 4—6 weeks ❑ Provide a management plan for comorbidities and their follow-up

Checklist at Follow-Up Visit 4—6 Weeks After Discharge

Action Items at Follow-Up Visit ❑ Smoking cessation measures ❑ Ability to cope in usual environment ❑ Reassess inhaler technique ❑ Measurement of FEV1 ❑ Inhaler technique ❑ Understanding of recommended treatment regimen ❑ Need for long-term oxygen therapy and/or home nebulizer ❑ Capacity to do physical activity and activities of daily living ❑ Chronic Obstructive Pulmonary Disease Assessment Test (CAT) ❑ Modified British Medical Research Council questionnaire on breathlessness (mMRC) ❑ Status of comorbidities

Do's

Assessment

• The presence of purulent sputum during an exacerbation can be sufficient indication for starting empirical antibiotic treatment.

Treatment

Treatment Setting

• When a patient comes to the ED, the first actions are to provide controlled oxygen therapy and to determine whether the exacerbation is life-threatening. If so, the patient should be admitted to the ICU immediately.

Short-Acting Bronchodilators

• Short-acting inhaled β2-agonists with or without short-acting anticholinergics are usually the preferred bronchodilators for treatment of an exacerbation.

• A systematic review found no significant differences in FEV₁ between MDI and nebulizers, although the latter can be more convenient for sicker or frail patients.

• Intravenous methylxanthines (theophylline or aminophylline) are only to be used in selected cases when there is insufficient response to short-acting bronchodilators.

Corticosteroids

• Systemic corticosteroids in COPD exacerbations shorten recovery time, improve FEV₁ and Pa_O2, and reduce the risk of early relapse, treatment failure, and length of hospital stay.

• Consensus on optimal corticosteroids dose and duration for COPD exacerbations has not been reached.

Antibiotics

• Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the most common bacterial pathogens involved in an exacerbation. However, the choice of the antibiotic should be based on the local bacterial resistance pattern.

• Empirical coverage of Pseudomonas aeruginosa in GOLD 3 and GOLD 4 patients is important.

• Procalcitonin may be of value in the decision to use antibiotics.

Adjunct Therapies

• An appropriate fluid balance with special attention to the administration of diuretics, anticoagulants, treatment of comorbidities, and nutritional aspects should be considered.

• Healthcare providers should strongly enforce stringent measures against active cigarette smoking.

Respiratory Support

• Once oxygen is started, arterial blood gases should be checked 30 to 60 minutes later to ensure satisfactory oxygenation without carbon dioxide retention or acidosis.

• Venturi masks offer more accurate and controlled delivery of oxygen than do nasal prongs but are less likely to be tolerated by the patient.

• Noninvasive mechanical ventilation improves respiratory acidosis and decreases respiratory rate, severity of breathlessness, complications such as ventilator-associated pneumonia, length of hospital stay, mortality, and intubation rates.

Hospital Discharge and Follow-up

• In the hospital prior to discharge, patients should start long-acting bronchodilators, either anticholinergics and/or β2-agonists with or without inhaled corticosteroids.

• For patients who are hypoxemic during an exacerbation, arterial blood gases and/or pulse oximetry should be evaluated prior to hospital discharge and in the following 3 months. If the patient remains hypoxemic, long-term supplemental oxygen therapy may be required.

Prevention of COPD Exacerbations

• Smoking cessation, influenza and pneumococcal vaccines, knowledge of current therapy including inhaler technique, and treatment with long-acting inhaled bronchodilators, with or without inhaled corticosteroids, and phosphodiesterase-4 inhibitors are all therapies that reduce the number of exacerbations and hospitalizations.

• Early outpatient pulmonary rehabilitation after hospitalization for an exacerbation is safe and results in clinically significant improvements in exercise capacity and health status at 3 months.

Don'ts

Assessment

• Spirometry is not recommended during an exacerbation because it can be difficult to perform and measurements are not accurate enough.

Treatment

Adjunct Therapies

• The use of mucolytics is not well-supported by evidence.

Respiratory Support

• NIPPV is not considered in the following conditions:

Contraindications for NIPPV ❑ Inability to cooperate/protect the airway ❑ Inability to clear respiratory secretions ❑ Facial surgery, trauma, or deformity ❑ Upper airway obstruction ❑ High risk for aspiration ❑ Cardiac or respiratory arrest ❑ Nonrespiratory organ failure ▸ Severe encephalopathy (e.g., GCS <10) ▸ Severe upper gastrointestinal bleeding ▸ Hemodynamic instability or unstable cardiac arrhythmia