A. Overview of Evidence-Based Recommendations [1]

1. Admission chest radiography in all patients (>20% have significant changes)
2. Acute spirometry and pulse oximetry to assess severity
3. Combination of inhaled anticholinergic agent + ß-agonist
4. Systemic glucocorticoids for moderate or severe exacerbations
5. Low dose oxygen in hypoxemic patients to saturation ~90%
6. Caution with oxygen due to concern about CO2 retention with higher levels O2
7. Non-invasive positive pressure ventilation (NIPPV) should be considered
8. Severe exacerbations should be treated with narrow-spectrum antibiotics
   1. Trimethoprim/sulfamethoxazole (TMP/SMX)
   2. Cefuroxime
   3. Role of bacteria in inducing exacerbations increasingly clear [22]
9. Avoid the following in acute COPD exacerbations
   1. Mucolytics
   2. Chest physiotherapy
   3. Methylxanthine bronchodilators
10. Early discharge from hospital with respiratory home-care followup is safe, reduces costs, and is associated with good patient satisfaction [4]

B. Evaluation

1. In emergency room setting
2. Rapid assessment is critical
3. Vital signs most important
   1. Degree of tachypnea
   2. Presence of hypertension or hypotension
4. Rule out Congestive Heart Failure (CHF) or other cardiac contribution
   1. Wheezing may be due to cardiac causes rather than bronchospastic causes
   2. Cardiac and pulmonary dysfunction are frequently coexistant, however
   3. Hypotension can signify severe right sided CHF
   4. Strongly consider echocardiography
5. In patients with unexplained exacerbation, 25% were shown to have pulmonary embolism on helical computed tomography [10]
6. Picornavirus or adenovirus infection may trigger COPD exacerbation [8]
7. Procalcitonin levels >0.25µg/L associated with infection as part of exacerbation [27]
8. Outpatient Management Classification [3]
   1. Uncomplicated: age <65, FEV1 >50%, <4 exacerbations/year, no comorbidity
   2. Complicated: age >65 or FEV1 <50% or >4 exacerbations/year, comorbidity, or antibiotic use in past 3 months
   3. Complicated with risk for pseucomonas: FEV1 <35% or recurrent antibiotics or recurrent glucocorticoid courses or bronchiectasis

C. Overview of Modalities

1. Pharmacologic Therapy
2. Oxygen
3. Ventilatory Support
4. Chest Physiotherapy (questionable benefit; do not use until patient stabilized)

D. Pharmacotherapy [1,2,3,9]

1. Summary
   1. Bronchodilators
   2. Oxygen - for hypoxemic patients, with caution
   3. Systemic Glucocorticoids
   4. Antibiotics
2. Nebulizers (see above)
   1. Anticholinergics are as (not more) effective than ß2-adrenergic agonists [23]
   2. Nebulizers strongly preferred over metered dose inhalers during exacerbation
   3. ß2 agonists - aerosolized agents or via endotrachial tube
   4. Ipratropium + albuterol - more effective for FEV1 increase than ß2-agonist alone in chronic stable COPD; unclear if more effective in exacerbation setting [23]
   5. Ipratropium 0.5mg + Albuterol 3.0mg now available as combination (DuoNeb®)
   6. N-acetyl cysteine (NAC, Mucomist®) may loosen secretions but little evidence for clinical benefit
3. Systemic Glucocorticoids [1,5,6]
   1. Benefits are clear for moderate and severe exacerbations
   2. Two weak course probably sufficient in most patients
   3. Initiate therapy with intravenous glucocorticoids
   4. Recommend 40-125mg IV methylprednisolone (SoluMedrol®) q6-8 hours
   5. Oral prednisone 40-60mg po qd may be used initially in moderately severe exacerbations
   6. High dose IV therapy recommended for 2-4 days, then oral glucocorticoid with taper
   7. Recommended taper for oral predisone, 40-60mg po qd over two weeks
   8. For non-severe (non-acidotic) exacerbations, 30mg po qd x 14 days improved function [6]
   9. For moderate exacerbations after emergency treatment, discharge on 50mg po qd x 14 days as outpatient reduces relapse rate (27% versus 43%) and improves lung function [24]
   10. Patients with high eosinophil counts in sputum may benefit most from systemic glucocorticoids [7]
   11. Must monitor for hyperglycemia and hypertension
   12. Hyperglycemia should be controlled with medications as needed during therapy
4. Antibiotics
   1. All patients with moderate to severe COPD exacerbation should receive antibiotics [3]
   2. Antibiotic treatment speeds recovery and reduces deterioration [9]
   3. It may be acceptable to withhold antibiotics if serum procalcitonin level <0.1µg/dL [27]
   4. Most COPD organisms produce ß-lactamases
   5. Narrow spectrum agents initially recommended unless resistance very likely [1,3]
   6. Antibiotic selection recommended based on risk factors and comorbidities
   7. Oral antibiotics for outpatients; all inpatients should receive parenteral agents
   8. Intravenous (IV) antibiotics for moderate to severe COPD exacerbations
   9. In patients without COPD, antibiotics provide no benefit for acute bronchitis
5. Oral Antibiotic Therapy [1,3]
   1. Mild and some moderate COPD exacerbations are treated with oral antibiotics
   2. If a major organism has been identified, then tailor antibiotic therapy
   3. Note, however, that COPD patients are colonized with multiple pathogenic bacteria
   4. New macrolides (clarithromycin, azithromycin) first line for uncomplicated (see above)
   5. Doxycycline alternative first line for uncomplicated
   6. Second or third generation cephalosporin or respiratory quinolone may also be used
   7. For complicated, respiratory quinolone or amoxicillin-clavulanate (Augmentin®)
   8. "Respiratory" fluoroquinolones (ofloxacin, levofloxacin, others) very effective [21]
   9. If pseuomonas suspected, then antipseudomonal fluoroquinolone is used, but caution as resistance can develop rapidly
   10. Fluoroquinolones have broadest overall coverage, followed by macrolides
6. Intravenous Antibiotics
   1. For moderate to severe COPD exacerbations, inpatients, multiple comorbidities
   2. Antibiotics IV are usually continued until symptoms subside (typically 5-10 days)
   3. Ceftriaxone or cefuroxime IV are also good choices (do not cover atypical organisms)
   4. Azithromycin (Zithromax®) IV is also effective and covers atypicals as well as typicals
   5. Anti-pseudomonal agents may be required in severe (FEV1<35%) or recurrent cases
   6. Patients with bronchiectasis should be treated with dual anti-gram negative coverage
   7. For moderate and severe exacerbations, IV antibiotics may be followed by oral drugs
7. Methylxanthines
   1. Mild bronchodilators theophylline (oral) and aminophylline (IV)
   2. Increase respiratory muscle (diaphragmatic) strength
   3. Mild diuretic (may improve oxygenation, see below)
   4. Chronic use may inhibit erythrocytosis in COPD
   5. Intubated patients who fail to wean (? due to poor muscle strength) may benefit
   6. Should not be used in acute exacerbations unless patients are severely refractory
   7. No apparent benefit in moderate acute exacerbations overall [25]
   8. IV aminophylline load is usually preferred (~5mg/kg slow bolus, then 0.5mg/kg/hr IV)
   9. Tachycardia, tremors, palpitations, hypertension may occur
8. Diuretics
   1. Many patients with COPD have CHF (RV and LV dysfunction)
   2. In addition, hypoxemia leads to cardiac ischemia
   3. This exacerbates chronic ischemia and may precipitate further cardiac dysfunction
   4. Therefore, consider underlying pulmonary edema in patients with COPD exacerbations
   5. Diuresis will improve oxygen transit if pulmonary edema is present
   6. Strongly consider cardiac evaluation and diuresis in patients with COPD exacerbations

E. Ventilatory Support

1. Evaluate patients for NIPPV versus endotracheal inbutation with mechanical ventilation
2. NIPPV [1]
   1. In general, NIPPV is highly preferred over endotracheal intubation
   2. Very effective mainly in those with severe COPD exacerbation [12]
   3. NIPPV clearly reduces mortality and need for endotracheal intubation in COPD flares
   4. NIPPV also permits improved weaning and may improve short term mortality [14,15]
   5. Reduced incidence of nosocomial pneumonia, other infections in COPD exacerbations [15]
   6. NIPPV used early in course of patients with COPD exacerbation and mild to moderate acidosis reduced mortality, time to pH correction, and normal respirations [16]
   7. NIPPV can be used on the general medicine / respiratory wards
   8. Questionable overall benefit in hospitalized patients with mild COPD exacerbations [12]
   9. Strongly recommended for moderate to severe exacerbations
3. Indications for Intubation [17]
   1. If possible, a trial of NIPPV should be initiated prior to intubation
   2. Persistent hypoxemia with O2 saturation <88-90% or pO2 <55-60mm Hg (with O2)
   3. Worsening acute respiratory acidosis despite therapy
   4. Signs of worsening respiratory muscle fatigue
   5. Deterioration of mental status (delirium)
   6. Inability of patient to protect airway
   7. Inability to clear secretions
   8. Noninvasive ventilation prior to decompensation may prevent need for intubation [16]
4. Pulmonary Physical Therapy - may provide benefits in clearing mucous, improved oxygen

F. Prevention of Acute Exacerbations

1. Stopping smoking reduces rate of acute exacerbations
2. Early medical intervention with worsening symptoms reduces decompensation
3. Influenza vaccination is critical
4. Pneumococcal vaccine is highly recommended
5. Tiotropium (Spiriva®) qd inhaler reduces COPD exacerbations and may reduce resource use in moderate to severe COPD [26]
6. Use of inhaled glucocorticoids may reduce exacerbation rates
7. Early hospital discharge with aggressive home nursing followup is safe and reduces costs [3,4]
8. Carbocisteine, an antioxidant, showed >25% reductions in exacerbations in Chinese COPD patients with good tolerability (but relatively low use of glucocorticoids) [13]

G. Prognosis [18]

1. In hospital mortality was 24% for patients in intensive care for COPD exacerbation
2. Most in hospital mortality was associated with non-respiratory organ dysfunction
3. For patients >65 year old, 1 year after hospital discharge, mortality was 60%
4. No reliable methods of risk stratification or inpatient mortality [1]
5. Reversible hypercapnia during COPD exacerbation was a good prognostic indicator [19]
6. Chronic inhaled glucocorticoids improve mortality in COPD patients [20]

Resources

Alveolar Gas Equation

References

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