A. Overview of Evidence-Based Recommendations [1]
- Admission chest radiography in all patients (>20% have significant changes)
- Acute spirometry and pulse oximetry to assess severity
- Combination of inhaled anticholinergic agent + ß-agonist
- Systemic glucocorticoids for moderate or severe exacerbations
- Low dose oxygen in hypoxemic patients to saturation ~90%
- Caution with oxygen due to concern about CO2 retention with higher levels O2
- Non-invasive positive pressure ventilation (NIPPV) should be considered
- Severe exacerbations should be treated with narrow-spectrum antibiotics
- Trimethoprim/sulfamethoxazole (TMP/SMX)
- Cefuroxime
- Role of bacteria in inducing exacerbations increasingly clear [22]
- Avoid the following in acute COPD exacerbations
- Mucolytics
- Chest physiotherapy
- Methylxanthine bronchodilators
- Early discharge from hospital with respiratory home-care followup is safe, reduces costs, and is associated with good patient satisfaction [4]
B. Evaluation
- In emergency room setting
- Rapid assessment is critical
- Vital signs most important
- Degree of tachypnea
- Presence of hypertension or hypotension
- Rule out Congestive Heart Failure (CHF) or other cardiac contribution
- Wheezing may be due to cardiac causes rather than bronchospastic causes
- Cardiac and pulmonary dysfunction are frequently coexistant, however
- Hypotension can signify severe right sided CHF
- Strongly consider echocardiography
- In patients with unexplained exacerbation, 25% were shown to have pulmonary embolism on helical computed tomography [10]
- Picornavirus or adenovirus infection may trigger COPD exacerbation [8]
- Procalcitonin levels >0.25µg/L associated with infection as part of exacerbation [27]
- Outpatient Management Classification [3]
- Uncomplicated: age <65, FEV1 >50%, <4 exacerbations/year, no comorbidity
- Complicated: age >65 or FEV1 <50% or >4 exacerbations/year, comorbidity, or antibiotic use in past 3 months
- Complicated with risk for pseucomonas: FEV1 <35% or recurrent antibiotics or recurrent glucocorticoid courses or bronchiectasis
C. Overview of Modalities
- Pharmacologic Therapy
- Oxygen
- Ventilatory Support
- Chest Physiotherapy (questionable benefit; do not use until patient stabilized)
D. Pharmacotherapy [1,2,3,9]
- Summary
- Bronchodilators
- Oxygen - for hypoxemic patients, with caution
- Systemic Glucocorticoids
- Antibiotics
- Nebulizers (see above)
- Anticholinergics are as (not more) effective than ß2-adrenergic agonists [23]
- Nebulizers strongly preferred over metered dose inhalers during exacerbation
- ß2 agonists - aerosolized agents or via endotrachial tube
- Ipratropium + albuterol - more effective for FEV1 increase than ß2-agonist alone in chronic stable COPD; unclear if more effective in exacerbation setting [23]
- Ipratropium 0.5mg + Albuterol 3.0mg now available as combination (DuoNeb®)
- N-acetyl cysteine (NAC, Mucomist®) may loosen secretions but little evidence for clinical benefit
- Systemic Glucocorticoids [1,5,6]
- Benefits are clear for moderate and severe exacerbations
- Two weak course probably sufficient in most patients
- Initiate therapy with intravenous glucocorticoids
- Recommend 40-125mg IV methylprednisolone (SoluMedrol®) q6-8 hours
- Oral prednisone 40-60mg po qd may be used initially in moderately severe exacerbations
- High dose IV therapy recommended for 2-4 days, then oral glucocorticoid with taper
- Recommended taper for oral predisone, 40-60mg po qd over two weeks
- For non-severe (non-acidotic) exacerbations, 30mg po qd x 14 days improved function [6]
- 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]
- Patients with high eosinophil counts in sputum may benefit most from systemic glucocorticoids [7]
- Must monitor for hyperglycemia and hypertension
- Hyperglycemia should be controlled with medications as needed during therapy
- Antibiotics
- All patients with moderate to severe COPD exacerbation should receive antibiotics [3]
- Antibiotic treatment speeds recovery and reduces deterioration [9]
- It may be acceptable to withhold antibiotics if serum procalcitonin level <0.1µg/dL [27]
- Most COPD organisms produce ß-lactamases
- Narrow spectrum agents initially recommended unless resistance very likely [1,3]
- Antibiotic selection recommended based on risk factors and comorbidities
- Oral antibiotics for outpatients; all inpatients should receive parenteral agents
- Intravenous (IV) antibiotics for moderate to severe COPD exacerbations
- In patients without COPD, antibiotics provide no benefit for acute bronchitis
- Oral Antibiotic Therapy [1,3]
- Mild and some moderate COPD exacerbations are treated with oral antibiotics
- If a major organism has been identified, then tailor antibiotic therapy
- Note, however, that COPD patients are colonized with multiple pathogenic bacteria
- New macrolides (clarithromycin, azithromycin) first line for uncomplicated (see above)
- Doxycycline alternative first line for uncomplicated
- Second or third generation cephalosporin or respiratory quinolone may also be used
- For complicated, respiratory quinolone or amoxicillin-clavulanate (Augmentin®)
- "Respiratory" fluoroquinolones (ofloxacin, levofloxacin, others) very effective [21]
- If pseuomonas suspected, then antipseudomonal fluoroquinolone is used, but caution as resistance can develop rapidly
- Fluoroquinolones have broadest overall coverage, followed by macrolides
- Intravenous Antibiotics
- For moderate to severe COPD exacerbations, inpatients, multiple comorbidities
- Antibiotics IV are usually continued until symptoms subside (typically 5-10 days)
- Ceftriaxone or cefuroxime IV are also good choices (do not cover atypical organisms)
- Azithromycin (Zithromax®) IV is also effective and covers atypicals as well as typicals
- Anti-pseudomonal agents may be required in severe (FEV1<35%) or recurrent cases
- Patients with bronchiectasis should be treated with dual anti-gram negative coverage
- For moderate and severe exacerbations, IV antibiotics may be followed by oral drugs
- Methylxanthines
- Mild bronchodilators theophylline (oral) and aminophylline (IV)
- Increase respiratory muscle (diaphragmatic) strength
- Mild diuretic (may improve oxygenation, see below)
- Chronic use may inhibit erythrocytosis in COPD
- Intubated patients who fail to wean (? due to poor muscle strength) may benefit
- Should not be used in acute exacerbations unless patients are severely refractory
- No apparent benefit in moderate acute exacerbations overall [25]
- IV aminophylline load is usually preferred (~5mg/kg slow bolus, then 0.5mg/kg/hr IV)
- Tachycardia, tremors, palpitations, hypertension may occur
- Diuretics
- Many patients with COPD have CHF (RV and LV dysfunction)
- In addition, hypoxemia leads to cardiac ischemia
- This exacerbates chronic ischemia and may precipitate further cardiac dysfunction
- Therefore, consider underlying pulmonary edema in patients with COPD exacerbations
- Diuresis will improve oxygen transit if pulmonary edema is present
- Strongly consider cardiac evaluation and diuresis in patients with COPD exacerbations
E. Ventilatory Support
- Evaluate patients for NIPPV versus endotracheal inbutation with mechanical ventilation
- NIPPV [1]
- In general, NIPPV is highly preferred over endotracheal intubation
- Very effective mainly in those with severe COPD exacerbation [12]
- NIPPV clearly reduces mortality and need for endotracheal intubation in COPD flares
- NIPPV also permits improved weaning and may improve short term mortality [14,15]
- Reduced incidence of nosocomial pneumonia, other infections in COPD exacerbations [15]
- 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]
- NIPPV can be used on the general medicine / respiratory wards
- Questionable overall benefit in hospitalized patients with mild COPD exacerbations [12]
- Strongly recommended for moderate to severe exacerbations
- Indications for Intubation [17]
- If possible, a trial of NIPPV should be initiated prior to intubation
- Persistent hypoxemia with O2 saturation <88-90% or pO2 <55-60mm Hg (with O2)
- Worsening acute respiratory acidosis despite therapy
- Signs of worsening respiratory muscle fatigue
- Deterioration of mental status (delirium)
- Inability of patient to protect airway
- Inability to clear secretions
- Noninvasive ventilation prior to decompensation may prevent need for intubation [16]
- Pulmonary Physical Therapy - may provide benefits in clearing mucous, improved oxygen
F. Prevention of Acute Exacerbations
- Stopping smoking reduces rate of acute exacerbations
- Early medical intervention with worsening symptoms reduces decompensation
- Influenza vaccination is critical
- Pneumococcal vaccine is highly recommended
- Tiotropium (Spiriva®) qd inhaler reduces COPD exacerbations and may reduce resource use in moderate to severe COPD [26]
- Use of inhaled glucocorticoids may reduce exacerbation rates
- Early hospital discharge with aggressive home nursing followup is safe and reduces costs [3,4]
- 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]
- In hospital mortality was 24% for patients in intensive care for COPD exacerbation
- Most in hospital mortality was associated with non-respiratory organ dysfunction
- For patients >65 year old, 1 year after hospital discharge, mortality was 60%
- No reliable methods of risk stratification or inpatient mortality [1]
- Reversible hypercapnia during COPD exacerbation was a good prognostic indicator [19]
- Chronic inhaled glucocorticoids improve mortality in COPD patients [20]
Resources
Alveolar Gas Equation
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