Acute COPD Exacerbation
Exacerbations are frequent events in the natural history of COPD and can adversely affect health-related quality of life, cause a deterioration in lung functions, frequent hospitalization, and may even increase mortality (1). Exacerbations are often under diagnosed and unreported (2). It is important to recognize these events, treat effectively and adopt measures for its prevention.
1.1. Definition
An exacerbation may be defined as an acute sustained deterioration of respiratory symptoms in a COPD patient beyond day-to-day variability which could not be explained by any other cause and this event may or may not lead to change in therapy (3). These events may resolve spontaneously or with treatment over a period of time.
1.2. Clinical Presentation
An acute change in symptoms, including coughing, change in the quantity and quality of sputum, and increase in baseline dyspnea. Signs of severe or life-threatening exacerbation include deterioration in the level of consciousness, marked respiratory distress, use of accessory muscles, PaO2< 50 mmHg or pH <7.3, or a rapid increase in PaCO2 to above 70 mmHg despite the use of oxygen and bronchodilators.
1.3. Precipitating Factors
It is estimated that 70-80% of COPD exacerbations are due to respiratory infections. Viral and bacterial infections cause most exacerbations, whereas atypical bacteria are a relatively uncommon cause (4). The remaining 20-30% are due to environmental pollution or have an unknown etiology (5). Less likely causes of exacerbation are heart failure, pneumonia, pulmonary embolism, pneumothorax, improper oxygen management, inappropriate drugs such as sedatives and electrolyte imbalance.
1.4. Risk Factors
According to observational studies, the risk of developing an exacerbation of COPD correlates with advanced age, duration of COPD, history of antibiotic therapy, COPD-related hospitalisation within the previous year, chronic mucous hyper-secretion, and having one or more comorbidities e.g. ischemic heart disease, chronic heart failure, or diabetes mellitus (6). A high FEV1 is associated with a lower risk of COPD exacerbation.
In the ECLIPSE study, 2138 patients with moderate to severe COPD (GOLD Stages II, III, or IV) were followed for 3 years. The single best predictor of exacerbations was a history of exacerbations in the preceding year, regardless of COPD severity (7).
1.5. Differential Diagnosis
Patients with COPD who present to the healthcare facility with acute worsening of dyspnea should be evaluated for potential alternative diagnoses, such as heart failure, pulmonary thromboembolism, and pneumonia. This was illustrated in an autopsy study of 43 patients with COPD who died within 24 hours of admission for a COPD exacerbation (8). The primary causes of death were heart failure (37%), pneumonia (28%), pulmonary thromboembolism (21%) and COPD (14%).
1.6. Goals of Treatment
The goals of treatment of acute exacerbation of COPD include:
· Identify and ameliorate the cause of the acute exacerbation, if possible.
· Optimize lung function by administering bronchodilators and other pharmacologic agents.
· Ensure adequate oxygenation and secretion clearance.
· Avoid the need for intubation, if possible.
· Prevent the complications of immobility, such as thromboembolism and deconditioning.
· Address nutritional needs.
1.7. Management
In general, mild exacerbations may be treated with inhaled bronchodilators only whereas moderate and severe exacerbations require treatment with steroids and/or antibiotics.
1.7.1. Antibiotics
The use of antibiotics appears to improve clinical success rate, lung functions and time to next exacerbation; however, some patients may improve without use of antibiotics.
A practical approach is to use antibiotics in patients who have two of three important symptoms; increasing breathlessness, increasing sputum volume, and/or increasing sputum purulence (9). However, patients with severe or life-threatening exacerbations or requiring admission to the hospital should receive antibiotics regardless of the above factors. Approximately one third of exacerbations are associated with viral infection (with rhinovirus and influenza virus predominating). Bacterial colonization is reported in 20-30% of cases during remissions and rises to 30-50% during exacerbations. The usual organisms are Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. Pseudomonas aeruginosais occasionally present in severe or long-standing COPD.
The following antibiotics are useful in COPD exacerbation: second-generation cephalosporins, amoxicillin-clavulinate, macrolide, quinolones such as moxifloxacin or levofloxacin; and doxycycline.
Recommendation:
· Antibiotics should be used to treat exacerbations in ambulatory patients with at least 2 symptoms; increasing breathlessness, increasing sputum volume, and/or increasing sputum purulence or presence purulent sputum alone. (Evidence C)
· Hospitalised patients due to severe exacerbation of COPD should receive antibiotics. (Evidence A)
1.7.2. Bronchodilator Therapy
Bronchodilator therapy should be maximized at home, using a combination of ipratropium and a 2-agonist by inhaler (with or without a spacer) or air-driven nebulization at more frequent intervals (2-4 per hour). The recommended doses for hospitalized patients are: Ipratropium 250-500 mcg plus salbutamol 2.5 -5 mg in 3 ml normal saline nebulized with 7-8 liters of air per minute to avoid CO2 narcosis.
1.7.3. Corticosteroids
Intravenous methylprednisolone or oral prednisolone should be routinely used for life-threatening exacerbations or moderately severe episodes, which have failed to respond to the above measures. Studies have confirmed their efficacy in acute exacerbations, with a more rapid improvement of FEV1 and shorter hospital stay (10).
Oral glucocorticoids equally efficacious as intravenous glucocorticoids for treatment of most exacerbations of COPD (11). The dose of systemic glucocorticoids for treating a COPD exacerbation ranges from prednisone 30-60 mg once daily, to methylprednisolone 60-125 mg 2-4 times daily. A growing body of evidence favors using a moderate, rather than high dose of glucocorticoids, for the majority of patients with an exacerbation of COPD. A comparative analysis of glucocorticoid dosing examined the outcomes of 79,985 patients admitted to the hospital with an exacerbation of COPD, excluding those individuals requiring intensive care. The median glucocorticoid dose administered in the first 2 days was 60 mg for those individuals on oral therapy and 556 mg for intravenous therapy. The risk of treatment failure was no greater with the lower dose (12). As this was an observational study and did not include objective measures of airflow limitation, it is possible that less ill patients were more likely to receive oral treatment.
Recently, a multicenter randomized clinical trial using shorter duration of prednisone in management of acute exacerbations had shown that prednisone 40 mg daily for 5 days was non-inferior to conventional prednisone 40 mg daily for 14 days in reducing exacerbations during 6 months study period. Moreover, the time to the first exacerbation, need for mechanical ventilation, improvement in lung function, duration of hospitalization and mortality were almost same in the 2 treatment groups (13).
Recommendation:
· All hospitalised patient with acute exacerbation of COPD should, in addition to other therapies, receive oral steroids or equivalent intravenous steroids if unable to take oral therapy. (Evidence A)
· The use of short course of oral steroids for a period of 5 days for moderate exacerbation is effective in redcucing dyspnea, risk of treatment failure and risk of hospitalisation. (Evidence A)
1.7.4. Theophylline
Published evidence and recent recommendations do not support the use of theophylline in the treatment of COPD exacerbations (14).
1.7.5. Oxygen
Oxygen should be administered by Venturi mask for accuracy, starting with low concentration of 24% or 28% to avoid inducing CO2 narcosis. The aim is to maintain oxygen saturation (SaO2) greater than 90%. Following a repeat of arterial blood gases, FiO2 should be cautiously adjusted to keep PaO2 around 60 mmHg while ensuring that the pH does not drop below 7.30.
1.7.6. Non-invasiveVentilation
NIV by face or nasal mask, is rapidly establishing itself as the method of choice for ventilatory support in patients with COPD exacerbation, as it is effective with reported success rate of 80-85% and avoids many of the problems of invasive ventilation and intubation (15). NIV is well documented to significantly decrease both mortality and the need for intubation (16). Contraindications to NIV include: hypotension, arrhythmias, drowsiness, un-cooperative patients, increased risk of aspiration like vomiting or copious secretions.
1.7.7. Mechanical Ventilation
Intubation and mechanical ventilation are required if there is severe acidosis (pH< 7.25), marked hypercapnea (PaCO2> 60 mmHg), life-threatening hypoxemia (PaO2/FIO2< 200) or if noninvasive ventilation failed to improve arterial blood gases. The selection of patients for invasive ventilation is of the utmost importance (17). Consider avoiding mechanical ventilation in patients with very advanced disease and without reversible factors and who may prove very difficult to extubate. Even after extubation, such patients have poor survival rates (18).
1.7.8. Other Treatment
Cautious oral or intravenous hydration should be considered in the presence of signs of hypovolemia. Prophylaxis against pulmonary embolism and deep venous thrombosis must be administered in immobilized patients.
1.8. Prognosis
It is estimated that 14% of patients admitted for an exacerbation of COPD will die within 3 months of admission (19). Even if the acute exacerbation resolves, many patients never return to their baseline level of health (20). Among patients with an acute exacerbation and a PaCO2 of 50 mmHg or more, the 6 and 12 month mortality rates are approximately 33% and 43% respectively (21).
References
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