25 Nov Acute COPD Exacerbation

Acute COPD Exacerbation

1.1. Definition

1.2. Clinical Presentation

1.3. Precipitating Factors

1.4. Risk Factors

1.5. Differential Diagnosis

1.6. Goals of Treatment

1.7. Management

1.7.1. Antibiotics

1.7.2. Bronchodilator Therapy

1.7.3. Oxygen

1.7.4. Corticosteroids

1.7.5. Theophylline

1.7.6. Non-invasiveVentilation

1.7.7. Mechanical Ventilation

1.7.8. Other Treatment

1.8. Prognosis

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1. 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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2. Langsetmo L, Platt RW, Ernst P, Bourbeau J. Underreporting exacerbation of chronic obstructive pulmonary disease in a longitudinal cohort. Am J Respir Crit Care Med 2008;177:396–401.

3. Burg S, Wadzicha JA. COPD exacerbations: definitions and classifications. EurRespir J Suppl 2003;41:46s-53s.

4. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 2008;359:2355-65.

5. Sapey E, Stockley RA. COPD exacerbations 2: Aetiology. Thorax 2006;61:250-8.

6. Miravitlles M, Guerrero T, Mayordomo C, Sánchez-Agudo L, Nicolau F, Segú JL. Factors associated with increased risk of exacerbation and hospital admission in a cohort of ambulatory COPD patients: a multiple logistic regression analysis. The EOLO Study Group. Respiration 2000;67:495-501.

7. Hurst JR, Vestbo J, Anzueto A, Locantore N, Müllerova H, Tal-Singer R, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med 2010;363:1128-38.

8. Zvezdin B, Milutinov S, Kojicic M, Hadnadjev M, Hromis S, Markovic M, Gajic O. A postmortem analysis of major causes of early death in patients hospitalized with COPD exacerbation. Chest 2009;136:376-80.

9. Miravitlles M, Anzueto A. Antibiotics for Acute and Chronic Respiratory Infection in Patients with Chronic Obstructive Pulmonary Disease.Am J Respir Crit Care Med 2013;188:1052-7.

10. Niewoehner DE, Erbland ML, Deupree RH, Collins D, Gross NJ, Light RW, et al. Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. N Engl J Med 1999;340:1941-7.

11. de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, van den Berg JW. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest 2007;132:1741-7.

12. LindenauerPK, Pekow PS, Lahti MC, Lee Y, Benjamin EM, Rothberg MB. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA 2010;303:2359-67.

13. Leuppi JD, Schuetz P, Bingisser R, Bodmer M, Briel M, Drescher T, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA 2013;309:2223-31.

14. Barr RG, Rowe BH, Camargo CA. Methylxanthines for exacerbations of chronic obstructive pulmonary disease (Updated 2008). Cochrane Database Syst Rev2003;(2):CD002168.

15. Conti G, Antonelli M, Navalesi P, Rocco M, Bufi M, Spadetta G, Meduri GU. Noninvasive vs conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial. Intensive Care Med 2002;28:1701-7.

16. Hess DR. The evidence for noninvasive positive-pressure ventilation in the care of patients in acute respiratory failure: a systematic review of the literature. Respir Care 2004;49:810-29.

17. Berkius J, Sundh J, Nilholm L, Fredrikson M, Walther SM. What determines immediate use of invasive ventilation in patients with COPD? Acta Anaesthesiol Scand 2013;57:312-9.

18. Alaithan AM, MemonJI, Rehmani RS, Qureshi AA, Salam A. Chronic obstructive pulmonary disease: hospital and intensive care unit outcomes in the Kingdom of Saudi Arabia. Int J Chron Obstruct Pulmon Dis 2012;7:819-23.

19. Roberts CM, Lowe D, Bucknall CE, Ryland I, Kelly Y, Pearson M. Clinical audit indicators of outcome following admission to hospital with acute exacerbation of chronic obstructive pulmonary disease. Thorax 2002;57:137-141.

20. Cote CG, Dordelly LJ, Celli BR. Impact of COPD exacerbations on patient-centered outcomes. Chest 2007;131:696-704.

21. Connors AF Jr, Dawson NV, Thomas C, Harrel FE Jr, Desbiens N, Fulkerson WJ, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med 1996;154:959-67.

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