Course

Chapter 5: Management of COPD

Component 4: Manage Exacerbations

Key Points

·        Exacerbations of respiratory symptoms requiring medical intervention are important clinical events in COPD.

·        The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of about one-third of severe exacerbations cannot be identified (Evidence B).

·        Inhaled bronchodilators (particularly inhaled ß₂-agonists and/or anticholinergics), theophylline, and systemic, preferably oral, glucocorticosteroids are effective treatments for acute exacerbations of COPD (Evidence A).

·        Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased volume and change of color of sputum, and/or fever) may benefit from antibiotic treatment (Evidence B).

·        Noninvasive intermittent positive pressure ventilation (NIPPV) in acute exacerbations improves blood gases and pH, reduces in-hospital mortality, decreases the need for invasive mechanical ventilation and intubation, and decreases the length of hospital stay (Evidence A).

Introduction

COPD is often associated with acute exacerbations of symptoms^1-4. In patients with Stage I: Mild COPD to Stage II: Moderate COPD, an exacerbation is associated with increased breathlessness, often accompanied by increased cough and sputum production, and may require medical attention outside of the hospita^l5. The need for medical intervention intensifies as the airflow limitation worsens. Exacerbations in Stage III: Severe COPD are associated with acute respiratory failure, representing a significant burden on the healthcare system. Hospital mortality of patients admitted for an acute exacerbation of COPD is approximately 10%, and the long-term outcome is poor. Mortality reaches 40% in one year^6-9, and is even higher (up to 59%) for patients older than 65 years⁹. These figures vary from country to country depending on the healthcare system and the availability of intensive care unit (ICU) beds.

The most common causes of an exacerbation (Figure 5-4-1) are infection of the tracheobronchial tree^10-14 and air pollution¹⁵, but the cause of about one-third of severe exacerbations cannot be identified^6,16. The role of bacterial infections, once believed to be the main cause of COPD exacerbations, is controversial^10-14,17-20. Conditions that may mimic an acute exacerbation include pneumonia, congestive heart failure, pneumothorax, pleural effusion, pulmonary embolism, and arrhythmia.

Diagnosis and Assessment of Severity

Medical History

Increased breathlessness, the main symptom of an exacerbation, is often accompanied by wheezing and chest tightness, increased cough and sputum, change of the color and/or tenacity of sputum, and fever. Exacerbations may also be accompanied by a number of nonspecific complaints, such as malaise, insomnia, sleepiness, fatigue, depression, and confusion. A decrease in exercise tolerance, fever, and/or new radiological anomalies suggestive of pulmonary disease may herald a COPD exacerbation. An increase in sputum volume and purulence points to a bacterial cause, as does prior history of chronic sputum production^4,14.

Assessment of Severity

Assessment of the severity of an acute exacerbation is based on the patient’s medical history before the exacerbation, symptoms, physical examination, lung function tests, arterial blood gas measurements, and other laboratory tests (Figure 5-4-2). Specific information is required on the frequency and severity of attacks of breathlessness and cough,

sputum volume and color, and limitation of daily activities. When available, prior tests of lung function and arterial blood gases are extremely useful for comparison with those made during the acute episode, as an acute change in these tests is more important than their absolute values. Thus, where possible, physicians should instruct their patients to bring the summary of their last evaluation when they come to the hospital with an exacerbation. In patients with very severe COPD, the most important sign of a severe exacerbation is a change in the alertness of the patient and this signals a need for immediate evaluation in the hospital.

Lung function tests. Even simple lung function tests can be difficult for a sick patient to perform properly. In general, a PEF < 100 L/min or an FEV₁ < 1.00 L indicates a severe exacerbation^21-23, except in patients with chronically severe airflow limitation. For instance, an FEV₁ of 0.75 L, or a PaO₂/FiO₂ (FiO₂ = fractional concentration of oxygen in dry inspired gas) of 33 kPa (24.5 mm Hg) may be well tolerated by a subject with severe COPD who copes with these values in stable conditions, whereas they may reflect a severe exacerbation for a subject with slightly higher values, e.g., an FEV₁ of 0.90 L or a PaO₂/FiO₂ of 38 kPa (28.2 mm Hg) in stable conditions²⁴.

Arterial blood gases. In the hospital, measurement of arterial blood gases is essential to assess the severity of an exacerbation. A PaO₂ < 8.0 kPa (60 mm Hg) and/or SaO₂ < 90% when breathing room air indicate respiratory failure. In addition, a PaO₂ < 6.7 kPa (50 mm Hg), PaCO₂ > 9.3 kPa (70 mm Hg), and pH < 7.30 point toward a life-threatening episode that needs ICU management²⁵.

Chest X-ray and ECG. Chest radiographs (posterior/anterior plus lateral) are useful in identifying alternative diagnoses that can mimic the symptoms of an exacerbation. Although the history and physical signs can be confusing, especially when pulmonary hyperinflation masks coexisting cardiac signs, most problems are resolved by the chest X-ray and ECG. An ECG aids in the diagnosis of right heart hypertrophy, arrhythmias, and ischemic episodes. Pulmonary embolism can be very difficult to distinguish from an acute exacerbation, especially in severe COPD, because right ventricular hypertrophy and large pulmonary arteries lead to confusing ECG and radiographic results. Spiral CT scanning and angiography, and perhaps specific D-dimer assays, are the best tools presently available for the diagnosis of pulmonary embolism in patients with COPD, but ventilation-perfusion scanning is of no value. A low systolic blood pressure and an inability to increase the PaO₂ above 8.0 kPa (60 mm Hg) despite high-flow oxygen also suggest pulmonary embolism. If there are strong indications that pulmonary embolism has occurred, it is best to treat for this along with the exacerbation.

Other laboratory tests. The whole blood count may identify polycythemia (hematocrit > 55%) or bleeding. White blood cell counts are usually not very informative. The presence of purulent sputum during an exacerbation of symptoms is sufficient indication for starting empirical antibiotic treatment. Streptococcus pneumoniae, Hemophiles influenzae, and Moraxella catarrhalis are the most common bacterial pathogens involved in COPD exacerbations. If an infectious exacerbation does not respond to the initial antibiotic treatment, a sputum culture and an antibiogram should be performed. Biochemical tests can reveal whether the cause of the exacerbation is an electrolyte disturbance(s) (hyponatremia, hypokalemia, etc.), a diabetic crisis, or poor nutrition (low proteins), and may suggest a metabolic acid-base disorder.

Home Management

There is increasing interest in home care for end-stage COPD patients, although economic studies of home-care services have yielded mixed results. One study found that quality of life improved and hospital days per admission fell after a home-care program was instituted²⁶, but a randomized controlled trial found that substituting home care for inpatient hospital care produced no better health outcomes while increasing costs^27,28. A major outstanding issue is when to treat an exacerbation at home and when to hospitalize the patient.

The algorithm reported in Figure 5-4-3 may assist in the management of an acute exacerbation at home; a stepwise therapeutic approach is recommended^29-32.

Figure 5.4.3 Algorithm for the Management of an Acute Exacerbation of COPD at Home

Bronchodilator Therapy

Home management of COPD exacerbations involves increasing the dose and/or frequency of existing bronchodilator therapy (Evidence A). If not already used, an anticholinergic can be added until the symptoms improve. In more severe cases, high-dose nebulizer therapy can be given on an as-needed basis for several days and if a suitable nebulizer is available. However, long-term use of nebulizer therapy after an acute episode is not routinely recommended.

Glucocorticosteroids

Systemic glucocorticosteroids are beneficial in the management of acute exacerbations of COPD. They shorten recovery time and help to restore lung function more quickly^33-35 (Evidence A). They should be considered in addition to bronchodilators if the patient’s baseline FEV₁ is < 50% predicted. A dose of 40 mg prednisolone per day for 10 days is recommended (Evidence D).

Antibiotics

Antibiotics are only effective when patients with worsening dyspnea and cough also have increased sputum volume and purulence⁴ (Evidence B). The choice of agents should reflect local patterns of antibiotic sensitivity among S. pneumoniae, H. influenzae, and M. catarrhalis.

Hospital Management

The risk of dying from an acute exacerbation of COPD is closely related to the development of respiratory acidosis, the presence of significant co-morbidities, and the need for ventilatory support⁶. Patients lacking these features are not at high risk of dying, but those with severe underlying COPD often require hospitalization in any case. Attempts at managing such patients entirely in the community have met with only limited success²⁸, but returning them to their homes with increased social support and a supervised medical care package after initial emergency room assessment has been much more successful³⁶. Several randomized controlled trials have confirmed that this is a safe alternative to hospitalization, although it probably only applies to about 25% of COPD admissions. Savings on inpatient expenditures³⁷ offset the additional costs of maintaining a community-based COPD nursing team. However, detailed cost-benefit analyses of these approaches are awaited.

Hospital assessment/admission should be considered for all patients who fit the criteria shown in Figure 5-4-4. Some patients need immediate admission to an intensive care unit (ICU). Admission of patients with severe COPD exacerbations to intermediate or special respiratory care units may be appropriate if personnel, skills, and equipment exist to identify and manage acute respiratory failure successfully.

Emergency Department or Hospital

The first actions when a patient reaches the emergency department 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. Otherwise, the patient may be managed in the emergency department or hospital as detailed in Figure 5-4-6.

Controlled oxygen therapy. Oxygen therapy is the cornerstone of hospital treatment of COPD exacerbations. Adequate levels of oxygenation (PaO₂ > 8.0 kPa, 60 mm Hg, or SaO₂ > 90%) are easy to achieve in uncomplicated exacerbations, but CO₂ retention can occur insidiously with little change in symptoms. Once oxygen is started, arterial blood gases should be checked 30 minutes later to ensure satisfactory oxygenation without CO₂ retention or acidosis. Venturi masks are more accurate sources of controlled oxygen than are nasal prongs but are more likely to be removed by the patient.

Bronchodilator therapy. Short-acting inhaled ß₂-agonists are usually the preferred bronchodilators for treatment of acute exacerbations of COPD^30,31,38 (Evidence A). If a prompt response to these drugs does not occur, the addition of an anticholinergic is recommended, even though evidence concerning the effectiveness of this combination is rather controversial^39,40. Despite its widespread clinical use, aminophylline’s role in the treatment of exacerbations of COPD remains controversial. Most studies of aminophylline have demonstrated minor improvements in lung volumes but also worsening of gas exchange and hypoxemia^41,42. In more severe exacerbations, addition of an oral or intravenous methylxanthine to the treatment can be considered. However, close monitoring of serum theophylline is recommended to avoid the side effects of these drugs^41,43-45.

Glucocorticosteroids. Oral or intravenous glucocorticosteroids are recommended as an addition to bronchodilator therapy (plus eventually antibiotics and oxygen therapy) in the hospital management of acute exacerbations of COPD^33-35 (Evidence A). The exact dose that should be recommended is not known, but high doses are associated with a significant risk of side effects. Thirty to 40 mg of oral prednisolone daily for 10 to 14 days is a reasonable compromise between efficacy and safety (Evidence D). Prolonged treatment does not result in greater efficacy and increases the risk of side effects.

Antibiotics. Antibiotics are only effective when patients with worsening dyspnea and cough also have increased sputum volume and purulence⁴. The choice of agents should reflect local patterns of antibiotic sensitivity among S. pneumoniae, H. influenzae, and M. catarrhalis.

Ventilatory support. The primary objectives of mechanical support in patients with acute exacerbations in Stage III: Severe COPD are to decrease mortality and morbidity and to relieve symptoms. Ventilatory support includes both noninvasive mechanical ventilation using either negative or positive pressure devices, and invasive (conventional) mechanical ventilation by oro/naso-tracheal tube or tracheostomy.

Noninvasive mechanical ventilation. Noninvasive intermittent positive pressure ventilation (NIPPV) has been studied in many uncontrolled and five randomized controlled trials in acute respiratory failure⁴⁶. The studies show consistently positive results with success rates of 80-85%⁴⁷. Taken together they provide evidence that NIPPV increases pH, reduces PaCO₂, reduces the severity of breathlessness in the first 4 hours of treatment, and decreases the length of hospital stay (Evidence A). More importantly, mortality - or its surrogate, intubation rate - is reduced by this intervention^48-51. However, NIPPV is not appropriate for all patients, as summarized in Figure 5-4-7⁴⁷.

Invasive (conventional) mechanical ventilation. During exacerbations of COPD the events occurring within the lungs include bronchoconstriction, airway inflammation, increased mucous secretions, and loss of elastic recoil, all of which prevent the respiratory system from reaching its passive functional residual capacity at the end of expiration, enhancing dynamic hyperinflation⁵². As a result of these processes, an elastic threshold load, referred to as intrinsic or auto-positive end-expiratory pressure (PEEPi), is imposed on the inspiratory muscles at the beginning of inspiration and increases the work of breathing. For these reasons, patients who show impending acute respiratory failure and those with life-threatening acid-base status abnormalities and/or altered mental status despite aggressive pharmacologic therapy are likely to be the best candidates for invasive (conventional) mechanical ventilation. The indications for initiating mechanical ventilation during exacerbations of COPD are shown in Figure 5-4-8, the first being the commonest and most important reason. Figure 5-4-9 details the factors determining benefit from invasive ventilation. The three ventilatory modes most widely used are assisted-control ventilation, and pressure support ventilation alone or in combination with intermittent mandatory ventilation⁵³.

The use of invasive ventilation in end-stage COPD patients is influenced by the likely reversibility of the precipitation event, the patient’s wishes, and the availability of intensive care facilities. Major hazards include the risk of ventilator-acquired pneumonia (especially when multi-resistant organisms are prevalent), barotrauma, and failure to wean to spontaneous ventilation. Contrary to some opinions, mortality among COPD patients with respiratory failure is no greater than mortality among patients ventilated for non-COPD causes.

A review of a large number of North American COPD patients ventilated for respiratory failure indicated an in-hospital mortality of 17-30%⁵⁴. Further attrition over the next 12 months was particularly high among those patients who had poor lung function before ventilation (FEV₁ < 30% predicted), had a non-respiratory comorbidity, or were housebound. Patients who did not have a previously diagnosed underlying disease, had respiratory failure due to a potentially reversible cause (such as an infection), or were relatively mobile and not using long-term oxygen did surprisingly well with ventilatory support. When possible, a clear statement of the patient’s own treatment wishes - an advance directive or “living will” - makes these difficult decisions much easier to resolve.

Weaning or discontinuation from mechanical ventilation can be particularly difficult and hazardous in patients with COPD. The most influential determinant of mechanical ventilatory dependency in these patients is the balance between the respiratory load and the capacity of the respiratory muscles to cope with this load⁵⁵. By contrast, pulmonary gas exchange by itself is not a major difficulty in patients with COPD^56-58. Weaning patients from the ventilator can be a very difficult and prolonged process and the best method remains a matter of debate^59,68. Whether pressure support or a T-piece trial is used, weaning is shortened when a clinical protocol is adopted (Evidence A). Non-invasive ventilation has been applied to facilitate the weaning process in COPD patients with acute or chronic respiratory failure⁵⁴. Compared with invasive pressure support ventilation, noninvasive intermittent positive pressure ventilation (NIPPV) during weaning shortened weaning time, reduced the stay in the intensive care unit, decreased the incidence of nosocomial pneumonia, and improved 60-day survival rates. Similar findings have been reported when NIPPV is used after extubation for hypercapnic respiratory failure⁶¹ (Evidence C).

Other measures. Further treatments that can be used in the hospital include: fluid administration (accurate monitoring of fluid balance is essential); nutrition (supplementary when the patient is too dyspneic to eat); low molecular heparin in immobilized, polycythemic, or dehydrated patients with or without a history of thromboembolic disease; and sputum clearance (by stimulating coughing and low-volume forced expirations as in home management). Manual or mechanical chest percussion and postural drainage may be beneficial in patients producing > 25 ml sputum per day or with lobar atelectasis.

Hospital Discharge and Follow-Up

Insufficient clinical data exist to establish the optimal duration of hospitalization in individual patients developing an exacerbation of COPD^1,62,63. Consensus and limited data support the discharge criteria listed in Figure 5-4-10. Figure 5-4-11 provides items to include in a follow-up assessment 4 to 6 weeks after discharge from the hospital. Thereafter, follow-up is the same as for stable COPD, including supervising smoking cessation, monitoring the effectiveness of each drug treatment, and monitoring changes in spirometric parameters³⁸.

Figure 5.4.11 Follow-up Assessment 4-6 Weeks After Discharge from Hospital for an Acute Exacerbation of COPD

·         Ability to cope in usual environment. ·         Measurement of FEV1. ·         Reassessment of inhaler technique. ·         Understanding of recommended treatment regimen. ·         Need for long-term oxygen therapy and/or home nebulizer (for patients with severe COPD.

If hypoxemia developed during the exacerbation, arterial blood gases should be rechecked at discharge and at the follow-up visit. If the patient remains hypoxemic, long-term oxygen therapy should be instituted. Decisions about suitability for continuous domiciliary oxygen based on the severity of the acute hypoxemia during an exacerbation are frequently misleading.

The opportunities for prevention of future exacerbations should be reviewed before discharge, with particular attention to future influenza vaccination plans, knowledge about current therapy including inhaler technique^{641, 65}, and how to recognize symptoms of exacerbations. Pharmacotherapy known to reduce the number of exacerbations should be considered. Social problems should be discussed and principal caregivers identified if the patient has a significant persisting disability.

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