Chronic obstructive pulmonary disease (COPD) management involves treatment of chronic stable disease and treatment of exacerbations.
Treatment of acute exacerbations involves
Oxygen supplementation
Bronchodilators
Corticosteroids
Antibiotics
Sometimes ventilatory assistance with noninvasive ventilation or intubation and ventilation
The immediate objectives are to ensure adequate oxygenation and near-normal blood pH, reverse airway obstruction, and treat any cause.
The cause of an acute exacerbation is often unknown, although most acute exacerbations result from bacterial or viral infections. Smoking, irritative inhalational exposure, and high levels of air pollution also contribute.
Patients with mild exacerbations and adequate home support can often be treated as outpatients. Older, frail patients and patients with comorbidities, a history of respiratory failure, or acute changes in blood gas measurements are admitted to the hospital for observation and treatment. Patients with life-threatening exacerbations manifested by uncorrected moderate to severe acute hypoxemia, acute respiratory acidosis, new arrhythmias, or deteriorating respiratory function despite hospital treatment should be admitted to an intensive care unit and their respiratory status monitored frequently.
Oxygen in Acute COPD Exacerbation
Many patients, even those who do not require chronic oxygen support, require oxygen supplementation during a COPD exacerbation. Hypercapnia may worsen in patients given oxygen. This worsening has traditionally been thought to result from an attenuation of hypoxic respiratory drive. Oxygen administration, even though it may worsen hypercapnia, is recommended. Many patients with COPD have chronic as well as acute hypercapnia and thus severe central nervous system depression is unlikely unless partial pressure of arterial carbon dioxide (PaCO2) is > 85 mm Hg. The target level for partial pressure of arterial oxygen (PaO2) is approximately 60 mm Hg; higher levels offer little advantage and increase the risk of hypercapnia. In most cases, low concentrations of oxygen will improve hypoxemia. The need for high concentrations of oxygen suggests right to left shunt physiology and other contributors to hypercapnia (eg, pneumonia or pulmonary edema).
In patients who are prone to hypercarbia (ie, an elevated serum bicarbonate may indicate the presence of a compensated respiratory acidosis), oxygen is given via nasal prongs or Venturi mask so it can be closely regulated, and the patient is closely monitored. Patients whose condition deteriorates during oxygen therapy (eg, those with severe acidemia or central nervous system depression) require ventilatory assistance.
Many patients who require oxygen at home for the first time when they are discharged from the hospital after an exacerbation improve within 30 days and no longer require oxygen. Thus, the need for home oxygen should be reassessed 60 to 90 days after discharge.
Ventilatory Assistance in Acute COPD Exacerbation
Noninvasive positive-pressure ventilation (eg, pressure support or positive airway pressure ventilation by face mask) is an alternative to full mechanical ventilation. Noninvasive ventilation appears to decrease the need for intubation, reduce hospital stay, and reduce mortality in patients with severe exacerbations (defined as a pH < 7.30 in hemodynamically stable patients not at immediate risk of respiratory arrest) (1).
Noninvasive ventilation appears to have no effect in patients with less severe exacerbation. However, it may be indicated for patients with less severe exacerbations whose arterial blood gases (ABGs) worsen despite initial medication or oxygen therapy or who appear to be imminent candidates for full mechanical ventilation but who do not require intubation for control of the airway or sedation for agitation. Patients who have severe dyspnea and hyperinflation and use of accessory muscles of respiration may also gain relief from positive airway pressure. Deterioration while receiving noninvasive ventilation necessitates invasive mechanical ventilation.
Deteriorating ABG values, deteriorating mental status, and progressive respiratory fatigue are indications for endotracheal intubation and mechanical ventilation. Ventilator settings, management strategies, and complications are discussed elsewhere. Risk factors for ventilatory dependence include
Forced expiratory volume in 1 second (FEV1) < 0.5 L
Stable ABGs with a PaO2 < 50 mm Hg, or a PaCO2 > 60 mm Hg
Severe exercise limitation
Poor nutritional status
If patients are at high risk, discussion of their wishes regarding intubation and mechanical ventilation should be initiated and documented (see Advance Directives) while their condition is stable and they are not hospitalized. However, overconcern about possible ventilator dependence should not delay management of acute respiratory failure; many patients who require mechanical ventilation can return to their pre-exacerbation level of health.
High-flow nasal oxygen therapy has also been used for patients with acute respiratory failure due to a COPD exacerbation and can be tried for those who do not tolerate noninvasive mask ventilation.
In patients who require prolonged intubation (eg, > 2 weeks), a tracheostomy is indicated to facilitate comfort, communication, and eating. With a good multidisciplinary pulmonary rehabilitation program, including nutritional and psychologic support, many patients who require prolonged mechanical ventilation can be successfully removed from a ventilator and can return to their former level of function.
Specialized programs are available for patients who remain ventilator-dependent after acute respiratory failure. Some patients can remain off the ventilator during the day. For patients with adequate home support, training of family members can permit some patients to be sent home with ventilators.
In patients with severe chronic hypercapnia who were hospitalized for an exacerbation, nocturnal non-invasive ventilation reduces hypercapnia and may improve survival (2). This treatment does not improve long-term quality of life, so implementation should involve shared decision-making with the patient.
Pearls & Pitfalls
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Ventilatory assistance references
1. Osadnik CR, Tee VS, Carson-Chahhoud KV, Picot J, Wedzicha JA, Smith BJ. Non-invasive ventilation for the management of acute hypercapnic respiratory failure due to exacerbation of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2017;7(7):CD004104. Published 2017 Jul 13. doi:10.1002/14651858.CD004104.pub4
1. Raveling T, Vonk J, Struik FM, et al. Chronic non-invasive ventilation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2021;8(8):CD002878. Published 2021 Aug 9. doi:10.1002/14651858.CD002878.pub3
Medication Therapy in Acute COPD Exacerbation
Beta-agonists and anticholinergics, with or without corticosteroids, should be started concurrently with oxygen therapy (regardless of how oxygen is administered) with the aim of reversing airway obstruction. Methylxanthines, once considered essential to treatment of acute COPD exacerbations, are no longer used; toxicities exceed benefits.
Beta-agonists
Anticholinergic agents
Ipratropium generally provides bronchodilating effect similar to that of usual recommended doses of beta-agonists.
The role of the longer-acting anticholinergics in treating acute exacerbations has not been defined.
Corticosteroids
Antibiotics
Antibiotics are recommended for exacerbations in patients with purulent sputum. Some clinicians give antibiotics empirically for change in sputum color or for nonspecific chest radiograph abnormalities. Routine cultures and Gram stains are not necessary before treatment unless an unusual or resistant organism is suspected (eg, in patients who are hospitalized, institutionalized, or immunosuppressed). Medications directed against oral flora are indicated.
Choice of medication is dictated by local patterns of bacterial sensitivity and patient history. Trimethoprim/sulfamethoxazole, amoxicillin, or doxycycline
When patients are seriously ill or clinical evidence suggests that the infectious organisms are resistant, broader spectrum second-line medications can be used. These medications include amoxicillin/clavulanate, fluoroquinolones (eg, ciprofloxacin, levofloxacin), and second-generation cephalosporins (eg, cefuroxime, cefaclor). These medications are effective against beta-lactamase–producing strains of Haemophilus influenzae and Moraxella catarrhalis (formerly known as Branhamella catarrhalis) but have not been shown to be more effective than first-line drugs for most patients.
Patients can be taught to recognize a change in sputum from normal to purulent as a sign of impending exacerbation and to start a 10- to 14-day course of antibiotic therapy.
If available, testing for low C-reactive protein (CRP) levels may guide which patients can avoid use of antibiotics (1).
Long-term antibiotic prophylaxis is recommended only for patients with underlying structural changes in the lung, such as bronchiectasis or infected bullae.
In patients with frequent exacerbations, long-term macrolide use reduces exacerbation frequency but may have adverse effects.
Other medications
Antitussives, such as dextromethorphan and benzonatate, have no role in treating COPD exacerbations.
Opioids (eg, codeine, hydrocodone, oxycodone) should be used judiciously for relief of symptoms (eg, severe coughing paroxysms, pain) because these medications may suppress a productive cough, impair mental status, and cause constipation.
Medication therapy reference
1. Butler CC, Gillespie D, White P, et al. C-Reactive Protein Testing to Guide Antibiotic Prescribing for COPD Exacerbations. N Engl J Med 2019;381(2):111-120. doi:10.1056/NEJMoa1803185
Key Points
Most patients hospitalized with exacerbation of chronic obstructive pulmonary disease (COPD) require oxygen supplementation during an exacerbation.
Inhaled short-acting beta-agonists are the cornerstone of medication therapy for acute exacerbations.
Use antibiotics if patients have acute exacerbations and purulent sputum.
For patients with severe COPD, address end-of-life care proactively, including preferences regarding mechanical ventilation and palliative sedation.
