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Treatment of Acute COPD Exacerbation


Robert A. Wise

, MD, Johns Hopkins Asthma and Allergy Center

Last review/revision Jun 2022 | Modified Sep 2022
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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 usually unknown, although some acute exacerbations result from bacterial or viral infections. Smoking, irritative inhalational exposure, and high levels of air pollution also contribute.

Mild exacerbations often can be treated on an outpatient basis in patients with adequate home support. 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 Respiratory Acidosis Respiratory acidosis is primary increase in carbon dioxide partial pressure (Pco2) with or without compensatory increase in bicarbonate (HCO3); pH is usually low but may be near... read more , new arrhythmias Overview of Arrhythmias The normal heart beats in a regular, coordinated way because electrical impulses generated and spread by myocytes with unique electrical properties trigger a sequence of organized myocardial... read more Overview of 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 require oxygen supplementation during a COPD exacerbation, even those who do not need it chronically. Hypercapnia may worsen in patients given oxygen. This worsening has traditionally been thought to result from an attenuation of hypoxic respiratory drive. However, increased ventilation/perfusion (V/Q) mismatch probably is a more important factor.

Before oxygen administration, pulmonary vasoconstriction minimizes V/Q mismatch by decreasing perfusion of the most poorly ventilated areas of the lungs. Increased V/Q mismatch occurs because oxygen administration attenuates this hypoxic pulmonary vasoconstriction.

The Haldane effect may also contribute to worsening hypercapnia, although this theory is controversial. The Haldane effect is a decrease in hemoglobin's affinity for carbon dioxide, which results in increased amounts of carbon dioxide dissolved in plasma. 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 PaCO2 is > 85 mm Hg. The target level for PaO2 is about 60 mm Hg; higher levels offer little advantage and increase the risk of hypercapnia.

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 with 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 Noninvasive positive pressure ventilation (NIPPV) (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).

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 drug 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, 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 Overview of Mechanical Ventilation Mechanical ventilation can be Noninvasive, involving various types of face masks Invasive, involving endotracheal intubation Selection and use of appropriate techniques require an understanding... read more .

Deteriorating ABG values, deteriorating mental status, and progressive respiratory fatigue are indications for endotracheal intubation and mechanical ventilation Overview of Mechanical Ventilation Mechanical ventilation can be Noninvasive, involving various types of face masks Invasive, involving endotracheal intubation Selection and use of appropriate techniques require an understanding... read more . Ventilator settings, management strategies, and complications are discussed elsewhere Means and Modes of Mechanical Ventilation Mechanical ventilation can be Noninvasive, involving various types of face masks Invasive, involving endotracheal intubation Selection and use of appropriate techniques require an understanding... read more . Risk factors for ventilatory dependence include an FEV1 < 0.5 L, stable ABGs with a PaO2 < 50 mm Hg, or a PaCO2 > 60 mm Hg, severe exercise limitation, and poor nutritional status. Therefore, if patients are at high risk, discussion of their wishes regarding intubation and mechanical ventilation should be initiated and documented (see Advance Directives Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more ) while they are stable outpatients. 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 Pulmonary Rehabilitation Pulmonary rehabilitation is the use of supervised exercise, education, support, and behavioral intervention to improve functional capacity and enhance quality of life in patients with chronic... read more , 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.

Pearls & Pitfalls

  • 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.

Drug 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.


Short-acting beta-agonists are the cornerstone of drug therapy for acute exacerbations. The most widely used drug is albuterol 2.5 mg by nebulizer or 2 to 4 puffs (100 mcg/puff) by metered-dose inhaler every 2 to 6 hours. Inhalation using a metered-dose inhaler causes rapid bronchodilation; there are no data indicating that doses taken with nebulizers are more effective than the same doses correctly taken with metered-dose inhalers. In cases of severe, unresponsive bronchospasm, continuous nebulizer treatments may sometimes be administered.

Anticholinergic drugs

Ipratropium, an anticholinergic, is effective in acute COPD exacerbations and should be given concurrently or alternating with beta-agonists. Dosage is 0.25 to 0.5 mg by nebulizer or 2 to 4 inhalations (17 to 18 mcg of drug delivered per puff) by metered-dose inhaler every 4 to 6 hours. Ipratropium generally provides bronchodilating effect similar to that of usual recommended doses of beta-agonists.

The role of the longer-acting anticholinergic drugs in treating acute exacerbations has not been defined.


Corticosteroids should be begun immediately for all but mild exacerbations. Options include prednisone 30 to 60 mg orally once a day for 5 to 7 days and stopped directly or tapered over 7 to 14 days depending on the clinical response. A parenteral alternative is methylprednisolone 60 to 500 mg IV once a day for 3 days and then tapered over 7 to 14 days. These drugs are equivalent in their acute effects.


Antibiotics are recommended for exacerbations in patients with purulent sputum. Some physicians give antibiotics empirically for change in sputum color or for nonspecific chest x-ray abnormalities. Routine cultures and Gram stains are not necessary before treatment unless an unusual or resistant organism is suspected (eg, in hospitalized, institutionalized, or immunosuppressed patients). Drugs directed against oral flora are indicated. Examples of antibiotics that are effective are

  • Trimethoprim/sulfamethoxazole 160 mg/800 mg orally twice a day

  • Amoxicillin 250 to 500 mg orally 3 times a day

  • Doxycycline 50 to 100 mg orally twice a day

  • Azithromycin 500 mg orally once a day

Choice of drug is dictated by local patterns of bacterial sensitivity and patient history. Trimethoprim/sulfamethoxazole, amoxicillin, and doxycycline are give for 7 to 14 days. An alternative first-line antibiotic is azithromycin 500 mg orally once a day for 3 days or 500 mg orally as a single dose on day 1, followed by 250 mg once a day on days 2 through 5.

When patients are seriously ill or clinical evidence suggests that the infectious organisms are resistant, broader spectrum 2nd-line drugs can be used. These drugs include amoxicillin/clavulanate, fluoroquinolones (eg, ciprofloxacin, levofloxacin), and 2nd-generation cephalosporins (eg, cefuroxime, cefaclor). These drugs are effective against beta-lactamase–producing strains of Haemophilus influenzae and Moraxella 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. 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 drugs

Antitussives, such as dextromethorphan and benzonatate, have little role.

Opioids (eg, codeine, hydrocodone, oxycodone) should be used judiciously for relief of symptoms (eg, severe coughing paroxysms, pain) insofar as these drugs may suppress a productive cough, impair mental status, and cause constipation.

End-of-Life Care

In patients with very severe disease, exercise is unwarranted and activities of daily living are arranged to minimize energy expenditure. For example, patients may arrange to live on one floor of the house, have several small meals rather than fewer large meals, and avoid wearing shoes that must be tied. End-of-life care The Dying Patient Dying patients can have needs that differ from those of other patients. So that their needs can be met, dying patients must first be identified. Before death, patients tend to follow 1 of 3... read more should be discussed, including whether to pursue mechanical ventilation, the use of palliative sedation, and appointment of a surrogate medical decision-maker in the event of the patient’s incapacitation.

Key Points

  • Most patients with exacerbation of chronic obstructive pulmonary disease (COPD) require oxygen supplementation during an exacerbation.

  • Inhaled short-acting beta-agonists are the cornerstone of drug therapy for acute exacerbations.

  • Use antibiotics if patients have acute exacerbations and purulent sputum.

  • For patients with end stage COPD, address end-of-life care proactively, including preferences regarding mechanical ventilation and palliative sedation.

Drugs Mentioned In This Article

Drug Name Select Trade
Accuneb, ProAir digihaler, Proair HFA, ProAir RespiClick, Proventil, Proventil HFA, Proventil Repetabs, Respirol , Ventolin, Ventolin HFA, Ventolin Syrup, Volmax, VoSpire ER
Atrovent, Atrovent HFA
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
A-Methapred, Depmedalone-40, Depmedalone-80 , Depo-Medrol, Medrol, Medrol Dosepak, Solu-Medrol
Primsol, Proloprim, TRIMPEX
Amoxil, Dispermox, Moxatag, Moxilin , Sumox, Trimox
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs
Azasite, Zithromax, Zithromax Powder, Zithromax Single-Dose , Zithromax Tri-Pak, Zithromax Z-Pak, Zmax, Zmax Pediatric
Cetraxal , Ciloxan, Cipro, Cipro XR, OTIPRIO, Proquin XR
Iquix, Levaquin, Levaquin Leva-Pak, Quixin
Alti-Cefuroxime , Ceftin, Kefurox, Zinacef, Zinacef Powder
Ceclor, Ceclor CD, Raniclor
AeroTuss, Buckley's Cough Suppressant , Buckley's DM, Buckley's Mixture, Cough DM, Cough Suppressant , Delsym, Delsym Children's, Delsym Children's Cough Relief, Delsym Cough, Dexalone, ElixSure Cough, ElixSure Cough DM, Giltuss DM, PediaCare Children's Long Acting Cough, PediaCare Infants' Long-Acting Cough, PediaCare Long-Acting Cough , Robafen Cough, Robitussin, Robitussin Children's Cough, Robitussin Cough, Robitussin CoughGels, Robitussin Lingering Cold Long-Acting Cough, Robitussin Pediatric Cough, Scot-Tussin CF, Silphen DM, Theraflu Long Acting Cough Strip, Triaminic Long Acting Cough , Triaminic Long Acting Cough Strip, Tylenol Children's Simply Cough, Vicks DayQuil Cough, Vicks DayQuil Nature Fusion, Vicks Formula 44, Vicks Nature Fusion Cough, Zicam Concentrated Cough, Zicam Cough Max, Zicam Cough Nite
Tessalon Perles, Zonatuss
No brand name available
Hysingla ER, Zohydro
Dazidox , Endocodone , ETH-Oxydose, Oxaydo, OXECTA, OxyContin, Oxydose , OxyFast, OxyIR, Percolone, Roxicodone, Roxybond, XTAMPZA
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