update

1. Management of exacerbations of chronic obstructive pulmonary disease
Author:
James K Stoller, MD, MS
Section Editor:
Peter J Barnes, DM, DSc, FRCP, FRS
Deputy Editor:
Helen Hollingsworth, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2017. | This topic last updated: Aug 03, 2017.
INTRODUCTION — The Global Initiative for Chronic Obstructive Lung Disease (GOLD), a report produced
by the National Heart, Lung, and Blood Institute (NHLBI) and the World Health Organization (WHO),
defines an exacerbation of chronic obstructive pulmonary disease (COPD) as "an acute event
characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day
variations and leads to a change in medication" [1]. This generally includes an acute change in one or more
of the following cardinal symptoms:
●Cough increases in frequency and severity
●Sputum production increases in volume and/or changes character
●Dyspnea increases
The management of patients with exacerbations of COPD is discussed in detail here. A table to assist with
emergency management of severe acute exacerbations of COPD is provided (table 1). The diagnosis and
treatment of infection in exacerbations and the management of stable COPD are discussed separately.
(See "Management of infection in exacerbations of chronic obstructive pulmonary
disease" and "Management of stable chronic obstructive pulmonary disease".)
RISK FACTORS FOR COPD EXACERBATION — According to observational studies, the risk of
developing an exacerbation of chronic obstructive pulmonary disease (COPD) correlates with advanced
age, productive cough, duration of COPD, history of antibiotic therapy, COPD-related hospitalization within
the previous year, chronic mucous hypersecretion, a peripheral blood eosinophil count >0.34 × 109
cells per
liter, theophylline therapy, and having one or more comorbidities (eg, ischemic heart disease, chronic heart
failure, or diabetes mellitus) [2-6]. In general, worsening airflow limitation (lower forced expiratory volume in
one second [FEV1]) is associated with an increasing risk of COPD exacerbation, although airflow limitation
alone does not provide a good assessment of exacerbation risk [1].
Other potential contributors to an increased risk of exacerbations include the following:
●Severity of COPD and history of prior exacerbations – In the prospective Evaluation of COPD
Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study, 2138 patients with
moderate to severe COPD (GOLD stages 2, 3, or 4 (table 2)) were followed for three years [7]. The
single best predictor of exacerbations was a history of prior exacerbations, regardless of COPD
severity.
The GOLD guidelines suggest using a combination of an individual's FEV1, history of exacerbations,
history of hospitalization for exacerbation, and symptoms to assess the exacerbation risk [1]. The
number of exacerbations in the previous 12 months is stratified: a history of zero or one exacerbation
suggests a low future risk of exacerbations, while two or more suggest a high future risk [1]. The
severity of lung function impairment is stratified based on the postbronchodilator FEV1, using the
GOLD classification of airflow limitation (table 2). These components are combined as follows:
•Low risk: Typically GOLD 1 or 2 (mild to moderate airflow limitation) and/or 0 to 1 exacerbation
per year, no hospitalization due to an exacerbation

2. •High risk: Typically GOLD 3 or 4 (severe or very severe airflow limitation) and/or ≥2
exacerbations per year or ≥1 hospitalization due to an exacerbation
The full COPD staging system used in the GOLD guidelines incorporates information about the
severity of symptoms (based on instruments such as the COPD Assessment Test [CAT] and the
modified Medical Research Council Dyspnea Scale), the degree of airflow limitation (based on the
FEV1), and the frequency of prior COPD exacerbations and is discussed separately [1]. (See "Chronic
obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging", section on
'Staging'.)
●Gastroesophageal reflux disease – Gastroesophageal reflux disease (GERD) may be an additional
risk factor for COPD exacerbations [8,9]. In the ECLIPSE study noted above, the occurrence of two or
more exacerbations in a year was associated with a history of GERD or heartburn [7]. A similar
observation was made in a case-control study that assessed the presence of GERD symptoms and
frequency of COPD exacerbations in 80 patients with COPD. The presence of GERD symptoms was
associated with an increased risk of COPD exacerbations (RR 6.55, 95% CI 1.86-23.11) [8]. However,
in an observational study of 638 patients with stable COPD, therapy with proton pump inhibitors did
not decrease the risk for severe exacerbations [10]. Additional studies are needed to determine
whether GERD contributes to the development of COPD exacerbations.
●Pulmonary hypertension – Secondary pulmonary hypertension may be an additional risk factor for
COPD exacerbations. In a follow-up to the ECLIPSE study, chest computed tomography scans were
used to compute the ratio of the diameter of the pulmonary artery to the diameter of the aorta (PA:A
ratio) [11]. In the study, a PA:A ratio greater than 1 was an independent risk factor for a future severe
exacerbation (OR 3.44, 95% CI 2.78-4.25). Notably, a PA:A ratio >1 suggests the presence of
pulmonary hypertension, although it does not clarify the cause of pulmonary hypertension (eg,
hypoxemia due to COPD or other lung disease, left heart failure, sleep apnea). The clinical usefulness
of this observation in terms of treatment decisions is unclear.
TRIGGERS — Respiratory infections are estimated to trigger approximately 70 percent of chronic
obstructive pulmonary disease (COPD) exacerbations (table 3). Viral and bacterial infections cause most
exacerbations, whereas atypical bacteria are a relatively uncommon cause [12,13]. The remaining 30
percent are due to environmental pollution, pulmonary embolism, or have an unknown etiology [1,14-16].
(See "Management of infection in exacerbations of chronic obstructive pulmonary disease".)
Some COPD exacerbations of unknown etiology may be related to other medical conditions, such as
myocardial ischemia, heart failure, aspiration, or pulmonary embolism [1,17]. The relationship between
COPD exacerbation and pulmonary embolism was illustrated by a meta-analysis of five observational
studies [18]. Among the 550 patients having a COPD exacerbation, the prevalence of pulmonary embolism
was 20 percent. The prevalence was even higher (25 percent) among those hospitalized. An important
limitation of the meta-analysis was its inability to determine whether the pulmonary embolism was the
cause of the COPD exacerbation, a result of the COPD exacerbation, or a mere bystander.
CLINICAL MANIFESTATIONS — The clinical manifestations of exacerbations of chronic obstructive
pulmonary disease (COPD) range from a mild increase in dyspnea or productive cough to respiratory
failure due to acute respiratory acidosis or hypoxemia.
Medical history — By definition, patients present with the acute onset or worsening of respiratory
symptoms, such as dyspnea, cough, and/or sputum production, over several hours to days. These
symptoms should be characterized further in terms of the following features:
●Time course of the symptoms
●Comparison to baseline level of symptoms
●Severity of respiratory compromise (eg, dyspnea at rest, dyspnea climbing stairs)

3. ●Delineation of sputum characteristics (eg, amount, purulence, blood)
Associated features that would suggest an alternate diagnosis or comorbidity include:
●Constitutional symptoms (eg, fever, chills, night sweats)
●Chest pain, chest pressure, or peripheral edema
●Risk factors for thromboembolic disease or coronary disease
●Upper respiratory symptoms that might suggest a viral respiratory infection
The past history of exacerbations should be ascertained: number of prior exacerbations, courses of
systemic glucocorticoids, and exacerbations requiring hospitalization or ventilatory support.
Physical examination — Physical findings associated with an exacerbation of COPD often include
wheezing and tachypnea and may include features of respiratory compromise such as difficulty speaking
due to respiratory effort, use of accessory respiratory muscles, and paradoxical
chest wall/abdominal movements (asynchrony between chest and abdominal motion with respiration). If
present, decreased mental status could reflect hypercapnia or hypoxemia and asterixis could indicate
increased hypercapnia.
Attention should also be paid to physical findings that might suggest a comorbidity or alternate diagnosis,
such as fever, hypotension, bibasilar fine crackles and peripheral edema.
EVALUATION AND DIAGNOSIS — The goals of the initial evaluation of a patient with a suspected
exacerbation of COPD are to confirm the diagnosis, identify the cause (when possible), assess the severity,
and determine whether comorbidities are contributing.
Initial evaluation — The choice of specific tests is guided by the severity of the exacerbation and the
particular associated clinical findings. (See 'Clinical manifestations' above.)
For patients with a mild exacerbation (absence of resting dyspnea or respiratory distress, preserved ability
to perform activities of daily living), who do not require emergency department treatment, the evaluation
may be limited to clinical assessment and possibly pulse oxygen saturation.
For patients who require emergency department care, the evaluation should generally include the following
(table 1):
●Assessment of pulse oxygen saturation
●A chest radiograph to exclude pneumonia, pneumothorax, pulmonary edema, pleural effusion
●Laboratory studies (eg, complete blood count and differential, serum electrolytes and glucose)
●Arterial blood gas analysis, if acute or acute-on-chronic respiratory acidosis is suspected or if
ventilatory support is anticipated. Concern about acute-on-chronic hypercapnia might be prompted by
a history of prior elevation in arterial tension of carbon dioxide (PaCO2), an elevated serum
bicarbonate (perhaps reflecting compensation for chronic hypercapnia), or the presence of severe
airflow obstruction (eg, GOLD III or IV (table 2)).
Additional tests are obtained depending on the clinical evaluation of the patient. Often an electrocardiogram
and cardiac troponins are obtained to evaluate tachycardia or potential myocardial ischemia. Studies such
as a plasma brain natriuretic peptide (BNP) to assess for heart failure and a D-dimer to assess for
thromboembolic disease are obtained, as indicated by features such as crackles on chest auscultation,
peripheral edema, suggestive chest radiographic findings (vascular congestion, pleural effusion), or risk
factors for thromboembolism. (See "Troponin testing: Clinical use" and "Natriuretic peptide measurement in
heart failure" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected
acute pulmonary embolism".)

4. Sputum Gram stain and culture are often not useful for identifying bacterial infection in patients with COPD
exacerbations and are not obtained for most exacerbations of COPD. Sputum culture may be helpful in
patients who are strongly suspected of having a bacterial infection but fail to respond to initial antibiotic
therapy. (See "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease", section
on 'Sputum studies'.)
While not necessary in most patients, evaluation for possible respiratory virus infection, including influenza,
may be useful in selected patients, such as those who are hospitalized and those with a clinical
presentation suggestive of influenza (eg, acute onset of fever, myalgias, coryza during an influenza
outbreak). Rapid antigen and immunofluorescence testing are useful screening tests for influenza infection,
but have limited sensitivity; polymerase chain reaction (PCR)-based testing is more sensitive and specific.
In addition, PCR diagnostic panels have been developed that can detect multiple respiratory viruses (eg,
influenza, adenovirus, parainfluenza virus, respiratory syncytial virus, human metapneumovirus,
coronavirus, and rhinovirus) simultaneously, although the exact indications for their use in COPD
exacerbations are not clear. (See "Management of infection in exacerbations of chronic obstructive
pulmonary disease", section on 'Antiviral therapy'.)
Differential diagnosis — Patients with COPD who present to the hospital with acute worsening of
dyspnea should be evaluated for potential alternative diagnoses, such as heart failure, pulmonary
thromboembolism, pneumonia, and pneumothorax [1,19,20]. The importance of considering these alternate
diagnoses was illustrated in an autopsy study of 43 patients with COPD who died within 24 hours of
admission for a COPD exacerbation [19]. The primary causes of death were heart failure, pneumonia,
pulmonary thromboembolism, and COPD in 37, 28, 21, and 14 percent, respectively. A chest radiograph
will differentiate among several of these possibilities (eg, heart failure, pneumonia, pneumothorax); a clear
chest radiograph may be a clue to pulmonary embolism, especially when dyspnea and hypoxemia are
more prominent than cough or sputum production.
TRIAGE TO HOME OR HOSPITAL — An important step in the initial evaluation is to determine whether
the patient needs hospitalization or can be safely managed at home. If the exacerbation appears life-
threatening or if there are indications for ventilatory support (eg, hypoxemic or hypercapnic respiratory
failure), the patient should be admitted to the intensive care unit as quickly as possible. (See 'Mechanical
ventilation' below.)
On the other hand, more than 80 percent of exacerbations of chronic obstructive pulmonary disease
(COPD) can be managed on an outpatient basis, sometimes after initial treatment in the office or
emergency department.
Other criteria that might lead to a decision to hospitalize the patient have been proposed in the GOLD
guidelines and include [1]:
●Inadequate response to outpatient or emergency department management
●Onset of new signs (eg, cyanosis, altered mental status, peripheral edema)
●Marked increase in intensity of symptoms over baseline (eg, new onset resting dyspnea)
accompanied by increased oxygen requirement or signs of respiratory distress
●Severe underlying COPD (eg, forced expiratory volume in one second [FEV1] ≤50 percent of
predicted)
●History of frequent exacerbations or prior hospitalization for exacerbations
●Serious comorbidities including pneumonia, cardiac arrhythmia, heart failure, diabetes mellitus, renal
failure, or liver failure
●Frailty
●Insufficient home support

5. Intensive home care, which generally includes nurse visits, home oxygen, and physical therapy, may be an
alternative in certain locations (eg, United Kingdom, Europe) for selected patients with an exacerbation of
COPD [21-25]. A meta-analysis of seven trials noted that intensive home care resulted in equivalent clinical
outcomes and substantial cost savings compared to hospitalization [26]. However, these trials excluded
sicker patients with an impaired level of consciousness, respiratory acidosis (arterial pH <7.35), acute
electrocardiographic or chest radiographic changes, or coexisting medical morbidities. Although care at
home is feasible in highly selected patients without these characteristics, implementation requires a
dedicated support team to conduct ongoing clinical assessments and provide home care. In general, home
management of the patient who satisfies criteria for hospitalization should be considered infrequently and
only when optimal home care is available.
HOME MANAGEMENT OF COPD EXACERBATIONS — Home management of chronic obstructive
pulmonary disease (COPD) exacerbations generally includes intensification of bronchodilator therapy and
initiation of a course of oral glucocorticoids; oral antibiotics are added based on individual characteristics.
Beta adrenergic agonists — Inhaled short-acting beta adrenergic agonists (eg, albuterol, levalbuterol) are
the mainstay of therapy for an acute exacerbation of COPD because of their rapid onset of action and
efficacy in producing bronchodilation [27,28]. For patients being managed at home, these medications are
usually administered by a metered dose inhaler (MDI) with a spacer device and may be combined with a
short acting anticholinergic agent (eg, ipratropium) [1,29]. (See "Delivery of inhaled medication in
adults" and "The use of inhaler devices in adults" and 'Anticholinergic agents' below.)
Patients who already have a nebulizer at home frequently find that administration of beta adrenergic
agonists via nebulizer is helpful during COPD exacerbations. However, most studies have not supported a
greater effect from nebulizer treatments over properly administered metered dose inhaler medication.
(See 'Beta adrenergic agonists' below and "Delivery of inhaled medication in adults", section on 'Home
use'.)
Anticholinergic agents — Ipratropium bromide, an inhaled short-acting anticholinergic agent (also known
as a short-acting muscarinic agent) is an effective bronchodilator for exacerbations of COPD and is often
used in combination with inhaled short-acting beta adrenergic agonists [1].
The usual dose of ipratropium for an acute exacerbation of COPD is two inhalations by metered dose
inhaler (MDI) every four to six hours. The usual doses of combined albuterol and ipratropium are two
inhalations by MDI every four to six hours OR one inhalation by soft mist inhaler (SMI, Respimat) every six
hours.
The evidence for using the combination of a short-acting beta agonist with a short acting anticholinergic
agent comes from several studies that found that combination therapy produces bronchodilation in excess
of that achieved by either agent alone in patients with a COPD exacerbation, an asthma exacerbation, or
stable COPD [29-31]. However, this finding has not been universal, and other studies not found an additive
effect in COPD exacerbations [32].
For patients who have a history of benign prostatic hypertrophy or prior urinary retention, the addition
of ipratropium to a long-acting anticholinergic agent (eg, tiotropium) may increase the risk of acute urinary
retention, although data are conflicting. (See "Role of anticholinergic therapy in COPD", section on 'Acute
urinary retention'.)
Oral glucocorticoid therapy — Systemic glucocorticoid therapy appears to have a small but beneficial
effect in outpatients with exacerbations of COPD. Our practice reflects current guidelines, which suggest
using a dose that is the equivalent of prednisone 40 mg per day for five days [1]. Occasional patients may
benefit from a higher dose or a longer course depending on the severity of the exacerbation and response
to prior courses of glucocorticoids.

6. The benefit of oral glucocorticoids in the outpatient management of COPD exacerbations was examined in
a randomized trial of 147 patients discharged from the emergency department after presenting with an
acute exacerbation of COPD [33]. Patients received oral prednisone (40 mg) or placebo for 10 days.
Patients who received prednisone were less likely to return to the emergency department or their clinician
with increasing dyspnea within 30 days (27 versus 43 percent, p=0.05) (figure 1). In addition to a lower rate
of relapse (the primary end point of the study), prednisone therapy was associated with decreased dyspnea
and a greater improvement in FEV1 (34 versus 15 percent) on day 10.
Studies of acute exacerbations typically exclude patients who have recently used systemic glucocorticoids,
which in some cases eliminated nearly one-half of all screened patients. This exclusion does not create a
major treatment dilemma, since clinicians would not be likely to withhold glucocorticoids from a
glucocorticoid-dependent patient during periods of acute illness. However, excluding patients who recently
received systemic glucocorticoids could affect the magnitude of the treatment benefits that would occur in
an unselected population of hospitalized COPD patients. (See "Major side effects of systemic
glucocorticoids".)
The efficacy of inhaled glucocorticoids on the course of a COPD exacerbation has not been studied in
randomized trials. Thus, they should not be used as a substitute for systemic glucocorticoid therapy in
COPD exacerbations.
Antibiotics — To try to maximize the benefit of antibiotic therapy, many clinical practice guidelines
recommend antibiotic therapy only for those patients who are most likely to have bacterial infection or are
most ill.
The GOLD guidelines recommend antibiotics for moderately or severely ill patients with COPD
exacerbations who have increased cough and sputum purulence [1]. We vary slightly from the GOLD
guidelines in our clinical practices (algorithm 1):
●We recommend antibiotics in outpatients with a moderate or severe exacerbation of COPD, which is
defined as having at least two of these three symptoms – increased dyspnea, increased sputum
volume, or increased sputum purulence.
●We do not initiate antibiotic therapy in patients whose exacerbation is mild, which we define as
having only one of these three symptoms and not requiring hospitalization.
The initial antibiotic regimen should target likely bacterial pathogens (Haemophilus influenzae, Moraxella
catarrhalis, and Streptococcus pneumoniae in most patients) and take into account local patterns of
antibiotic resistance (algorithm 1). The role of antibiotics in exacerbations of COPD, including antibiotic
selection, is discussed separately. (See "Management of infection in exacerbations of chronic obstructive
pulmonary disease", section on 'Summary and recommendations' and "Evaluation for infection in
exacerbations of chronic obstructive pulmonary disease", section on 'Summary and recommendations'.)
Adjunctive care — For patients being managed at home, supportive care may include efforts at cigarette
smoking cessation, nutritional support, and continuation of ongoing supplemental oxygen therapy. Patients
who have a new requirement for supplemental oxygen are usually managed in the hospital, at least initially.
(See 'Triage to home or hospital' above and "Overview of smoking cessation management in
adults" and "Nutritional support in advanced lung disease" and "Pulmonary rehabilitation".)
HOSPITAL MANAGEMENT OF COPD EXACERBATIONS — Similar to at-home management, the major
components of in-hospital management of exacerbations of chronic obstructive pulmonary disease (COPD)
include reversing airflow limitation with inhaled short-acting bronchodilators and systemic glucocorticoids,
treating infection, ensuring adequate oxygenation, and averting intubation and mechanical ventilation
[1,34]. An approach to emergency management of severe exacerbations of COPD is summarized in the
table (table 1).

7. Other goals of care are to prevent complications of immobility, such as thromboemboli and deconditioning,
improve nutritional status, and aid patients who smoke with smoking cessation.
In-hospital monitoring typically includes frequent assessment of respiratory status (eg, respiratory rate and
effort, wheezing, pulse oxygen saturation), heart rate and rhythm, and also fluid status. Arterial blood gas
measurement is performed to look for respiratory acidosis (eg, if the patient's respiratory status is
deteriorating), confirm the accuracy of pulse oxygen saturation, and to monitor known hypercapnia.
(See "Simple and mixed acid-base disorders", section on 'Respiratory acid-base disorders'.)
Oxygen therapy — Supplemental oxygen is a critical component of acute therapy. Because of the risk of
prompting worsened hypercapnia with excess supplemental oxygen, administration of supplemental
oxygen should target a pulse oxygen saturation (SpO2) of 88 to 92 percent or an arterial oxygen tension
(PaO2) of approximately 60 to 70 mmHg [1,34,35]. In two small randomized trials, titrating supplemental
oxygen to SpO2 88 to 92 percent resulted in a lower mortality compared with high flow (nontitrated) oxygen
[35]. (See "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory
failure".)
There are numerous devices available to deliver supplemental oxygen during an exacerbation of COPD:
●Venturi masks are the preferred means of oxygen delivery because they permit a precise delivered
fraction of inspired oxygen (FiO2). Venturi masks can deliver an FiO2 of 24, 28, 31, 35, 40, or 60
percent.
●Nasal cannula can provide flow rates up to 6 L per minute with an associated FiO2 of approximately
40 percent (calculator 1). They are more comfortable and convenient for the patient, especially during
oral feedings.
●When a higher FiO2 is needed, simple facemasks can provide an FiO2 up to 55 percent using flow
rates of 6 to 10 L per minute. However, variations in minute ventilation and inconsistent entrainment of
room air affect the FiO2 when simple facemasks (or nasal cannula) are used.
●Non-rebreathing masks with a reservoir, one-way valves, and a tight face seal can deliver an inspired
oxygen concentration up to 90 percent, but are generally not needed in this setting.
A high FiO2 is not required to correct the hypoxemia associated with most exacerbations of COPD. Inability
to correct hypoxemia with a relatively low FiO2 (eg, 4 L/min by nasal cannula or 35 percent by mask) should
prompt consideration of pulmonary emboli, acute respiratory distress syndrome, pulmonary edema, or
severe pneumonia as the cause of respiratory failure. (See "Oxygenation and mechanisms of hypoxemia".)
Adequate oxygenation (ie, to achieve an oxygen saturation of 88 to 92 percent) must be assured, even if it
leads to acute hypercapnia. Hypercapnia is generally well tolerated in patients whose arterial carbon
dioxide tension (PaCO2) is chronically elevated. However, mechanical ventilation may be required if
hypercapnia is associated with depressed mental status, profound acidemia, or cardiac dysrhythmias.
(See "Oxygen toxicity", section on 'Accentuation of hypercapnia' and 'Mechanical ventilation' below
and "The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory
failure".)
Beta adrenergic agonists — As noted above, inhaled short-acting beta adrenergic agonists
(eg, albuterol, levalbuterol) are the mainstay of therapy for an exacerbation of COPD because of their rapid
onset of action and efficacy in producing bronchodilation [27,28]. These medications may be administered
via a nebulizer or a metered dose inhaler (MDI) with a spacer device and may be combined with a short
acting muscarinic agent (eg, ipratropium) [1,29]. (See "Delivery of inhaled medication in adults" and "The
use of inhaler devices in adults" and 'Anticholinergic agents' below.)

8. Despite evidence that MDI devices may have equal efficacy during exacerbations of COPD, many
clinicians prefer nebulized therapy on the presumption of more reliable delivery of drug to the airway [1].
We favor nebulized therapy because many patients with COPD have difficulty using proper MDI technique
in the setting of an exacerbation.
Typical doses of albuterol for this indication are 2.5 mg (diluted to a total of 3 mL) by nebulizer every one to
four hours as needed, or four to eight puffs (90 mcg per puff) by MDI with a spacer every one to four hours
as needed. Increasing the dose of nebulized albuterol to 5 mg does not have a significant impact on
spirometry or clinical outcomes [36]. Similarly, continuously nebulized beta agonists have not been shown
to confer an advantage in COPD.
Patients with severe COPD are at risk for hypercapnia with administration of supplemental oxygen, so
concern has been raised about the risk of hypercapnia during bronchodilator treatments that are
administered using oxygen-driven nebulizers [37]. We concur with the British Thoracic Society guidelines
that suggest using air, rather than oxygen-driven bronchodilator nebulization, or limiting oxygen-driven
treatments to six minutes [38].
Subcutaneous injection of short-acting beta adrenergic agonists (eg, terbutaline, epinephrine) carries a high
risk for inotropic and chronotropic adverse effects, such as arrhythmias or myocardial ischemia, and is
almost never used for COPD exacerbations.
Anticholinergic agents — As noted above, the evidence is conflicting regarding the use of inhaled short-
acting anticholinergic agents (eg, ipratropium bromide) in combination with inhaled short-acting beta
adrenergic agonists to treat exacerbations of COPD [1]. Nonetheless these agents are typically used
together for patients who require hospital-based treatment of a COPD exacerbation. (See 'Anticholinergic
agents' above.)
Typical doses of ipratropium in this situation are 500 mcg by nebulizer every four hours as needed.
Alternatively, two to four puffs (18 mcg per puff) can be administered by MDI with a spacer every four hours
as needed. (See "Role of anticholinergic therapy in COPD".)
Systemic glucocorticoids
●Efficacy – Systemic glucocorticoids, when added to the bronchodilator therapies described above,
improve symptoms and lung function, and decrease the length of hospital stay [1,39-41]. In a
systematic review and meta-analysis of nine studies (n = 917), systemic glucocorticoids reduced the
risk of treatment failure by over 50 percent compared with placebo and, in two studies (n = 415),
reduced the risk of relapse at one month (hazard ratio 0.78 [95% CI 0.63-0.97]) [41]. The forced
expiratory volume in one second showed significant improvement in the glucocorticoid group up to 72
hours after initiation, but not after that time point. Hospital stay was significantly shorter with
glucocorticoid treatment (mean difference -1.22 days; 95% CI -2.26 to -0.18). The risk of
hyperglycemia was significantly increased with glucocorticoids compared with placebo (odds ratio
2.79; 95% CI 1.86-4.19).
●Route – Oral glucocorticoids are rapidly absorbed (peak serum levels achieved at one hour after
ingestion) with virtually complete bioavailability and appear equally efficacious to intravenous
glucocorticoids for treating most exacerbations of COPD [41-43]. In the systematic review described
above, parenteral glucocorticoids were compared with oral glucocorticoids and no significant
differences were noted in the primary outcomes of treatment failure, relapse, or mortality or for any
secondary outcomes [41]. However, intravenous glucocorticoids are typically administered to patients
who present with a severe exacerbation, who have not responded to oral glucocorticoids at home, who
are unable to take oral medication, or who may have impaired absorption due to decreased splanchnic
perfusion (eg, patients in shock).

9. ●Dose – The optimal dose of systemic glucocorticoids for treating a COPD exacerbation is unknown
[1,43]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines advise using the
equivalent of prednisone 40 mg once daily for the majority of COPD exacerbations (table 4) [1].
Frequently used regimens range from prednisone 30 to 60 mg, once daily, to methylprednisolone 60 to
125 mg, two to four times daily, depending on the severity of the exacerbation [42,44,45]. A growing
body of evidence favors using a moderate, rather than high dose of glucocorticoids, for most patients
with an exacerbation of COPD. As an example, a comparative analysis of glucocorticoid dosing
examined outcomes of 79,985 patients admitted to the hospital with an exacerbation of COPD,
excluding those requiring intensive care [44]. The median glucocorticoid dose administered in the first
two days was 60 mg for those on oral therapy and 556 mg for intravenous therapy. The risk of
treatment failure was no greater with the lower dose. 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.
On the other hand, for patients with impending or actual acute respiratory failure due to a COPD
exacerbation, many clinicians use an intravenous formulation at a higher dose, such as the equivalent
of methylprednisolone 60 mg intravenously, one to four times daily, although outcomes data to guide
this practice are limited. In an observational cohort study, among 17,239 patients admitted to an
intensive care unit (ICU) with an exacerbation of COPD, a dose of methylprednisolone of
240 mg/day or less, compared with a higher dose (methylprednisolone >240 mg/day), was not
associated with a mortality benefit, but was associated with slightly shorter hospital (-0.44 days, 95%
CI -0.67 to -0.21) and ICU (-0.31 days; 95% CI -0.46 to -0.16) lengths of stay [46]. Length of
mechanical ventilation and need for insulin therapy were also lower in the lower dose group. As this
was an observational study, further research is needed to determine the optimal glucocorticoid dose in
this setting.
●Duration – The optimal duration of systemic glucocorticoid therapy is not clearly established and
often depends on the severity of the exacerbation and the observed response to therapy [1,43,47].
The GOLD guidelines suggest that glucocorticoids (eg, prednisone 30 to 40 mg/day) be given for five
days [1], while the European Respiratory Society/American Thoracic Society guidelines suggest a
course of therapy ≤14 days in duration [43]. Thus, a range of 5 to 14 days appears reasonable.
•Data in support of a 14-day course, rather than a longer duration, comes from the Systemic
Corticosteroids in COPD Exacerbations (SCCOPE) trial, which compared two and eight week
regimens and did not find any additional benefit to the longer course [39]. Patients in the eight
week group experienced more glucocorticoid-related side effects.
•Other studies have examined whether courses shorter than 14 days are also effective for COPD
exacerbations. As an example, the Reduction in the Use of Corticosteroids in Exacerbated COPD
(REDUCE) trial randomly assigned 314 patients with exacerbations of COPD, of whom 289
required hospitalization, to prednisone 40 mg daily for 5 or 14 days [45]. No difference was noted
in the time to the next exacerbation, the likelihood of an exacerbation in the subsequent 180
days, or the recovery of lung function. The mean cumulative prednisone dose was significantly
higher in the 14-day group, but treatment-related adverse effects, such as hyperglycemia and
hypertension, were not different between the groups. While this study suggests that a five-day
course may be comparable to 14 days for many patients, further study is needed to determine
whether some patients might do better with the longer course.
•A systematic review compared different durations of systemic glucocorticoid therapy and found
no difference in the risk of treatment failure with courses of three to seven days compared with
longer courses [47]. Including the data from the REDUCE trial above, the systematic review
concluded that a five-day course of oral glucocorticoids is probably comparable to a 14-day or
longer course, but that further research is needed to conclude equivalence.
At the end of the treatment course, glucocorticoid therapy may be discontinued rather than tapered, if
the patient has substantially recovered. Alternatively, the dose is tapered over another seven days, as

10. a trial to determine whether a longer course of glucocorticoid therapy is required. However, long-term
systemic glucocorticoids should rarely be used for stable COPD if therapy is otherwise optimized.
Tapering solely because of concerns about adrenal suppression is not necessary if the duration of
therapy is less than three weeks (a duration too brief to cause adrenal atrophy). (See "Management of
refractory chronic obstructive pulmonary disease", section on 'Systemic
glucocorticoids' and "Glucocorticoid withdrawal", section on 'Recommended tapering regimen'.)
Antibiotics and antiviral agents — Most clinical practice guidelines recommend antibiotics for patients
having a moderate to severe COPD exacerbation that requires hospitalization [1]. The optimal antibiotic
regimen for the treatment of exacerbations of COPD has not been determined. We use a "risk stratification"
approach when selecting initial antibiotic therapy, providing a broader antibiotic regimen for patients at risk
for resistant organisms (algorithm 2). The rationale, diagnosis, and treatment of infection in exacerbations
of COPD, including antibiotic selection, are discussed separately. (See "Management of infection in
exacerbations of chronic obstructive pulmonary disease", section on 'Summary and
recommendations' and "Evaluation for infection in exacerbations of chronic obstructive pulmonary disease",
section on 'Summary and recommendations'.)
Antiviral therapy is recommended for patients with clinical and laboratory evidence of influenza infection
who require hospitalization for an exacerbation of COPD. Because of the risk of acute bronchoconstriction
with inhalation of zanamivir, oseltamivir is preferred unless local resistance patterns suggest a likelihood of
oseltamivir-resistant influenza. Antiviral treatment of influenza is discussed in greater detail separately.
(See "Treatment of seasonal influenza in adults", section on 'Antiviral therapy'.)
Information regarding antiviral resistance that emerges during the influenza season is available through
the United States Centers for Disease Control and Prevention. Clinicians should review antiviral resistance
patterns and the CDC's web site for updated antiviral recommendations should increased resistance
emerge.
Supportive care — Supportive care for patients hospitalized with an exacerbation of COPD may include
one or more of the following therapies:
●Cigarette smoking cessation – Hospitalization may provide an opportunity for patients who continue
to smoke to move towards cigarette smoking cessation. (See "Overview of smoking cessation
management in adults", section on 'Hospitalized smokers'.)
●Thromboprophylaxis – Hospitalization for exacerbations of COPD increases the risk for deep venous
thrombosis and pulmonary embolism [1]. (See "Prevention of venous thromboembolic disease in
acutely ill hospitalized medical adults".)
●Nutritional support – Oral nutritional supplementation may have some benefit in the rate of
improvement in pulmonary function during COPD exacerbations [48]. (See "Nutritional support in
advanced lung disease", section on 'Frequency of malnutrition'.)
Palliative care — Given the high one-year mortality rate after hospitalization for a COPD exacerbation, it
may be appropriate to consider a palliative care referral during or shortly after a hospitalization for COPD.
Palliative care assessment can help explore the patient's understanding of their illness and prognosis,
assess and manage symptoms, discuss the patient's goals of care and advance care planning, and help
plan end-of-life care. (See "Palliative care for adults with nonmalignant chronic lung disease".)
Treatments without documented benefit — Mucoactive agents, methylxanthines, and mechanical
techniques to augment sputum clearance have not been shown to confer benefit for patients with a COPD
exacerbation.

11. ●Mucoactive agents – There is little evidence supporting the use of mucoactive agents (eg, N-
acetylcysteine) in exacerbations of COPD [27,28,49]. Some mucoactive agents may worsen
bronchospasm. (See "Role of mucoactive agents and secretion clearance techniques in COPD".)
The lack of efficacy of mucoactive agents in the treatment of COPD exacerbations was best
demonstrated by a double-blind trial that randomly assigned 50 patients with a COPD exacerbation to
receive N-acetylcysteine (600 mg, twice daily) or placebo for seven days [49]. There was no difference
in the rate of change of FEV1, vital capacity, oxygen saturation, breathlessness, or length of stay
between the two groups.
●Methylxanthines – The methylxanthines, aminophylline and theophylline, are considered second-
line therapy for exacerbations of COPD [1]. Randomized controlled trials of intravenous aminophylline
in this setting have failed to show efficacy beyond that induced by inhaled bronchodilator and
glucocorticoid therapy. In addition to lack of efficacy, methylxanthines caused significantly more
nausea and vomiting than placebo and trended toward more frequent tremor, palpitations, and
arrhythmias. (See "Role of methylxanthines in the treatment of COPD", section on 'Acute
exacerbation'.)
●Nebulized magnesium – While intravenous magnesium has a bronchodilator effect in acute severe
exacerbations of asthma, nebulized isotonic magnesium (151 mg per dose) had no effect on
FEV1when added to nebulized salbutamol (albuterol) in patients with exacerbations of COPD [50].
●Chest physiotherapy – Mechanical techniques to augment sputum clearance, such as directed
coughing, chest physiotherapy with percussion and vibration, intermittent positive pressure breathing,
and postural drainage, have not been shown to be beneficial in COPD and may provoke
bronchoconstriction. Their use in exacerbations of COPD (in the absence of bronchiectasis) is not
supported by clinical trials [1,27,28].
MECHANICAL VENTILATION — Ventilatory support may be needed for patients with more severe
exacerbations of COPD, such as those characterized by severe dyspnea with clinical signs of respiratory
muscle fatigue, increased work of breathing, or both, and also respiratory acidosis (arterial pH ≤7.35 and
arterial tension of carbon dioxide [PaCO2] ≥45 mmHg [≥6 kPa]) [1]. Prior to initiating ventilatory support, it is
important to review existing advance directives and ensure that ventilatory support is consistent with the
patient's goals of care. (See "Advance care planning and advance directives".)
Noninvasive ventilation — Noninvasive ventilation (NIV, also known as noninvasive positive pressure
ventilation or NPPV) refers to mechanical ventilation delivered through a noninvasive interface, such as a
face mask, nasal mask, or nasal prongs. It improves numerous clinical outcomes and is the preferred
method of ventilatory support in many patients with an exacerbation of COPD [43]. Most commonly, NIV is
initiated in the emergency department, intensive care unit, or a specialized respiratory unit to enable close
monitoring, although this has not been formally studied and varies among hospitals. (See "Noninvasive
ventilation in acute respiratory failure in adults".)
The optimal initial mode and settings for NIV have not been established. A reasonable approach is to
initiate NIV in a spontaneously triggered mode with a backup respiratory rate, an inspiratory pressure of 8
to 12 cm H2O, and an expiratory pressure of 3 to 5 cm H2O. The inspiratory pressure is gradually increased
as needed to achieve alleviation of dyspnea and good patient-ventilator synchrony. NIV is discussed in
detail elsewhere. (See "Noninvasive ventilation in acute respiratory failure in adults", section on 'Initiation'.)
Invasive ventilation — Invasive mechanical ventilation should be administered when patients fail NIV, do
not tolerate NIV, or have contraindications to NIV. Invasive mechanical ventilation for acute respiratory
failure due to a COPD exacerbation is discussed separately. (See "Invasive mechanical ventilation in acute
respiratory failure complicating chronic obstructive pulmonary disease".)
PROGNOSIS — Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with
increased mortality [1]. In-hospital mortality ranges from three to nine percent [51-53]. Mortality following

12. hospital discharge after an exacerbation of COPD is influenced by a number of factors, including older age,
the severity of the underlying COPD, requirement for long-term oxygen at discharge, presence of
comorbidities (eg, cardiovascular disease or lung cancer), and the presence of Pseudomonas
aeruginosa in the patient's sputum as described in the following studies [54-59]:
●It is estimated that 14 percent of patients admitted for an exacerbation of COPD will die within three
months of admission [54,55].
●Among 1016 patients with an exacerbation of COPD and a PaCO2 of 50 mmHg or more, the 6 and 12
month mortality rates were 33 and 43 percent, respectively [56].
●In a study of 260 patients admitted with a COPD exacerbation, the one year mortality was 28 percent
[57]. Independent risk factors for mortality were age, male gender, prior hospitalization for COPD,
PaCO2 ≥45 mmHg (6 kPa), and urea >8 mmol/L.
●Patients hospitalized for a COPD exacerbation who have Pseudomonas aeruginosa in their sputum
have a higher risk of mortality at three years than those without (59 versus 35 percent, HR 2.33, 95%
CI 1.29-3.86), independent of age, comorbidity, or COPD severity [58].
Even if the COPD exacerbation resolves, many patients never return to their baseline level of health [60].
PREVENTION
General measures — Several measures have been shown to reduce chronic obstructive pulmonary
disease (COPD) exacerbations, including smoking cessation, pulmonary rehabilitation, increased physical
activity [61], proper use of medications (including metered dose inhaler technique), and vaccination against
seasonal influenza and pneumococcus [1,62,63]. (See "Pulmonary rehabilitation" and "The use of inhaler
devices in adults" and "Management of stable chronic obstructive pulmonary disease", section on
'Supportive therapy' and "Overview of smoking cessation management in adults" and "Management of
infection in exacerbations of chronic obstructive pulmonary disease", section on 'Vaccination'.)
A number of medications, such as tiotropium, combination inhaled glucocorticoid and long-acting beta
agonist (LABA), roflumilast, and N-acetylcysteine (NAC), can help to reduce the frequency of COPD
exacerbations, although the evidence for roflumilast and NAC is less convincing than for the other two [63].
The effect of long-term therapy with these agents on exacerbation frequency is discussed separately.
(See "Management of stable chronic obstructive pulmonary disease", section on 'Long-acting muscarinic
agents' and "Management of refractory chronic obstructive pulmonary disease", section on
'Phosphodiesterase inhibitors' and "Management of refractory chronic obstructive pulmonary disease",
section on 'Mucoactive agents' and "Management of stable chronic obstructive pulmonary disease", section
on 'LABA plus inhaled glucocorticoid'.)
Pulmonary rehabilitation — While pulmonary rehabilitation is associated with a number of benefits in
terms of exercise tolerance and quality of life, the effect on COPD exacerbations and rehospitalization is
less clear and may be dependent on timing relative to hospitalization [63].
In a systematic review, participation in pulmonary rehabilitation immediately after a hospitalization (within
four weeks) reduced rehospitalization (odds ratio 0.24, 95% CI 0.07-0.88), but significant heterogeneity was
noted among studies [63]. Participation in pulmonary rehabilitation more than four weeks after an
exacerbation does not appear to reduce exacerbations, although it has other important benefits.
In a randomized trial, 389 patients hospitalized with an acute exacerbation of COPD were assigned to a six
week course of rehabilitation starting within 48 hours of admission or usual care [64]. Early rehabilitation did
not reduce the risk of subsequent readmission or enhance recovery. Furthermore, the rehabilitation group
had a higher one-year mortality (odds ratio 1.74, 95% CI 1.05-2.88). While the cause of increased mortality

13. was unclear, these data suggest that pulmonary rehabilitation should not be initiated during an acute
illness.
Action plan — A COPD exacerbation "action plan" may help patients mitigate the severity of
exacerbations. Approximately two-thirds of patients know when an exacerbation of COPD is imminent
because symptoms tend to be similar from one exacerbation to another [65]. An action plan encourages
early intervention by giving patients guidelines on how to recognize an exacerbation, how to change their
medication regimen accordingly, and when to contact their healthcare provider.
A systematic review and meta-analysis of seven randomized, controlled trials (1550 participants with
moderate to severe airflow limitation) revealed that use of an action plan reduced hospitalizations and
emergency department visits over the subsequent 12 months and increased the use of antibiotics and
glucocorticoids [66]. Action plans were associated with a small improvement in quality of life (St. George's
Respiratory Questionnaire (SGRQ), but no significant benefit in mortality.
In contrast, the role of a comprehensive COPD management program including such action plans has been
questioned since a 2012 randomized trial was terminated early for excess mortality in the "comprehensive
management program" arm [63,67]. Importantly, reasons for the excess mortality in this trial were not clear
and further study of the issue is needed.
Prophylactic antibiotics — Prevention of infection, a precipitant of exacerbations of COPD, is discussed
separately. (See "Management of infection in exacerbations of chronic obstructive pulmonary disease",
section on 'Prophylactic antibiotics'.)
Potential benefit of beta-blockers — Preliminary observational data suggest that therapy with selective
beta-blockers for comorbid cardiovascular disease is associated with a reduction in COPD exacerbations
[68,69]. A meta-analysis of 15 observational studies found that beta-blocker use was associated with a
decrease in exacerbations (relative risk 0.63, 95% CI 0.57-0.71) and a decrease in mortality (relative risk
0.72, 95% CI 0.63-0.83) [68]. A subsequent observational study followed 3464 patients with COPD
(severity GOLD class 2 to 4) for a median duration of 2.1 years [69]. Beta-blocker use was associated with
a significantly lower risk of exacerbations (incidence risk ratio 0.73, 95% CI 0.60-0.90), but no decrease in
mortality.
Further study with a randomized trial is needed to determine whether beta-blockers can improve COPD
outcomes in this setting. (See "Management of the patient with COPD and cardiovascular disease".)
Ineffective interventions — High dose vitamin D supplementation and statins (hydroxymethylglutaryl
[HMG] CoA reductase inhibitors) were not found to diminish COPD exacerbations, although they may have
other health benefits. (See "Vitamin D and extraskeletal health" and "Vitamin D deficiency in adults:
Definition, clinical manifestations, and treatment" and "Statins: Possible noncardiovascular
benefits"and "Management of low density lipoprotein cholesterol (LDL-C) in secondary prevention of
cardiovascular disease".)
The effect of high dose vitamin D supplementation on the incidence of COPD exacerbations was assessed
in patients with moderate or more severe COPD who were randomly assigned to take vitamin D 100,000 IU
or placebo orally every four weeks for a year [70]. The median time to first exacerbation did not differ
between the groups, nor did exacerbation rates, FEV1, hospitalization, quality of life, or death. However,
patients with severe vitamin D deficiency (serum 25-[OH] D levels <10 ng/mL) at baseline experienced a
significant reduction in exacerbations. Further research is needed to determine whether daily dosing of
vitamin D supplementation for a longer period would be beneficial and whether this effect is dependent on
the baseline vitamin D level [71].

14. In observational studies of COPD, statins have been associated with a reduced rate and severity of
exacerbations, rate of hospitalizations, and mortality [72-75]. However, these beneficial effects were not
supported in a trial that randomly assigned 885 participants with COPD, but without other indications or
contraindications for statin therapy, to simvastatin 40 mg daily or placebo for up to 36 months [76].
Simvastatin did not reduce the rate of exacerbations or the time to first exacerbation. (See "Management of
elevated low density lipoprotein-cholesterol (LDL-C) in primary prevention of cardiovascular
disease"and "Management of low density lipoprotein cholesterol (LDL-C) in secondary prevention of
cardiovascular disease".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected
countries and regions around the world are provided separately. (See "Society guideline links: Chronic
obstructive pulmonary disease".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The
Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the
5th
to 6th
grade reading level, and they answer the four or five key questions a patient might have about a
given condition. These articles are best for patients who want a general overview and who prefer short,
easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and
more detailed. These articles are written at the 10th
to 12th
grade reading level and are best for patients who
want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Chronic bronchitis (The Basics)" and "Patient education:
Medicines for chronic obstructive pulmonary disease (COPD) (The Basics)")
●Beyond the Basics topics (see "Patient education: Chronic obstructive pulmonary disease (COPD)
treatments (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●A table to assist with emergency management of severe exacerbations of COPD is provided (table
1).
●An exacerbation of COPD is characterized by an acute increase in symptoms beyond normal day-to-
day variation that leads to a change in medication. (See 'Introduction' above.).
●We recommend that all patients having a COPD exacerbation receive inhaled short-acting
bronchodilator therapy (Grade 1B). Short-acting beta-adrenergic agonists (SABA,
eg, albuterol, levalbuterol) are the mainstay of therapy; a short-acting anticholinergic agent
(eg, ipratropium) may be used as an alternative, or in combination with the SABA. For more severe
exacerbations, the combination is usually preferred. (See 'Beta adrenergic agonists' above
and 'Anticholinergic agents' above.)
●We recommend that all patients having a COPD exacerbation receive systemic glucocorticoids
(Grade 1A). A reasonable dose for patients not requiring intensive care unit admission
is prednisone 40 to 60 mg orally once daily, or the equivalent, for 5 to 14 days. (See 'Systemic
glucocorticoids' above.)
●Antibiotics are indicated for many patients having a COPD exacerbation. (See "Management of
infection in exacerbations of chronic obstructive pulmonary disease", section on 'Summary and
recommendations' and "Evaluation for infection in exacerbations of chronic obstructive pulmonary
disease", section on 'Summary and recommendations'.)

15. ●Mucoactive agents, methylxanthines, and mechanical techniques to augment sputum clearance have
not been shown to confer benefit for COPD exacerbations. (See 'Treatments without documented
benefit' above.)
●Patients with hypoxemia due to an exacerbation of COPD should receive supplemental oxygen. We
suggest that supplemental oxygen be titrated to a target of 88 to 92 percent pulse oxygen saturation,
rather than using high-flow, untitrated oxygen (Grade 2B). (See 'Oxygen therapy' above.)
●Noninvasive ventilation (NIV) improves numerous clinical outcomes and is the preferred method of
ventilatory support in many patients with an acute exacerbation of COPD. Invasive mechanical
ventilation is required in patients with respiratory failure who fail NIV, do not tolerate NIV, or who have
contraindications to NIV. Both NIV and invasive mechanical ventilation for patients with an
exacerbation of COPD are discussed separately. (See "Noninvasive ventilation in acute respiratory
failure in adults" and "Invasive mechanical ventilation in acute respiratory failure complicating chronic
obstructive pulmonary disease".)
●Several measures have been shown to reduce COPD exacerbations, including smoking cessation,
pulmonary rehabilitation, proper use of medications (including metered dose inhaler technique), and
vaccination against seasonal influenza and pneumococcus. (See 'Prevention' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
GRAPHICS
Rapid overview: Emergency management of severe COPD exacerbations
Clinical features
Features of COPD exacerbation: Diffuse wheezing, distant breath sounds, barrel-shaped chest, tachypnea, tachycardia, smoking >20 pack
years
Features of severe respiratory insufficiency: Use of accessory muscles; brief, fragmented speech; inability to lie supine; profound
diaphoresis; agitation; asynchrony between chest and abdominal motion with respiration; failure to improve with initial emergency treatment
Features of impending respiratory arrest: Inability to maintain respiratory effort, cyanosis, hemodynamic instability, and depressed mental
status
Features of cor pulmonale: Jugular venous distension, prominent left parasternal heave, peripheral edema
COPD exacerbations are most often precipitated by infection (viral or bacterial)
Severe respiratory distress in a patient with known or presumed COPD can be due to an exacerbation of COPD or a comorbid process, such
as acute coronary syndrome, decompensated heart failure, pulmonary embolism, pneumonia, pneumothorax, sepsis
Management
Assess patient's airway, breathing, and circulation; secure as necessary
Provide supplemental oxygen to target a pulse oxygen saturation of 88 to 92% or PaO2 of 60 to 70 mmHg (7.98 to 9.31 kPa); Venturi mask
can be useful for titrating FiO2; high FiO2 usually not needed and can contribute to hypercapnia (high FiO2 requirement should prompt
consideration of alternative diagnosis [eg, PE])
Determine patient preferences regarding intubation based on direct questioning or advance directive whenever possible
Provide combination of aggressive bronchodilator therapy and ventilatory support (NPPV or invasive ventilation)

16. Noninvasive positive pressure ventilation (NPPV): Appropriate for the majority of patients with severe exacerbations of COPD unless
immediate intubation is needed or NPPV is otherwise contraindicated
Contraindications to NPPV include: Severely impaired consciousness, inability to clear secretions or protect airway, high aspiration risk
Initial settings for bilevel NPPV: 8 cm H2O inspiratory pressure (may increase up to 15 cm H2O if needed to aid ventilation); 3 cm H2O
expiratory pressure
Administer bronchodilators via nebulizer or MDI: Nebulizer usually requires interruption of NPPV; MDIs can be delivered in line using
adaptor (see dosing below)
Obtain ABG after two hours of NPPV and compare with baseline: Worsening or unimproved gas exchange and pH <7.25 are indications for
invasive ventilation
Tracheal intubation and mechanical ventilation: Indicated for patients with acute respiratory failure, hemodynamic instability (eg, heart rate
<50/minute, uncontrolled arrhythmia) and those in whom NPPV is contraindicated or who fail to improve with NPPV and aggressive
pharmacotherapy
Rapid sequence induction (eg, etomidate, ketamine, or propofol)
Intubate with #8 endotracheal tube (8 mm internal diameter) or larger, if possible
Initial ventilator settings aim to maintain adequate oxygenation and ventilation while minimizing elevated airway pressures: SIMV, tidal
volume 6 to 8 mL/kg, respiratory rate 10 to 12/minute, inspiratory flow rate 60 L/min (increase if needed to enable longer expiratory phase),
PEEP 5 cm H2O. May need to tolerate elevated PaCO2 to avoid barotrauma (ie, permissive hypercapnia). In patients with chronic
hypercapnia, aim for PaCO2 close to baseline.
Administer inhaled bronchodilator therapy: Usually via MDI with in-line adaptor (see dosing below)
Diagnostic testing
Assess oxygen saturation with continuous pulse oximetry
Obtain ABG in all patients with severe COPD exacerbation
ETCO2 monitoring (capnography) has only moderate correlation with arterial PaCO2 in COPD exacerbations
Do not assess peak expiratory flow or spirometry in acute severe COPD exacerbations as results are not accurate
Obtain portable chest radiograph: Look for signs of pneumonia, acute heart failure, pneumothorax
Obtain complete blood count, electrolytes (Na+, K+, Cl–, HCO3–), BUN, and creatinine; also obtain cardiac troponin, BNP, or NT-proBNP,
if diagnosis is uncertain
Test for influenza infection during influenza season
Obtain ECG: Look for arrhythmia, ischemia, cor pulmonale
Pharmacotherapy
Inhaled beta agonist: Albuterol 2.5 mg diluted to 3 mL via nebulizer or 4 to 8 inhalations from MDI every hour
Inhaled anticholinergic agent: Ipratropium 500 micrograms via nebulizer or 4 to 8 inhalations from MDI every four hours
Intravenous glucocorticoid (eg, methylprednisolone 60 mg to 125 mg IV, repeat every 6 to 12 hours)

17. Antibiotic therapy*: Appropriate for majority of severe COPD exacerbations; select antibiotic based on likelihood of particular pathogens
(eg, Pseudomonas risk factors¶
, prior sputum cultures, local patterns of resistance)
 No Pseudomonas risk factor(s)¶
: Ceftriaxone 1 to 2 grams IV, OR levofloxacin 750 mg IV or orally, OR moxifloxacin 400 mg IV or
orally
 Pseudomonas risk factor(s)¶
: Levofloxacin 750 mg IV or orally, OR piperacillin-tazobactam 4.5 grams IV, OR cefepime 1 to 2 grams
IV, OR ceftazidime 1 to 2 grams IV
Antiviral therapy (influenza suspected)*: Oseltamivir 75 mg orally every 12 hours OR peramivir 600 mg IV once (for patients unable to take
oral medication)
Monitoring
Perform continual monitoring of oxygen saturation, blood pressure, heart rate, respiratory rate
Close monitoring of respiratory status
Continuous ECG monitoring
Monitor blood glucose
Disposition
Criteria for ICU admission include:
 Patients with high-risk comorbidities (pneumonia, cardiac arrhythmia, heart failure, diabetes mellitus, renal failure, liver failure)
 Continued need for NPPV or invasive ventilation
 Hemodynamic instability
 Need for frequent nebulizer treatments or monitoring
COPD: chronic obstructive pulmonary disease; PaO2: arterial tension of oxygen; FIO2: fraction of inspired oxygen; PE:
pulmonary embolism; NPPV: noninvasive mechanical ventilation; MDI: metered dose inhaler; ABG: arterial blood gas;
SIMV: synchronized intermittent mechanical ventilation; PEEP: positive end-expiratory pressure; PaCO2: arterial tension
of carbon dioxide; ETCO2: end-tidal carbon dioxide; BUN: blood urea nitrogen; BNP: brain natriuretic peptide; NT-
ProBNP: N-terminal pro-BNP; ECG: electrocardiogram; IV: intravenous; ICU: intensive care unit.
* Doses shown are for patients with normal renal function. Some agents require dose adjustment for renal impairment;
refer to separate UpToDate algorithms of antibiotic treatment of exacerbations of COPD.
¶ Pseudomonas infection risk factors: Frequent administration of antibiotics (four or more courses over the past year);
recent hospitalization (two or more days duration in the past 90 days); isolation of Pseudomonas during a previous
hospitalization; severe underlying COPD (FEV1 <50 percent predicted).
Graphic 65420 Version 4.0
Multidimensional assessment of COPD
GOLD: Severity of airflow limitation (based on postbronchodilator FEV1)
Stage Severity FEV1 (percent predicted)

18. In patients with FEV1/FVC <0.7:*
GOLD 1 Mild ≥80
GOLD 2 Moderate 50 to 79
GOLD 3 Severe 30 to 49
GOLD 4 Very severe <30
GOLD: Assessment of symptoms and risk of exacerbations
Exacerbations/hospitalizations
Symptom assessment
mMRC¶
0 to 1; CAT <10Δ
mMRC ≥2; CAT ≥10
0 or 1 exacerbations without hospitalization A B
≥2 exacerbations or ≥1 hospitalization C D
COPD: chronic obstructive pulmonary disease; FEV1: forced expiratory volume in one second; FVC: forced vital capacity;
CAT: COPD Assessment Test; mMRC: modified Medical Research Council (mMRC) dyspnea scale.
* The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (www.goldgopd.org) prefer the threshold
of <0.7 to the alternative of the fifth percentile LLN for FEV1/FVC.
¶ mMRC dyspnea scale: Refer to UpToDate graphic.
Δ http://www.catestonline.org.
From the Global Strategy for the Diagnosis, Management and Prevention of COPD 2017, © Global Initiative for Chronic
Obstructive Lung Disease (GOLD), www.goldcopd.org. Adapted with permission.
Graphic 82690 Version 9.0
Relative frequency of bacterial pathogens isolated from 14 antibiotic comparison
trials in exacerbations of chronic obstructive pulmonary disease*
Pathogen Percentage of bacterial isolates (range)
Haemophilus influenzae 13 to 50
Moraxella catarrhalis 9 to 21
Streptococcus pneumoniae 7 to 26
Pseudomonas aeruginosa 1 to 13
* Enterobacteriaceae have been isolated from the respiratory tract of 3 to 19 percent of patients with chronic obstructive
pulmonary disease (COPD) exacerbations and Staphylococcus aureus has been isolated from the respiratory tract of 1 to
20 percent of patients with COPD exacerbations, but their pathogenic significance in this setting has not been
defined. Haemophilus parainfluenzae has been isolated from the respiratory tract of 2 to 32 percent of patients with
COPD exacerbations, but these organisms are unlikely to cause COPD exacerbations.
Modified with permission from the American Thoracic Society. Copyright © 2004 American Thoracic Society. Sethi S.
Bacteria in exacerbations of chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society 2004;
1:109. Official Journal of the American Thoracic Society.

19. Graphic 70203 Version 9.0
Kaplan-Meier estimates of the probability of remaining relapse-free at 30 days for
outpatients with acute exacerbations of COPD treated with prednisone or placebo
Tick marks represent censored data. p=0.04 by the log-rank test.
Data from: N Engl J Med 2003; 348:2623.
Graphic 60719 Version 1.0
Outpatient management of exacerbations of COPD

20. COPD: chronic obstructive pulmonary disease.
* Pseudomonas risk factors:
 Advanced COPD
 Previous isolation of Pseudomonas from sputum
 Concomitant bronchiectasis
 Frequent administration of antibiotics
 Frequent hospital admissions
 Systemic glucocorticoid use
Adapted with permission from: Sethi S, Murphy TF. Acute exacerbations of chronic bronchitis: New developments
concerning microbiology and pathophysiology--impact on approaches to risk stratification and therapy. Infect Dis Clin N
Am 2004; 18:861. Illustration used with permission of Elsevier Inc. All rights reserved. Copyright © 2004 Elsevier Inc.
Graphic 66357 Version 8.0
Comparison of representative glucocorticoid preparations
Equivalent doses*
(mg)
Relative anti-
inflammatory
activity
Relative
mineralocorticoid
activity
Duration of
action
(hours)
Hydrocortisone
(cortisol)
20 1 1 8 to 12
Cortisone acetate 25 0.8 0.8 8 to 12
Prednisone 5 4 0.8 12 to 36
Prednisolone 5 4 0.8 12 to 36
Methylprednisolone 4 5 0.5 12 to 36
Triamcinolone 4 5 0 12 to 36
Fludrocortisone Not used for an anti-
inflammatory effect
10 125¶
12 to 36
Dexamethasone 0.75 30 0 36 to 72
Prednisone and prednisolone are potent glucocorticoids and weak mineralocorticoids. Dexamethasone has no
mineralocorticoid effect.
* Equivalent anti-inflammatory dose shown is for oral or intravenous (IV) administration. Relative potency for intra-
articular or intramuscular administration may vary considerably.
¶ Glucocorticoid doses which provide a mineralocorticoid effect that is approximately equivalent to 0.1 mg fludrocortisone
are prednisone or prednisolone 50 mg or hydrocortisone 20 mg.
Data from:
1. Schimmer BP, Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors
of the synthesis and actions of adrenocortical hormones. In: The Pharmacological Basis of Therapeutics, 11th ed,
Brunton LL, Lazo JS, Parker KL (Eds), McGraw Hill, NY. p.1587. Copyright © 2006.

21. 2. Donohoue PA. The adrenal gland and its disorders. Kappy MS, Allen DB, Geffner ME (Eds), Charles C Thomas,
Springfield, IL. p.403. Copyright © 2005 Charles C Thomas, Publisher, Ltd.
Graphic 64138 Version 18.0
Antibiotic treatment of exacerbations of COPD in hospitalized patients
The doses recommended above are intended for patients with normal renal function; the doses must be adjusted
in patients with renal insufficiency.
COPD: chronic obstructive pulmonary disease.
* Pseudomonas risk factors:
 Advanced COPD
 Previous isolation of Pseudomonas from sputum
 Concomitant bronchiectasis
 Frequent administration of antibiotics
 Frequent hospital admissions
 Systemic glucocorticoid use