COPD EXACERBATIONS: MANAGEMENT

AUTHOR: James K Stoller, MD, MS | SECTION EDITOR: Peter J Barnes, DM, DSc, FRCP, FRS | DEPUTY EDITOR: Paul Dieffenbach,
MD; Contributor Disclosures.

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current
through: May 2023. This topic last updated: Dec 30, 2022.

Practice Changing UpDate  (See "COPD exacerbations: Prognosis, discharge plan-

ning, and prevention".)
PULMONARY AND CRITICAL CARE MEDICINE (August 2022)
 (See "Evaluation for infection in exacerbations of
Intravenous magnesium in severe COPD exacerbation chronic obstructive pulmonary disease".)
 (See "Management of infection in exacerbations of
 For patients having an acute COPD exacerbation who ex- chronic obstructive pulmonary disease".)
perience limited benefit from short-acting inhaled bron-  (See "Stable COPD: Overview of management".)
chodilators, we suggest intravenous magnesium (Grade
2C). TRIAGE TO HOME OR HOSPITAL

Intravenous magnesium has short-acting bronchodilator ac- An important step in the initial evaluation is to determine
tivity that is helpful for severe asthma attacks, but it has not whether the patient needs hospitalization or can be safely
previously been recommended for chronic obstructive pul- managed at home (algorithm 1) [1,3]. More than 80 percent
monary disease (COPD). A new systematic review and meta- of exacerbations of COPD can be managed on an outpatient
analysis found a decrease in hospitalization rates with emer- basis, sometimes after initial treatment in the office or emer-
gency department intravenous magnesium administration gency department. If the exacerbation appears life-threaten-
compared with placebo [1]. The effect size is similar to or ing or if there are indications for ventilatory support (eg, hy-
better than that seen in the setting of asthma exacerbation. poxemic or hypercapnic respiratory failure), the patient
Based on these data, we now suggest intravenous magne- should be admitted to the intensive care unit as quickly as
sium for patients with severe COPD exacerbations who are possible. (See 'Ventilatory support' below.)
not improving with inhaled bronchodilator therapy. (See
Other criteria that might lead to a decision to hospitalize the
"COPD exacerbations: Management", section on 'Magne-
patient have been proposed in the Global Initiative for
sium sulfate'.)
Chronic Obstructive Lung Disease (GOLD) guidelines and in-
INTRODUCTION ternational consensus statements include [1,2,4]:

The Global Initiative for Chronic Obstructive Lung Disease  Inadequate response to outpatient or emergency de-
(GOLD), a report produced by the National Heart, Lung, and partment management
Blood Institute (NHLBI) and the World Health Organization  Onset of new signs (eg, cyanosis, altered mental status,
(WHO), defines an exacerbation of chronic obstructive pul- peripheral edema)
monary disease (COPD) as "an event characterized by dysp-  Marked increase in intensity of symptoms over baseline
nea and/or cough and sputum that worsens over ≤14 days, (eg, new onset resting dyspnea) accompanied by in-
which may be accompanied by tachypnea and/or tachycar- creased oxygen requirement
dia and is often associated with increased local and systemic  Signs of respiratory distress (use of accessory respira-
inflammation caused by airway infection, pollution, or other tory muscles or paradoxical chest wall movements, or
insult to the airways" [1,2]. This generally includes an acute both)
change in one or more of the following cardinal symptoms:  Serious comorbidities including pneumonia, cardiac ar-
rhythmia, heart failure, diabetes mellitus, renal failure,
 Cough increases in frequency and severity
or liver failure
 Sputum production increases in volume and/or changes
 Hemodynamic instability
character
 Insufficient home support
 Dyspnea increases
Prior guidelines have also included severe airflow limitation,
The management of patients with exacerbations of COPD is
a history of frequent or severe exacerbations, and frailty as
discussed here. A table to assist with emergency manage-
factors associated with increased risk for severe exacerba-
ment of severe acute exacerbations of COPD is provided (ta-
tions. These factors may also be considered in triaging COPD
ble 1). The diagnosis and treatment of infection in exacerba-
patients for hospital admission.
tions and the management of stable COPD are discussed sep-
arately. Intensive home care, which generally includes nurse visits,
home oxygen, and physical therapy, may be an alternative to
 (See "COPD exacerbations: Clinical manifestations and
hospitalizations in certain locations (eg, United Kingdom, Eu-
evaluation".)
rope) for selected patients with an exacerbation of COPD [5-
9]. A meta-analysis of seven trials noted that intensive home
care resulted in equivalent clinical outcomes and substantial The usual dose of ipratropium for an acute exacerbation of
cost savings compared to hospitalization [10]. However, COPD is two inhalations by MDI every four to six hours. The
these trials excluded sicker patients with an impaired level usual dose of a combination ipratropium and albuterol SMI
of consciousness, respiratory acidosis (arterial pH <7.35), is one inhalation by SMI (Respimat) every four to six hours.
acute electrocardiographic or chest radiographic changes, or When administering by nebulizer, the dose of ipratropium is
coexisting medical morbidities. Although care at home is fea- 0.5 mg/2.5 mL (0.02 percent; one unit-dose vial) every 6 to 8
sible in highly selected patients without these characteris- hours. Alternatively, ipratropium 0.5 mg/2.5 mL can be com-
tics, implementation requires a dedicated support team to bined with albuterol 2.5 mg/0.5 mL (total 3 mL). (See 'Beta
conduct ongoing clinical assessments and provide home adrenergic agonists' above.)
care. In general, home management of the patient who sat-
The evidence for adding a SAMA to SABA comes from a few
isfies criteria for hospitalization should be considered infre-
studies in which combination therapy produced bronchodi-
quently and only when optimal home care is available.
lation in excess of that achieved by either agent alone in pa-
HOME OR OFFICE MANAGEMENT OF COPD EXACERBA- tients with a COPD exacerbation or stable COPD [13,14].
TIONS However, this finding has not been universal, and other stud-
ies not found an additive effect in COPD exacerbations
Home management of COPD exacerbations generally in-
[15,16]. A longer duration of bronchodilation has been ob-
cludes intensification of bronchodilator therapy and initia-
served with the addition of ipratropium to albuterol in stable
tion of a course of oral glucocorticoids; oral antibiotics are
COPD [17].
added based on individual characteristics.
For patients who have a history of benign prostatic hypertro-
Beta adrenergic agonists — We recommend that all patients
phy or prior urinary retention, the addition of ipratropium to
with a COPD exacerbation receive inhaled short-acting bron-
a long-acting muscarinic antagonist (LAMA; eg, aclidinium,
chodilator therapy. Inhaled short-acting beta (adrenergic)
glycopyrrolate, tiotropium, umeclidinium) may increase the
agonists (SABA; eg, albuterol, levalbuterol) are the mainstay
risk of acute urinary retention, although data are conflicting.
of therapy for an acute exacerbation of COPD because of
(See "Role of muscarinic antagonist therapy in COPD", sec-
their rapid onset of action and efficacy in producing bron-
tion on 'Acute urinary retention'.)
chodilation [1,11,12].
Continued use of long-acting bronchodilators during exac-
Albuterol is sometimes combined with an additional short-
erbations — While continuation of ongoing therapy with
acting bronchodilator (the short-acting muscarinic antago-
long-acting beta agonists (LABAs) or LAMAs has not been
nist [SAMA] ipratropium) in a soft mist inhaler (SMI). (See
specifically studied, the Global Initiative for Chronic Obstruc-
'Muscarinic antagonists' below.)
tive Lung Disease (GOLD) strategy advises their continuation
Occasional patients with more severe COPD or difficulty with [1].
inhaler technique may take albuterol or levalbuterol by neb-
Oral glucocorticoid therapy — For outpatients with a COPD
ulization at home. The usual dose of albuterol for nebuliza-
exacerbation characterized by breathlessness that interferes
tion is 2.5 mg (diluted to a total of 3 mL with sterile normal
with daily activities, systemic glucocorticoid therapy appears
saline, resulting in 2.5 mg/3 mL or 0.083 percent). For COPD
to have a small but beneficial effect with a reduction in rate
exacerbations, this dose can be repeated every hour for two
of relapse. Our practice reflects current guidelines, which
to three doses and then every two to four hours as needed
suggest using a dose that is the equivalent of prednisone 40
based on the patient’s response. Levalbuterol dosing for
mg per day for 5 to 14 days [1,3,12]. Occasional patients may
nebulization is 0.63 to 1.25 mg (diluted to 3 mL) and admin-
benefit from a higher dose or a longer course depending on
istered at the same intervals as noted for albuterol.
the severity of the exacerbation and response to prior
Patients who already have a nebulizer at home frequently courses of glucocorticoids.
report that bronchodilator administration via nebulizer is
The benefit of oral glucocorticoids in the outpatient manage-
helpful during COPD exacerbations. However, most studies
ment of COPD exacerbations was examined in a randomized
have not supported a greater effect from nebulizer treat-
trial of 147 patients discharged from the emergency depart-
ments over properly administered metered dose inhaler
ment after presenting with an acute exacerbation of COPD
medication. Nebulized albuterol can be combined with
[18]. Patients received oral prednisone (40 mg) or placebo
ipratropium. (See 'Beta adrenergic agonists' below and "De-
for 10 days. Patients who received prednisone were less
livery of inhaled medication in adults", section on 'Home use'
likely to return to the emergency department or their clini-
and 'Muscarinic antagonists' below.)
cian with increasing dyspnea within 30 days (27 versus 43
Muscarinic antagonists — Ipratropium bromide, an inhaled percent, p = 0.05) (figure 1). In addition to a lower rate of
SAMA (also known as a short-acting anticholinergic agent) is relapse (the primary end point of the study), prednisone
often used in combination with inhaled SABA [1]. It is gener- therapy was associated with decreased dyspnea and a
ally not used as monotherapy due to the longer time to onset greater improvement in forced expiratory volume in one sec-
of action compared with SABAs. (See 'Beta adrenergic ago- ond (FEV1; 34 versus 15 percent) on day 10.
nists' above.)
The REDUCE trial showed that a five-day course of varies based on both patient-specific factors and local
methylprednisolone (day one intravenously, orally thereaf- resistance patterns (algorithm 2).
ter) was noninferior to a 14-day course regarding the risk of  Antiviral agents – For patients with a COPD exacerba-
recurrent exacerbation over six months of follow-up [19]. tion during influenza season, we screen for influenza in-
Although over 90 percent of the patients in the trial were in- fection, with a preference for molecular assays over
itially admitted, these findings can likely be extrapolated to rapid antigen tests. If influenza infection is suspected,
the less ill outpatient population. (See 'Systemic glucocorti- we initiate empiric antiviral therapy without waiting for
coids' below.) laboratory confirmation. (See "Management of infec-
tion in exacerbations of chronic obstructive pulmonary
Patients should be warned of potential adverse effects of
disease", section on 'Respiratory virus treatment' and
systemic glucocorticoids that may require mitigation, partic-
"Seasonal influenza in adults: Clinical manifestations
ularly hyperglycemia (in patients with diabetes mellitus),
and diagnosis".)
fluid retention, and hypertension. (See "Major side effects of
Severe acute respiratory syndrome coronavirus (SARS-
systemic glucocorticoids".)
CoV)-2, the cause of coronavirus disease-2019 (COVID-
Inhaled glucocorticoids — A few trials have examined high- 2019), can mimic or result in a COPD exacerbation.
dose budesonide as an alternative to systemic glucocorti- When an exacerbation of COPD occurs in the course of
coids for COPD exacerbations, but have largely studied hos- COVID-19, the usual guidelines for prompt initiation of
pitalized patients who did not require intensive care unit systemic glucocorticoids for a COPD exacerbation
(ICU) admission and have examined physiologic outcomes, should be followed, as delaying therapy can increase the
such as FEV1 improvement [20,21]. Further study is needed risk of a life-threatening exacerbation. Patients with
to establish efficacy before this strategy is broadly used. COPD are at increased risk for severe respiratory illness
associated with COVID-19 and therefore qualify for pri-
In a systematic review and meta-analysis (9 studies, nearly oritized outpatient therapy. Diagnosis and treatment of
1000 patients), high-dose nebulized budesonide (4 to 8 COVID-19 are discussed separately. (See "COVID-19: Di-
mg/day) had a similar effect to oral glucocorticoids in pa- agnosis" and 'Antiviral and antimicrobial agents' below
tients hospitalized for a COPD exacerbation for change in and "COVID-19: Management of adults with acute ill-
FEV1 (weighted mean difference 0.05 L/sec [95% CI -0.01– ness in the outpatient setting".)
0.12]) or arterial tension of carbon dioxide (PaCO2), but was
slightly inferior for oxygenation improvement [20]. Adjunctive care — For patients being managed at home,
supportive care often includes advice regarding cigarette
A separate trial in 109 out-patients with a COPD exacerba- smoking cessation and medication adherence. Some pa-
tion found that use of the high-dose combination inhaler, tients may need nutritional support and a review of goals of
budesonide-formoterol (320 mcg-9 mcg) 1 inhalation four care. Patients who have a new requirement for supple-
times daily, resulted in a similar change in FEV1 compared mental oxygen are usually managed in the hospital, at least
with oral prednisolone 30 mg daily plus inhaled formoterol initially. (See 'Triage to home or hospital' above and "Over-
[22]. view of smoking cessation management in adults" and "Mal-
nutrition in advanced lung disease" and "Pulmonary rehabil-
Antimicrobial therapy
itation".)
 Antibiotics – To try to maximize the benefit of antibiotic
EMERGENCY DEPARTMENT AND HOSPITAL MANAGEMENT
therapy, clinical practice guidelines recommend antibi-
otic therapy only for those patients who are most likely Similar to at-home management, the major components of
to have bacterial infection or are most ill. The role of an- emergency department or in-hospital management of exac-
tibiotics in exacerbations of COPD, including antibiotic erbations of COPD include reversing airflow limitation with
selection, is discussed in detail separately. (See "Man- inhaled short-acting bronchodilators and systemic glucocor-
agement of infection in exacerbations of chronic ob- ticoids, treating infection, ensuring appropriate oxygena-
structive pulmonary disease", section on 'Summary and tion, and averting intubation and mechanical ventilation
recommendations' and "Evaluation for infection in exac- [1,23]. An approach to emergency management of severe
erbations of chronic obstructive pulmonary disease", exacerbations of COPD is summarized in the table (table 1).
section on 'Summary and recommendations'.)
In brief, the GOLD strategy recommends empiric antibi- For patients who are admitted to the hospital, the severity
otics for patients with COPD exacerbations who have in- of the exacerbation is classified based on clinical signs [1,2]:
creased sputum purulence and either increased sputum
 No respiratory failure – Respiratory rate ≤24 breaths
volume or increased dyspnea, or for patients who re-
per minute; heart rate (HR) <95 beats per minute; no
quire ventilatory assistance [1]. Patients without these
use of accessory respiratory muscles; no change in men-
risk factors should not receive up-front antibiotic ther-
tal status; pulse oxygen saturation (SpO2) 88 to 92 per-
apy without radiographic or microbiologic evidence of
cent with Venturi mask 24 to 35 percent inspired oxygen
pulmonary infection. The choice of empiric therapy
(or equivalent); no hypercapnia.
 Acute nonlife-threatening respiratory failure – Respir- Oxygen therapy — Supplemental oxygen is a critical compo-
atory rate >24 breaths per minute; use of accessory nent of acute therapy. Administration of supplemental oxy-
muscles of respiration; no change in mental status; SpO2 gen should target an SpO2 of 88 to 92 percent or an arterial
88 to 92 percent with Venturi mask 24 to 35 percent (or oxygen tension (PaO2) of approximately 60 to 70 mmHg, to
equivalent); arterial tension of carbon dioxide (PaCO2) minimize the risk of worsening hypercapnia with excess sup-
50 to 60 mmHg or increased over baseline. plemental oxygen [1,23,24]. In two small randomized trials,
 Acute life-threatening respiratory failure – Respiratory titrating supplemental oxygen to SpO2 88 to 92 percent re-
rate >24 breaths per minute; use of accessory muscles sulted in a lower mortality compared with high-flow
of respiration; acute change in mental status; requiring (nontitrated) oxygen [24]. (See "The evaluation, diagnosis,
fraction of inspired oxygen (FiO2) ≥40 percent to main- and treatment of the adult patient with acute hypercapnic
tain SpO2 88 to 92 percent; PaCO2 increased compared respiratory failure".)
with baseline or >60 mmHg or associated with acidosis
There are numerous devices available to deliver supple-
(pH ≤7.25).
mental oxygen during an exacerbation of COPD:
Monitoring — In-hospital monitoring typically includes fre-
 Venturi masks permit a precise upper limit for the FiO2,
quent assessment of respiratory status (eg, respiratory rate
which may be preferable for patients at risk of hyper-
and effort, wheezing, pulse oxygen saturation), heart rate
capnia. Venturi masks can deliver an FiO2 of 24, 28, 31,
and rhythm, blood pressure, and also fluid status. Patients
35, 40, or 60 percent.
who require admission to the intensive care unit (ICU) should
 Nasal cannula can provide flow rates up to 6 L per mi-
have continuous monitoring of vital signs and oxygenation.
nute with an associated FiO2 of approximately 40 per-
Arterial blood gas measurement is performed to assess for
cent (table 2). They are more comfortable and conven-
respiratory acidosis (eg, prior hypercapnia, severe exacerba-
ient for the patient, especially during oral feedings.
tion, or deterioration of patient's respiratory status during
treatment), confirm the accuracy of pulse oxygen saturation,  When a higher FiO2 is needed, simple facemasks can
and to monitor known hypercapnia. (See "Simple and mixed provide an FiO2 up to 55 percent using flow rates of 6 to
acid-base disorders", section on 'Respiratory acid-base dis- 10 L per minute. However, variations in minute ventila-
orders'.) tion and inconsistent entrainment of room air affect the
FiO2 when simple facemasks (or nasal cannula) are used.
Supportive and palliative care — Supportive care for pa-  Non-rebreathing masks with a reservoir, one-way
tients hospitalized with an exacerbation of COPD includes valves, and a tight face seal can deliver an inspired oxy-
the following therapies, as needed: gen concentration up to 90 percent, but are generally
not needed in this setting.
General measures
 High-flow nasal cannula (HFNC) provide supplemental
 Cigarette smoking cessation – Hospitalization can oxygen (adjustable FiO2) at a high flow rate (up to 60
sometimes provide an opportunity for patients who L/min that results in a low level of continuous positive
continue to smoke to move towards cigarette smoking airway pressure. The specific indications for HFNC re-
cessation. Nicotine replacement therapy can help re- main unclear, and robust comparisons of HFNC with
duce symptoms of nicotine withdrawal during hospitali- noninvasive ventilation (NIV) in patients with COPD ex-
zation. (See "Overview of smoking cessation manage- acerbations are lacking [1,25,26]. (See "Heated and hu-
ment in adults", section on 'Hospitalized patients' and midified high-flow nasal oxygen in adults: Practical con-
"Pharmacotherapy for smoking cessation in adults".) siderations and potential applications".)
 Thromboprophylaxis – Hospitalization for exacerba-
A high FiO2 is generally not required to correct the hypox-
tions of COPD increases the risk for deep venous throm-
emia associated with exacerbations of COPD. Inability to cor-
bosis and pulmonary embolism [1]. For patients without
rect hypoxemia with a relatively low FiO2 (eg, 4 L/min by na-
a risk factor for bleeding who require ICU admission, we
sal cannula or 35 percent by mask) should prompt consider-
recommend pharmacologic thromboprophylaxis; for
ation of an additional cause of hypoxemia, such as pulmo-
those not requiring ICU admission, we suggest pharma-
nary emboli, acute respiratory distress syndrome, pulmo-
cologic thromboprophylaxis. Low molecular weight hep-
nary edema, or severe pneumonia. (See "Measures of oxy-
arin is generally preferred. Preventive measures are dis-
genation and mechanisms of hypoxemia".)
cussed in greater detail separately. (See "Prevention of
venous thromboembolic disease in acutely ill hospital- Adequate oxygenation (ie, to achieve an oxygen saturation
ized medical adults".) of 88 to 92 percent) must be assured, even if it leads to acute
 Nutritional support – Oral nutritional supplementation hypercapnia. Hypercapnia is generally well tolerated in pa-
may be of benefit for malnourished patients hospital- tients whose PaCO2 is chronically elevated. However, me-
ized with a COPD exacerbation. (See "Malnutrition in ad- chanical ventilation may be required if hypercapnia is asso-
vanced lung disease", section on 'Frequency of malnu- ciated with depressed mental status, profound acidemia, or
trition'.) cardiac dysrhythmias. (See 'Ventilatory support' below and
"The evaluation, diagnosis, and treatment of the adult
patient with acute hypercapnic respiratory failure" and "Ad- goals of care discussion with their physician and will have an
verse effects of supplemental oxygen", section on 'Accentu- advance directive in place. For those who do not have an ad-
ation of hypercapnia'.) vance directive, it is helpful for patients, their families, and
their healthcare providers to review the patient’s under-
Compared with oxygen-driven nebulization, air-driven nebu-
standing of their diagnosis and expected disease course, and
lization of inhaled medications is less likely to cause an in-
then reflect on the patient’s goals, values, and beliefs. This
crease in PaCO2 and is therefore preferred [27]. (See 'Beta
information is used to inform decision-making in the context
adrenergic agonists' below.)
of care that is medically reasonable and appropriate. (See
Ventilatory support — For patients who fail supportive ther- "Discussing goals of care" and "Advance care planning and
apy with oxygen and medications, ventilatory support is nec- advance directives" and "Palliative care for adults with non-
essary assuming this is consistent with the patient’s goals of malignant chronic lung disease" and "Palliative care: Issues
care (see 'Palliative care' below). HFNC is not routinely ad- in the intensive care unit in adults".)
ministered in patients with acute exacerbations of COPD, alt-
For patients with COPD, an important component of deci-
hough some experts administer it cautiously in this popula-
sion-making is whether intubation and mechanical ventila-
tion prior to the application of NIV. (See "Heated and humid-
tion are appropriate and desirable in the event of respiratory
ified high-flow nasal oxygen in adults: Practical considera-
failure. When discussing a potential trial of mechanical ven-
tions and potential applications".)
tilation for an exacerbation of COPD, parameters for discon-
●Noninvasive ventilation – NIV (also known as noninvasive tinuing mechanical ventilation should be included. The po-
positive pressure ventilation [NPPV]) refers to mechanical tential outcomes of intubation/mechanical ventilation
ventilation delivered through a noninvasive interface, such should be described to help the patient’s decision-making.
as a face mask, nasal mask, orofacial mask, or nasal prongs While prognostic uncertainty and variable trajectory of ill-
(nasal pillows). NIV reduces mortality and the intubation rate ness make communication about these issues difficult [28],
and is the preferred method of ventilatory support in many it is important to incorporate this uncertainty into advance
patients with an exacerbation of COPD [11]. care planning.

Most commonly, NIV is initiated in the emergency depart- Given the high one-year mortality rate after hospitalization
ment, intensive care unit (ICU), or a specialized respiratory for a COPD exacerbation, it may be appropriate to consider
unit to enable close monitoring, although this has not been a palliative care referral during or shortly after a hospitaliza-
formally studied and varies among hospitals. Patients who tion for COPD. Palliative care consultation can help explore
develop acute respiratory acidosis (PaCO2 >45 mmHg [6 kPa] the patient's understanding of their illness and prognosis, as-
or pH <7.35) are the subgroup who are most likely to benefit sess and manage symptoms (eg, dyspnea, anxiety, panic, de-
from an initial trial of NIV (typically with bilevel positive air- pression), discuss the patient's goals of care, place of death
way pressure). For other patients with nonhypercapnic res- preferences, and advance directives, and help implement
piratory failure due to COPD exacerbation, a trial of NIV is end-of-life care. (See "Palliative care for adults with nonma-
also appropriate, although the derived benefit may be con- lignant chronic lung disease" and "Assessment and manage-
siderably less. (See "Noninvasive ventilation in adults with ment of dyspnea in palliative care".)
acute respiratory failure: Benefits and contraindications".)
Initial pharmacologic therapy
A reasonable approach is to initiate bilevel NIV in a sponta-
Beta adrenergic agonists — We recommend that all patients
neously triggered mode with a backup respiratory rate (eg, 8
with an exacerbation of COPD receive prompt treatment
breaths/minute); typical initial settings include an inspira-
with an inhaled short-acting beta (adrenergic) agonist
tory positive airway pressure (IPAP) of 8 to 12 cm H2O and
(SABAs; eg, albuterol, levalbuterol) because of their rapid
an expiratory pressure (EPAP) of 3 to 5 cm H2O. NIV is dis-
onset of action and efficacy in producing bronchodilation in
cussed in detail separately. (See "Noninvasive ventilation in
COPD [1,3]. These medications may be administered via a
adults with acute respiratory failure: Practical aspects of ini-
nebulizer, metered dose inhaler (MDI) with a spacer device,
tiation".)
or dry powder inhaler (DPI) and may be combined with a
 Invasive ventilation – Invasive mechanical ventilation short-acting muscarinic antagonist (SAMA; eg, ipratropium)
should be administered when patients fail NIV, do not [1,13]. (See "Delivery of inhaled medication in adults" and
tolerate NIV, or have contraindications to NIV. Invasive "The use of inhaler devices in adults" and 'Muscarinic antag-
mechanical ventilation for acute respiratory failure due onists' below.)
to a COPD exacerbation is discussed separately. (See "In-
 Dose and administration – Typical doses of albuterol in
vasive mechanical ventilation in acute respiratory fail-
this setting are 2.5 mg (diluted to a total of 3 mL with
ure complicating chronic obstructive pulmonary dis-
sterile normal saline) by nebulizer or one to two inhala-
ease".)
tions (most commonly two, occasionally four; 90 mcg
Palliative care — The goals of palliative care are to prevent per inhalation) by MDI with a spacer every one hour for
and relieve suffering and aid in the end-of-life care of pa- two to three doses and then every two to four hours as
tients with advanced disease. Some patients may have had a needed, guided by the response to therapy [1]. In
 patients with potential viral infections resulting in COPD mixed with albuterol 2.5 mg in 3 mL and given every
exacerbation, particularly SARS-CoV-2, nebulized medi- hour for two or three doses and then every two to four
cations should ideally be avoided or limited to use in hours as needed. In patients with potential viral infec-
negative pressure rooms in order to decrease disease tions resulting in COPD exacerbation, particularly SARS-
spread. CoV-2, nebulized medications should ideally be avoided
In this setting, levalbuterol, which contains one of the or limited to use in negative pressure rooms in order to
enantiomers of albuterol called R-albuterol, is dosed decrease disease spread.
1.25 mg (diluted to a total of 3 mL with sterile saline) by Alternatively, a combination ipratropium-albuterol soft
nebulizer at the same frequency as albuterol. Levalbut- mist inhaler (SMI) can be used, 1 inhalation, approxi-
erol (45 mcg/actuation) by MDI is given one to two in- mately every hour for two to three doses and then every
halations (most commonly two, occasionally four) every two to four hours as needed, guided by the response to
one hour for two to three doses, then every two to four therapy [33]. Ipratropium is also available in an MDI that
hours as needed. For patients requiring mechanical ven- can be used with a spacer, 2 to 4 inhalations every hour
tilation, up to eight inhalations may be given if needed. for two to three doses, and then every two to four hours
Increasing the dose of nebulized albuterol to 5 mg does as needed. (See "Role of muscarinic antagonist therapy
not have a significant benefit on spirometry or clinical in COPD".)
outcomes [29]. Similarly, continuously nebulized beta  Efficacy – A systematic review identified a small number
agonists have not been shown to confer an advantage in of trials that compared a combination of SAMA (ipratro-
COPD and may increase adverse effects. When com- pium) plus SABA (albuterol, metaproterenol, fenoterol)
bined with ipratropium, albuterol 2.5 mg is mixed with with SABA alone and did not find an added benefit to
ipratropium bromide 0.5 mg in 3 mL. the combination when assessed at 90 minutes [16].
 MDI versus nebulizer – Despite evidence that MDI de- However, in stable COPD, the combination of SAMA plus
vices have equal efficacy during exacerbations of COPD, SABA provides superior bronchodilation compared with
many clinicians prefer nebulized therapy on the pre- SABA alone. Thus, this combination is often used to treat
sumption of more reliable delivery of drug to the airway COPD exacerbations.
[1]. We favor nebulized therapy because many patients
Magnesium sulfate — For patients who present with a se-
with COPD have difficulty using proper MDI technique in
vere exacerbation that is not responding promptly to short-
the setting of an exacerbation. Air-driven nebulizers are
acting inhaled bronchodilators, we suggest intravenous ad-
preferred over oxygen delivered nebulizers to minimize
ministration of a single dose of magnesium sulfate (2 g in-
the risk of increasing PaCO2 [27,30].
fused over 20 minutes). Intravenous magnesium sulfate has
 Efficacy – Placebo-controlled trials are lacking for SABAs
bronchodilator activity thought to arise from inhibition of
in acute COPD exacerbation, so the main evidence
calcium influx into airway smooth muscle cells [34]. The best
comes from long-term clinical experience and extrapo-
evidence for benefit in COPD exacerbations comes from a
lation from the treatment of asthma and stable COPD.
systematic review (3 studies, 170 participants) that found a
Studies comparing SABAs with SAMAs are limited, but
decrease in hospitalizations with intravenous magnesium
do not demonstrate a clear benefit to either medication
compared with placebo (odds ratio [OR] 0.45, 95% CI 0.23-
[16]. Combination therapy with albuterol and ipratro-
0.88) [35], which is similar to or better than the effect seen
pium is clearly superior to albuterol alone in stable
in severe asthma exacerbations [36]. (See "Acute exacerba-
COPD, but studies in acute exacerbations are limited
tions of asthma in adults: Emergency department and inpa-
[14,16]. Nonetheless, it is common practice to use the
tient management", section on 'Magnesium sulfate'.)
combination for COPD exacerbations.
Subcutaneous injection of SABAs (eg, terbutaline, epi- Intravenous magnesium has an excellent safety profile; how-
nephrine) carries a high risk for inotropic and chrono- ever, it is contraindicated in the presence of renal insuffi-
tropic adverse effects, such as arrhythmias or myocar- ciency, and hypermagnesemia can result in muscle weak-
dial ischemia, and is virtually never used for COPD exac- ness. (See "Hypermagnesemia: Causes, symptoms, and
erbations. treatment", section on 'Symptoms of hypermagnesemia'.)
It is not known whether a rapid-onset, long-acting beta
agonist, like indacaterol, would be a reasonable substi- Continuing long-acting bronchodilators — While continua-
tute for albuterol nebulizer treatments in patients not tion of ongoing therapy with long-acting beta agonists
already using indacaterol [31]. (LABAs) and/or long-acting muscarinic agents (LAMAs) has
not been specifically studied, the GOLD strategy advises their
Muscarinic antagonists — We suggest use of the combina- continuation during exacerbations [1].
tion of a SAMA (eg, ipratropium) and SABA for exacerbations
that require emergency department or hospital-based treat- Systemic glucocorticoids — For patients requiring emer-
ment, based on the benefit of dual therapy in stable COPD gency department or hospital-based treatment for a COPD
[1,16,32]. (See 'Muscarinic antagonists' above.) exacerbation, we recommend a course of systemic glucocor-
ticoids.
 Dose and administration – When combined with albut-
erol for nebulization, ipratropium 0.5 mg (500 mcg) is
 Route – Oral glucocorticoids are rapidly absorbed (peak  Duration – The optimal duration of systemic glucocorti-
serum levels achieved at one hour after ingestion) with coid therapy is not clearly established and often de-
virtually complete bioavailability and appear equally ef- pends on the severity of the exacerbation and the ob-
ficacious to intravenous glucocorticoids for treating served response to therapy [1,11,41-43]. The GOLD
most exacerbations of COPD [11,37,38]. In a systematic guidelines suggest that glucocorticoids (eg, prednisone
review, parenteral glucocorticoids were compared with 30 to 40 mg/day) be given for five days [1], while the
oral glucocorticoids and no significant differences were European Respiratory Society/American Thoracic Soci-
noted in the primary outcomes of treatment failure, re- ety guidelines suggest a course of therapy up to 14 days
lapse, or mortality or for any secondary outcomes [37]. in duration [11]. Thus, a range of 5 to 14 days appears
However, intravenous glucocorticoids are typically ad- reasonable.
ministered to patients who present with a severe exac- o Data in support of a 14-day course, rather than a
erbation, who have not responded to oral glucocorti- longer duration, come from the Systemic Cortico-
coids at home, who are unable to take oral medication, steroids in COPD Exacerbations (SCCOPE) trial,
or who may have impaired absorption due to decreased which compared two and eight week regimens and
splanchnic perfusion (eg, patients in shock). did not find any additional benefit to the longer
 Dose – The optimal dose of systemic glucocorticoids for course [44]. Patients in the eight week group expe-
treating a COPD exacerbation is unknown [1,11]. The rienced more glucocorticoid-related side effects.
Global Initiative for Chronic Obstructive Lung Disease o Other studies have examined whether courses
(GOLD) guidelines advise using the equivalent of predni- shorter than 14 days are also effective for COPD
sone 40 mg once daily for the majority of COPD exacer- exacerbations. As an example, the Reduction in the
bations (table 3) [1]. Frequently used regimens range Use of Corticosteroids in Exacerbated COPD (RE-
from prednisone 30 to 60 mg, once daily, to methylpred- DUCE) trial randomly assigned 314 patients with
nisolone 60 to 125 mg, two to four times daily, depend- exacerbations of COPD, of whom 289 required hos-
ing on the severity of the exacerbation [19,38,39]. A pitalization, to prednisone 40 mg daily for 5 or 14
growing body of evidence favors using a moderate, ra- days [19]. No difference was noted in the time to
ther than high dose of glucocorticoids, for most patients the next exacerbation, the likelihood of an exacer-
with an exacerbation of COPD. As an example, a com- bation in the subsequent 180 days, or the recovery
parative analysis of glucocorticoid dosing examined out- of lung function. The mean cumulative prednisone
comes of 79,985 patients admitted to the hospital with dose was significantly higher in the 14-day group,
an exacerbation of COPD, excluding those requiring in- but treatment-related adverse effects, such as hy-
tensive care [39]. The median glucocorticoid dose ad- perglycemia and hypertension, were not different
ministered in the first two days was 60 mg for those on between the groups. While this study suggests that
oral therapy and 556 mg for intravenous therapy. The a five-day course may be comparable to 14 days for
risk of treatment failure was no greater with the lower many patients, further study is needed to deter-
dose. As this was an observational study and did not in- mine whether some patients might do better with
clude objective measures of airflow limitation, it is pos- the longer course.
sible that less ill patients were more likely to receive oral o A systematic review compared different durations
treatment. of systemic glucocorticoid therapy (eight studies,
On the other hand, for patients with impending or actual 457 participants) and found no difference in the
acute respiratory failure due to a COPD exacerbation, risk of treatment failure with courses of three to
many clinicians use an intravenous formulation at a seven days compared with longer courses of 10 to
higher dose, such as the equivalent of methylpredniso- 15 days (OR 1.04, 95% CI 0.70-1.56) [41]. Including
lone 60 mg intravenously, one to four times daily, alt- the data from the REDUCE trial above, the system-
hough outcomes data to support this practice are lim- atic review concluded that a five-day course of oral
ited. In an observational cohort study, among 17,239 pa- glucocorticoids is probably comparable to a 14-day
tients admitted to an intensive care unit with an exacer- or longer course, but that further research is
bation of COPD, a dose of methylprednisolone of 240 needed to conclude equivalence.
mg/day or less, compared with a higher dose At the end of the treatment course, glucocorticoid ther-
(methylprednisolone >240 mg/day), was not associated apy may be discontinued rather than tapered, if the pa-
with a mortality benefit, but was associated with slightly tient has substantially recovered. Alternatively, the dose
shorter hospital (-0.44 days; 95% CI -0.67 to -0.21) and is tapered over another seven days, as a trial to deter-
ICU (-0.31 days; 95% CI -0.46 to -0.16) lengths of stay mine whether a longer course of glucocorticoid therapy
[40]. Length of mechanical ventilation and need for in- is required. However, long-term systemic glucocorti-
sulin therapy were also lower in the lower dose group. coids should rarely be used for stable COPD if therapy is
As this was an observational study, further research is otherwise optimized. Tapering solely because of con-
needed to determine the optimal glucocorticoid dose in cerns about adrenal suppression is not necessary if the
this setting. duration of therapy is less than three weeks (a duration
too brief to cause adrenal atrophy). (See "Glucocorticoid
 withdrawal", section on 'Recommended tapering regi- zanamivir, oseltamivir is preferred unless local resistance
men' and "Management of refractory chronic obstruc- patterns suggest a likelihood of oseltamivir-resistant influ-
tive pulmonary disease", section on 'The limited role for enza. Antiviral treatment of influenza is discussed in greater
systemic glucocorticoids in refractory disease'.) detail separately. (See "Seasonal influenza in nonpregnant
 Efficacy – Systemic glucocorticoids, when added to the adults: Treatment".)
bronchodilator therapies described above, improve
Information regarding antiviral resistance that emerges dur-
symptoms and lung function, and decrease the length of
ing the influenza season is available through the United
hospital stay [1,19,37,44,45]. In a systematic review and
States Centers for Disease Control and Prevention. Clinicians
meta-analysis of nine studies (n = 917), systemic gluco-
should review antiviral resistance patterns for updated anti-
corticoids reduced the risk of treatment failure by over
viral recommendations should resistant strains emerge.
50 percent compared with placebo (OR 0.48, 95% CI
0.35-0.67) and, in two studies (n = 415), reduced the risk COPD is associated with a greater likelihood of intensive care
of relapse at one month (hazard ratio 0.78, 95% CI 0.63- unit admission, mechanical ventilation, or death among pa-
0.97) [37]. For each nine treated subjects, one treat- tients with COVID-19 due to SARS-CoV-2 [48-50]. Potential
ment failure was avoided. The forced expiratory volume treatments for hospitalized patients with SARS-coronavirus-
in one second (FEV1) showed significant improvement in 2 infection (COVID-19) are discussed separately. (See
the glucocorticoid group up to 72 hours after initiation, "COVID-19: Management in hospitalized adults" and
but not after that time point. Hospital stay was signifi- "COVID-19: Management of the intubated adult".)
cantly shorter with glucocorticoid treatment (mean dif-
ference -1.22 days, 95% CI -2.26 to -0.18). Mortality up Adjusting therapy for poor response — Assess several po-
to 30 days was not decreased by systemic glucocorti- tential contributors:
coids. The risk of hyperglycemia was significantly in-
 Optimize schedule for delivery of inhaled medications to
creased with glucocorticoids compared with placebo
ensure doses are not being missed.
(odds ratio 2.79, 95% CI 1.86-4.19).
 Ask patients about continued smoking and discuss ways
Preliminary evidence suggests that using total serum eo-
to reduce or stop smoking.
sinophil counts to guide systemic glucocorticoid therapy
 Evaluate for conditions that might contribute to or
may reduce the duration of glucocorticoid exposure
mimic symptoms and signs of a COPD exacerbation,
[46]. After an initial intravenous dose of methylpredni-
such as viral respiratory tract infection, pneumonia, pul-
solone 80 mg, subsequent doses were only given when
monary emboli, pneumothorax, heart failure, dysrhyth-
the eosinophil count was ≥0.3 x109/L. Further study of
mias, tracheomalacia, diaphragmatic dysfunction, and
this strategy is needed prior to implementation.
intraabdominal processes limiting diaphragmatic excur-
 Adverse events – Even short courses of systemic gluco-
sion. Testing may include complete blood count and dif-
corticoids are associated with an increased risk of harm,
ferential, serum brain natriuretic peptide, microbiologic
such as hyperglycemia, pneumonia, sepsis, venous
testing, lower extremity compression ultrasonography
thromboembolism, and fracture. The adverse effects of
for deep venous thrombosis, transthoracic echocardio-
systemic glucocorticoids and their mitigation are dis-
gram, chest radiograph, and/or computed tomography
cussed separately. (See "Major side effects of systemic
with or without pulmonary angiography. (See "COPD ex-
glucocorticoids".)
acerbations: Clinical manifestations and evaluation",
Antiviral and antimicrobial agents — Most clinical practice section on 'Differential diagnosis'.)
guidelines recommend antibiotics for patients having a mod-
Discharge planning — It is hoped that comprehensive dis-
erate to severe COPD exacerbation that requires hospitaliza-
charge planning will help speed symptom resolution and re-
tion [1,11,47]. The optimal antibiotic regimen for the treat-
duce readmissions for COPD exacerbations. However, the
ment of exacerbations of COPD has not been determined.
optimal components of discharge planning have not been
We use a "risk stratification" approach when selecting initial
determined, so discharge-related decision-making is largely
antibiotic therapy, providing a broader antibiotic regimen for
guided by good medical practice, as described separately.
patients at risk for resistant organisms (algorithm 3). The ra-
(See "COPD exacerbations: Prognosis, discharge planning,
tionale, diagnosis, and treatment of infection in exacerba-
and prevention".)
tions of COPD, including antibiotic selection, are discussed
separately. (See "Management of infection in exacerbations A meta-analysis of 13 randomized controlled trials of pulmo-
of chronic obstructive pulmonary disease", section on 'Sum- nary rehabilitation within four weeks of hospitalization for
mary and recommendations' and "Evaluation for infection in acute exacerbation of COPD showed benefits of reduced
exacerbations of chronic obstructive pulmonary disease", mortality and hospital readmissions and enhanced
section on 'Summary and recommendations'.) healthcare-related quality of life and walking distance [51].

Antiviral therapy is recommended for patients with clinical TREATMENTS WITHOUT DOCUMENTED BENEFIT
and laboratory evidence of influenza infection who require
hospitalization for an exacerbation of COPD. Because of the
risk of acute bronchoconstriction with inhalation of
Mucoactive agents, methylxanthines, and mechanical tech- These articles are best for patients who want a general over-
niques to augment sputum clearance have not been shown view and who prefer short, easy-to-read materials. Beyond
to confer benefit for patients with a COPD exacerbation. the Basics patient education pieces are longer, more sophis-
ticated, and more detailed. These articles are written at the
 Mucoactive agents – There is little evidence supporting 10th to 12th grade reading level and are best for patients who
the use of mucoactive agents (eg, N-acetylcysteine) in want in-depth information and are comfortable with some
exacerbations of COPD [52-54]. Some mucoactive medical jargon.
agents may worsen bronchospasm. (See "Role of muco-
active agents and secretion clearance techniques in Here are the patient education articles that are relevant to
COPD".) this topic. We encourage you to print or e-mail these topics
The lack of efficacy of mucoactive agents in the treat- to your patients. (You can also locate patient education arti-
ment of COPD exacerbations was best demonstrated by cles on a variety of subjects by searching on "patient info"
a double-blind trial that randomly assigned 50 patients and the keyword(s) of interest.)
with a COPD exacerbation to receive N-acetylcysteine
 Basics topics (see "Patient education: Chronic bronchitis
(600 mg, twice daily) or placebo for seven days [54].
(The Basics)" and "Patient education: Medicines for
There was no difference in the rate of change of forced
chronic obstructive pulmonary disease (COPD) (The Ba-
expiratory volume in one second (FEV1), vital capacity,
sics)")
oxygen saturation, breathlessness, or length of stay be-
tween the two groups.  Beyond the Basics topics (see "Patient education:
Chronic obstructive pulmonary disease (COPD) treat-
 Methylxanthines – The methylxanthines, aminophylline
ments (Beyond the Basics)")
and theophylline, are considered second-line therapy
for exacerbations of COPD [1]. Randomized trials of in- SUMMARY AND RECOMMENDATIONS
travenous aminophylline in this setting have failed to
show efficacy beyond that induced by inhaled broncho-  Triage – An exacerbation of COPD is characterized by an
dilator and glucocorticoid therapy. In addition to lack of acute increase in symptoms (ie, cough, sputum produc-
efficacy, methylxanthines caused significantly more tion, dyspnea) beyond normal day-to-day variation that
nausea and vomiting than placebo and trended toward leads to a change in medication. An approach to deter-
more frequent tremor, palpitations, and arrhythmias. mining whether a patient needs hospitalization or can
 Nebulized magnesium – Nebulized isotonic magnesium be safely managed at home is provided in the algorithm
(151 mg per dose) had no effect on FEV1 when added to (algorithm 1). (See 'Introduction' above and 'Triage to
nebulized salbutamol (albuterol) in one study of pa- home or hospital' above.)
tients with exacerbations of COPD [55]. A subsequent  Rapid overview of management for severe exacerba-
systematic review including four additional studies tions – A rapid overview for the evaluation and manage-
found no effect of nebulized magnesium on hospital ad- ment of severe exacerbations of chronic obstructive pul-
mission or the need for invasive or noninvasive breath- monary disease (COPD) in the emergency department is
ing support [35]. provided in the table (table 1). (See 'Emergency depart-
 Chest physiotherapy – Mechanical techniques to aug- ment and hospital management' above.)
ment sputum clearance, such as directed coughing,  Titrating supplemental oxygen – Patients with hypox-
chest physiotherapy with percussion and vibration, in- emia due to an exacerbation of COPD should receive
termittent positive pressure breathing, and postural supplemental oxygen. We suggest that supplemental
drainage, have not been shown to be beneficial in COPD oxygen be titrated to a target of 88 to 92 percent pulse
and may provoke bronchoconstriction. Their use in ex- oxygen saturation, rather than using high-flow,
acerbations of COPD (in the absence of bronchiectasis) nontitrated oxygen (Grade 2B). (See 'Oxygen therapy'
is not supported by clinical trials [1,52,53]. above.)
 Ventilatory support – Noninvasive ventilation (NIV) im-
SOCIETY GUIDELINE LINKS proves numerous clinical outcomes and is the preferred
Links to society and government-sponsored guidelines from method of ventilatory support in many patients with an
selected countries and regions around the world are pro- acute exacerbation of COPD. Invasive mechanical venti-
vided separately. (See "Society guideline links: Chronic ob- lation is required in patients with respiratory failure who
structive pulmonary disease" and "Society guideline links: fail NIV, do not tolerate NIV, or who have contraindica-
Pulmonary rehabilitation".) tions to NIV. Both NIV and invasive mechanical ventila-
tion for patients with an exacerbation of COPD are dis-
INFORMATION FOR PATIENTS cussed separately. (See 'Ventilatory support' above and
"Noninvasive ventilation in adults with acute respiratory
UpToDate offers two types of patient education materials,
failure: Benefits and contraindications" and "Invasive
"The Basics" and "Beyond the Basics." The Basics patient ed-
mechanical ventilation in acute respiratory failure com-
ucation pieces are written in plain language, at the 5th to 6th
plicating chronic obstructive pulmonary disease".)
grade reading level, and they answer the four or five key
questions a patient might have about a given condition.
 Short-acting bronchodilators – We recommend that all discussed separately. (See 'Antimicrobial therapy' above
patients having a COPD exacerbation receive inhaled and 'Antiviral and antimicrobial agents' above and
short-acting bronchodilator therapy (Grade 1B). Short- "Management of infection in exacerbations of chronic
acting beta adrenergic agonists (SABA; eg, albuterol, obstructive pulmonary disease", section on 'Summary
levalbuterol) have a more rapid onset of action than the and recommendations' and "COVID-19: Management in
short-acting muscarinic antagonist (SAMA) ipratropium, hospitalized adults" and "COVID-19: Management of
so a SAMA-SABA combination (our choice) or SABA adults with acute illness in the outpatient setting".)
alone is preferred over monotherapy with ipratropium  Treatments without clear benefit – Mucoactive agents,
(algorithm 4). (See 'Beta adrenergic agonists' above and methylxanthines, and mechanical techniques to aug-
'Muscarinic antagonists' above.) ment sputum clearance have not been shown to confer
o The usual dose for relief of acute symptoms is two benefit for COPD exacerbations. (See 'Treatments with-
inhalations every hour for two to three doses and out documented benefit' above.)
then every two to four hours based on the pa-
Use of UpToDate is subject to the Terms of Use.
tient’s response. (See 'Beta adrenergic agonists'
above.)
o Typical doses of albuterol in this emergency de-
partment or hospital are one to two inhalations
(most commonly two, occasionally four; 90 mcg
per inhalation) by MDI with a spacer or 2.5 mg (di-
luted to a total of 3 mL with sterile normal saline)
by nebulizer every hour for two to three doses and
then every two to four hours as needed. (See 'Beta
adrenergic agonists' above.)
o When given by nebulization, ipratropium 0.5 mg
(500 mcg) is mixed with albuterol 2.5 mg in 3 mL
and administered every hour for two or three
doses and then every two to four hours as needed.
Alternatively, a combination ipratropium-albuterol
soft mist inhaler (SMI) can be used, one inhalation,
approximately every hour for two to three doses
and then every two to four hours as needed. (See
'Muscarinic antagonists' above.)
o For patients with limited benefit from short-acting
inhaled bronchodilators, we suggest intravenous
magnesium (Grade 2C). (See 'Magnesium sulfate'
above.)
 Systemic glucocorticoids – For patients hospitalized due
to an acute exacerbation of COPD, we recommend a
course of systemic glucocorticoids (Grade 1B); we also
suggest glucocorticoids for patients who do not require
hospitalization (Grade 2B). A reasonable dose for the
majority of patients is prednisone 40 to 60 mg once daily
(or the equivalent) for 5 to 14 days. A higher dose of glu-
cocorticoids may occasionally be used in patients with
impending or actual respiratory failure. In general, re-
sults with oral dosing are similar to those with intrave-
nous dosing. (See 'Oral glucocorticoid therapy' above
and 'Systemic glucocorticoids' above.)
 Antibiotics and antiviral agents – Antibiotics are indi-
cated for many patients having a COPD exacerbation,
particularly those who require hospitalization for their
exacerbation (algorithm 2 and algorithm 3). Antiviral
therapy (eg, oral oseltamivir or an intravenous agent)
may be appropriate for exacerbations triggered by influ-
enza virus, depending on timing and susceptibility pat-
terns. The use of COVID-19-specific therapies (eg, mon-
oclonal antibodies, JAK inhibitors, anti-interleukin-6
agents, remdesivir) for patients with COVID-19 is