Management of Acute Exacerbations of Asthma in Adults - UpToDate

30/4/2018 Management of acute exacerbations of asthma in adults - UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Management of acute exacerbations of asthma in adults
Author: Christopher H Fanta, MD
Section Editors: Bruce S Bochner, MD, Robert S Hockberger, MD, FACEP
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: Mar 2018. | This topic last updated: Apr 09, 2018.
INTRODUCTION — The best strategy for management of acute exacerbations of asthma is early recognition and intervention, before attacks become severe and
potentially lifethreatening. Detailed investigations into the circumstances surrounding fatal asthma have frequently revealed failures on the part of both patients and
clinicians to recognize the severity of the disease and to intensify treatment appropriately [1].
The management of acute asthma exacerbations will be presented here. An overview of asthma management, the identification of risk factors for fatal asthma, and the use
of mechanical ventilation in severe exacerbations of asthma are discussed separately. (See "An overview of asthma management" and "Identifying patients at risk for fatal
asthma" and "Invasive mechanical ventilation in adults with acute exacerbations of asthma".)
ALGORITHMS FOR ASSESSMENT AND TREATMENT — The National Asthma Expert Panel has published useful algorithms on the management of acute
exacerbations of asthma for both the home and acute care settings (algorithm 1 and algorithm 2) [2]. These algorithms may be used for asthma exacerbations of any
severity. A table outlining the emergency management of severe asthma exacerbations in adults is also provided (table 1).
The basic principles of care are the following:
Assess the severity of the attack
Assess potential triggers (eg, inhaled allergens such as animal dander, pollen, and mold; respiratory infection; medications such as beta blockers or nonsteroidal anti
inflammatory drugs [NSAIDs] in susceptible individuals; inhaled irritants such as chemical fumes or cigarette smoking; and medication nonadherence)
Use inhaled shortacting beta agonists early and frequently, and consider concomitant use of ipratropium for severe exacerbations
Start systemic glucocorticoids if there is not an immediate and marked response to the inhaled shortacting beta agonists
Make frequent (every one to two hours) objective assessments of the response to therapy until definite, sustained improvement is documented
Admit patients who do not respond well after four to six hours to a setting of high surveillance and care
Educate patients about the principles of selfmanagement for early recognition and treatment of a recurrent attack and develop an "asthma action plan" for recurrent
symptoms (see "What do patients need to know about their asthma?")
Ideally, patients assess the severity of an attack at home by following an individualized written "asthma action plan." Asthma action plans are based upon symptoms and
peak flow measurements and provide clear instructions on how to detect and respond to changes in these parameters [2,3]. An example is available through the National
Heart Lung and Blood Institute (NHLBI Asthma action plan). Peak flow meters are available at low cost (eg, $30 or less). The asthma action plan should include clear
instructions about how to reach the clinician during exacerbations. Instructions to a patient regarding selfadministration of medications and selfmonitoring differ depending
upon the patient's history (eg, medications currently used to treat asthma, prior history of severe exacerbations, and prior experience with oral glucocorticoids) and ability to
understand and follow directions. (See "What do patients need to know about their asthma?", section on 'Asthma action plans' and "What do patients need to know about
their asthma?", section on 'Attack prevention'.)
DETECTING AN EXACERBATION — Some patients are very sensitive to increased asthma symptoms, while others perceive reduced airflow only when it becomes
marked. For the latter group, a decrease in peak expiratory flow may be the first sign that asthma control is deteriorating.
Symptoms — Symptoms that patients should recognize as suggesting an asthma exacerbation include breathlessness, wheezing, cough, and chest tightness. Some
patients also report reduced exercise tolerance and fatigue as a symptoms of an asthma exacerbation.
Peak flow — Measurement of expiratory airflow with a peak expiratory flow (PEF) meter (or spirometer) provides an assessment of the severity of airflow limitation [4].
Peak flow measurements take less than one minute to perform and are safe and inexpensive. However, careful instruction is needed to obtain reliable measurements.
Peak flow monitoring is particularly useful in patients with poor perception of asthma symptoms. (See "Peak expiratory flow rate monitoring in asthma".)
Normal values for PEF differ with sex, height, and age (table 2AB). Each patient should establish a baseline measure with which to compare future readings. A decrement
in peak flow of greater than 20 percent from normal, or from the patient's personal best value, signals the presence of an asthma exacerbation. The difference in peak flow
from the patient’s baseline helps one gauge the severity of the change. A PEF less than 50 percent of baseline should be considered a severe attack.
Risk factors for fatal asthma — Some patients are at greater risk for lifethreatening and potentially fatal asthma attacks. It is helpful to identify such patients and to
educate them about identifying early warning signs of deterioration based on PEF monitoring, following a prednisonebased action plan, and seeking emergency care
promptly. (See "Identifying patients at risk for fatal asthma", section on 'Identifying highrisk patients'.)
Risk factors for a fatal asthma attack include [3]:
Previous severe exacerbation (eg, intubation or intensive care unit admission)
Hospitalization for asthma in the past year
Three or more emergency department visits for asthma in the past year
Not currently using inhaled glucocorticoids
Recent or current course of oral glucocorticoids
Use of more than one canister of shortacting beta agonist per month
Difficulty perceiving asthma symptoms or severity of exacerbations
History of poor adherence with asthma medications and/or written asthma action plan
Illicit drug use and major psychosocial problems, including depression
Comorbidities, such as cardiovascular or chronic lung disease
https://www.uptodate.com/contents/management-of-acute-exacerbations-of-asthma-in-adults/print?topicRef=558&source=related_link 1/23
INITIAL HOME TREATMENT — The goals of initial home management are to relieve symptoms and prevent deterioration to a severe and potentially lifethreatening
attack. Patients with serious exacerbations frequently require evaluation in the office or urgent care center and may need to proceed to the emergency department if
improvement is not quickly apparent. Home management is not meant to replace supervised medical care in seriously ill patients.
Patients with a history of recurrent, severe asthma exacerbations may have been prescribed oral glucocorticoids to have available at home and may be advised by their
clinician to take an initial dose (eg, prednisone 40 mg) and notify their clinician.
Shortacting beta agonist — When the onset of an exacerbation is recognized, the patient should selfadminister an inhaled shortacting beta agonist (SABA; eg,
albuterol, levalbuterol) by one of the following methods (table 3) [2,3,5]:
Two to eight puffs from a metered dose inhaler (depending upon the dose that is typically effective and tolerated by that individual; typically two to four puffs are used
for a mild to moderate exacerbation), preferably with a valved holding chamber (“spacer”) device. This dose can be repeated every 20 minutes for the first hour.
A nebulized treatment (eg, albuterol 2.5 mg), repeated every 20 minutes for the first hour, if needed.
After the first hour, if the patient feels initial improvement with the SABA, he or she should repeat a peak flow measurement. Based upon the response to the inhaled beta
agonist, the patient should either continue selfcare or seek medical attention, as described below (algorithm 1). The subsequent dose of the SABA depends on the
severity of the exacerbation. Mild exacerbations usually respond to two to four puffs every three to four hours, while more severe exacerbations may require six to eight
puffs every one to two hours. Patients should contact their clinician if they need high doses of inhaled beta agonists beyond the first hour of selftreatment. (See
'Disposition based on response' below.)
If after initial home treatment the patient has symptoms or signs suggestive of a severe exacerbation (eg, marked breathlessness, inability to speak more than short
phrases, use of accessory muscles) or a peak flow less than 50 percent of baseline, he or she should seek urgent medical attention.
Risks associated with inhaled epinephrine — Racemic epinephrine liquid for inhalation (eg, Asthmanefrin and S2) and epinephrine inhalers are available overthe
counter in some countries and marketed directly to consumers for temporary relief of asthma symptoms. These products are administered via handheld nebulizer or by dry
powder inhalation and have not been evaluated by the US Food and Drug Administration (FDA) for safety or efficacy. The FDA has issued a warning about multiple
adverse events associated with these products, including symptoms such as chest pain, nausea and vomiting, increased blood pressure, tachycardia, and hemoptysis, and
also defective atomizer devices [6]. Epinephrine is NOT beta2 adrenergic receptor selective, so it carries a greater risk of beta1 and alpha adrenergic type adverse
effects, especially when used in excess doses.
It is important to ensure that patients have ready access to the more effective, inhaled shortacting beta2 selective agonists (SABA) and to advise against use of the
nonselective epinephrinebased products [79].
Disposition based on response — The assessment of response to initial home therapy is based on the degree of improvement in symptoms and return of peak flow to
baseline.
Good response — If the patient’s symptoms (wheezing, dyspnea) resolve and the repeat peak flow measurement increases to above 80 percent of the patient's
personal best over the course of approximately one hour, then the patient may safely continue selftreatment (algorithm 1). Other important early interventions include
removal of or from the offending stimulus (if known), continued administration of inhaled shortacting beta agonists, and consideration of a short course of oral
glucocorticoids if beta agonists do not fully correct the decrement in peak flow or if symptoms recur.
The patient should contact their clinician for instructions about how to continue care. Depending on the clinical situation, the clinician may advise continuing the current
therapy, increasing the dose of inhaled glucocorticoids, or initiating a short course of oral glucocorticoids. If the patient’s symptoms resolve, his or her peak expiratory flow
(PEF) returns to >80 percent of baseline after the initial dose(s) of SABA, and he or she remains improved for three to four hours, oral glucocorticoids are usually not
necessary.
For these patients, the clinician may decide that no change in therapy is needed (eg, prompt improvement after a transient exposure to an allergen)
Alternatively, the clinician may determine that the patient is experiencing a more general deterioration in asthma control that warrants an increase in the inhaled
glucocorticoid dose (see "Treatment of moderate persistent asthma in adolescents and adults", section on 'Assessing control')
For patients with more severe initial symptoms or a more profound decrease in PEF, oral glucocorticoids are usually appropriate despite the good initial response to SABA
treatment. (See 'Oral versus intravenous dosing' below.)
Incomplete response — An incomplete response to inhaled shortacting bronchodilator is manifest by continued symptoms and a PEF <80 percent of personal best or
predicted value [3]. The patient should contact his or her clinician for advice and initiate oral glucocorticoids according to his or her prednisonebased action plan (eg,
prednisone 40 to 50 mg daily for 5 to 7 days) (algorithm 1). Timely administration of oral glucocorticoids for asthma exacerbations is probably the single most effective
strategy for reducing emergency department visits and hospitalizations for acute asthmatic attacks.
Other early interventions include removal of or from the offending stimulus (if known), continued administration of inhaled shortacting beta agonists every three to four
hours, and intermittent measurements of peak flow to assess response.
Need for urgent medical attention — Patients should seek immediate medical attention if they have a PEF less than 50 percent of baseline after one or two doses of
inhaled betaagonist by a metered dose inhaler or nebulizer, report symptoms or signs of severe exacerbation (eg, marked breathlessness), or are at high risk for a fatal
attack. (See 'Risk factors for fatal asthma' above.)
Under these circumstances patients should not drive themselves to an urgent care setting.
Inhaled beta agonists should continue to be administered while help is arriving.
Increasing the dose of inhaled glucocorticoid — For some adolescents and adults with asthma, a substantial increase in the inhaled glucocorticoid dose (eg, four times
baseline) may prevent or reduce the severity or duration of an exacerbation when given early in response to a deterioration in asthma control, such as at the first sign of a
viral respiratory infection [3,10,11]. However, parameters that predict which patients would benefit from this approach have not been determined. In our practice, we
reserve this strategy for selected patients who have mildtomoderate asthma, a mild flare in symptoms, peak flow ≥60 percent of predicted, good selfmanagement skills,
and no prior history of lifethreatening asthma exacerbations. Patients should return to their baseline inhaled glucocorticoid dose after normalization of symptoms and peak
flow or at a maximum of 14 days.
Evidence in favor of quadrupling the inhaled glucocorticoid dose includes the following:
In an openlabel trial, 1871 patients (≥16 years old) who were receiving inhaled glucocorticoids for asthma and had one or more exacerbations of asthma in the prior
year were assigned to selfmanagement with quadrupling the dose of inhaled glucocorticoids in response to a deterioration in asthma control or selfmanagement
without such an increase (nonquadrupling group) [10]. After 12 months of followup, 45 percent of the quadrupling group experienced an exacerbation compared with
52 percent of the nonquadrupling group with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.710.92). Further
study is needed to determine whether certain patient or exacerbation characteristics predict which patients would benefit from this strategy.
Among 403 patients with a mild increase in asthma symptoms and a small decrease in peak flow (eg, 15 percent for two days or 30 percent for one day), quadrupling
the dose of inhaled glucocorticoids, rather than no change, resulted in a decrease in the likelihood of needing oral glucocorticoids (relative risk [RR] 0.43, 95% CI 0.24
0.78) [12]. (See 'Highdose inhaled glucocorticoids' below.)
In contrast, doubling the dose of inhaled glucocorticoids is not adequate to abort an asthma exacerbation once an exacerbation has developed [1315]. Additionally,
quintupling the dose of inhaled glucocorticoids in children with an incipient asthma exacerbation appears ineffective [16]. (See "Acute asthma exacerbations in children:
Home/office management and severity assessment", section on 'Outpatient management'.)
ASSESSMENT IN EMERGENCY DEPARTMENT OR URGENT CARE SETTING — Once the patient presents for evaluation, a number of clinical findings and objective
tests can assist the clinician in confirming that the symptoms are caused by an exacerbation of asthma, assessing the severity of an asthma attack, and excluding
complicating factors (eg, pneumonia, atelectasis, pneumothorax, pneumomediastinum) (algorithm 2). The diagnosis of asthma and the differential diagnosis of
nonasthmatic wheezing are discussed separately. (See "Diagnosis of asthma in adolescents and adults" and "Evaluation of wheezing illnesses other than asthma in
adults".)
Clinical findings — A focused history and physical are obtained concurrently with the initiation of therapy in order to confirm the diagnosis and assess the severity. A
severe asthma exacerbation is potentially lifethreatening and needs prompt and intense care.
Signs of a severe exacerbation – The presence of certain clinical findings may help to identify patients experiencing severe asthma attacks. Tachypnea (>30
breaths/min), tachycardia >120 beats/min, use of accessory muscles of inspiration (eg, sternocleidomastoid muscles), diaphoresis, inability to speak in full sentences
or phrases, inability to lie supine due to breathlessness, and pulsus paradoxus (ie, a fall in systolic blood pressure by at least 12 mmHg during inspiration) all are
indicative of severe airflow obstruction [3,17]. Unfortunately, these findings are not sensitive indicators of severe attacks; up to 50 percent of patients with severe
airflow obstruction will not manifest any of these abnormalities [18]. Risk factors for fatal asthma are discussed separately. (See 'Risk factors for fatal asthma' above
and "Identifying patients at risk for fatal asthma", section on 'Identifying highrisk patients' and "Examination of the arterial pulse", section on 'Pulsus paradoxus'.)
Features suggesting an alternate or comorbid condition – Concomitant symptoms such as fever, purulent sputum production, urticaria, or pleuritic chest pain
should raise the possibility of an alternative diagnosis such as pneumonia, flare of bronchiectasis, anaphylaxis, or pneumothorax.
Peak flow measurement — Measurement of expiratory airflow with a peak flow meter (or spirometer) is the best method for objective assessment of the severity of an
asthma attack in patients who are able to perform testing. Patients with signs of impending respiratory failure should not be asked to perform this testing. Normal values
differ with sex, height, and age (table 2AB), but in general, a peak flow rate below 200 L/min indicates severe obstruction for most adults except those who are very short
or elderly [2]. A peak flow ≤50 percent of baseline for that individual signifies a severe exacerbation [3]. (See "Peak expiratory flow rate monitoring in asthma".)
Peak flow or spirometric measurements can also be used to monitor a patient's response to treatment and as a predictive marker for the possibility of hypercapnia, as
discussed below.
Oxygenation — The ready availability of pulse oxygen saturation testing by transcutaneous oximetry allows noninvasive screening for hypoxemia among patients with
severe asthma attacks. Current guidelines recommend the use of transcutaneous pulse oximetry monitoring particularly among patients who are in severe distress, have a
forced expiratory volume in one second (FEV1) or peak expiratory flow less than 50 percent of baseline, or are unable to perform lung function measurements [2]. There is
no contraindication to the use of continuous transcutaneous oximetry during all asthmatic attacks.
Marked hypoxemia (arterial partial pressure of oxygen [PaO2] <60 mmHg [8 kPa], pulse oxygen saturation [SpO2] <90 percent) is infrequent during uncomplicated asthma
attacks; its presence suggests lifethreatening asthma and possible complicating conditions, such as pneumonia or atelectasis due to mucus plugging. Severe hypoxemia
poses the risk for severe cardiovascular or neurologic complications and death.
Hypercapnia — The correlation between peak expiratory flow and oxygen saturation is poor. On the other hand, peak flow measurements provide a useful screening tool
for hypercapnia (eg, PaCO2 >45 mmHg or >6 kPa), making routine assessment of arterial blood gases (ABG) unnecessary in the majority of patients. In the absence of
respiratory depressant medications such as narcotics or sedatives, hypercapnia is rarely present when the peak expiratory flow (PEF) is ≥25 percent of normal or ≥200
L/min [1921]. Thus, arterial blood gas measurements in acute asthma are indicated in the following settings:
Patients with persistent dyspnea whose PEF is below 25 percent of normal or below 200 L/min despite initial bronchodilator therapy (meaning that if the PEF is this low
initially, give bronchodilator and see if there is improvement rather than doing an immediate ABG)
Selected patients with a PEF 25 to 50 percent of normal whose respiratory status is deteriorating despite intensive therapy
Patients who are too ill to perform a peak flow measurement
Patients who demonstrate signs or symptoms of hypercapnia, such as depressed consciousness, inappropriately slow respiratory rate, or myoclonus
Respiratory drive is almost invariably increased in acute asthma, resulting in hyperventilation and a correspondingly decreased PaCO2. Thus, a normal PaCO2 (eucapnia)
during an asthma exacerbation indicates that airway narrowing is so severe that the respiratory system cannot respond adequately to the output of the respiratory center.
Hypercapnia and respiratory failure can then develop rapidly with any further airway obstruction or with respiratory muscle fatigue. Progressive hypercapnia during an
exacerbation of asthma is generally an indication for mechanical ventilation. Asthmatic exacerbations, with an associated sense of suffocation, are often associated with
anxiety and at times with a counterproductive breathing pattern of rapid, shallow breaths. It is tempting to treat this manifestation of the exacerbation with anxiolytics such
as benzodiazepines, but such treatment comes with the risk of central respiratory depression and potential precipitation of hypercapnic respiratory failure. A preferable
strategy in most cases is effective bronchodilation to relieve the sense of dyspnea and ongoing reassurance, with encouragement to take slowdeep breaths (to minimize
dead space ventilation and breathstacking with excessive hyperinflation).
Measurement of the tension of carbon dioxide in peripheral venous blood (PvCO2) is becoming a more common practice in emergency departments. A normal or low
venous blood PvCO2 reliably predicts a normal or low arterial tension of carbon dioxide (PaCO2) and can be used to exclude hypercapnia, although the overall correlation
between PvCO2 and PaCO2 is poor [22]. (See "Venous blood gases and other alternatives to arterial blood gases", section on 'Venous blood gases'.)
Chest radiograph — Chest radiographs are generally unrevealing in acute asthma attacks and are not routinely required in the urgent care setting [3,23]. However, a
chest radiograph should be obtained when a complicating cardiopulmonary process is suspected (eg, temperature >38.3ºC, unexplained chest pain, leukocytosis, or
hypoxemia), when a patient requires hospitalization, and when the diagnosis is uncertain [3]. The most common abnormality is pulmonary hyperinflation. Other abnormal
findings (eg, pneumothorax, pneumomediastinum, pneumonia, or atelectasis) are infrequent, occurring in only approximately 2 percent of chest radiographs obtained
among patients presenting to emergency departments for the treatment of acute asthma [24,25].
Chest radiographs are also useful for patients at high risk for comorbidities (eg, a history of intravenous drug abuse, immunosuppression, granulomatous disease, recent
seizures, cancer, chest surgery, or heart failure) [23,26].
TREATMENT IN EMERGENCY DEPARTMENT OR URGENT CARE SETTING — A table outlining the emergency management of severe asthma exacerbations in adults
is provided (table 1).
Approach — The primary goals of therapy for acute severe asthma are the rapid reversal of airflow limitation and the correction, if necessary, of hypercapnia or
hypoxemia. Airflow limitation is most rapidly alleviated by the combination of repeated administration of inhaled bronchodilators and early institution of systemic
glucocorticoids (table 1 and algorithm 2).
Until their respiratory distress has abated, patients should receive close monitoring, including serial measurements of vital signs, pulse oximetry, and lung function (eg,
peak expiratory flow), to assess the response to treatment.
Oxygen — Supplemental oxygen should be administered to most patients with a moderate or severe asthma exacerbation, particularly those who are hypoxemic (SpO2
<90 percent) or for whom continuous oxygen saturation monitoring is not available. The specific target for SpO2 varies among guidelines [2,3,5], but we aim for a SpO2
above 92 percent (>95 percent in pregnancy) [3]. Usually, oxygenation is easily maintained with nasal cannula, but occasionally face mask delivery is needed.
For patients with severe exacerbations and risk for hypercapnia, there is some evidence that titrating oxygen supplementation to an oxygen saturation of 93 to 95 percent
is preferable to highflow 100 percent oxygen therapy [3]. In a trial that randomly assigned 106 patients with severe asthma exacerbations to mask oxygen at 8 L/min or
titrated oxygen to achieve 93 to 95 percent saturation for 60 minutes, the transcutaneous carbon dioxide tension increased ≥4 mmHg in 44 percent of the high oxygen
concentration group compared with 19 percent of the titrated oxygen group (relative risk [RR] 2.3, 95% CI 1.24.4) [27].
Titrated lowflow supplemental oxygen is particularly appropriate for patients at risk for chronic hypercapnia, such as those with asthmaCOPD overlap syndrome, in whom
a target SpO2 of 88 to 92 percent is reasonable. (See "Management of exacerbations of chronic obstructive pulmonary disease", section on 'Oxygen therapy'.)
Inhaled beta agonists — The mainstay of bronchodilator treatment is inhalation of shortacting beta2selective adrenergic agonists (SABA), such as albuterol,
levalbuterol, or fenoterol (available outside the United States) [2,3,5,28]. (See "Beta agonists in asthma: Acute administration and prophylactic use".)
Dosing — The standard therapy for initial care in the emergency department is inhaled albuterol (or an equivalent) (table 3). Typically, three treatments are administered
within the first hour. The delivery method varies with the setting and severity of the attack (table 3) [2]: Highdose inhaled SABA therapy can be associated with
hypokalemia and lactic acidosis.
Standard nebulization – Albuterol 2.5 to 5 mg by jet (also called "handheld" or "updraft") nebulization every 20 minutes for three doses, then 2.5 mg to 5 mg every
one to four hours as needed. Of note, the higher doses are associated with more frequent and severe sympathomimetic side effects and are generally reserved for
very severe, refractory attacks. (See "Delivery of inhaled medication in adults", section on 'Nebulizers'.)
Metered dose inhaler (MDI) – Albuterol by MDI with a spacer or valvedholding chamber device (eg, Aerochamber, Optichamber, Vortex, and others), four to eight
puffs every 20 minutes, for the first hour. Most patients can then transition to dosing every one to four hours, and rarely require dosing at more frequent intervals.
Continuous nebulization – The practice of administering “stacked” nebulizer treatments refers to delivering one nebulizer treatment immediately after the other
without pause between treatments. In the intensive care unit, some clinicians use a special apparatus to achieve continuous nebulization, administering 10 to 15 mg
over one hour (figure 1). The technique of continuous nebulization is discussed separately. (See "Delivery of inhaled medication in adults", section on 'Continuous
nebulization'.)
Nebulizer versus MDI — The relatively large particle size generated by jet nebulizers and the loss of medication from the expiratory port of many nebulizer systems
make this method of delivery relatively inefficient compared to a metered dose inhaler (MDI). Comparisons of MDI plus valvedholding chamber with nebulizer delivery,
using the same beta agonist but in much reduced doses when given by MDI, have demonstrated comparable improvements in lung function [2934]. (See "Delivery of
inhaled medication in adults" and "The use of inhaler devices in adults", section on 'MDI technique with spacer/chamber'.)
In a systematic review and metaanalysis that included 13 trials (5 openlabel) with a total of 729 adults, the outcomes of delivery of betaagonist via MDIchamber/spacer
or nebulizer were examined [33]. The risk ratio (RR) of admission after emergency department administration of betaagonist via spacer versus nebulizer was 0.94 (95% CI
0.611.43). Peak flow and FEV1 responses and the duration of emergency department stay were similar between groups. The baseline severity of asthma varied from
moderate to severe. Four to six carefully administered inhalations from an MDI with chamber/spacer have generally been found to equal one nebulizer treatment, although
the equivalent dose has not been precisely defined. In comparative trials, administration of beta agonist by MDI with chamber/spacer was directly supervised to ensure the
patient's proper coordination and inhalational technique.
Many emergency departments (including our own) continue to rely on nebulized administration of beta agonists for acutely ill asthmatic patients, taking advantage of the
simplicity of delivery during the patient's tidal breathing. As patients recover in the hospital from acute, severe attacks, the transition can be made from nebulized beta
agonists to beta agonists by MDI with a valved holding chamber (“spacer”) without loss of efficacy and with the opportunity for patient education in proper inhaler technique
[35]. (See "The use of inhaler devices in adults", section on 'Spacers and holding chambers'.)
Inhaled anticholinergics — In accordance with current guidelines for asthma management, we suggest that inhaled ipratropium be used in addition to inhaled albuterol
for patients with severe exacerbations who are in the emergency department [2,3].
The adult dosing of ipratropium for nebulization is 500 mcg every 20 minutes for three doses, then as needed [2]. Alternatively, ipratropium can be administered by MDI at
a dose of four to eight inhalations every 20 minutes, as needed for up to three hours. Albuterol and ipratropium can be delivered simultaneously by nebulizer or softmist
inhaler.
We typically stop inhaled shortacting anticholinergic therapy once the patient is admitted to the hospital, except in patients with refractory asthma who require treatment in
the intensive care unit, are on monoamine oxidase inhibitor therapy (who may have increased toxicity from sympathomimetic therapy due to impaired drug metabolism),
have chronic obstructive pulmonary disease with an asthmatic component, and those whose asthma has been triggered by betablocker therapy. Discontinuation of short
acting anticholinergic bronchodilator therapy in hospitalized patients is based on studies in children that found no benefit from continuation of inhaled anticholinergic
bronchodilators in hospitalized patients [36,37] and is supported by current guidelines [2,3].
The efficacy of using both a shortacting anticholinergic agent and a SABA to treat asthma exacerbations has been examined in a number of trials and systematic reviews
[3844]. A systematic review and metaanalysis found that patients presenting with an asthma exacerbation who were treated with both a SABA and a shortacting
anticholinergic agent were less likely to be admitted to the hospital than those treated with a SABA alone (RR 0.72, 95% CI 0.590.87; 2120 participants; 16 studies), but
the benefit pertained only to those with severe exacerbations, not those with mild or moderate exacerbations [41]. Combination therapy was associated with improved
FEV1 and peak expiratory flow, but results were variable among studies. The rates of adverse effects such as tremor, palpitations, and agitation were greater with
combination therapy than SABA alone.
Systemic glucocorticoids — Systemic glucocorticoid therapy is essential for the resolution of asthma exacerbations that are refractory to intensive bronchodilator therapy
because the persistent airflow obstruction is likely due to airway inflammation and intraluminal mucus plugging. Consistent with current guidelines, we recommend early
administration of systemic glucocorticoids for patients with the following [2]:
A severe exacerbation with a peak expiratory flow ≤50 percent of baseline. Immediate administration is warranted.
A moderate exacerbation with a peak expiratory flow >50 but <70 percent of baseline that does not reverse to normal after initial bronchodilator therapy.
An asthma exacerbation that occurs despite ongoing daily or alternateday oral glucocorticoid therapy. Such patients require supplemental glucocorticoids above their
baseline dose.
Among patients with significant airflow obstruction despite intensive treatment with bronchodilators, systemic glucocorticoids speed the rate of improvement [45]. However,
the onset of action of systemic glucocorticoids is not clinically apparent until as long as six hours after administration. Thus, the beneficial effect is not likely to be observed
during the few hours that the patient spends in the medical office or emergency department [46]. Early administration helps to minimize the delay in improvement
anticipated with systemic glucocorticoids [47].
Oral versus intravenous dosing — The optimal dose for systemic glucocorticoids in asthmatic exacerbations remains unknown [48]. The equivalent of prednisone 40
to 60 mg (or prednisolone 0.5 to 1 mg/kg) per day in a single or divided dose is typical for most asthma exacerbations (table 4 and table 5), although a higher dose is often
used for lifethreatening asthma exacerbations [2]. When comparable doses are administered, the effect of glucocorticoids by oral and intravenous routes of administration
is identical. Thus, in the absence of vomiting or respiratory failure, oral administration can be used instead of intravenous administration. Oral prednisone and
methylprednisolone are rapidly absorbed (peak serum levels achieved at one hour after ingestion) with virtually complete bioavailability, and their efficacy is comparable to
intravenous methylprednisolone. Thus, 40 to 60 mg of prednisone administered in a medical office may provide the maximal benefit to be derived from systemic
glucocorticoids in acute asthma.
Intravenous glucocorticoids should be given to patients who present with impending or actual respiratory arrest, or are intolerant of oral glucocorticoids [2]. The exact dose
of glucocorticoids to use for patients with lifethreatening asthma is largely based on expert opinion and concern that a lower dose might be insufficient in a criticallyill
patient, rather than being evidencebased [49]. A higher initial dose of methylprednisolone 60 to 80 mg every 6 to 12 hours is often chosen for patients who are admitted to
the intensive care unit. A lower initial dose of 40 to 60 mg every 12 to 24 hours is likely adequate for patients who are admitted to the hospital, but do not require intensive
care. A massive initial dose (eg, methylprednisolone 500 mg intravenous bolus) is no more effective than a large initial dose (125 mg) [50]. Glucocorticoids can be given
intramuscularly if intravenous and oral access is not available, although the onset of action of intramuscular glucocorticoids is delayed.
Transition from parenteral to oral administration of glucocorticoids can occur when the patient can tolerate and absorb oral medication.
Duration — The duration of systemic therapy necessary to effect complete resolution of symptoms and return of lung function to baseline varies from patient to patient
and attack to attack. As a rough guide, most severe attacks that require hospitalization will resolve (with return of lung function to baseline) in 10 to 14 days. The duration of
glucocorticoid therapy can be tailored to individual responses. Patients can stop their oral glucocorticoids upon resolution of their symptoms together with recovery of their
selfmonitored peak flow values (eg, when peak expiratory flow is greater than 70 percent of baseline) as long as they begin or maintain use of inhaled glucocorticoids
following discontinuation of oral glucocorticoids. (See 'Medications upon discharge' below.)
Tapering oral glucocorticoids is not necessary if the duration of glucocorticoid treatment is less than three weeks (a duration too brief to cause adrenal atrophy) and if
inhaled glucocorticoids are concomitantly prescribed for ongoing therapy (to prevent relapse).
Magnesium sulfate — Intravenous administration of a single dose of magnesium sulfate (2 g infused over 20 min) is suggested for patients who have a lifethreatening
exacerbation or whose exacerbation remains severe (peak expiratory flow <40 percent of baseline) after one hour of intensive conventional therapy [2]. Intravenous
magnesium sulfate has bronchodilator activity in acute asthma, possibly due to inhibition of calcium influx into airway smooth muscle cells [51]. Although the routine use of
this agent does not seem to confer significant benefit beyond that achieved with the conventional use of beta agonists and systemic glucocorticoids, systematic reviews
have concluded that it is helpful in the subgroup of patients with severe attacks [5255].
Intravenous magnesium has an excellent safety profile; however, it is contraindicated in the presence of renal insufficiency, and hypermagnesemia can result in muscle
weakness. (See "Symptoms of hypermagnesemia".)
In contrast, inhaled magnesium is of marginal benefit in acute asthma exacerbations, when added to inhaled albuterol or the combination of inhaled albuterol and
ipratropium. A systematic review found a borderline benefit to adding inhaled magnesium to inhaled albuterol plus ipratropium in reducing hospital admissions (RR 0.95,
95% CI 0.91 to 1.00) and no significant improvement in peak expiratory flow when inhaled magnesium was added to inhaled albuterol plus ipratropium or inhaled albuterol
alone [56].
Nonstandard therapies — Several nonstandard therapies for particularly severe, lifethreatening exacerbations of asthma may be helpful, but cannot be recommended for
routine use, due to insufficient evidence of efficacy. These include anesthetic agents (eg, ketamine), enoximone, parenteral betaagonists, highdose inhaled
glucocorticoids, heliumoxygen gas mixtures, and leukotriene receptor antagonists.
Anesthetic agents — Some anesthetic agents (eg, intravenous ketamine, inhaled halothane, isoflurane, and sevoflurane) have bronchodilating effects, and case
reports have described favorable responses in patients with refractory status asthmaticus. The mechanism by which bronchodilation is produced remains unclear; a direct
relaxant effect on airway smooth muscle and attenuation of cholinergic tone have both been proposed [57,58]. None of these agents has been evaluated in a randomized
trial and some adverse outcomes have been reported [59].
Inhalational agents – Experience is greatest with halothane for status asthmaticus, but isoflurane and sevoflurane have also shown effectiveness in case reports [60
65]. Idiosyncratic reactions to these anesthetics have been described, and a given patient may respond better to one than to another. The dose of inhalational
anesthetic is titrated to the clinical response (eg, improvement in airway resistance) and avoidance of intolerable side effects. Hypotension is often the limiting factor in
the administration of these agents, and myocardial depression and increased ventricular irritability have been observed with halothane, particularly when used in the
presence of acidosis, betaagonists, and theophylline.
The use of inhalational anesthetics for treatment of status asthmaticus is limited by its expense, the need for a fulltime anesthesiologist at the bedside, adaptation of
equipment for prolonged provision of anesthetics, and the abrupt return of bronchoconstriction upon discontinuation. There is also the issue of scavenging anesthetic
gases released into the immediate environment in order to avoid secondhand inhalation of aerosolized anesthetic gases by health care personnel or other patients.
Intravenous ketamine – Several case reports have described successful treatment of children and adults with status asthmatics with intravenous ketamine [6670].
Although experience with this therapy is limited, an intravenous bolus of 0.5 to 1 mg/kg is usually infused over two to four minutes, followed by a continuous infusion of
0.5 to 2 mg/kg per hour [69,70]. In one report, improvement followed increasing the infusion rate to 3 mg/kg per hour [69]. Beneficial results are seen within 30 minutes
to several hours. Depending on the setting, ketamine infusions in this dose range may fall under the category of conscious sedation or of anesthesia and require
appropriate monitoring. In general, though, ketamine can be administered in the intensive care unit, rather than the operating room, making it preferable to general
anesthesia. (See "Induction agents for rapid sequence intubation in adults outside the operating room", section on 'Ketamine'.)
Enoximone — Enoximone, a selective phosphodiesterase III inhibitor available in Europe, was administered intravenously to eight patients with severe asthma
exacerbations, six of whom had a respiratory arrest or hypercapnia [71]. The dose of enoximone varied, ranging from two doses of 25 mg to two doses of 100 mg. Three
patients were given enoximone by continuous infusion after the initial boluses. Response to enoximone is described as rapid, within one to twenty minutes. The amount of
standard medications (eg, inhaled betaadrenergic agonist, inhaled ipratropium, systemic glucocorticoid) given prior to enoximone was unclear from the report.
Phosphodiesterase inhibitors are associated with ventricular and atrial arrhythmias, hypotension, and hepatotoxicity. Further study is needed to evaluate the safety and
efficacy of intravenous enoximone in patients with acute exacerbations of asthma that are refractory to standard measures.
Parenteral betaagonists — Intravenous and subcutaneous betaagonists are generally avoided when treating asthma exacerbations in adults, because inhaled short
acting selective beta agonists have equal or greater efficacy and lower incidence of adverse effects (eg, tachycardia, arrhythmias, myocardial injury) compared with
parenteral betaagonists.
A systematic review found no significant benefit to parenteral betaagonists compared with inhaled beta2agonists in adults with acute severe asthma [72], and parenteral
betaagonists are not recommended for adults by current guidelines [3].
Two exceptions would be patients suspected of having an anaphylactic reaction and those unable to use inhaled bronchodilators for a severe asthma exacerbation, in
which case epinephrine 0.3 to 0.5 mg may be given subcutaneously (eg, 0.3 to 0.5 mL of 1 mg/mL [also labeled 1:1000] solution). For patients unable to use inhaled
bronchodilators, terbutaline 0.25 mg administered subcutaneously, is an alternative.
Highdose inhaled glucocorticoids — While increasing the dose of inhaled glucocorticoids is recommended for patients with gradually deteriorating control of asthma,
highdose inhaled glucocorticoids are not recommended as an alternative to oral glucocorticoids for patients who present to the emergency department with a discrete
asthma exacerbation. A few reports suggested that highdose inhaled glucocorticoids might have an effect comparable to oral or intravenous glucocorticoids in patients
with mild to moderate asthma following initial stabilization in the emergency department [11,73,74]. However, several larger controlled trials and metaanalyses have drawn
the opposite conclusion [15,7577].
The role of increasing the dose of inhaled glucocorticoids early in the course of an asthma exacerbation is discussed above. (See 'Increasing the dose of inhaled
glucocorticoid' above.)
Heliumoxygen — Heliumoxygen (heliox) mixtures (eg, helium 70 to 80 percent mixed with oxygen 30 to 20 percent, respectively) are used at some centers for severe
asthma exacerbations that are unresponsive to standard therapy or appear to have a component of upper airway obstruction. Routine use of heliox mixtures for asthma
exacerbations alone cannot be recommended due to conflicting data about efficacy.
The rationale for using heliox is that the low density of helium decreases resistance to airflow under conditions of turbulent flow, such as in the central airways and at
branch points, which would in turn decrease the work of breathing and improve ventilation. Airflow in smaller airways is typically laminar, dependent on gas viscosity rather
than density, and not improved with heliox. The physiology and clinical application of heliox are reviewed separately. (See "Physiology and clinical use of heliox" and
"Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults".)
Despite the theoretical benefits of heliox, studies have reported conflicting results concerning its efficacy in asthma exacerbations. Two systematic reviews of the published
literature found insufficient evidence, due to the small size and nonrandomized design of available studies, to recommend the use of heliumoxygen gas mixtures in the
treatment of asthmatic attacks. These analyses are discussed separately. (See "Physiology and clinical use of heliox", section on 'Use in adults'.)
Nebulization of albuterol using a heliumoxygen gas mixture as the driving gas, instead of the usual compressed air or oxygen, results in a smaller particle size, which may
improve drug penetration to the small airways. However, clinical trials have failed to provide consistent evidence of benefit. The use of heliox for aerosol delivery is
discussed separately. (See "Physiology and clinical use of heliox", section on 'Aerosol delivery'.)
Leukotriene receptor antagonists — Leukotriene receptor antagonists are an established therapy for chronic asthma, but the role of these medications in the
management of acute exacerbations is unclear [7882]. We do not administer leukotriene receptor antagonists as part of routine treatment of acute exacerbations, except
in patients whose exacerbation was triggered by ingestion of aspirin or a nonsteroidal antiinflammatory drug (NSAID), events associated with dramatic overproduction of
leukotrienes.
The value of acute administration of an intravenous leukotriene receptor antagonist was assessed in a randomized trial of 201 adults with acute asthma [78]. Patients who
had a onesecond forced expiratory volume (FEV1) <70 percent of predicted following inhalation of nebulized albuterol were randomly assigned to treatment with
montelukast (7 mg or 14 mg IV) or placebo. Montelukast therapy was associated with a 15 percent increase in FEV1 at both dosages, compared with a 4 percent increase
in patients treated with placebo (figure 2). However, no intravenous preparation of a leukotriene receptor antagonist is currently available in the United States.
A larger randomized trial assessed the effect of zafirlukast in 641 adults with acute asthma [79]. Patients treated in the emergency department with a single oral dose of
zafirlukast 160 mg (four times the usual total daily dose) were less likely than those receiving placebo to require prolonged observation or hospital admission (10 versus 15
percent, respectively). In addition, patients who received oral zafirlukast 20 mg twice daily for 28 days after leaving the emergency department were slightly less likely than
patients given placebo to require medical care for relapse during the 28day followup period (24 versus 29 percent, respectively).
These significant findings are of small magnitude and need to be confirmed in larger trials.
Ineffective therapies — Intravenous methylxanthines and empiric antibiotic therapy are not recommended as treatments for acute asthma exacerbations [2].
Methylxanthines — The use of intravenous methylxanthines, once the standard of care for severe asthmatic attacks, has been shown to be relatively ineffective and is
no longer recommended in this setting [2,3,83]. These agents are not as potent as the beta agonists when used alone for the treatment of asthma and provide no further
bronchodilation beyond that achieved with inhaled beta agonists alone when used in combination (figure 3) [84,85]. In addition, methylxanthines appear to increase the
incidence of adverse effects when combined with betaagonist bronchodilators [85].
Studies extending over several hours of emergency department care have also failed to show a benefit of theophylline therapy in terms of need for or duration of
subsequent hospitalization (figure 4) [86]. For patients who are taking oral theophylline at presentation, we typically continue maintenance oral therapy (and check a
theophylline blood level) during hospitalization; but if continued oral intake is not possible, we would very rarely use intravenous therapy with aminophylline or theophylline.
Empiric antibiotics — Clinical practice guidelines recommend against empiric antibiotic therapy for the treatment of an asthma exacerbation, because most respiratory
infections that trigger an exacerbation of asthma are viral rather than bacterial [3]. In general, we reserve antibiotics for treatment of suspected bacterial sinusitis or
pneumonia complicating an asthmatic attack. (See "Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment" and "Treatment of communityacquired
pneumonia in adults in the outpatient setting" and "Treatment of communityacquired pneumonia in adults who require hospitalization".)
Evidence against routine antibiotic therapy for asthma exacerbations includes a randomized trial of 199 patients with an acute exacerbation of asthma requiring systemic
glucocorticoids, who had not received antibiotics in the prior month [87]. Participants were assigned to azithromycin 500 mg a day or placebo for three days in addition to
usual care. No difference was noted in symptom scores or lung function at day 10 or in time to reach a 50 percent reduction in symptoms. In this study, 5 percent of
azithromycintreated participants tested positive for Chlamydophila pneumoniae or Mycoplasma pneumoniae. Of note, 2044 patients (45 percent of the screened
population) were excluded because they had already received an antibiotic. The high number of patients excluded because they had been deemed unlikely to benefit from
antibiotics may have resulted in selection bias.
A separate trial of telithromycin versus usual care found a greater reduction in asthma symptoms with telithromycin, but no other significant treatment effect [88]. While 61
percent of participants had elevated antibody titers for Chlamydophila pneumoniae or Mycoplasma pneumoniae, bacteriologic status did not correlate with response to
treatment. Two possible explanations for the observed benefit to telithromycin include the high rate of atypical bacterial infection and an antiinflammatory effect of
telithromycin that may have benefited patients who did not receive concomitant glucocorticoids. Due to the high rate of hepatotoxicity and exacerbations of myasthenia
gravis, use of telithromycin is restricted.
It is possible that measurement of serum procalcitonin levels will allow identification of a bacterial etiology among patients whose asthma exacerbations are triggered or
complicated by a respiratory tract infection [89].
Nebulized furosemide — Nebulized furosemide has been studied both as prophylactic treatment for patients with exerciseinduced bronchoconstriction and as therapy
for acute asthma. However, the therapeutic value of this intervention, if any, appears limited. Small early studies reported that nebulized furosemide in combination with
albuterol was safe, well tolerated, and resulted in significantly improved peak expiratory flow rates compared with albuterol alone [90].
However, subsequent larger trials have not noted a significant clinical benefit when nebulized furosemide was used in conjunction with albuterol or compared to placebo
[9193].
Other ineffective therapies not recommended for treatment of acute exacerbations of asthma include hydration (in the absence of evidence of dehydration), expectorants
such as guaifenesin, antihistamines, and chest physiotherapy.
MECHANICAL VENTILATION AND NONINVASIVE POSITIVE PRESSURE VENTILATION — The decision to intubate and initiate mechanical ventilation during a severe
asthma attack is clinical. Slowing of the respiratory rate, depressed mental status, inability to maintain respiratory effort, worsening hypercapnia and associated respiratory
acidosis, or inability to maintain an oxygen saturation >92 percent despite highflow supplemental oxygen suggest that the patient requires intubation. In the absence of
anticipated intubation difficulty, rapid sequence intubation is preferred. Nasal intubation is not recommended. (See "Emergency airway management in acute severe
asthma" and "Invasive mechanical ventilation in adults with acute exacerbations of asthma", section on 'General approach'.)
The role of noninvasive positive pressure ventilation (NIV) is not as well studied in asthma as in chronic obstructive pulmonary disease and heart failure. A short trial of NIV
may be appropriate in cooperative patients not responding to medical therapy who do not require immediate intubation. (See "Noninvasive ventilation in acute respiratory
failure in adults", section on 'Asthma'.)
DISPOSITION — Patients with acute, severe asthmatic exacerbations are at risk for further deterioration in lung function, respiratory failure, and asphyxic death. In many
cases, airway obstruction remains labile for days following an acute exacerbation, with wide swings in expiratory flow over minutes or hours. Nocturnal deteriorations are
common.
Indications for hospitalization or discharge — The purpose of hospitalization during an acute exacerbation of asthma is close observation and availability of aggressive
interventions in the event of worsening asthma. Hospitalization also serves to remove the patient from stimuli in the home environment that potentially aggravate asthma,
ensure medication compliance, and permit inactivity during recovery from the illness.
Identifying patients who should be kept for overnight observation or hospital admission versus discharged to home remains largely a matter of clinical judgment guided by
the patient’s response to therapy, severity of respiratory symptoms, and degree of airflow limitation, as assessed by peak expiratory flow (PEF). The patient’s home living
circumstances will also influence this decision. Guidelines from the Expert Panel 3 of the National Asthma Education and Prevention Program and from the Global Initiative
on Asthma are available to help guide decision making (algorithm 2) [2,3].
Patients who have not experienced substantial improvement after four to six hours of emergency department management including frequent inhaled betaagonist
bronchodilator treatments and oral glucocorticoids should be hospitalized.
Severe symptoms of coughing, wheezing, and shortness of breath that preclude selfcare are indications for inhospital care.
PEF measurements provide objective data and are useful for determining which patients are "at risk" for poor outcomes if discharged home and which are safe for
transition to home management. The following PEF parameters can help guide disposition decisions [3,94,95]:
• Measured at the time of disposition (after approximately 60 minutes of treatment), a PEF <40 percent of predicted or of the patient's personal best value is a
reason for continued supervised medical care and consideration of admission to an intensive care setting [3].
• Patients with a PEF of 40 to 60 percent of predicted after initial therapy should generally continue to receive intensive therapy and close observation and may be
appropriate for hospital admission or overnight observation. Among the factors favoring continued observation in this group are: new onset asthma, multiple prior
hospitalizations or emergency department visits for asthma, use of oral glucocorticoids at the time of presentation with the acute deterioration, and complicating
psychosocial difficulties. However, some patients with a PEF in this range who demonstrate improving lung function and have good asthma selfcare skills and a
supportive home environment may be candidates for discharge to home [3].
• Most patients with improving symptoms and a PEF >60 percent of predicted can be safely discharged, if they are knowledgeable about their asthma and have
good availability of followup care [3]. This decision is made on a casebycase basis.
Medications upon discharge — In general, an asthmatic attack has not fully resolved even when symptoms have abated. Residual airflow obstruction due to airway
inflammation may last for several days. Thus, in addition to shortacting beta agonists to be used as needed, the patient will need glucocorticoids to treat the inflammation
and prevent recurrent symptoms.
Oral glucocorticoids — Nearly all patients with a significant asthma exacerbation requiring emergency department evaluation should receive a course of oral
glucocorticoids for 5 to 10 days [2,3]. A short course of oral glucocorticoids (eg, prednisone 40 to 60 mg/day for five to seven days) significantly reduces the likelihood of a
repeat severe exacerbation with emergency department bounce back ("relapse") within the succeeding two weeks and lessens the frequency of persistent severe
symptoms evaluated at a twoweek telephone followup [96,97]. However, the optimal regimen has not been determined. Accumulated clinical experience favors
prednisone 40 to 60 mg/day for 5 to 7 days; preliminary evidence suggests that one to two doses of dexamethasone may have comparable benefit in uncomplicated
patients.
In a systematic review, no difference was found between higher dose/longer course and lower dose/shorter course prednisone or prednisolone, although the quality of the
evidence was rated as low [48]. In the same review, based on a single study, the relapse rate for dexamethasone 16 mg/day for two days was not different from prednisone
50 mg/day for five days [98]. In a separate emergency department trial published after the systematic review, 376 adults with an acute asthma exacerbation not requiring
hospitalization were randomly assigned to dexamethasone 12 mg for one dose or prednisone 60 mg a day for five days [99]. The 14day relapse rates for dexamethasone
and prednisone were 12.1 versus 9.8 percent, respectively, difference 2.3 percent (95% CI 4.18.6).
For glucocorticoid courses lasting three weeks or less, there is no need to taper the dose if patients are also taking inhaled glucocorticoids.
Intramuscular glucocorticoids — Intramuscular injection of a longacting glucocorticoid formulation at the time of discharge from the emergency department is
occasionally used for patients without access to oral medication or at high risk of medical nonadherence. Intramuscular longacting glucocorticoid formulations appear to be
as effective as oral therapy in this setting [100105]. In a randomized trial of 190 adult patients with acute asthma, intramuscular injection of longacting methylprednisolone
(160 mg) resulted in a similarly low rate of relapse as oral methylprednisolone given in a tapering schedule over eight days (total dose = 160 mg) [100].
A disadvantage of intramuscular glucocorticoids is that the duration of effect varies from one individual to another, and the time that the effect ceases is unknown in a given
patient. Cutaneous atrophy at the injection site is also possible.
Inhaled glucocorticoids — Treatment with regular inhaled glucocorticoids constitutes an important method to prevent recurrent asthma attacks after discontinuation of
oral glucocorticoids and to prevent the potential decline in lung function associated with any future severe asthma exacerbation [2,47]. Virtually every patient who has
suffered an asthma attack severe enough to require urgent care should receive an inhaled glucocorticoid as part of his or her discharge medication plan (table 6). (See "An
overview of asthma management".)
Among hospitalized patients, we typically begin (or resume, if previously taking) inhaled glucocorticoids as soon as patients are able to tolerate medication delivery from
drypowder inhalers or metereddose inhalers (with spacers). The use of combination inhaled glucocorticoids plus longacting betaagonists during hospitalization has not
been well studied. It seems reasonable to delay their use until administration of shortacting beta agonists has decreased in frequency to fewer than four times per day.
Upon discharge from the hospital or emergency department, some clinicians delay initiation (or reinitiation) of inhaled glucocorticoids until the oral glucocorticoid dose has
been reduced to approximately 20 mg of prednisone or the equivalent. However, in our experience this approach more often leads to confusion and medication
noncompliance than use of these inhaled medicines in parallel with oral glucocorticoids.
Patient education — Patients should be provided with information about asthma, avoidance of asthma triggers, and if they do not already have one, a personalized action
plan (form 1). Followup care with a primary provider should be facilitated whenever possible. (See "What do patients need to know about their asthma?" and "Trigger
control to enhance asthma management" and 'Information for patients' below.)
SOCIETY GUIDELINE LINKS — Links to society and governmentsponsored guidelines from selected countries and regions around the world are provided separately.
(See "Society guideline links: Asthma in adults".)
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, easytoread 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 indepth 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 email 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.)
Beyond the Basics topics (see "Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)" and "Patient education: Trigger avoidance in
asthma (Beyond the Basics)" and "Patient education: How to use a peak flow meter (Beyond the Basics)" and "Patient education: Asthma inhaler techniques in adults
(Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS — A table outlining the emergency management of severe asthma exacerbations in adults is provided (table 1).
Early recognition and intervention are critical for successful management of asthma exacerbations. The basic principles of care are assessment of attack severity,
repeated use of inhaled shortacting betaagonists, early administration of oral or intravenous glucocorticoids, and frequent reassessment. (See 'Introduction' above.)
Patients should be taught how to identify symptoms of an asthma exacerbation, and those patients with poor symptom perception should be taught how to measure
peak expiratory flow (PEF). Patients should also learn what steps to take upon recognition of increased asthma symptoms and/or peak flow decline (form 1). These
include immediate treatment with shortacting inhaled beta agonists, monitoring of medication response, and in some cases early selfadministration of oral
glucocorticoids (algorithm 1). (See 'Initial home treatment' above.)
In the urgent care setting, the severity of an asthma exacerbation is assessed based upon symptoms, physical findings, peak expiratory flow (or forced expiratory
volume in one second [FEV1]) measurements, pulse oxygen saturation (SpO2), and in certain circumstances, arterial blood gas measurement. (See 'Assessment in
emergency department or urgent care setting' above.)
An approach to the management of patients presenting to the emergency department with an asthma exacerbation is provided in the algorithm (algorithm 2). Focused
treatment of severe asthma exacerbations is described in the rapid overview (table 1).
The standard regimen for initial care in the emergency department is to titrate supplemental oxygen to maintain the SpO2 >92 percent (>95 percent in pregnancy) and
to administer albuterol (or an equivalent) 2.5 mg by jet nebulization every 20 minutes for three doses, then 2.5 mg every one to four hours as needed. Alternatively,
albuterol can be given by metered dose inhaler (MDI) with a spacer, four to eight puffs every 20 minutes for three doses, then four to eight puffs every one to four
hours as needed. For critically ill patients, some clinicians prefer continuous nebulization, administering 10 to 15 mg over one hour. (See 'Oxygen' above and 'Inhaled
beta agonists' above and "Delivery of inhaled medication in adults", section on 'Continuous nebulization'.)
Early systemic glucocorticoids should be given to all patients who have a moderate or severe exacerbation, or in whom inhaled shortacting beta agonists do not fully
correct the decrement in peak flow. The optimal dose is unknown; however, the equivalent of a prednisone dose of 40 to 60 mg per day in a single dose or two divided
doses is typical for outpatient management. (See 'Systemic glucocorticoids' above.)
The initial dose of systemic glucocorticoids used for the inpatient management of acute asthma exacerbations ranges from methylprednisolone 60 to 80 mg every 6 to
12 hours for patients in the intensive care unit to 40 to 60 mg every 12 to 24 hours for patients not requiring intensive care, depending on the severity of the asthma
exacerbation and the patient’s pattern of response to systemic glucocorticoids during previous exacerbations. The higher glucocorticoid doses given to criticallyill
patients are not evidence based but rather derive from the gravity of the medical situation and concern that underdosing might lead to deterioration. (See 'Systemic
glucocorticoids' above.)
Inhaled ipratropium may be helpful to patients with severe exacerbations who are in the emergency department; ipratropium does not appear to provide additional
benefit to inhaled beta agonists during hospitalization. Adult dosing of ipratropium for nebulization is 500 mcg every 20 minutes for three doses, then as needed.
Alternatively, ipratropium can be administered by MDI at a dose of four to eight inhalations every 20 minutes, then as needed for up to three hours. (See 'Inhaled
anticholinergics' above.)
A onetime infusion of magnesium sulfate, 2 grams administered intravenously over 20 minutes, is suggested for patients who have lifethreatening exacerbations (ie,
impending intubation for respiratory failure) or those whose exacerbation remains severe after one hour of intensive conventional therapy. (See 'Magnesium sulfate'
above.)
We advise admitting patients to the hospital in a setting with a high level of patient monitoring and care if they do not respond well after four to six hours of intensive
therapy, if they have symptoms of coughing, wheezing, and shortness of breath that preclude selfcare, and/or have a PEF ≤50 percent of predicted or their personal
best value (algorithm 2). Patients with a PEF >50 but <80 percent may need hospitalization, especially if they have new onset asthma, are at high risk for fatal asthma,
or presented during a course of oral glucocorticoids. (See 'Indications for hospitalization or discharge' above.)
Patients who are well enough to go home should be given a brief course of oral glucocorticoids (or an injection of intramuscular glucocorticoids), a prescription for
inhaled glucocorticoids, a personalized asthma action plan (NHLBI Asthma Action Plan), and instructions to seek followup care (form 1). (See 'Disposition' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
Topic 528 Version 48.0
GRAPHICS
Management of asthma exacerbations: home treatment
ED: emergency department; MDI: metereddose inhaler; PEF: peak expiratory flow; SABA: shortacting
beta 2 agonist (quickrelief inhaler).
Reproduced from: National Heart, Blood, and Lung Institute Expert Panel Report 3 (EPR 3): Guidelines for the
Diagnosis and Management of Asthma. NIH Publication no. 084051, 2007.
Graphic 56621 Version 4.0
Management of asthma exacerbations in adults: Emergency department or urgent care
Features that help with assessment of severity (may or may not be present):
Impending respiratory failure:
Cyanosis, inability to maintain respiratory effort, depressed mental status, SpO 2 <90%
PaCO 2 >40 mmHg
Severe exacerbation:
Speaks in single words
Sits hunched forward
Agitated, diaphoretic
Respiratory rate >30 breaths/minute
Heart rate >120 beats/minute
SpO 2 (on air) <90%
PEF ≤50% predicted or personal best
Mild to moderate exacerbation:
Talks in phrases or sentences
Prefers sitting to lying
Not agitated
Respiratory rate 16 to 30 breaths/minute
Heart rate 100 to 120 beats/minute
SpO 2 >90%
PEF >50% but <80% predicted or personal best
PEF: peak expiratory flow; ICU: intensive care unit; SABA: shortacting beta agonist (eg, albuterol); SpO 2 : pulse oxygen saturation; COPD: chronic obstructive pulmonary disease; MDI: metered dose
inhaler; GC: glucocorticoid; PaCO 2 : carbon dioxide tension.
* Titrate oxygen to SpO 2 93 to 95% for patients with severe exacerbations, particularly if at risk for hypercapnia. Aim for SpO 2 >95% in pregnant patients. Titrate to SpO 2 88 to 92%, if asthmaCOP
overlap.
¶ Magnesium sulfate is 4.06 mmol/g (2 g = 8.1 mmol).
Δ Please refer to the UpToDate topic on treatment of asthma exacerbations in adults.
◊ Adding ipratropium to albuterol nebulizer treatments is preferred for patients with severe exacerbations; alternatively, SABA/ipratropium can be given via MDI 4 to 8 inhalations every 20 minutes, a
needed for up to 3 hours.
§ The dose and duration of therapy can be modified based on the patient's past history of response, severity of exacerbation, and response to current treatment.
Severe asthma exacerbation in adults: Rapid overview
Clinical danger signs
Use of accessory muscles of respiration; brief, fragmented speech; inability to lie supine; profound diaphoresis; agitation; severe symptoms that fail to improve with initial emergency
department treatment
Lifethreatening airway obstruction can still occur when these signs are NOT present
Signs of imminent respiratory arrest: cyanosis, inability to maintain respiratory effort, and depressed mental status
Assessment
Measurement of expiratory airflow (peak expiratory flow rate or PEFR) is the best measure of severity; PEFR <40 percent predicted (or <200 L/minute in most adults) indicates severe
obstruction; patients in severe distress are often unable to perform peak flow tests
Severe hypoxemia (eg, SpO 2 ≤95 percent despite high flow O 2 treatment by nonrebreather mask) portends imminent respiratory arrest or possibly severe complication (eg,

pneumothorax); continuous pulse oximetry monitoring should be performed
Patients in extremis should be managed clinically without waiting for arterial blood gases (ABGs). ABGs can aid assessment of hypercapnia or impending respiratory failure: hypercapnia
usually does not occur unless PEF is <25 percent of normal (generally <100 to 150 L/min).
Chest radiograph is generally unhelpful; obtain if complications suspected (eg, pneumonia, pneumothorax), diagnosis is in doubt, or patient is highrisk (eg, IV drug abuser,
immunosuppressed, chronic pulmonary disease, heart failure)
Standard treatments
Inhaled beta agonist: give albuterol 2.5 to 5 mg by nebulization every 20 minutes for three doses, then 2.5 to 5 mg every one to four hours as needed, or give 4 to 8 puffs by metered
dose inhaler (MDI) with spacer every 20 minutes for three doses, then every one to four hours as needed. Alternatively, for severe exacerbations, 10 to 15 mg can be administered by
continuous nebulization over one hour.
Oxygen: give sufficient oxygen to maintain SpO 2 ≥92 percent (>95 percent in pregnancy)
IV: establish intravenous access; may give normal saline for repletion, if patient is dehydrated due to reduced intake and prolonged episode
Ipratropium bromide: give 500 mcg by nebulization every 20 minutes for 3 doses, or 4 to 8 puffs by MDI with spacer every 20 minutes as needed for up to 3 hours
Systemic glucocorticoids: for patients with impending respiratory failure, give methylprednisolone 60 to 125 mg IV. For the majority of less severe asthma exacerbations, give
prednisone 40 to 60 mg orally; alternatives include: dexamethasone 6 to 10 mg IV or hydrocortisone 150 to 200 mg IV; glucocorticoids may be given IM or orally if IV access is
unavailable.
Magnesium sulfate: give 2 g (8 mmol) IV over 20 minutes for lifethreatening exacerbations and exacerbations that remain severe after one hour of intensive bronchodilator therapy
Potential additional treatments*
Epinephrine: for patients suspected of having an anaphylactic reaction or unable to use inhaled bronchodilators for severe asthma exacerbation, give epinephrine 0.3 to 0.5 mg IM (eg, 0.3
to 0.5 mL of 1 mg/mL [also labeled 1:1000] solution); if severe asthma but no evidence of anaphylaxis, can give epinephrine 0.3 to 0.5 mg SC (eg, 0.3 to 0.5 mL of 1 mg/mL [also labeled
1:1000] solution); give epinephrine OR terbutaline but not both
Terbutaline: may give 0.25 mg by SC injection every 20 minutes times 3 doses for severe asthma unresponsive to standard therapies; give terbutaline OR epinephrine but not both
Endotracheal intubation and ventilation
The decision to intubate during the first few minutes of a severe asthma attack is clinical. Slowing of the respiratory rate, depressed mental status, inability to maintain respiratory effort, or
severe hypoxemia suggests the patient requires intubation. In the absence of anticipated intubation difficulty, rapid sequence intubation is preferred. Nasal intubation is not recommended.
The goal of mechanical ventilation is to maintain adequate oxygenation and ventilation while minimizing elevations in airway pressures. This is accomplished by using low tidal volumes (6
to 8 mL/kg), and low respiratory rates (10 to 12/minute). In some patients, elevations in PaCO 2 must be tolerated to avoid barotrauma (ie, permissive hypercapnia). ¶
IM: intramuscular; IV: intravenous; MDI: metered dose inhaler; PEFR: peak expiratory flow rate; SC: subcutaneous; SpO 2 : pulse oxygen saturation.
* For information on additional therapies for severe asthma exacerbations, please refer to the UpToDate topic on the management of asthma exacerbations.
¶ Please refer to the UpToDate topics on mechanical ventilation in adults with acute severe asthma and permissive hypercapnia.
Predicted average peak expiratory flow (PEF) for normal males (L/min)
Height
Age
60 inches/152 cm 65 inches/165 cm 70 inches/178 cm 75 inches/191 cm 80 inches/203 cm
20 554 602 649 693 740
25 543 590 636 679 725
30 532 577 622 664 710
35 521 565 609 651 695
40 509 552 596 636 680
45 498 540 583 622 665
50 486 527 569 607 649
55 475 515 556 593 634
60 463 502 542 578 618
65 452 490 529 564 603
70 440 477 515 550 587
These values represent average normal values within 100 L/min. Predicted values for African American and Hispanic minorities are approximately 10 percent lower.
From: Leiner GC, Abramowitz S, Small MJ, et al. Expiratory peak flow rate. Standard values for normal subjects. Use as a clinical test of ventilatory function. Am Rev Respir Dis 1963; 88:644.
Predicted average peak expiratory flow (PEF) for normal women (liters/minute)
Height (inches/centimeters)
Age
55/140 60/152 65/165 70/178 75/190
20 390 423 460 496 529
25 385 418 454 490 523
30 380 413 448 483 516
35 375 408 442 476 509
40 370 402 436 470 502
45 365 397 430 464 495
50 360 391 424 457 488
55 355 386 418 451 482
60 350 380 412 445 475
65 345 375 406 439 468
70 340 369 400 432 461
These values represent average normal values within 80 liters/minute. Predicted values for African American and Hispanic minorities are approximately 10 percent lower.
Data from: Leiner GC, Abramowitz S, Small MJ, et al. Expiratory Peak Flow Rate. Standard Values for Normal Subjects. Use as a Clinical Test of Ventilatory Function. Am Rev Respir Dis 1963;
88:644.
Doses of beta agonists for asthma exacerbations
Doses
Medication
Child dose* Adult dose Comments
Inhaled shortacting beta 2 agonists (SABA)
Albuterol (salbutamol)
Nebulizer solution 0.15 mg/kg (minimum 2.5 mg, maximum 5 2.5 to 5 mg every 20 minutes for three Only selective beta 2 agonists are

(0.63 mg/3 mL, 1.25 mg/3 mL, 2.5 mg) every 20 minutes for three doses then doses, then 2.5 to 10 mg every one to four recommended. For optimal delivery, dilute
mg/3 mL, 5 mg/mL) 0.15 to 0.3 mg/kg up to 10 mg every one to hours as needed, or 10 to 15 mg/hour aerosols to minimum of 3 mL at gas flow of
four hours as needed, or 0.5 mg/kg/hour by continuously. 6 to 8 L/min. Use large volume nebulizers for
continuous nebulization (maximum 20 mg continuous administration. May mix with
per hour). ipratropium nebulizer solution.
MDI Four to eight puffs every 20 minutes for Four to eight puffs every 20 minutes up to In mildtomoderate exacerbations, MDI plus

(90 microgram/puff) three doses, then every one to four hours as four hours, then every one to four hours as VHC is as effective as nebulized therapy with
needed. Use VHC; add mask in children less needed. appropriate administration technique and
than four years. coaching by trained personnel.
Levalbuterol (Ralbuterol, levosalbutamol)
Nebulizer solution 0.075 mg/kg (minimum 1.25 mg, maximum 1.25 to 2.5 mg every 20 minutes for three Levalbuterol administered in onehalf the mg

(0.63 mg/3 mL, 1.25 mg/0.5 mL 1.25 2.5 mg) every 20 minutes for three doses, doses, then 1.25 to 5 mg every one to four dose of albuterol provides comparable
mg/3 mL) then 0.075 to 0.15 mg/kg up to 5 mg every hours as needed. efficacy and safety. Has not been evaluated
one to four hours as needed. by continuous nebulization.
MDI See albuterol MDI dose. See albuterol MDI dose.

(45 microgram/puff)
Bitolterol ¶
Nebulizer solution See albuterol dose (thought to be half as See albuterol dose (thought to be half as Has not been studied in severe asthma

(2 mg/mL) potent as albuterol on mg basis). potent as albuterol on mg basis). exacerbations. Do not mix with other drugs.
MDI See albuterol MDI dose. See albuterol MDI dose. Has not been studied in severe asthma

(370 microgram/puff) exacerbations.
Systemic (injected) beta 2 agonists Δ
Terbutaline 0.01 mg/kg (maximum 0.4 mg) every 20 0.25 mg every 20 minutes for three doses, Subcutaneous/intramuscular administration

minutes for three doses then every two to subcutaneously or intramuscularly. is reserved for patients with poor inspiratory
six hours as needed subcutaneously or flow or who cannot cooperate with inhaled
intramuscularly. therapy. No proven advantage over aerosol.
OR as intravenous infusion initiated with 10 Intravenous terbutaline is rarely indicated.
microgram/kg (maximum 0.4 mg) bolus over Selected patients who are poorly responsive
10 minutes followed by 0.3 to 0.5 to standard therapies may receive parenteral
microgram/kg per minute. Every 30 minutes terbutaline or epinephrine, NOT both. See
infusion may be increased if needed by 0.1 text.
to 0.5 microgram/kg/minute up to maximum
10 microgram/kg per minute. ◊
Epinephrine 0.01 mg/kg (maximum 0.4 mg) every 20 0.3 mg every 20 minutes for three doses, Subcutaneous/intramuscular administration

1:1000 (1 mg/mL) minutes for three doses, subcutaneously or subcutaneously or intramuscularly. is reserved for patients with anaphylaxis or
intramuscularly. poor inspiratory flow or who cannot
cooperate with inhaled therapy. No proven
advantage of systemic epinephrine over
aerosol except in the treatment of
anaphylaxis.
MDI: metered dose inhaler; VHC: valved holding chamber.
* Children ≤12 years of age.
¶ Not available in the United States or Canada.
Δ The use of systemic terbutaline or epinephrine requires cardiopulmonary monitoring, such as that available in a critical care setting. Orally administered systemic beta 2 agonists are not
recommended.
◊ For patients who require doses of intravenous terbutaline above 3 microgram/kg per minute, prompt transfer to an intensive care unit is advisable due to potential cardiac toxicity and
respiratory failure.
Adapted from: National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and
Blood Institute, 2007. (NIH publication no. 084051). Available at www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
Aeroneb Solo mesh nebulizer for intermittent or
continuous nebulization
Nebulizers like the Aeroneb Solo mesh nebulizer can be used for intermittent or
continuous nebulization. The Aeroneb Pro controller accommodates nebulization
cycles of 15 to 30 minutes.
Reproduced with permission. Copyright © 2012 Aerogen. All rights reserved.
Usual dosages for oral glucocorticoids in asthma
Medication Oral preparations Dose Comments
Methylprednisolone 2, 4, 8, 16, and 32 mg tablets Shortcourse "burst" for asthma Short course therapy:

exacerbation: 32 to 48 mg per day as a Short courses or "bursts" are effective for
single dose in the morning for 3 to 10 days; establishing control when initiating
typically 32 mg daily for 5 days. therapy, during an acute exacerbation or
a period of deterioration.
The burst should be continued until
patient achieves substantial symptom
improvement or resolution, which is
usually associated with PEFR >70 to 80
Prednisolone* 5 mg tablets; 10, 15, and 30 mg orally Shortcourse "burst" for asthma
percent of predicted or personal best. This
disintegrating tablets (ODT) exacerbation: 40 to 60 mg per day as single
usually requires 3 to 10 days, but may
dose in the morning for 3 to 10 days;
require longer treatment.
typically 40 mg daily for 5 days.
In patients receiving inhaled
glucocorticoids, there is no evidence that
Prednisone* 1, 2.5, 5, 10, 20, and 50 mg tablets tapering the oral dose following
improvement prevents relapse.
Longterm control:
Dexamethasone* 0.5, 0.75, 1, 1.5, 2, 4, and 6 mg tablets Shortcourse "burst" to achieve symptom Oral glucocorticoids are used only rarely
control: 6 to 9 mg per day as a single dose as longterm control medications, eg, in
in the morning for 3 to 10 days; typically 6 patients with very poorly controlled
mg daily for 5 days. symptoms despite an optimal treatment
regimen and environmental controls.
The lowest effective dose is given daily in
the morning, or on alternate days to
minimize adrenal suppression.
For specific recommendations about the use of oral glucocorticoids in asthma, refer to UpToDate reviews on the management of asthma exacerbations and severe asthma.
PEFR: peak expiratory flow rate.
* Oral liquids are available for use by patients who are unable to swallow pills.
Data from:
1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017. Available from: www.ginaasthma.org (accessed February 17, 2017).
2. Lexicomp Online. Copyright © 19782018 Lexicomp, Inc. All Rights Reserved.
Comparison of representative glucocorticoid preparations
Relative antiinflammatory
Equivalent doses* (mg) Duration of action (hours)
activity
Glucocorticoids
Short acting
Hydrocortisone (cortisol) 20 1 8 to 12
Cortisone acetate 25 0.8 8 to 12
Intermediate acting
Prednisone 5 4 12 to 36
Prednisolone 5 4 12 to 36
Methylprednisolone 4 5 12 to 36
Triamcinolone 4 5 12 to 36
Long acting
Dexamethasone 0.75 30 36 to 72
Betamethasone 0.6 30 36 to 72
Mineralocorticoids
Fludrocortisone Not used for an antiinflammatory effect ¶ 12 to 36
The mineralocorticoid effect of commonly administered glucocorticoids may be estimated as follows:
20 mg hydrocortisone provides a mineralocorticoid effect that is approximately equivalent to 0.1 mg fludrocortisone.
25 mg of cortisone acetate provides a mineralocorticoid effect that is approximately equivalent to 0.1 mg fludrocortisone.
Prednisone or prednisolone given at antiinflammatory doses ≥50 mg per day provide a mineralocorticoid effect that is approximately equivalent to 0.1 mg of fludrocortisone.
When given at replacement doses, the other glucocorticoids listed in this table have minimal or no clinically relevant mineralocorticoid effect.
* Equivalent antiinflammatory dose shown is for oral or intravenous (IV) administration. Relative potency for intraarticular or intramuscular administration may vary considerably.
¶ The antiinflammatory potency is 10 to 15 times that of hydrocortisone; however, fludrocortisone is not used clinically as an antiinflammatory agent.
Data from:
1. Schimmer BP, Funder JW. ACTH, Adrenal Steroids, and Pharmacology of the Adrenal Cortex. In: Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12th ed, Brunton LL,
Chabner BA, Knollmann BC (Eds), McGrawHill Education 2011.
2. Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol 2013, 9:30.
Effect of intravenous montelukast versus standard
therapy in acute asthma
Patients received standard therapy plus either intravenous montelukast or
placebo infused over 5 minutes; FEV 1 responses were determined at the
indicated times. Results are expressed as the percentage changes from the
preallocation baseline FEV 1 . Montelukast at either dose caused a rapid
improvement in FEV 1 compared with placebo. There were no differences
between the montelukast treatment groups.
FEV 1 : forced expiratory volume in one second; SE: standard error; IV: intravenous.
* p<0.05 for montelukast versus placebo.
¶ p<0.01 for montelukast versus placebo.
Data from: Camargo CA Jr, Smithline HA, Malice M, et al. Montelukast in acute
asthma. Am J Resp Crit Care Med 2003; 167:528.
Lack of efficacy of aminophylline in asthma
Change in FEV 1 in 20 patients treated with both intravenous aminophylline and
inhaled metaproterenol (blue squares) and in 20 patients treated with inhaled
metaproterenol alone (red triangles). There was no added benefit from
aminophylline.
Data from: Siegel D, Sheppard D, Gelb A, Weinberg PF. Am Rev Respir Dis 1985;
132:283.
Lack of effect of theophylline during hospitalization for
acute asthma
Change in total asthma score during hospital stay in patients treated with
theophylline or placebo, showing the mean regression line of the asthma score until
the time that discharge criteria were achieved (asthma score = 2). There was no
difference between the two groups.
From DiGiulio, GA, Kercsmar, CM, Krug, SE, et al, J Pediatr 1993; 122:464.
Estimated comparative daily doses for inhaled glucocorticoids in adolescents and adults
Drug Low dose Medium dose High dose
Beclomethasone HFA 80 to 160 mcg >160 to 320 mcg >320 mcg

(Qvar product available in United States)*
40 mcg per puff 2 to 4 puffs ¶ ¶
80 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs
Beclomethasone HFA 100 to 200 mcg >200 to 400 mcg >400 mcg

(Qvar product available in Canada, Europe, and elsewhere)
100 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs
Budesonide DPI 180 to 360 mcg >360 to 720 mcg >720 mcg

(Pulmicort Flexhaler product available in United States)*
90 mcg per inhalation 2 to 4 inhalations ¶ ¶
180 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations >4 inhalations
Budesonide DPI 200 to 400 mcg >400 to 800 mcg >800 mcg

(Pulmicort Turbuhaler product available in Canada, Europe, and
elsewhere)
200 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations
400 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations
Ciclesonide HFA 80 to 160 mcg >160 to 320 mcg >320 mcg

(Alvesco product available in United States, Europe, and elsewhere)*
80 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶
160 mcg per puff 1 puff 2 puffs >2 puffs
Ciclesonide HFA 100 to 200 mcg >200 to 400 mcg >400 mcg

(Alvesco product available in Canada)
100 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶
200 mcg per puff 1 puff 2 puffs >2 puffs
Flunisolide MDI 320 mcg >320 to 640 mcg Insufficient data

(Aerospan product available in United States)*
80 mcg per puff 4 puffs 5 to 8 puffs Insufficient data
Fluticasone propionate HFA 88 to 220 mcg >220 to 440 mcg >440 mcg

(Flovent HFA product available in United States)*
110 mcg per puff 1 to 2 puffs 3 to 4 puffs
220 mcg per puff Δ 2 puffs >2 puffs
Fluticasone propionate HFA 100 to 250 mcg >250 to 500 mcg >500 mcg

(Flovent HFA product available in Canada, Europe, and elsewhere)
125 mcg per puff 1 to 2 puffs 3 to 4 puffs
250 mcg per puff Δ 2 puffs >2 puffs
Fluticasone propionate DPI 100 to 250 mcg >250 to 500 mcg >500 mcg

(Flovent Diskus product available in United States and Canada)*
100 mcg per inhalation 1 to 2 inhalations 3 to 5 inhalations
500 mcg per inhalation (strength not available in United States) Δ 1 inhalation >1 inhalation
Fluticasone furoate DPI Not available for low dose 100 mcg 200 mcg

(Arnuity Ellipta product available in United States)*
NOTE: Inhaled fluticasone furoate has a greater antiinflammatory
potency per microgram than fluticasone propionate inhalers. Thus,
fluticasone furoate is administered at a lower daily dose and used only
once daily.
100 mcg per inhalation Low dose not available in this 1 inhalation 2 inhalations

preparation
200 mcg per actuation Low dose not available in this Δ 1 inhalation

preparation
Mometasone DPI ◊ 110 to 220 mcg >220 to 440 mcg >440 mcg

(Asmanex DPI product available in United States)*
Mometasone HFA ◊ 100 to 200 mcg >200 to 400 mcg >400 mcg

(Asmanex HFA product available in United States)*
100 mcg per actuation 1 to 2 inhalations ¶ ¶
200 mcg per actuation 1 inhalation 2 inhalations >2 inhalations
Mometasone DPI ◊ 200 mcg >200 to 400 mcg >400 mcg

(Asmanex Twisthaler product available in Canada, Europe, and
elsewhere)
400 mcg per inhalation Δ 1 inhalation >1 inhalation
The most important determinant of appropriate dosing is the clinician's judgment of the patient's response to therapy. The clinician must monitor the patient's response
on several clinical parameters and adjust the dose accordingly. The stepwise approach to therapy emphasizes that once control of asthma is achieved, the dose of medication should
be carefully titrated to the minimum dose required to maintain control, thus reducing the potential for adverse effects.
Depending on the specific product, total daily doses are administered once or twice daily. Some doses may be outside approved product information.
DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant metered dose inhaler.
* Doses shown and strengths (ie, mcg per puff or inhalation) are based upon product descriptions approved in the United States which may differ from how strengths are described for products
available in other countries. Consult local product information before use.
¶ Select alternate preparation with higher mcg/puff to improve convenience.
Δ Select preparation with fewer mcg/puff.
◊ Approved for oncedaily dosing in mild asthma in some countries.
National Heart, Blood, and Lung Institute Expert Panel Report 3 (EPR 3): Guidelines for the Diagnosis and Management of Asthma; 2007. NIH Publication 084051 available at
http://www.nhlbi.nih.gov/healthpro/guidelines/current/asthmaguidelines/fullreport; updated with additional data from Global Initiative for Asthma (GINA); Global Strategy for Asthma
Management and Prevention; 2014. Available at www.ginasthma.org.
Asthma action plan
Reproduced from: National Heart, Blood, and Lung Institute Expert Panel Report 3 (EPR 3): Guidelines for the
Diagnosis and Management of Asthma. NIH Publication no. 084051, 2007.

Management of Acute Exacerbations of Asthma in Adults - UpToDate

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Management of Acute Exacerbations of Asthma in Adults - UpToDate

Uploaded by

Copyright:

Available Formats

30/4/2018 Management of acute exacerbations of asthma in adults - UpToDate

Severe hypoxemia (eg, SpO 2 ≤95 percent despite high flow O 2 treatment by nonrebreather mask) portends imminent respiratory arrest or possibly severe complication (eg,

20 554 602 649 693 740

25 543 590 636 679 725

30 532 577 622 664 710

35 521 565 609 651 695

40 509 552 596 636 680

45 498 540 583 622 665

50 486 527 569 607 649

55 475 515 556 593 634

60 463 502 542 578 618

65 452 490 529 564 603

70 440 477 515 550 587

20 390 423 460 496 529

25 385 418 454 490 523

30 380 413 448 483 516

35 375 408 442 476 509

40 370 402 436 470 502

45 365 397 430 464 495

50 360 391 424 457 488

55 355 386 418 451 482

60 350 380 412 445 475

65 345 375 406 439 468

70 340 369 400 432 461

Nebulizer solution 0.15 mg/kg (minimum 2.5 mg, maximum 5 2.5 to 5 mg every 20 minutes for three Only selective beta 2 ­agonists are

MDI Four to eight puffs every 20 minutes for Four to eight puffs every 20 minutes up to In mild­to­moderate exacerbations, MDI plus

Nebulizer solution 0.075 mg/kg (minimum 1.25 mg, maximum 1.25 to 2.5 mg every 20 minutes for three Levalbuterol administered in one­half the mg

MDI See albuterol MDI dose. See albuterol MDI dose.

Nebulizer solution See albuterol dose (thought to be half as See albuterol dose (thought to be half as Has not been studied in severe asthma

MDI See albuterol MDI dose. See albuterol MDI dose. Has not been studied in severe asthma

Terbutaline 0.01 mg/kg (maximum 0.4 mg) every 20 0.25 mg every 20 minutes for three doses, Subcutaneous/intramuscular administration

Epinephrine 0.01 mg/kg (maximum 0.4 mg) every 20 0.3 mg every 20 minutes for three doses, Subcutaneous/intramuscular administration

Medication Oral preparations Dose Comments

Methylprednisolone 2, 4, 8, 16, and 32 mg tablets Short­course "burst" for asthma Short course therapy:

Cortisone acetate 25 0.8 8 to 12

Dexamethasone 0.75 30 36 to 72

Betamethasone 0.6 30 36 to 72

Fludrocortisone Not used for an anti­inflammatory effect ¶ 12 to 36

Drug Low dose Medium dose High dose

Beclomethasone HFA 80 to 160 mcg >160 to 320 mcg >320 mcg

80 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs

Beclomethasone HFA 100 to 200 mcg >200 to 400 mcg >400 mcg

100 mcg per puff 1 to 2 puffs 3 to 4 puffs >4 puffs

Budesonide DPI 180 to 360 mcg >360 to 720 mcg >720 mcg

180 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations >4 inhalations

Budesonide DPI 200 to 400 mcg >400 to 800 mcg >800 mcg

200 mcg per inhalation 1 to 2 inhalations 3 to 4 inhalations

400 mcg per inhalation 1 inhalation 2 inhalations >2 inhalations

Ciclesonide HFA 80 to 160 mcg >160 to 320 mcg >320 mcg

80 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶

160 mcg per puff 1 puff 2 puffs >2 puffs

Ciclesonide HFA 100 to 200 mcg >200 to 400 mcg >400 mcg

100 mcg per puff 1 to 2 puffs 3 to 4 puffs ¶

200 mcg per puff 1 puff 2 puffs >2 puffs

Flunisolide MDI 320 mcg >320 to 640 mcg Insufficient data

80 mcg per puff 4 puffs 5 to 8 puffs Insufficient data

Fluticasone propionate HFA 88 to 220 mcg >220 to 440 mcg >440 mcg

110 mcg per puff 1 to 2 puffs 3 to 4 puffs

220 mcg per puff Δ 2 puffs >2 puffs

Fluticasone propionate HFA 100 to 250 mcg >250 to 500 mcg >500 mcg

125 mcg per puff 1 to 2 puffs 3 to 4 puffs

250 mcg per puff Δ 2 puffs >2 puffs

Fluticasone propionate DPI 100 to 250 mcg >250 to 500 mcg >500 mcg

Nebulizer solution 0.15 mg/kg (minimum 2.5 mg, maximum 5 2.5 to 5 mg every 20 minutes for three Only selective beta 2 agonists are

MDI Four to eight puffs every 20 minutes for Four to eight puffs every 20 minutes up to In mildtomoderate exacerbations, MDI plus

Nebulizer solution 0.075 mg/kg (minimum 1.25 mg, maximum 1.25 to 2.5 mg every 20 minutes for three Levalbuterol administered in onehalf the mg

Methylprednisolone 2, 4, 8, 16, and 32 mg tablets Shortcourse "burst" for asthma Short course therapy:

Fludrocortisone Not used for an antiinflammatory effect ¶ 12 to 36