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Treatment of Acute Asthma Exacerbations

By Victor E. Ortega, MD, PhD, Assistant Professor, Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy, and Immunologic Diseases, Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine ; Emily J. Pennington, MD, Pulmonologist, Wake Forest School of Medicine

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(See also Asthma.)

The goal of asthma exacerbation treatment is to relieve symptoms and return patients to their best lung function. Treatment includes

  • Inhaled bronchodilators (beta-2 agonists and anticholinergics)

  • Usually systemic corticosteroids

Patients having an asthma exacerbation are instructed to self-administer 2 to 4 puffs of inhaled albuterol or a similar short-acting beta-2 agonist up to 3 times spaced 20 min apart for an acute exacerbation and to measure PEF if possible. When these short-acting rescue drugs are effective (symptoms are relieved and PEF returns to > 80% of baseline), the acute exacerbation may be managed in the outpatient setting. Patients who do not respond, have severe symptoms, or have a PEF persistently < 80% should follow a treatment management program outlined by the physician or should go to the emergency department (see Table: Drug Treatment of Asthma Exacerbations*, † for specific dosing information).

Drug Treatment of Asthma Exacerbations*, †

Drug

Form

Dosage in Children

Dosage in Adults

Comments

Systemic beta-2 agonists

Epinephrine

Injectable solution: 1 mg/mL (1:1000)

0.01 mL/kg /dose sc (maximum 0.4–0.5 mL q 20 min for 3 doses or q 4 h prn)

0.2–0.5 mg sc q 20 min (for maximum of 3 doses) or q 2 h prn

Subcutaneous administration is no more effective than inhalation and may have more adverse effects.

Use in adults is controversial and may be contraindicated if significant cardiovascular disease is present.

Terbutaline

Injectable solution: 1 mg/mL

< 12 yr: 0.005–0.01 mg/kg q 20 min up to 3 doses; may repeat q 2–6 h prn

12 yr: Same as adults

0.25 mg sc once

May repeat in 15–30 min (maximum 0.5 mg over 4 h)

Short-acting beta-2 agonists

Albuterol

HFA: 90 mcg/puff

Same as adults

4–8 puffs q 20 min for 3 doses, then q 1–4 h prn

MDI is as effective as nebulized solution if patients can coordinate inhalation maneuver using spacer and holding chamber.

Nebulized solution: 5 mg/mL and 0.63, 1.25, and 2.5 mg/3 mL

0.15 mg/kg (minimum 2.5 mg) q 20 min for 3 doses, then 0.15–0.3 mg/kg up to 10 mg q 1–4 h prn

Alternatively, 0.5 mg/kg/h continuous nebulization

2.5–5 mg q 20 min for 3 doses, then 2.5–10 mg q 1–4 h prn

(Alternatively, 10–15 mg/h continuous nebulization is similarly effective but increases frequency of adverse effects.)

Levalbuterol

HFA: 90 mcg/puff

Same as adults

4–8 puffs q 20 min for 3 doses, then q 1–4 h prn

Levalbuterol is the R-isomer of albuterol.

0.63 mg is equivalent to 1.25 mg racemic albuterol.

Levalbuterol may have fewer adverse effects than albuterol.

Nebulized solution: 0.63 and 1.25 mg/3 mL

0.075 mg/kg (minimum 1.25 mg) q 20 min for 3 doses, then 0.075–0.15 mg/kg up to 5 mg q 1–4 h prn

Alternatively, 0.25 mg/kg/h continuous nebulization

1.25–2 mg q 20 min for 3 doses, then 1.25–5 mg q 1–4 h prn

Alternatively, 5–7.5 mg/h continuous nebulization

Anticholinergics

Ipratroprium

Nebulized solution: 500 mcg/2.5 mL (0.02%)

0.25–0.5 mg q 20 min for 3 doses, then q 2–4 h prn

0.5 mg q 20 min for 3 doses, then q 2–4 h prn

Ipratropium should be added to beta-2 agonists and not used as first-line therapy.

It may be mixed in same nebulizer as albuterol.

Dose delivered from MDI is low and has not been studied in exacerbations.

Combination drugs

Ipratroprium and albuterol

SMI:

20 mcg ipratroprium and 100 mcg albuterol/puff

Same as adults

1 puff q 30 min for 3 doses, then q 2–4 h prn

Ipratropium prolongs bronchodilator effect of albuterol.

Nebulized solution: 0.5 mg ipratropium and 2.5 mg albuterol in a 3-mL vial

1.5 mL q 20 min for 3 doses, then q 2–4 h prn

3 mL q 30 m for 3 doses, then q 2–4 h prn

Systemic corticosteroids

Methylprednisolone

Tablets: 2, 4, 8, 16, and 32 mg

Inpatient:1 mg/kg q 6 h for 48 h, then 0.5–1.0 mg/kg bid (maximum, 60 mg/day) until PEF = 70% of predicted or personal best

Outpatient burst: 0.5–1.0 mg/kg bid (maximum 60 mg/day for 3–5 days)

Inpatient: 40–60 mg q 6 h or q 8 h for 48 h, then 60–80 mg/day until PEF = 70% of predicted or personal best

Outpatient burst: 40–60 mg in single or 2 divided doses for 5–7 days

IV has no advantage over oral administration if GI function is normal.

Higher doses provide no advantage in severe exacerbations.

Usual regimen is to continue frequent multiple daily doses until FEV1 or PEF = 50% of predicted or personal best and then lower the dose to bid, usually within 48 h.

Therapy after a hospitalization or ED visit may last 5–10 days.

Tapering the dose is not needed if patients are also given inhaled corticosteroids.

Prednisolone

Tablets: 5 mg

Orally disintegrating tablets: 10, 15, and 30 mg

Solution: 5, 10, 15, 20 and 25 mg/5 mL

Prednisone

Tablets: 1, 2.5, 5, 10, 20, and 50 mg

Solution: 5 mg/mL and 5 mg/5 mL

*All ages unless specified differently.

Amount and timing of ongoing doses are dictated by clinical response.

ED = emergency department; FEV1= forced expiratory volume in 1 sec; HFA = hydrofluoroalkane; MDI = metered-dose inhaler; PEF = peak expiratory flow.

Adapted from National Heart, Lung, and Blood Institute: Expert Panel Report 3: Guidelines for the diagnosis and management of asthma—full report 2007. August 28, 2007. Available at www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.

Emergency department care

Inhaled bronchodilators (beta-2 agonists and anticholinergics) are the mainstay of asthma treatment in the emergency department. In adults and older children, albuterol given by an MDI and spacer is as effective as that given by nebulizer. Nebulized treatment is preferred for younger children because of difficulties coordinating MDIs and spacers; evidence suggests that bronchodilator response improves when the nebulizer is powered with a mixture of helium and oxygen (heliox) rather than with oxygen.

Subcutaneous epinephrine 1:1000 solution or terbutaline is an alternative for children. Terbutaline may be preferable to epinephrine because of its lesser cardiovascular effects and longer duration of action, but it is no longer produced in large quantities and is expensive.

Subcutaneous administration of beta-2 agonists in adults raises concerns of adverse cardiostimulatory effects. However, clinically important adverse effects are few, and subcutaneous administration may benefit patients unresponsive to maximal inhaled therapy or patients unable to receive effective nebulized treatment (eg, those who cough excessively, have poor ventilation, or are uncooperative).

Nebulized ipratropium can be co-administered with nebulized albuterol for patients who do not respond optimally to albuterol alone; some evidence favors simultaneous high-dose beta-2 agonist and ipratropium as first-line treatment, but no data favor continuous beta-2 agonist nebulization over intermittent administration. Theophylline has very little role in treatment.

Systemic corticosteroids (prednisone, prednisolone, methylprednisolone) should be given for all but the mildest acute exacerbation; they are unnecessary for patients whose PEF normalizes after 1 or 2 bronchodilator doses. IV and oral routes of administration are probably equally effective. IV methylprednisolone can be given if an IV line is already in place and can be switched to oral dosing whenever necessary or convenient. . In general, higher doses (prednisone 50 to 60 mg once/day) are recommended for the management of more severe exacerbations requiring in-patient care while lower doses (40 mg once/day) are reserved for outpatient treatment of milder exacerbations. Although evidence about optimal dose and duration is weak, a treatment duration of 3 to 5 days in children and 5 to 7 days in adults is recommended as adequate by most guidelines and should be tailored to the severity and duration of an exacerbation (1, 2).

Antibiotics are indicated only when history, examination, or chest x-ray suggests underlying bacterial infection; most infections underlying asthma exacerbations are probably viral in origin.

Supplemental oxygen is indicated for hypoxemia and should be given by nasal cannula or face mask at a flow rate or concentration sufficient to maintain oxygen saturation > 90%.

Reassurance is the best approach when anxiety is the cause of asthma exacerbation. Anxiolytics and morphine are relatively contraindicated because they are associated with increased mortality and the need for mechanical ventilation.

Hospitalization

Hospitalization generally is required if patients have not returned to their baseline within 4 h of aggressive emergency department treatment. Criteria for hospitalization vary, but definite indications are

  • Failure to improve

  • Worsening fatigue

  • Relapse after repeated beta-2 agonist therapy

  • Significant decrease in Pao2 (< 50 mm Hg)

  • Significant increase in Paco2 (> 40 mm Hg)

A significant increase in PaCO2 indicates progression to respiratory failure.

Noninvasive positive pressure ventilation (NIPPV) may be needed in patients whose condition continues to deteriorate despite aggressive treatment, to alleviate the work of breathing. Endotracheal intubation and invasive mechanical ventilation may be needed for respiratory failure. NIPPV can be used to prevent intubation if used early in the course of a severe exacerbation and should be considered in patients with acute respiratory distress with a level of PaCO2 that is inappropriately high in relation to the degree of tachypnea. NIPPV should be reserved for exacerbations that, despite immediate therapy with bronchodilators and systemic corticosteroids, result in respiratory distress, using criteria such as tachypnea (respiratory rate > 25 per minute), use of accessory respiratory muscles, PaCO2 > 40 but < 60 mm Hg, and hypoxemia. Mechanical ventilation should be used rather than NIPPV if patients have any of the following:

  • PaCO2 > 60 mm Hg

  • Decreased level of consciousness

  • Excessive respiratory secretions

  • Facial abnormalities (ie, surgical, traumatic) that could impede noninvasive ventilation

Mechanical ventilation should be strongly considered if there is no convincing improvement after 1 h of NIPPV.

Intubation and mechanical ventilation allows the provision of sedation to further alleviate the work of breathing, but the routine use of neuromuscular blocking agents should be avoided because of possible interactions with corticosteroids that can cause prolonged neuromuscular weakness.

Generally, volume-cycled ventilation in assist-control mode is used because it provides constant alveolar ventilation when airway resistance is high and changing. The ventilator should be set to a relatively low frequency with a relatively high inspiratory flow rate (>80 L/min) to prolong exhalation time, minimizing auto positive end-expiratory pressure (PEEP). Initial tidal volumes can be set to 6 to 8 mL/kg of ideal body weight. High peak airway pressures will generally be present because they result from high airway resistance and inspiratory flow rates. In these patients, peak airway pressure does not reflect the degree of lung distention caused by alveolar pressure. However, if plateau pressures exceed 30 to 35 cm water, then tidal volume should be reduced to limit the risk of pneumothorax. When reduced tidal volumes are necessary, a moderate degree of hypercapnia is acceptable, but if arterial pH falls below 7.10, a slow sodium bicarbonate infusion is indicated to maintain pH between 7.20 and 7.25. Once airflow obstruction is relieved and Paco2 and arterial pH normalize, patients can usually be quickly weaned from the ventilator. (For further details, see Respiratory Failure and Mechanical Ventilation.)

Other therapy

Other therapies are reportedly effective for asthma exacerbation, but none have been thoroughly studied. A mixture of helium and oxygen (heliox) is used to decrease the work of breathing and improve ventilation through a decrease in turbulent flow attributable to helium, a gas less dense than oxygen. Despite the theoretical benefits of heliox, studies have reported conflicting results concerning its efficacy; lack of ready availability and inability to concurrently provide high concentrations of oxygen (due to the fact that 70 to 80% of the inhaled gas is helium) may also limit its use. Magnesium sulfate relaxes smooth muscle, but efficacy in management of asthma exacerbation in the emergency department is debated. General anesthesia in patients with status asthmaticus causes bronchodilation by an unclear mechanism, perhaps by a direct relaxant effect on airway smooth muscle or attenuation of cholinergic tone.

General references

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • ELIXOPHYLLIN
  • ORAPRED, PRELONE
  • ATROVENT
  • No US brand name
  • XOPENEX
  • ADRENALIN
  • DURAMORPH PF, MS CONTIN
  • RAYOS
  • MEDROL
  • PROVENTIL-HFA, VENTOLIN-HFA