The goal of asthma exacerbation treatment is to alleviate symptoms and restore patients’ lung function. Inhaled bronchodilators (beta-2 agonists and anticholinergics) and, in most cases, systemic corticosteroids are used to treat the condition.
For an acute exacerbation of asthma, patients are instructed to self-administer 2 to 4 puffs of inhaled albuterol or a similar short-acting beta agonist up to 3 times spaced 20 minutes apart, and to measure peak expiratory flow (PEF) if possible. When these short-acting rescue medications are effective (symptoms are relieved and PEF returns to greater than 80% of baseline), the acute exacerbation can be managed in the outpatient setting. Patients who do not respond, have severe symptoms, or have a PEF for an extended period of time should follow the physician’s treatment plan or go to the emergency department.
Emergency department care
In the emergency department, inhaled bronchodilators (beta-2 agonists and anticholinergics) are the mainstay of asthma treatment. Albuterol delivered via metered-dose inhaler (MDI) and spacer is as effective as nebulizer in adults and older children. Because of the difficulties in coordinating MDIs and spacers, nebulized treatment is preferred for younger children.
Contrary to popular belief, no data support continuous beta-2 agonist nebulization over intermittent administration. Evidence suggests that when the nebulizer is powered by a mixture of helium and oxygen (heliox) rather than pure oxygen, the bronchodilator response improves. Helium’s lower density is thought to aid in the delivery of bronchodilators to distal airways. However, technical issues with using helium for nebulization (availability, helium concentration calibration, and the need for custom masks to avoid dilution with room air) have limited its widespread adoption.
Subcutaneous epinephrine
For children, a 1 mg/mL (1:1000) solution or terbutaline is an option. Terbutaline may be preferable to epinephrine due to its lower cardiovascular effects and longer duration of action, but it is no longer widely available and is costly.
Subcutaneous beta-2 agonist administration in adults raises concerns about adverse cardiostimulatory effects. However, there are few clinically significant side effects, and subcutaneous administration may benefit patients who are unresponsive to maximal inhaled therapy or who are unable to receive effective nebulized treatment (eg, those who cough excessively, have poor ventilation, or are uncooperative).
Nebulized ipratropium
For patients who do not respond optimally to albuterol alone, this can be combined with nebulized albuterol; some evidence supports concurrent high-dose beta-2 agonist and ipratropium as first-line treatment.
Systemic corticosteroids (prednisone, prednisolone, methylprednisolone)
These steroids should be used for all but the most minor acute exacerbations; they are unnecessary for patients whose PEF returns to normal after 1 or 2 bronchodilator doses. The IV and oral routes of administration are likely to be equally effective. If an IV line is already in place, IV methylprednisolone can be administered and then switched to oral dosing as needed or convenient.
In general, higher doses (prednisone 50 to 60 mg once daily) are recommended for in-patient treatment of more severe exacerbations, while lower doses (40 mg once daily) are reserved for outpatient treatment of milder exacerbations. Although evidence on optimal dose and duration is lacking, most guidelines recommend a treatment duration of 3 to 5 days in children and 5 to 7 days in adults as adequate and should be tailored to the severity and duration of an exacerbation.
Theophylline plays a minor role in the treatment of an acute asthma attack.
Although magnesium sulfate relaxes smooth muscle, its effectiveness in the treatment of asthma exacerbations in the emergency department is debatable.
Oral vs. IV steroids in asthma exacerbation
There are many different steroids that can be used for asthma exacerbation. These steroids usually fall into two categories, oral steroids or injectable steroids. The main difference between their mode of administration. Oral steroids are taken by mouth, IV steroids are taken with the use of injections. Another difference is that injectable steroids may cause an increase in the number of red blood cells which can lead to less inflammation and less mucous production.
Oral steroids most commonly used for asthma are prednisone, beclometasone, fluticasone propionate, budesonide, ciclesonide, and mometasone furoate. Injectable steroids that are used to reduce symptoms of asthma include methylprednisolone acetate (Medrol), and dexamethasone. The use of systemic corticosteroids may result in a decreased need for rescue inhalers, but it is important to monitor the patient’s symptoms closely while on corticosteroids and ensure they are still being adequately treated with their rescue inhaler to prevent complications.
Antibiotics
These are only indicated when a history, examination, or chest x-ray suggests an underlying bacterial infection; the majority of infections underlying asthma exacerbations are most likely viral in nature.
Supplemental oxygen
This is indicated for hypoxemia and should be administered via nasal cannula or face mask at a flow rate or concentration high enough to keep oxygen saturation above 90%.
When anxiety is the cause of an asthma exacerbation, reassurance is the best approach. Anxiolytics and morphine are generally contraindicated because they are associated with respiratory depression, and morphine may cause anaphylactoid reactions due to mast cell histamine release; these medications may increase mortality and the need for mechanical ventilation.
Hospitalization
If patients have not returned to their baseline within 4 hours of aggressive emergency department treatment, hospitalization is usually required. The criteria for hospitalization vary, but there are clear indications.
- Inability to improve
- Increasing fatigue
- Relapse following beta-2 agonist therapy.
- Significant reduction in PaO2 (to 50 mm Hg)
- Significant increase in PaCO2 (to greater than 40 mm Hg)
A significant rise in PaCO2 indicates the onset of respiratory failure.
Noninvasive positive pressure ventilation (NIPPV) may be required to relieve the work of breathing in patients whose condition continues to deteriorate despite aggressive treatment. Respiratory failure may necessitate endotracheal intubation and invasive mechanical ventilation. If used early in the course of a severe exacerbation, NIPPV can be used to avoid intubation and should be considered in patients with acute respiratory distress and a PaCO2 level that is excessively high in relation to the degree of tachypnea.
It should be reserved for exacerbations that result in respiratory distress despite immediate treatment with bronchodilators and systemic corticosteroids, using criteria such as tachypnea (respiratory rate > 25 per minute), use of accessory respiratory muscles, PaCO2 > 40 but less than 60 mm Hg, and hypoxemia. If a patient has any of the following conditions, mechanical ventilation should be used instead of NIPPV:
- PaCO2 > 60 mm Hg
- Decreased level of consciousness
- Excessive respiratory secretions
- Facial abnormalities (ie, surgical, traumatic) that could impede noninvasive ventilation
If there is no discernible improvement after 1 hour of NIPPV, mechanical ventilation should be seriously considered.
Sedation can be provided through intubation and mechanical ventilation, but the routine use of neuromuscular blocking agents should be avoided due to potential interactions with corticosteroids, which can cause prolonged neuromuscular weakness. If the user is familiar with its use and adverse effects, ketamine may be used for awake intubation (eg, laryngospasm, rigidity, and bronchorrhea).
When airway resistance is high and changing, volume-cycled ventilation in assist-control mode is commonly used because it provides constant alveolar ventilation. To maximize exhalation time while minimizing auto positive end-expiratory pressure, the ventilator should be set to a relatively low frequency with a relatively high inspiratory flow rate (> 80 L/minute) (auto-PEEP).
Extrinsic PEEP should be used to facilitate patient-initiated triggering and minimize ventilator dyssynchrony caused by auto-PEEP. Initial tidal volumes can be set to 6 to 8 mL/kg of ideal body weight, and extrinsic PEEP should be used to facilitate patient-initiated triggering and minimize ventilator dyssynchrony caused by auto-PEEP. High peak airway pressures are common as a result of high airway resistance and inspiratory flow rates. Peak airway pressure does not reflect the degree of lung distention caused by alveolar pressure in these patients.
Tidal volume should be reduced if plateau pressures exceed 30 to 35 cm water to reduce the risk of pneumothorax. When tidal volumes are reduced, a moderate degree of hypercapnia (“permissive hypercapnia”) is acceptable; however, if arterial pH falls below 7.10, a slow sodium bicarbonate infusion can be considered to maintain pH between 7.20 and 7.25, particularly if there is hemodynamic instability. Patients can usually be weaned from the ventilator as soon as the airflow obstruction is relieved and PaCO2 and arterial pH return to normal.
Other therapy
Other therapies for asthma exacerbation are said to be effective, but none have been thoroughly studied. Heliox, a helium-oxygen mixture, is used to reduce work of breathing and improve ventilation by reducing turbulent flow caused by helium, a gas less dense than oxygen. Despite the theoretical benefits of heliox, studies on its efficacy have yielded conflicting results; lack of ready availability and inability to simultaneously provide high concentrations of oxygen (due to the fact that 70 to 80% of the inhaled gas is helium) may also limit its use. Heliox, on the other hand, may be useful in the treatment of patients with vocal cord dysfunction.
In patients with status asthmaticus, general anesthesia with agents such as sevoflurane and isoflurane causes bronchodilation via an unknown mechanism, possibly via a direct relaxant effect on airway smooth muscle or attenuation of cholinergic tone.
