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Controlling Asthma: Acute Asthma

 

During an acute asthma episode, outflow obstruction leads to a prolonged expiratory phase. Typical findings are dyspnea, expiratory wheezing, tachypnea, tachycardia, and coughing. Pulmonary function tests provide the most useful objective measure of the extent of airflow obstruction. A PEFR can be used acutely to assess both the initial degree of airflow obstruction and the response to bronchodilator therapy. Arterial blood gas (ABG) measurements are useful in patients who do not respond to initial therapy. In acute asthma, the ABG may indicate hypoxemia (decreased pO2) and hypocapnea (decreased pCO2), with the pCO2 the more sensitive measure of ventilation. The increased respiratory rate initially leads to a decreased pCO2 and respiratory alkalosis. However, if airway obstruction persists or worsens, pCO2 concentrations will rise into the normal range and higher, potentially leading to respiratory failure.

The mainstay of therapy for acute asthma is a beta-agonist. A pharmacologic comparison of the beta-agonists available is presented in Table 1. During an acute asthma attack, beta-agonists can be administered either by inhalation or systemically. Inhalation is generally preferred due to a faster onset of effect and less systemic side effects. Inhalation therapy utilizes metered dose inhalers (MDI) or nebulization. A recent meta-analysis analyzed 12 studies (totaling 507 patients) comparing MDI with nebulization in acute airflow obstruction. Outcome measures, including changes in PFTs, hospital days, and costs, were not statistically different between the two. In ten of the studies a spacer was used with the metered dose inhaler to minimize the difficulty of coordinating inhalation with canister actuation.

Table 1. Pharmacologic Comparison of Beta-agonists Used in Asthma
Agent Dosage Forms Beta2 selectivity Beta2 potency Duration of
action
Epinephrine Inj, AS, MDI 2 +
Isoproterenol
(Isuprel)
Inj, AS, MDI, SL 1 +
Isoetharine
(Bronkosol)
AS, MDI + 6 +
Metaproterenol
(Alupent)
AS, MDI, PO 10 +++
Terbutaline
(Brethine)
Inj, AS, MDI, PO +++ 4 ++++
Albuterol
(Proventil, Ventolin)
AS, MDI, PO +++ 2 ++++
Bitolterol
(Tornalate)
MDI +++ 4 ++++
Pirbuterol
(Maxair)
MDI +++ 4 ++++
Levalbuterol
(Xopenex)
AS +++ 1 ++++
Salmeterol**
(Serevent)
MDI ++++ 1 (>12 hr)
Inj = injectable; AS = aerosol solution; MDI = metered dose inhaler; PO = oral; SL = sublingual
*Beta-2 potency: 1 = most potent, 10 = least potent
**Salmeterol is not indicated for acute asthma due to its delayed onset of action

Various dosage regimens of inhaled beta-agonists have been compared. Frequent low doses (0.05 mg/kg up to 1.7 mg q20 min), less frequent high doses (0.15 mg/kg q1 hr), and frequent high doses (0.15 mg/kg q20 min) have been compared in children. The frequent high-dose regimen elicited the best effect on PFTs without an increase in side effects. In addition, several small trials have studied continuous nebulized beta-agonists (approximately 7.5 mg albuterol/hr) which appears to be at least as effective as intermittent administration. Systemic administration of beta-agonist (usually subcutaneous) is generally avoided since inhaled beta-agonists provide as much or greater bronchodilation with fewer systemic adverse effects.

Inhaled anticholinergics such as atropine and ipratropium are effective bronchodilators; however, their effect in acute airflow obstruction is delayed and inconsistent. Several studies have shown inhaled beta-agonists to be superior to anticholinergics. The question of whether combining an anticholinergic with a beta-agonist provides any additional benefit remains to be answered. Ipratropium is available as an MDI (Atrovent), in combination with albuterol in an MDI (Combivent), and as a solution for aerosol administration. If an anticholinergic is selected for acute airflow obstruction, it should be combined with a beta agonist in the same solution. Ipratropium is preferred to atropine since it has fewer systemic anticholinergic side effects.

Until recently, theophylline had been standard therapy in managing acute asthma. Several studies comparing beta-agonist therapy with intravenous aminophylline for initial therapy of acute asthma have clearly shown beta-agonist therapy to be superior. In impending respiratory failure from acute asthma, adding theophylline to a regimen of beta-agonists may provide additional improvement in ventilation. However, this regimen is controversial. The theophylline is administered IV as a bolus followed by a continuous infusion. Table 2 lists empiric dosage selection for IV aminophylline (80% theophylline) based on patient characteristics.

Table 2. Empiric Dosage Guidelines for IV Aminophylline
Patient Population Age Aminophylline Infusion Rate (mg/kg/hr)
Children 1–9 years
9–12 years
1.0
0.875
Cigarette or marijuana smokers Adolescent (12–16 years)
Adults (16–50 years)
0.875
Non-smokers Adolescent (12–16 years)
Adults (>16 years)
0.625
0.5
Cardiac decompensation or hepatic dysfunction Adults (>16 years) 0.25
Dosage rate for infusion to maintain theophylline concentration of 10 mcg/mL after a bolus.
Theophylline = 0.8 x aminophylline

Corticosteroids are clearly indicated to control inflammation as chronic therapy in patients with asthma, but their use in acute asthma is more controversial. The anti-inflammatory effects are not seen early in therapy. However, systemic corticosteroids can increase bronchial responsiveness to beta-agonists within one hour of administration. Systemic corticosteroids should be initiated in anyone requiring hospitalization for acute asthma. Inhaled corticosteroids should be avoided during the acute attack since they may act as an airway irritant. Also, the time to onset of anti-inflammatory effects is delayed when corticosteroids are given by inhalation. Initial dosage should be 0.5 mg/kg methylprednisolone (or its equivalent) IV every six hours. Although it is typical to initiate corticosteroid therapy intravenously, oral corticosteroids may also be appropriate. Table 3 compares the relative anti-inflammatory potencies and mineralocorticoid activity of systemic cortico-steroids. Due to its mineralocorticoid activity, hydrocortisone is probably best avoided for patients in whom sodium and water retention might be detrimental (e.g., congestive heart failure). As the patient improves, therapy can be changed to oral prednisone 60–80 mg/day (1–2 mg/kg/day in children) and continued for 3–10 days. If patients begin on inhaled corticosteroids, there is no need to taper the systemic corticosteroid after hospital discharge.

Table 3. Comparison of Systemic Corticosteroids
Drug Dosage Forms Equivalent Anti-inflammatory Dose Relative Mineralocorticoid Activity Half-life (hrs)
Short-acting agents
Cortisone PO, Inj 25 0.8 0.5
Hydrocortisone PO, Liq, Inj 20 1 1.5
Intermediate-acting agents
Methylprednisolone PO, Inj 4 0.5 2.3
Prednisolone PO, Liq, Inj 5 0.8 2–5
Prednisone PO, Liq 5 0.8 3.4
Triamcinolone PO, Liq, Inj 4 0 2.6
Long-acting agents
Betamethasone PO, Liq, Inj 0.6 0 5+
Dexamethasone PO, Liq, Inj 0.75 0 3
PO = solid oral dosage form, Liq = liquid oral dosage form, Inj = injectable

Chronic Asthma

Therapy for chronic asthma aims for long-term control that addresses the underlying inflammatory component. Inhaled corticosteroids are the cornerstone of long-term control therapy and have been clearly documented to improve patient outcomes. In randomized, controlled trials, inhaled steroids have been shown to reduce the number of symptomatic days, improve lung function, reduce the number of exacerbations and hospitalizations, and reduce the need for rescue beta-agonist use. Long-term studies indicate that they affect the degree of airway remodeling. The NAEPP has published Guidelines for the Diagnosis and Management of Asthma to assist clinicians caring for patients with asthma.

 

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