Levalbuterol Versus Albuterol
Sometimes children or their caregivers are intolerant of albuterol’s side effects, namely palpitations, tremors, hyperactivity, insomnia, and tachycardia. Levalbuterol (Xopenex), the (r)-enantiomer of racemic albuterol, was first introduced in 1999 and was subsequently FDA approved in 2002 for use in children ages 6 to 11 at a dose of 0.31 mg three times a day via nebulization. There is debate on whether levalbuterol’s higher cost justifies its questionable therapeutic benefits over albuterol. Anecdotally, only a minor subgroup of patients seem to experience fewer incidences of tachycardia, palpitations, and tremors when switched from albuterol to levalbuterol.
Interestingly, though, a recent trial by Carl et al demonstrated a 9% reduction in hospitalizations from the ED in children ages 1 to 18 (mean age, about 7) with asthma who received 1.25 mg of levalbuterol (n = 278) or 2.5 mg of albuterol (n = 269). However, levalbuterol failed to decrease the number of ED visits and hospital lengths of stay. There was no difference in mean heart rates between the two groups. Of concern is the uniform dosing of 1.25 mg of levalbuterol and 2.5 mg of albuterol in all age groups; this results in higher doses than recommended. To the authors’ credit, in clinical practice, many children do not receive age- or weight-appropriate doses of albuterol or levalbuterol. Perhaps a trial of albuterol dose-reduction, or prescribing of weight-appropriate albuterol dosages, may suffice to minimize side effects without compromising the patient’s outcome.
Ipratropium bromide is rarely used as monotherapy, but it is an acceptable alternative to albuterol or levalbuterol if the child is allergic to or intolerant of these drugs. Combination treatment with albuterol is most beneficial in children with severe exacerbations if administered during the first two hours of management and can lead to improvements in FEV1 (forced expiratory volume in one second) and possibly decreased hospitalizations.
However, routine use of ipratropium bromide in already hospitalized patients does not offer additional clinical benefit after repeated beta-agonist treatments and systemic corticosteroids. Of note, pharmacists should screen for food allergies, especially to peanuts, to avoid anaphylactic reactions after ipratropium metered dose inhaler (MDI) administration because it contains soy lecithin as an excipient.
Nebulization Versus MDI Treatment
Nebulizers are ideal for children with an acute severe exacerbation or who are too young to use an metered dose inhaler (MDI). However, they are bulky, expensive, and inconvenient when traveling. Much literature now supports the use of MDIs with a spacer/holding chamber to deliver bronchodilators during acute exacerbations, even in moderate and severe attacks. Sometimes as many as six actuations of the inhaler may be needed for a more severe exacerbation, as opposed to the two puffs that are usually prescribed.
Overall, metered dose inhalers (MDIs) are preferred by parents and caregivers because they offer portability, speed of use, cost savings, and, most important, effectiveness and safety similar to those of nebulizer treatments. Oftentimes, children have both modes of delivery at home. Caregivers should be educated to avoid overreliance on nebulizers at home instead of seeking prompt medical care.
A short-course burst of prednisone or prednisolone at 1 to 2 mg/kg/day (maximum 60 mg/day) or intravenous (IV) methylprednisolone 0.25 to 2 mg/kg/day in divided doses for three to 10 days or longer is the mainstay of acute treatment for children who do not completely respond to initial bronchodilation for prompt control. It is also recommended at the onset of viral infections that trigger a moderate to severe exacerbation, especially if a history of severe exacerbations exists. The oral route is as effective as the intravenous route, thus it is preferred unless the patient is intolerant of oral administration, in severe respiratory distress, or comatose.
Of note, children may have preferences regarding oral liquid prednisolone products or may not want them at all due to poor palatability. The pharmacist may help in getting children to take the medications or can recommend tablets, providing the child can swallow them. Parenteral corticosteroids should be converted to oral corticosteroids when the patient is stable and can tolerate the oral route. Common side effects are transient leukocytosis and hyperglycemia. Some patients may have an increased appetite. Tapering of corticosteroids is not necessary for therapy continued for less than two weeks. Children who have received multiple short-burst courses of systemic corticosteroids may benefit from a taper.
Once the standard initial treatment for acute asthma exacerbations, subcutaneous (SC) epinephrine is becoming antiquated due to its adverse effect profile. Instead, in clinical practice it is reserved for severe exacerbations refractory to inhaled bronchodilators and systemic steroids. One dose of SC epinephrine is usually administered. Two subsequent doses may be given at 20-minute intervals if the response is insufficient. Alternatively, a dose of intravenous (IV) magnesium may precede the use of SC epinephrine, depending on the preference of the clinician. Health care professionals should monitor for cardiac side effects after each dose of subcutaneous (SC) epinephrine is given.
The use of intravenous (IV) magnesium for bronchodilation is becoming increasingly popular but remains controversial in children who have moderate to severe asthma; neither the NAEPP nor the FDA currently recommends IV magnesium for this indication. One small, randomized, double-blind, placebo-controlled trial (RCT) of 31 children (mean age, 11.4 years) receiving 25 mg/kg (maximum 2 g) of magnesium (n = 15) or placebo (n = 16) in the ED after three beta2-agonist treatments demonstrated a statistically significant improvement in the magnesium group in pulmonary function without side effects within 80 minutes postinfusion and in hospitalization rates.
Another small RCT of 54 children (24 vs 30 placebo, 75 mg/kg/dose magnesium vs placebo, respectively) in the ED demonstrated that IV magnesium administered after conventional nebulized albuterol and methylprednisolone did not change clinical outcome. A single dose of 25 mg/kg (maximum 2 g) of intravenous (IV) magnesium may be considered in patients who are unresponsive to conventional therapy.
Theophylline, or aminophylline, is not a first-line treatment due to its questionable efficacy and safety concerns. However, a recent placebo-controlled trial (RCT) of 47 children (mean age, about 9 years) examining the role of theophylline after conventional rescue therapy in severe status asthmaticus in the pediatric intensive care unit demonstrated improvement of recovery time with a bolus of 7 mg/kg followed by infusions run at age-appropriate rates. Acceptable serum concentrations were 12 to 17 µg/mL. Theophylline may be considered for moderate to severe exacerbations with close monitoring of serum concentrations and side effects (nausea, emesis, agitation, and seizures).