Adjunctive Pharmacotherapies in Children With Asthma Exacerbations Requiring Continuous Albuterol Therapy: Findings From The Ohio Pediatric Asthma Repository

Abstract

Ipratropium and magnesium were both often used in children with severe asthma hospitalizations that required continuous albuterol therapy. Magnesium use was associated with unfavorable outcomes, possibly reflecting preferential treatment to patients with more severe cases and differing practices between centers. Given the high prevalence of asthma, wide variations in practice, and the potential to improve outcomes and costs, prospective trials of these adjunctive therapies are needed.

The effectiveness of magnesium sulfate for status asthmaticus outside the intensive care setting

“…Magnesium, when compared with other therapies, has the advantage of widespread availability, low cost, and minimal adverse effects . The only study to date that has evaluated the use of magnesium sulfate in asthmatic patients on the pediatric ward also included those in the intensive care unit and did not demonstrate shorter duration of continuous albuterol or LOS in those who received intravenous magnesium sulfate . Our study expands on these findings in that those who received magnesium did not have shorter length of continuous albuterol therapy or shorter length of stay than those who had a similar respiratory assessment score but did not receive magnesium.…”

“…The predominant theories include: 1) inhibition of cellular uptake of calcium across smooth muscle membranes leading to bronchial smooth muscle relaxation; 2) inhibition of degranulation of mast cells thus reducing inflammatory mediators such as histamine, thromboxanes, and leukotrienes; 3) inhibition of acetylcholine release at motor nerve terminals depressing the excitability of muscle fiber membranes; and 4) stimulation of nitric oxide and prostacyclin synthesis . Another potential explanation for the lack of benefit seen in our study is the possibility that maximum bronchodilator effect had been achieved through albuterol administration early and now the primary disease burden was mediated through bronchial inflammation; this is supported by numerous studies demonstrating efficacy of magnesium administration early in hospital presentation with less benefit seen later in the disease course . Other potential reasons include the possibility that patients receiving magnesium may have been more ill than reflected by RAS, there were unaccounted for confounding factors, or that magnesium sulfate may not have a positive impact in the treatment of status asthmaticus outside the ED or intensive care setting.…”

“…Emerging evidence suggests that continuous albuterol is safe to administer outside the intensive care unit (ICU); however, no studies to date have evaluated the use of adjunctive therapies outside the ED or the intensive care setting. We sought to assess the efficacy of magnesium sulfate administration among pediatric patients admitted to the general medical floor or intermediate care unit who required continuous albuterol for at least 6 h after having already received three doses of albuterol plus ipratropium and systemic corticosteroids.…”

Randomized pilot trial of ipratropium versus placebo in children with critical asthma

“…The results of our study may be useful in guiding the usage of adjunctive therapies in the ICU. Recent data show that ipratropium is frequently used in some ICUs, though hardly at all in others 10,11 . This suggests that a major factor influencing ipratropium use is institutional or regional practice patterns.…”

“…Conversely, ipratropium bromide does not decrease hospital length of stay or improve patient outcomes when used as adjunctive therapy in children admitted to the general ward 8,9 . There have been no prospective trials of ipratropium in the pediatric ICU (PICU), and use varies widely between ICUs, but overall approximately 70% of children with critical asthma are treated with it 10,11 . We, therefore, conducted a pilot randomized, double‐blind, placebo‐controlled trial to examine the effect of ipratropium on clinical outcomes for patients admitted to the PICU with critical asthma.…”