Limited Evidence Supports Escalation of Therapy for Acute Asthma Exacerbations in Kids

By Will Boggs MD

September 08, 2020

NEW YORK (Reuters Health) - Various interventions might improve outcomes in children with acute asthma exacerbations, but the paucity of evidence makes it difficult to assess the balance between benefits and potential harms, according to an overview of systematic reviews from the Cochrane Collaboration.

"There really isn't much evidence to support most of the treatments we use when treating children with acute asthma who fail to respond to first-line treatment," Dr. Simon S. Craig of Monash University, in Clayton, and Murdoch Children's Research Institute, in Parkville, Australia told Reuters Health by email.

Most children who present with mild or moderate exacerbations of asthma respond well to first-line therapy, which includes titrated oxygen delivery, inhaled short-acting beta-agonists, and systemic corticosteroids. How best to treat the small proportion of seriously ill children who do not respond to these therapies remains unclear.

Dr. Craig and colleagues evaluated the efficacy and safety of second-line escalation of therapy for children with acute exacerbations of asthma whose symptoms persist after first-line treatments by summarizing 13 Cochrane Reviews that included 67 trials of various interventions.

There was no evidence to suggest that any intervention reduced the risk of requiring intensive care. However, intravenous magnesium sulfate significantly cut the risk of hospital admission and the length of hospital stays, the researchers report in the Cochrane Database of Systematic Reviews.

The risk of hospitalization was also reduced by the addition of inhaled anticholinergic agents to inhaled beta2-agonists and by the use of inhaled heliox (a mixture of helium and oxygen).

The addition of inhaled magnesium sulfate to usual bronchodilator therapy also appeared to reduce serious adverse events during hospital admission.

Aminophylline increased vomiting compared with placebo and increased nausea and vomiting compared with intravenous beta2-agonists, whereas the addition of anticholinergic therapy to short-acting beta2-agonists appeared to reduce the risk of nausea and tremor (but not vomiting).

"Our findings provide some reassurance to clinicians in that - pretty much whatever you are doing - it's unlikely that you are doing the 'wrong' thing," Dr. Craig said. "It's just that we don't know what the best treatment is, as the existing research hasn't been able to provide this information."

"That being said, if your hospital already has an existing protocol, then it makes sense for everyone to be practicing in a similar manner," he said. "Although there isn't a robust evidence base, it doesn't make sense for each clinician to treat children with a completely different approach every time. There are many advantages to having an agreed way of doing things."

"Major problems with studies in acute severe asthma in children are small clinical trials which use inconsistent outcomes - this makes it really hard to compare treatments," Dr. Craig explained.

"We really need a consistent set of outcomes to be used between different studies and for the studies to be large enough to be able to show a difference between treatments," he said. "Given that severe asthma is quite rare, it's likely that most of these studies are going to need to be conducted across many hospitals. If we have sufficient numbers of patients and consistent outcome measures, we will then be able to work out which treatment is best."

Dr. Kyle J. Rehder of Duke Children's Hospital, in Durham, North Carolina, who has reviewed adjunct therapies for refractory status asthmaticus in children, told Reuters Health by email, "Once a child with severe asthma exacerbation is admitted to the hospital, we have a multitude of second-tier therapies with theoretical benefit, none of which consistently show benefit when studied. Unfortunately, this provides little guidance to clinicians who are caring for these hospitalized children, beyond the tincture of time allowing the disease to respond to steroid treatment and its natural course."

"For meaningful outcomes (including likelihood of hospital admission, ICU admission, or shortened hospital length of stay), the interventions showing the greatest benefit are those which are delivered during the first few hours of treatment in the emergency department - namely, intravenous magnesium and inhaled anticholinergics," he said. "Therefore, given the current evidence, the early emergency management of severe asthma will have the greatest impact on the disease course leading to recovery."

"For children in the emergency department with severe asthma exacerbation, inhaled anticholinergics should be provided with the initial treatment of inhaled beta-agonists and steroids," said Dr. Rehder, who was not involved in the new research. "If the child does not respond in the first 30-60 minutes, rapid escalation to intravenous magnesium has the best chance to prevent hospital admission or shorten their hospital stay."

He agreed with the authors "that more research is needed into secondary treatments for severe asthma exacerbation - a common cause for child hospitalization. Missing in this review is a summary of research findings on noninvasive ventilation, which has been shown to be safe and well-tolerated, but also has unclear benefit. Another area for research involves care delivery, including the utility of care pathways and protocols and optimizing unique roles on the multidisciplinary team."

SOURCE: Cochrane Database of Systematic Reviews, online August 5, 2020.