Can less be more in critical asthma in children?

Status asthmaticus is notoriously hard to study. Although status asthmaticus is one of the most common causes of admission to a Pediatric Intensive Care Unit (PICU), given the heterogeneity of disease processes within a PICU there are relatively few admissions per year to any particular PICU and so recruiting for a clinical trial can take years. Additionally, most children with status asthmaticus in the PICU improve rapidly over 1–2 days regardless of the treatment received. This makes it difficult to demonstrate the effect of any particular therapy. With few clinical trials, clinicians fall back on anecdotal evidence and experience, resulting in strongly held beliefs about which therapies work despite the paucity of evidence. These strongly held beliefs further make collaboration between PICUs even more challenging since each PICU has its local firmly held status asthmaticus pathway. Despite this environment, first‐line therapy for status asthmaticus is consistent across centers. Inhaled β‐agonists and corticosteroids are the mainstay of acute asthma treatment. However absent clinical trials, children who do not respond sufficiently to first‐line therapy receive one or more of several second‐line therapies. This choice is primarily based on local and regional practice and individual clinician preference. Ipratropium is one of these second‐line therapies and is frequently used in the PICU. More than 20 years ago, a study in the Emergency Department setting showed that ipratropium was associated with decreased hospitalizations in children. However, since then, several studies have failed to show improved outcomes with ipratropium in other settings. It is in this environment that a study such as Dr. Murphy's is impressively conducted. Performing clinical trials of status asthmaticus in children at a single center requires a sustained effort over several asthma seasons. This sort of persistence is challenging, and the investigators should be congratulated on finishing and publishing this trail. In this issue of Pediatric Pulmonology, Murphy et al. conducted a randomized double‐blinded placebo‐controlled trial of ipratropium in children with critical asthma. Children were randomized to receive either ipratropium or placebo until they had been weaned to intermittent albuterol therapy every 2 h. This study, which stretched over 3 years, found no improvement in outcomes in the group that received ipratropium including similar hospital and PICU length of stay and similar time until spaced to every 2‐h albuterol. A multivariate linear regression adjusting for confounders also failed to show a benefit to ipratropium. Recently, there has been a concerted movement to more cautiously consider therapies that have no proven benefit, and to attempt to provide less therapy when possible. This more conservative approach involves tolerating some degree of pathophysiology and adaptive responses while avoiding an interventionalist approach to restore normalcy for normalcy's sake. We tend to overestimate the positive effects of our therapies and underestimate the negative effects. Just a decade ago, PICUs were filled with intubated children with bronchiolitis for weeks on end. Now, many of these children are treated with noninvasive ventilation, and although they may have significant tachypnea and some respiratory acidosis, the overall outcomes are much improved in this population with significantly shorter PICU length of stays and less invasive devices. This balanced and more holistic approach to intensive care may also be applicable in critical asthma in children. Children with critical asthma are frequently treated with multiple second‐line therapies at the same time, rather than in a stepwise fashion to assess whether a child is responding to a particular therapy. Many of these children might improve with standard first‐line therapies of albuterol and corticosteroids if allowed time to respond. There is frequently a pressure to do “something” in the PICU, even if these therapies have no proven benefit. Time and observation are underutilized therapeutic tools in critical care. With several negative clinical trials, it might be time just to stop using some of these unproven second‐line asthma therapies (such as ipratropium) for critical asthma in children. Even in the PICU, less can be more.