2014 Update

Though a meta-analysis shows that racemic epi may help on the initial visit, the AAP recommended that it not be used as a trial therapy for most outpatient providers in its latest clinical practice guideline. You’ll see that my original post and recommendation aligns with what the AAP says.

Welcome to part 3 of the bronchiolitis series. Parts 1 and 2 are here and here. We’ve already explored how (un)helpful albuterol can be, so what about other respiratory treatments. Well, it turns out that other options exist. Most of you are familiar with its use in croup – but Racemic Epinephrine has theoretical benefits for patients with bronchiolitis due to alpha and beta agonist effects.

Alpha agonist: Vasoconstriction leading to reduction of airway edema

Beta agonist: Bronchoconstriction leading to decreased airway resistance

Let’s take a look at some of the studies, both inpatient and outpatient, that have attempted to address the effectiveness of racemic epi in bronchiolitis.

An example of the case FOR racemic epi
Kristjansson et al, Archives of Disease in Childhood, 1993  

In this randomized study of admitted children <18 months with bronchiolitis the investigators noted improvements in clinical score and O2 sat at 30, 45, and 60 minutes after racemic epi treatment. It was limited by low numbers (29 patients), and did show a small (though likely clinically insignificant increase) in systolic BP immediately after and 45 minutes after treatment.

An example of the case AGAINST racemic epi
Wainwright et al, NEJM, 2003 

This randomized, double-blinded placebo controlled trial compared racemic epi with placebo in nearly 200 Australian bronchiolitics. The authors noted that “the use of nebulized epinephrine did not significantly reduce the length of the hospital stay or the time until the infant was ready for discharge,

[or the total time that supplemental O2 was required] among infants admitted to the hospital with bronchiolitis.”

Just get to the meta-analysis already!
Hartling et al, Cochrane Database, 2011

Lest I bombard you with tons of studies – let’s take a look at a recent Cochrane database systematic review. The authors included RCTs comparing racemic epi with placebo or another therapy (albuterol, steroids etc,.) in children <2 years with bronchiolitis. The primary outcomes investigated included rate of admission for outpatients and length of stay for inpatients. The secondary outcomes included clinical severity scores, pulmonary function, symptoms, quality of life and adverse events. In the interest of brevity let’s take a look at a few of the results. I’ll be reporting the outcome, along with risk ratios and 95% CI for all. Go ahead an take a guess at what you think the outcomes are, and click the + sign to check the answer.

[toggle_box] [toggle_item title=”Racemic Epi & Hospital Admission” active=”false”]Reduces the risk of admission at Day 1 post emergency department visit     0.67 [0.50, 0.89][/toggle_item] [toggle_item title=”Racemic Epi vs Albuterol & Hospital Admission” active=”false”]No difference in the risk of hospital admission     0.67 [0.41, 1.09][/toggle_item] [toggle_item title=”Racemic Epi & Hospital Length of Stay” active=”false”]No difference in overall LOS     -0.35 [-0.87, 0.17][/toggle_item] [toggle_item title=”Racemic Epi vs Albuterol & Hospital Length of Stay” active=”false”]Racemic epi reduces the overall LOS     -0.28 [-0.46, -0.09][/toggle_item] [toggle_item title=”Racemic Epi & Clinical Score at 30 minutes – Outpatient” active=”false”]Racemic epi improves clinical score in outpatients at 30 minutes     -0.73 [-1.13, -0.33][/toggle_item] [toggle_item title=”Racemic Epi & Clinical Score at 30 minutes – Inpatient” active=”false”]Racemic epi makes no difference in clinical score in inpatients at 30 minutes     -0.04 [-0.49, 0.40][/toggle_item] [toggle_item title=”Racemic Epi vs Albuterol & Clinical Score at 30 minutes – Outpatient” active=”false”]Racemic epi improves clinical score at 30 minutes for outpatients better than albuterol     -0.50 [-0.98, -0.02][/toggle_item] [/toggle_box]

What does this all mean?

Well, here are my take home points? There isn’t great evidence to support the use of racemic epi in all inpatients even though it reduces the overall LOS slightly when compared to albuterol, but not vs placebo. There is some evidence to suggest that it does improve clinical score at 30 minutes (and at other time intervals – not shown in this post) in a manner that is superior to albuterol. It also has similar adverse effects (tachycardia, hypertension). Hey Brad, so if we give a racemic epi do we need to wait 2 or 3 hours like we do in croup for the “rebound” effect? That isn’t so clear. The rebound effect does exist, which is manifested in increased wheezing and worsening edema. These rebound effects are worse after repeated use.

Finally, since racemic epi’s effects are transient and home use is not possible/practical discharging a patient home after use in the ED/monitored setting raises concerns about illness progression even if you wait for the rebound effect.  The above systematic review did show a decrease in first visit admission rates vs placebo – but no change in rate of return visits. So, in short, racemic epi may help, but you better know why you are using it and its limitations. For most clinicians it isn’t appropriate for outpatient use, but in the ED setting, with parents that are knowledgable and have follow up it might be a good idea.

Stay tuned for more content coming really soon. And thanks again to Todd Florin, MD, MSCE.