by Nicholas Otts, MD
Edited by Gal Altberg, MD and Abbas Husain, MD
A common problem:
6 year old female with a PMHx of asthma presents to the ED with shortness of breath and wheezing.
What medications and routes have the best evidence?
A Small Dose of EBM:
There have been a wealth of studies that show a small benefit (or at least a non inferiority) with using a metered dose inhaler (MDI) with valved holding chamber (one-quarter to one-third puff/kg, minimum two puffs and maximum eight puffs per dose), versus nebulizer (.15 mg/kg, minimum 2.5 mg and maximum of 5mg per dose) for exacerbations requiring treatment.
A popular hypothesis as to why nebulizers are more nebulous with the administration of albuterol: much of the drug is lost to the surrounding environment before reaching the patient’s lungs, exacerbated by non-perfect use in the pediatric patient.
Studies below show either a non inferiority or a benefit to MDI including a decrease in hospital admission rate in those with a severe exacerbation, an improvement “severity” scores, and a decrease in length of stay in the ED (1,2,3).
That this benefit does not apply to adults further advances the theory that nebulous nebs lose some of the drug to the surrounding environment when not used perfectly (3).
Some of the advantages of using nebulized treatment include the simultaneous administration of oxygen and ipratropium bromide, as well as the ease of administration (vs. MDI) for a child in respiratory distress. Thus, when considering the best route of treatment, one must make a judgement call on the patient in front of them. If they can handle proper use of a metered dose inhaler, I think the evidence supports its use.
I like to think of the prednisolone versus dexamethasone debate as TexMex versus traditional Mexican food. TexMex is less traditional but gets the job done with equal efficacy.
A non inferior (and better if you consider parent convenience) treatment for these patients would be a single dose of dexamethasone (.6mg/kg) in the ED versus additional days of prednisolone at home. (A traditional course of 2mg/kg/day for first day and then 1mg/kg/day for next 4 days.)
A randomized trial compared a single-dose oral dexamethasone (0.3mg/kg) versus multi dose prednisolone (1mg/kg/day) and found no difference in subsequent hospital admission rates or return visits to a health care professional (4). Why prescribe the longer course and risk the bitter taste, potential for vomiting, and decreased compliance?
Some would argue that this trial only compared dexamethasone with three days of prednisolone and that we usually prescribe four additional days of steroids. To that I would site a meta analysis that showed no difference between a 3-5 day course of prednisolone (2mg/kg first day, 1mg/kg/day for subsequent 2-4 days) and dexamethasone given as a single intramuscular dose (0.3 to 1.7 mg/kg) or one to two daily oral doses (0.6mg/kg) (5).
I think time will prove that one dose is equivalent, and I think there is evidence to practice that way now (additional studies I have not cited in the adult world). If you are stuck on five days of steroids, a compromise solution would be one additional dose of dexamethasone the next day. Some would say there is nothing wrong with DexMex twice, but I think once is enough.
1 Castro-Rodriguez JA, Rodrigo GJ. Beta-agonists through metered-dose inhaler with valved holding chamber versus nebulizer for acute exacerbation of wheezing or asthma in children under 5 years of age: a systematic review with meta-analysis. J Pediatr. 2004; 145 (2): 172
2 Ploin D, Chapuis FR, et. all.High-dose albuterol by metered-dose inhaler plus a spacer device versus nebulization of preschool children with recurrent wheezing: A double-blind, randomized equivalence trial. Pediatrics. 2000; 106 (2 Pt 1): 311.
3 Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013
4 Cronin JJ, McCoy S, et.all. A Randomized Trial of Single-Dose Oral Dexamethasone Versus Multidose Prednisolone for Acute Exacerbations of Asthma in Children Who Attend the Emergency Department. Ann Emerg Med. 2016 May; 67 (5): 593-601. e3. Epub 2015 Oct 14.
5 Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics 2014; 133: 493.