Written by Sam Parnell
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Low dose dexamethasone 0.15 mg/kg and prednisolone 1 mg/kg had similar efficacy to the standard dexamethasone 0.6 mg/kg for treatment of croup. In addition, length of stay, use of nebulized epinephrine, recurrent presentations, and adverse events were similar for all steroids used for croup treatment.
Why does this matter?
Multiple studies have shown steroids significantly decrease the rate of hospital admission, length of stay, return visits, endotracheal intubation, and admission to ICUs in patients with croup. Oral dexamethasone 0.6 mg/kg is the traditional steroid used for croup management. However, are other steroid formulations such as low dose dexamethasone or prednisolone similarly effectively?
Croup on steroids…
This was a prospective, double blind, randomized controlled trial at 2 hospitals in Australia with 1,252 patients comparing the standard 0.6 mg/kg oral dexamethasone to lower-dose dexamethasone (0.15 mg/kg) and prednisolone (1 mg/kg) for croup management. The primary endpoints were croup severity measurements (using the Westley Croup Score – WCS) from baseline to 1, 2, and 3 hours after treatment as well as the rate of unscheduled medical re-attendance in the week after initial treatment.
There was no statistically significant difference between the groups for croup severity score at the 1 and 2 hour assessments after steroid administration. The vast majority (92%) of patients were successfully treated and discharged within 2 hours, improving from an average WCS of ∼1.5 to ∼0.5 over the first hour after treatment, with no differences between the 3 groups. The WCS was 0.23 higher at 3 hours for the 0.15 mg/kg dexamethasone group compared to the 0.6 mg/kg dexamethasone group which was statistically significant (P=.04) but within the non-inferiority margin. See Figure below from the article for reference.
From cited article
Re-attendance rates for medical care were modest at 17.8% (dexamethasone), 19.5% (low-dose dexamethasone), and 21.7% (prednisolone), and similarly, repeat ED visit rates were low at 5.9% (dexamethasone), 8.8% (low-dose dexamethasone), and 7.5% (prednisolone), with no statistical difference between treatment groups.
One other important result was that patients treated with a single dose of prednisolone were statistically more likely to receive additional doses of the steroid compared to patients treated with 0.6 mg/kg dexamethasone (18.9% vs 11.3%, P = .02), which is likely related to prednisolone’s shorter duration of action. The length of stay, use of nebulized epinephrine, and adverse events were similar for all steroids used for croup treatment.
These results suggest low dose dexamethasone 0.15 mg/kg and prednisolone 1 mg/kg are safe and effective alternatives to dexamethasone 0.6 mg/kg for the treatment of croup. However, further investigation is likely needed before dexamethasone 0.6 mg/kg is dethroned as the gold standard for croup management.
Source
Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial. Pediatrics. 2019 Aug 15. pii: e20183772. doi: 10.1542/peds.2018-3772. [Epub ahead of print]
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Reviewed by Clay Smith and Thomas Davis
I believe there is a flaw in the statistical approach to this research and for this reason am less sanguine about using 0.15mg/kg for croup. The standard is a 1-sided CI, whereas they used a 2-sided CI to draw their conclusion. Perhaps 0.3mg/kg (prednisone equivalent of about 2mg/kg). From a brief review of noninferiority trials in JAMA, 6/15/15:
"Although superiority or inferiority of a new treatment can be
demonstrated by a superiority trial, it would generally be incorrect
to conclude that the absence of a significant difference in a superiority trial demonstrates that the therapies have similar effects; absence of evidence of a difference is not reliable evidence that there
is no difference."
Don, thank you so much for this comment. I am not ready to accept a low-dose strategy. Appreciate your stats expertise as always.
These Australian trials of low dose Dex have been tried in North America and failed in the past.