Endogenous Glucocorticoid Response to Single-Dose Dexamethasone for Croup in Children

Abstract

Objectives Dexamethasone is associated with adrenal insufficiency in adults and children with chronic disease. This association has not been studied after single-dose oral dexamethasone, the standard of care for children with croup. We hypothesized that single-dose oral dexamethasone in children with croup is associated with a transient decrease in endogenous glucocorticoids. Methods We conducted a prospective, 2-arm, pharmacodynamic study of single-dose oral dexamethasone 0.6 mg/kg (maximum, 12 mg) in children older than 2 years with croup compared with controls (children with febrile upper respiratory tract infections who did not receive dexamethasone). Primary outcome was urinary 6β-hydroxycortisol–cortisol ratio. Results Twenty-seven children were analyzed (22 with croup and 5 with upper respiratory tract infections). Median 6β-hydroxycortisol–cortisol ratios before dexamethasone, the following morning, and on days 1, 3, and 7 were 2.8, 2.2, 2.0, 2.8, and 2.6, respectively. Among controls, the median 6β-hydroxycortisol–cortisol ratios at the same time intervals was 1.9, 1.5, 1.8, 2.5, and 1.7, respectively. There were no significant differences in the change from time 0 between groups at any time point. There were no serious adverse events or infectious complications. Conclusions Single-dose oral dexamethasone is not associated with decreased endogenous corticosteroid levels in children with croup. Future studies should use criterion standard tests to rule out suppression of the hypothalamic-pituitary-adrenal axis and be powered sufficiently to identify adverse clinical outcomes.

Safety of corticosteroids in young children with acute respiratory conditions: a systematic review and meta-analysis

“…The number of studies contributing to each meta-analysis ranged from one to seven (range 58–2178 children). There were no statistically significant differences between: (1) systemic corticosteroid compared with placebo for severe infections,30 74 96 99 systemic infections,30 40 43 83 infections of the lung/trachea30 40 54 74 96 98 105 and the upper respiratory tract,30 43 54 65 67 74 and voice complaints43 (estimated pORs between 0.15 and 1.26) and (2) inhaled corticosteroid compared with placebo for severe infections,45 systemic infections,43 45 lung/trachea,45 infections of the upper respiratory tract37 44 45 65–67 or voice complaints37 43 100 101 (estimated pORs between 0.54 and 1.51). No study comparing dexamethasone with another corticosteroid reported infections or respiratory AEs.…”

“…Database and grey literature searches yielded 9134 records. Eighty-six papers (85 studies)23–108 involving 11 505 participants were included (figure 1). Characteristics of the included studies are in online supplementary file 3.…”