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Endogenous Glucocorticoid Response to Single-Dose Dexamethasone for Croup in Children: A Pharmacodynamic Study
Natasha Gill1,2, Natalie Sirizzotti1,2, David Johnson3
1From the Children's Hospital, London Health Sciences Centre.
Insights
Single-dose oral dexamethasone for croup in children does not suppress endogenous corticosteroid levels. This common treatment for croup in children is not associated with adrenal insufficiency.
Area of Science:
- Pediatric Endocrinology
- Pharmacodynamics
- Clinical Pharmacology
Background:
- Dexamethasone is linked to adrenal insufficiency in children with chronic conditions.
- Single-dose oral dexamethasone is the standard treatment for pediatric croup.
- The impact of single-dose dexamethasone on adrenal function in croup is not well-established.
Purpose of the Study:
- To investigate the association between single-dose oral dexamethasone and endogenous glucocorticoid levels in children with croup.
- To test the hypothesis that dexamethasone causes a transient decrease in glucocorticoids.
Main Methods:
- A prospective, two-arm pharmacodynamic study was conducted.
- Participants included children over 2 years old with croup receiving dexamethasone and controls with upper respiratory infections.
- The primary outcome measured was the urinary 6β-hydroxycortisol-cortisol ratio.
Main Results:
- No significant differences in the change of 6β-hydroxycortisol-cortisol ratios were observed between the dexamethasone and control groups at any time point.
- Median ratios in the dexamethasone group were 2.8 (baseline), 2.2 (morning), 2.0 (day 1), 2.8 (day 3), and 2.6 (day 7).
- No serious adverse events or infectious complications were reported.
Conclusions:
- Single-dose oral dexamethasone is not associated with decreased endogenous corticosteroid levels in children with croup.
- Further research using criterion standard tests is recommended to definitively rule out hypothalamic-pituitary-adrenal axis suppression.
- Future studies should also be adequately powered to detect adverse clinical outcomes.
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.