24-hour Pretreatment with Low Dose (0.25mg/Kg/dose) versus High Dose
(0.5mg/Kg/dose) Dexamethasone for prevention of Post-Extubation Airway
Obstruction in Children: A Randomized Open-label Non-inferiority Trial
Abstract
Objective: Multi-dose dexamethasone pretreatment prevents postextubation
airway obstruction (PEAO), however, its optimal dose in children is not
known. We planned to compare effect of 24h pretreatment of low dose (LD)
(0.25mg/kg/dose) versus high dose (HD) (0.5mg/kg/dose) dexamethasone for
prevention of PEAO. Design: Stratified (for age and intubation duration)
randomized open-label non-inferiority trial. Setting: 15-bed Pediatric
Intensive Care Unit in a tertiary care teaching hospital of a
lower-middle income country. Patients: Children (3mo-12yrs) intubated
for ≥48h and planned for first extubation over 26 months (Feb’17 to
Mar’19). Children with preexisting upper airway conditions, chronic
respiratory diseases, steroid or IVIG therapy in last 7 days,
gastrointestinal bleeding, hypertension and hyperglycemia were excluded.
Interventions: Low dose (n=144) or high dose (n=143) dexamethasone (q6h)
for 6 doses. Extubation was planned after 5th dose. Measurements and
Main Results: Patients were monitored for PEAO (Westley’s Croup Score
>4) for 24 hours. 238 patients were included in
per-protocol analysis. 78 patients (33%) developed PEAO; both groups
were similar (LD, 41/121, 34% vs HD, 37/117, 32% p=0.71). Risk
difference of LD vs HD touches the non-inferiority margin of 0.12 and
hence the overall result is non-significant. Incidence of reintubation
was also similar (LD, 10/121, 8.3% vs HD, 9/117, 7.7%; p=0.87).
Intubation for more than 7 days was an independent risk factor for
development of PEAO. Conclusions: Multi-dose 24-hour pretreatment with
low dose dexamethasone is not inferior to high dose in preventing PEAO
and reintubation among unselected patients in the studied clinical
setting. Multi-centric trials with larger sample size among children at
high risk of developing PEAO are needed.