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 perprotocol 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.

Nasotracheal vs. Orotracheal Intubation and Post-extubation Airway Obstruction in Critically Ill Children: An Open-Label Randomized Controlled Trial

“…The rate of PEAO (15%) in the index study was within the range of the documented rates of PEAO among critically ill children (18-40%) (20,23,(27)(28)(29). However, the rate of PEAO in index study was lower than the reported rates of Unplanned extubation, n (%) 9 ( 12 PEAO in the recent studies from our unit (32.8-34%) (21,23).…”

“…Enteral feeding was started as soon as possible, preferably within 24 h of admission to the PICU. Among children intubated for >48 h, six dosage of dexamethasone (0.5 mg/kg/dose) were used peri-extubation, with first dose given 24 h prior to extubation (20,21). Feeding was withheld for 6 h prior to extubation and 4-6 h after extubation.…”

“…The sample size was calculated based on the incidence of PEAO (32.8-34%) documented in previous studies from our PICU (21,23). As a superiority trial, with the incidence of PEAO in nasotracheal group as 15% and β-error of 0.2, the required sample size was 90 cases in each group (n = 180).…”