Effectiveness of steroids versus placebo in preventing upper airway obstruction after extubation in critically ill children: rationale and design of a multicentric, double-blind, randomized study

Abstract

Background: Post-extubation upper airway obstruction (UAO) is a frequent complication causing stridor and respiratory distress, which occasionally require reintubation, thereby increasing morbidity and mortality rates. Contradictory results have been obtained in studies assessing the effectiveness of steroids in preventing postextubation UAO, and the available evidence is limited. We designed a multicentric randomized, placebo-controlled study to explore the effectiveness of dexamethasone in preventing post-extubation UAO in children. Methods: A multicentric, prospective, double-blind, randomized, placebo-controlled, phase IV clinical trial has been designed. The sample will include pediatric patients who are between 1 month and 16 years of age and who have been intubated for more than 48 h. Patients who have airway disorders or who have received steroids within the previous seven days will be excluded. Patients will be randomly assigned to receive either placebo or a therapy with dexamethasone 0.25 mg/kg every 6 h to be started 6 to 12 h prior to extubation (to a total of four doses). Randomization will be performed at a 1:1 ratio. Follow-up of patients will be carried out for 48 h after extubation. The main objective of this study is to access the reduction in the incidence of moderate to severe UAO symptoms following extubation. Secondary objectives include assessing the decrease in the incidence of reintubation, evaluating the use of additional therapies for UAO, and monitoring potential side effects of dexamethasone. Discussion: The results of this study will contribute to the existing evidence on prophylaxis for post-extubation airway obstruction.

Multicenter randomized clinical trial comparing dexamethasone versus placebo in preventing upper airway obstruction after extubation in critically ill children

“…It was conducted in five Spanish pediatric intensive care units that care for general and cardiac critically ill patients. The study protocol 12 was developed in accordance with the Standard Protocol (SPIRIT). The study was approved by local Ethics Committee of all participating centers (Fundación para la investigación biosanitaria del Hospital Gregorio Marañón Institutional Review Board, FIBHGM-ECNC003-2010; FIBHGM-10-01).…”

“…Sample size was established to detect a 50% reduction in the incidence of UAO according to previously published studies (which is estimated to be around 30%). Approximately 110 subjects were expected to be included in each treatment group 12 .…”

“…Details about sample size determination are specified in the published study protocol 12 . Continuous variables are presented as mean values and standard deviation (SD), or as median values and interquartile range (IQR), depending on result of Kolmogorov–Smirnov test.…”

Predictores de extubación fallida en el paciente pediátrico y neonatal

“…Existen registros significativamente más bajos de reintubación cuando se utilizan corticosteroides previos a la extubación (OR 0,56; IC del 95%: 0,41 a 0,77; I2 = 38%, número necesario a tratar [NNT] = 35 eventos prevenidos por cada 1000 extubaciones; 13 estudios), con disminución del edema laríngeo relacionado con el croup post extubación o la estenosis subglótica (OR 0,36; IC del 95%: 0,27 a 0,49; I2 = 71%, NNT absoluto = 84 por 1000; 9 estudios) (46). La administración de corticoides sistémicos es una estrategia costo efectiva que reduce la morbimortalidad asociada (47,48,49).…”

Post-extubation Airway Obstruction in Children: Are Steroids the Key to Prevention?

“…3 In an effort to answer some of the remaining questions, a multi-center, prospective, double-blind, randomized, placebo-controlled, phase IV clinical trial is now underway in Spain designed to evaluate the effectiveness of steroids versus placebo at preventing upper airway obstruction after extubation in 200 children. 9 In this study, the investigators plan to use a steroid regimen of dexamethasone at 0.25 mg/kg/dose every six hours for a total of four doses, which would fall into line with the LD regimen used in the study by Parajuli et al…”