Adjunct Low-Dose Dexmedetomidine for Sedation in Mechanically Ventilated Children: An Exploratory Randomized Trial

Abstract

Background: Effective sedation in the pediatric intensive care unit (PICU) is complicated by the adverse effects of benzodiazepines and opioids. Dexmedetomidine may provide a benzodiazepine-sparing alternative with distinct pharmacologic properties. Objectives: We hypothesized that adjunct, fixed low-dose, no-bolus dexmedetomidine would reduce midazolam and fentanyl exposure per ventilator-day in mechanically ventilated children. Methods: In a triple-blind randomized controlled trial, 60 mechanically ventilated patients aged 1 month to 12 years were randomized to standard sedation (continuous midazolam and fentanyl) plus low-dose dexmedetomidine (a fixed-rate continuous infusion at 0.2 µg/kg/h without a loading bolus) or matched placebo (0.9% normal saline). In both groups, midazolam and fentanyl were titrated per protocol to achieve the target Richmond Agitation-Sedation Scale (RASS) level. Results: Among 60 randomized children, adjunct fixed low-dose dexmedetomidine did not reduce the prespecified primary outcome of fentanyl or midazolam exposure per ventilator-day. Median fentanyl exposure per ventilator-day was 70.0 µg·kg-1·day-1 in the control group and 90.6 µg·kg-1·day-1 in the dexmedetomidine group; median midazolam exposure per ventilator-day was 7.0 mg·kg-1·day-1 and 9.1 mg·kg-1·day-1, respectively. Neither primary comparison remained statistically significant after Holm correction. In an unadjusted secondary analysis, the median time to first successful extubation was 6 days in the dexmedetomidine group and 15 days in the control group. This finding was exploratory and was not confirmed by the prespecified competing-risk or longitudinal ventilation analyses. Conclusions: Adjunct fixed low-dose dexmedetomidine without a loading bolus did not reduce fentanyl or midazolam exposure per ventilator-day. Early sedative-analgesic exposure was higher with dexmedetomidine, and the apparent early-extubation signal was exploratory and was not confirmed by competing-risk or longitudinal analyses of ventilation.