Dexmedetomidine for prevention of opioid/benzodiazepine withdrawal syndrome in pediatric intensive care unit: Interim analysis of a randomized controlled trial

Study Objective: Withdrawal syndrome (WS) may be a critical drawback of opioid/benzodiazepine weaning in children. The most effective intervention to reduce WS prevalence is yet to be determined. Dexmedetomidine (DEX) was estimated to be effective in reducing WS-related symptoms, but no randomized trial has been conducted to prove its efficacy so far. We aimed to evaluate the efficacy and safety of DEX in reducing the occurrence of WS. Design and Setting: This was an adaptive randomized double-blind placebo-controlled trial conducted at three Italian Pediatric Intensive Care Units (PICUs). Patients: It included children admitted to PICU, undergoing at least five days of opioids/benzodiazepines continuous infusion, and ready to start the analgosedation weaning. Intervention: Twenty-four hours before the start of weaning, an infusion of DEX/placebo was started. WS symptoms were monitored using the Withdrawal-Assessment-Tool-version-1 (WAT-1). In case of WS symptoms (WAT-1 ≥ 3) an opioid/benzodiazepine bolus was given and the DEX/placebo infusion-rate was increased. Measurements: The primary outcome measure was the prevalence of WS. Secondary outcomes were the trend of WAT-1 over time, number of rescue doses, length of weaning and PICU-stay, and onset of adverse events (AEs). Main Results: Forty-five patients were enrolled, of whom 5 dropped-out and 40 entered the interim analysis. There were no significant baseline differences between groups. WS prevalence did not significantly differ between groups (77.8% DEX vs 90.9% placebo, p = 0.381). By generalized linear mixed modeling, the WAT-1 trend showed a significant increase per unit of time in the DEX arm (estimate 0.27, CI 0.07–0.47, p = 0.009) compared to placebo. Most frequent AEs were hemodynamic, and all of them happened in the DEX arm. Conclusions: A continuous infusion of DEX, started 24 h before the analgosedation weaning and increased based on WS signs, was not able to significantly modify the prevalence of WS in children who received at least five days of opioids/benzodiazepines treatment compared to placebo.