Introduction

Withdrawal syndrome (WS) is 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.

Objectives

We aimed to evaluate the efficacy and safety of DEX in reducing the occurrence of opioid/benzodiazepine WS in critically ill pediatric patients.

Methods

This was an adaptive, randomized, double-blind, placebo-controlled trial conducted at three Italian pediatric intensive care units (PICUs). The trial included children admitted to the PICU, undergoing at least 5 days of opioid/benzodiazepine continuous infusions, and ready to start the analgosedation weaning. Twenty-four hours before the start of weaning, an infusion of DEX or 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. The primary outcome measure was the prevalence of WS among patients treated with DEX compared with patients treated with placebo. 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).

Results

Forty-five patients were enrolled, of whom 5 dropped-out and 40 entered the interim analysis. No significant baseline differences were found between groups except for the pediatric index of mortality 3 (PIM3) score. 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, confidence interval (CI) 0.07-0.47, p=0.009) compared to placebo. Most frequent AEs were hemodynamic and all occurred in the DEX arm.

Conclusion

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 5 days of opioids/benzodiazepines treatment, compared to placebo.