Comparison of plasma concentration and sedative effect of sublingual and intranasal dexmedetomidine in children: A double-blind randomised controlled study.

Abstract

Background: Pharmacokinetics and sedative effects of sublingual dexmedetomidine have not been established in children. The primary aim was to compare peak plasma concentration, time to reach peak plasma concentration and area under the curve with 2 μg/kg sublingual and intranasal dexmedetomidine. The secondary aims were to compare the depth of sedation, parental separation anxiety, mask acceptance, heart rate changes, analgesic requirements and recovery time with 2 μg/kg sublingual and intranasal dexmedetomidine in children.

Method: Thirty children between 2 and 12 years, weighing 10-30 kg, scheduled for surgeries were divided into two groups. Thirty minutes before the induction of anaesthesia, children were premedicated with 2 μg/kg dexmedetomidine either by intranasal drops (Group N) or sublingual wafer (Group S). Five venous blood samples were collected to measure dexmedetomidine plasma concentrations at 15, 30, 45, 60 and 120 min from dexmedetomidine administration. Sedation, parental separation anxiety, mask acceptance and heart rate were recorded. Recovery, pain and fentanyl requirements were assessed.

Results: Demographic data was comparable. Median interquartile range (IQR) dexmedetomidine peak plasma concentration in Group N (0.764 [0.650-0.820]) ng/mL was significantly higher than in Group S (0.593 [0.364-0.754]) ng/mL (p = .014). Plasma concentration was significantly higher at 30 and 45 min in Group N as compared to Group S (p < .05). The median (IQR) time to reach peak plasma concentration was shorter in Group N (45 [45-120]) minutes than in Group S (60 [45-60]) minutes, (p = .814). The median (IQR) area under the concentration-time curve was significantly higher in Group N (1.062 [0.848-1.20]) ng/mL.h in comparison to Group S (0.866 [0.520-1.05]) ng/mL.h (p = .031). Comparable sedation was achieved at 25 min in both groups. No child required treatment for decreased heart rate. Parental separation anxiety, mask acceptance, recovery and analgesic requirements were comparable.

Conclusions: Intranasal 2 μg/kg dexmedetomidine resulted in significantly higher peak plasma concentration and time to reach peak plasma concentration than sublingual wafers. Sublingual and intranasal dexmedetomidine resulted in comparable sedation, parental separation and mask acceptance.

Editorial comment: This study compared the pharmacokinetics and sedative effects of sublingual versus intranasal dexmedetomidine in children, finding that intranasal administration resulted in significantly higher peak plasma concentration and faster time to peak concentration. Both routes achieved comparable sedation, parental separation anxiety scores and mask acceptance, with no significant adverse effects observed.