A Phase II/III, Multicenter, Safety, Efficacy, and Pharmacokinetic Study of Dexmedetomidine in Preterm and Term Neonates

ObjectiveTo investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates ≥28 to ≤44 weeks gestational age.Study designForty-two intubated, mechanically ventilated patients (n = 42) were grouped by gestational age into group I (n = 18), ≥28 to <36 weeks, and group II (n = 24), ≥36 to ≤44 weeks. Within each age group, there were 3 escalating dose levels, including a loading dose (LD, μg/kg) followed by a maintenance dose (MD, μg·kg−1·h−1) for 6-24 hours: level 1, 0.05 LD/MD; level 2, 0.1 LD/MD; and level 3, 0.2 LD/MD. The primary endpoint was the number of patients requiring sedation as determined by the Neonatal Pain, Agitation, Sedation Scale.ResultsDuring dexmedetomidine infusion, 5% of Neonatal Pain, Agitation, Sedation Scale scores were >3, indicating agitation/pain, with 4 patients (10%) requiring more sedation and 17 (40%) requiring more analgesia. Though there was significant variability in pharmacokinetic variables, group I appeared to have lower weight-adjusted plasma clearance (0.3 vs 0.9 L·h−1·kg−1) and increased elimination half-life (7.6 vs 3.2 hours) compared with group II. Fifty-six adverse events (AEs) were reported in 26 patients (62%); only 3 AEs (5%) were related to dexmedetomidine. There were no serious AEs and no AEs or hemodynamic changes requiring dexmedetomidine discontinuation.ConclusionDexmedetomidine is effective for sedating preterm and full-term neonates and is well-tolerated without significant AEs. Preterm neonates had decreased plasma clearance and longer elimination half-life.