A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates

J Pediatr. 2014 Feb;164(2):276-82.e1-3. doi: 10.1016/j.jpeds.2013.10.002. Epub 2013 Nov 14.


Objective: To investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates ≥ 28 to ≤ 44 weeks gestational age.

Study design: Forty-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.

Results: During 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.

Conclusion: Dexmedetomidine 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.

Trial registration: ClinicalTrials.gov NCT01159262 NCT01508455.

Keywords: AE; AUC; Adverse event; Area under the concentration curve; BP; Blood pressure; CL(W); HR; Half-life; Heart rate; LD; Loading dose; MD; Maintenance dose; N-PASS; Neonatal Pain, Agitation, Sedation Scale; PK; Pharmacokinetic; Plasma clearance; t(1/2).

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dexmedetomidine / administration & dosage
  • Dexmedetomidine / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Gestational Age
  • Half-Life
  • Humans
  • Hypnotics and Sedatives / administration & dosage
  • Hypnotics and Sedatives / pharmacokinetics
  • Infant, Newborn
  • Infant, Premature*
  • Infant, Premature, Diseases / blood
  • Infant, Premature, Diseases / drug therapy*
  • Infusions, Intravenous
  • Male
  • Pain Measurement
  • Prospective Studies
  • Respiration, Artificial
  • Treatment Outcome


  • Hypnotics and Sedatives
  • Dexmedetomidine

Associated data

  • ClinicalTrials.gov/NCT01159262
  • ClinicalTrials.gov/NCT01508455