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

• Published in: The Journal of pediatrics Vol. 164; no. 2; pp. 276 - 282.e3
• Main Authors: Chrysostomou, Constantinos, MD, Schulman, Scott R., MD, Herrera Castellanos, Mario, MD, Cofer, Benton E., MD, Mitra, Sanjay, MD, da Rocha, Marcelo Garcia, MD, Wisemandle, Wayne A., MA, Gramlich, Lisa, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2014
• Subjects: 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; Pediatrics; Prospective Studies; Respiration, Artificial; Treatment Outcome; AE; Adverse event; N-PASS; HR; Area under the concentration curve; BP; Pharmacokinetic; AUC; Heart rate; Loading dose; Plasma clearance; MD; LD; Maintenance dose; t 1/2; Blood pressure; PK; Half-life; Neonatal Pain, Agitation, Sedation Scale; CL W; t1/2; CLW; CL(W); t(1/2)
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2013.10.002

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.