A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates.
OBJECTIVE
To investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates ≥ 28 to ≤ 44 weeks gestational age.


METHODS
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.


CONCLUSIONS
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.
Department of Pediatric Critical Care Medicine, Cardiac Intensive Care Unit, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA. Electronic address: chrycx@chp.edu.
Constantinos
C
Chrysostomou
Department of Anesthesiology, Duke Children's Hospital, Durham, NC.
Scott R
SR
Schulman
Department of Pediatrics, Hospital Roosevelt, Guatemala City, Guatemala.
Mario
M
Herrera Castellanos
Neonatology, Greenville Hospital System, Greenville, SC.
Benton E
BE
Cofer
Department of Pediatrics, West Virginia University Hospitals and Clinics, Ruby Memorial Hospital, Morgantown, WV.
Sanjay
S
Mitra
Global Clinical R & D and Medical Affairs, Hospira Inc, Lake Forest, IL.
Marcelo Garcia
MG
da Rocha
Global Clinical R & D and Medical Affairs, Hospira Inc, Lake Forest, IL.
Wayne A
WA
Wisemandle
Department of Anesthesiology, Loyola University Medical Center, Maywood, IL.
Lisa
L
Gramlich
D020927:Dexmedetomidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000097:blood / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D010147:Pain Measurement; D011446:Prospective Studies; D012121:Respiration, Artificial; D016896:Treatment Outcome
D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine
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)