Elsevier

The Journal of Pediatrics

Volume 164, Issue 2, February 2014, Pages 276-282.e3
The Journal of Pediatrics

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

https://doi.org/10.1016/j.jpeds.2013.10.002Get rights and content
Under a Creative Commons license
open access

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.

AE
Adverse event
AUC
Area under the concentration curve
BP
Blood pressure
CLW
Plasma clearance
HR
Heart rate
LD
Loading dose
MD
Maintenance dose
N-PASS
Neonatal Pain, Agitation, Sedation Scale
PK
Pharmacokinetic
t1/2
Half-life

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Sponsored and funded by Hospira, Inc (Lake Forest, IL). G.dR. and W.W. are employees of Hospira, the manufacturer of Precedex (dexmedetomidine HCl), and hold Hospira stock options. The sponsor was involved in study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the manuscript for publication. Assistance in the preparation of this manuscript was provided by MMS Holdings Inc (editing for grammatical errors, preparation of Tables and Figures, and proper formatting for references). The other authors declare no conflicts of interest.

Registered with ClinicalTrials.gov: NCT01159262 and NCT01508455.