Dexmedetomidine is an effective, well-tolerated sedative for preterm and full-term neonates. Preterm neonates have decreased plasma clearance and a longer elimination half-life than term neonates.
Constantinos Chrysostomou, MD, from the Cardiac Intensive Care Unit of Children's Hospital of Pittsburgh, Pennsylvania, and colleagues present the results of their phase 2/phase 3 study in an article published online November 18 in the Journal of Pediatrics. The investigators evaluated 2 groups of neonates: group 1 (n = 18) had a gestational age of from 28 to less than 36 weeks, and group 2 (n = 24) had a gestational age of from 36 to 44 or fewer weeks.
Each group had 3 escalating dose levels, including a loading dose (LD) followed by a maintenance dose (MD) for 6 to 24 hours. The 3 escalating dose levels were 0.05 LD/MD, 0.1 LD/MD, and 0.2 LD/MD.
"[I]n our study cohort, dexmedetomidine was effective in sedating critically ill, initially intubated, and mechanically ventilated preterm and term neonates and was well tolerated. The [pharmacokinetic] profile of dexmedetomidine appears to be different in neonates compared with older children and adults, exhibiting a longer t1/2 and a larger [area under the concentration curve], indicating that lower doses may be required to achieve the same level of sedation and to avoid adverse effects," the authors write.
The study was powered for efficacy, and safety results should be considered in this light. The investigators report that most of the adverse events are predictable and dose-dependent. None of the patients had liver failure.
Dexmedetomidine has been approved by the US Food and Drug Administration since 1999 for the sedation of initially intubated and mechanically ventilated adults. It is considered a full α2 agonist, and its activation of these receptors in the locus coeruleus results in both sedation and anxiolysis. It is metabolized extensively by the liver via the cytochrome P450, 2A6 pathway.
Preterm neonates and term neonates had a larger volume of distribution and increased free unbound dexmedetomidine when compared with adults, the investigators report.
The clinical trial is consistent with retrospective reports that have previously indicated that dexmedetomidine provides adequate sedation and analgesia for neonates and infants.
"This study provides physicians with pharmacokinetic data on dexmedetomidine in preterm and term neonates, which has not been previously reported and therefore will be valuable for selecting the appropriate dose in this population," J. Craig Jackson, MD, MHA, neonatal intensive care unit medical director at Seattle Children's Hospital in Washington, told Medscape Medical News. "The study was not designed to study efficacy for sedation from this drug, and such a study is needed before this drug is routinely used for this population. The number of patients studied was too small to be sure, but there were no safety concerns seen in this population beyond changes in heart rate (12% lower) and systolic blood pressure (14% lower), which are to be expected from the drug's sympatholytic properties (it is a selective alpha-2 adrenergic agonist)."
The study was sponsored and funded by Hospira, Inc. Dr. Jackson has disclosed no relevant financial relationships.
J Peds. Published online November 18, 2013. Abstract
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Cite this: Dexmedetomidine Effective Sedative for Neonates - Medscape - Dec 19, 2013.