A Phase II/III, Multicenter, Safety, Efficacy, and Pharmacokinetic Study of Dexmedetomidine in Preterm and Term Neonates - 22/01/14
, Scott R. Schulman, MD 2, Mario Herrera Castellanos, MD 3, Benton E. Cofer, MD 4, Sanjay Mitra, MD 5, Marcelo Garcia da Rocha, MD 6, Wayne A. Wisemandle, MA 6, Lisa Gramlich, MD 7Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keyword : AE, AUC, BP, CLW, HR, LD, MD, N-PASS, PK, t1/2
Plan
| ☆ | 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 Table I and Figure 1, and proper formatting for references). The other authors declare no conflicts of interest. |
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| Registered with clinicaltrials.gov: NCT01159262 and NCT01508455. |
Vol 164 - N° 2
P. 276 - février 2014 Retour au numéro
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