Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist. It is approved by the Food and Drug Administration (FDA) in 1999 for the sedation of mechanically ventilated adults in the intensive care setting. In the pediatric population, DEX is not yet FDA-approved however data on its use in children are increasing. Based on its efficacy in adults, DEX has been evaluated in small studies and case reports in pediatric patients as off-label with a favorable efficacy and safety profile1-5. In those studies, DEX has been used for maintaining ICU sedation in combination with other agents during mechanical ventilation as well as for invasive and noninvasive procedural sedation.
In neonates, the experience with DEX is very limited. Very few studies have described its use in term neonates and only one retrospective study was conducted on preterm neonates6-8.
Dexmedetomidine was evaluated in a recent phase II/III multicenter trial in term and preterm neonates for efficacy, safety, and pharmacokinetics (PK)9. Inclusion criteria were mechanically ventilated neonates, gestational age ≥ 28 to ≤ 44 weeks, anticipated to require a minimum of six hours of continuous intravenous sedation in an intensive care unit. A total of 42 patients met the inclusion criteria. Patients were classified into two groups according to their gestational age; group I (aged ≥ 28 to < 36 weeks, n=18) and group II (≥ 36 to ≤ 44 weeks, n=24). The patients in each group received DEX in a dose escalating manner consisting of three levels, level 1: loading dose (LD) 0.05 µg/kg; maintenance dose (MD) 0.05 µg/kg/h; level 2: LD, 0.1 µg/kg; MD, 0.1 µg/kg/h; level 3: LD 0.2 µg/kg; MD, 0.2 µg/kg/h. The maintenance dose was administered continuously for 6 to 24 hours.
With regard to efficacy, the primary endpoint was the number of patients requiring midazolam for sedation while on DEX. The secondary endpoints were the use of analgesics (fentanyl of morphine), changes in vital signs from baseline (heart rate (HR), blood pressure (BP), respiratory rate (RR), and O2 saturation), time spent with a total score > 3 on the sedation assessment scale N-PASS; and time to extubation from DEX initiation.
The result of the study showed that only 9% of patients required extra sedation and 40% required additional analgesia. All patients completed a minimum of 6 hours infusion of DEX with the majority of patients received the infusion for 6 to 12 hours. There were no significant adverse effects necessitated drug discontinuation. Heart rate and blood pressure decreased by 12% - 14%, and 20% of patients could be extubated while on DEX infusion. Since the study was powered to assess efficacy, the author stresses careful consideration of any safety result. For PK analysis, the study found that the younger age group (gp I) appeared to have lower clearance (0.3 vs. 0.9 L.h-1.kg-1), prolonged t1/2 (7.6 vs 3.2 hours), and increased area under the curve (AUC) compared with patients in group II. The author could not exclude bias for the PK analysis since several patients had undetectable DEX levels and those patients were not included in the analysis.
This is the first prospective study evaluating the use of DEX in preterm neonates suggesting its potential utility in the management of sedation in this age group. Although it appears well tolerated, its potential effect ...