Atomized Intranasal Dexmedetomidine Shows Promise as Pediatric Sedative

Published May 1, 2018 | British Journal of Anaesthesia

Atomized intranasal dexmedetomidine has proven to be an effective sedation drug, but its pharmacokinetics have previously only been studied in adults. Its potential value during diagnostic procedures in children, with the inherent advantage of not requiring vascular access, was unknown. The risk of instability in heart rate caused by dexmedetomidine is challenging in the pediatric landscape, particularly in infants and toddlers.

A team of researchers from the divisions of Anesthesia and Clinical Pharmacology, joined by a physician from China who was a visiting scholar at Cincinnati Children’s, examined arterial plasma concentrations of dexmedetomidine in 18 infants and toddlers. Unlike adults, children often need sedation for non-painful, diagnostic testing, including echocardiographs and radiological imaging.

Researchers saw that, within 20 minutes, the patients approached 100 pg ml-1, considered the low end for sedative efficacy, after being administered 1 mg kg-1 of the intranasal analgesia. Doubling the dosage reached the same concentration within just 10 minutes, and reached nearly twice the peak concentration. Peak plasma concentrations with both doses were achieved within 47 minutes, quantifying the drug’s potential value. This could be crucial, because in infants, dexmedetomidine is one of the few sedatives believed to have minimal effect on neurodevelopment. Unlike most available sedatives, it does not depress respiration. Also, administration is painless.

“Our study provides the first rigorous data to give a pharmacokinetic understanding to guide pediatric dosage,” says first-author Jeff Miller, MD, a retired pediatric cardiac anesthesiologist.

“The maximum plasma levels obtained after our dosage were in the low range targeted in ongoing multicenter trials,” he says. “Consequently, we can consider higher doses of intranasal dexmedetomidine, which should provide faster onset of sedation and greater efficacy.”

An image showing concentrations of dexmedetomidine in arterial plasma over time.

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An image showing a comparison of extravascular administration of dexmedetomidine.

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A photo of Jeff Miller, MD.

Jeff Miller, MD

Citation

Miller JW, Balyan R, Dong M, Mahmoud M, Lam JE, Pratap JN, Paquin JR, Li BL, Spaeth JP, Vinks A, Loepke AW. Does intranasal dexmedetomidine provide adequate plasma concentrations for sedation in children: a pharmacokinetic study. Br J Anaesth. 2018 May;120(5):1056-1065.