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Scheepers LD, Montgomery CJ, Kinahan AM, Dunn GS, Bourne RA, McCormack JP. Canadian Journal of Anaesthesia 2000; 47:120-124.

Review: The author of this study conducted a single dose pharmacokinetic study of 11 ASA 1 and 2 patients age 2-6 to determine plasma flumazenil level after intranasal administration. No benzodiazepines were administered to these patients prior to surgery. Patients received a standard intravenous induction. Flumazenil 40 mcg/kg (0.1mg/ml solution) was then administered as nose drops immediately preceding nasotracheal intubation. 12 blood samples were drawn over a 2-hour time span, serum separated, stored at -70°C and analyzed for serum flumazenil level by HPLC.

Ten patients had sufficient sampling of blood for analysis. The mean Cmax was 67.8 ± 41.9 ng/ml with Tmax at two minutes. The calculated half-life was 122 ± 99 minutes. This peak concentration was similar to that seen after intravenous administration. Therapeutic levels were estimated to be between 10-30ng/ml in adult studies. The authors concluded intranasal fentanyl is effectively absorbed in a very rapid fashion after intranasal administration.

Comments: The problem of paradoxical excitation following administration of midazolam can be very frustrating for parents and hospital staff. Short of starting an IV or whisking the patient back for a rapid (and often brutal) induction, there is little in the way of treatment options. Although further studies need to be done, nasal flumazenil has potential to create a niche as a noninvasive method for the treatment of paradoxical excitement after benzodiazepine administration in children.

Reviewed by: Jeffrey Galinkin, MD
Childrens Hospital of Philadelphia