Research Committee Update

Intranasal Dexmedetomidine – on the Rise!

By Joseph Cravero, MD

If one can judge by the amount of discussion on social media and list-serves, intranasal medication use is growing faster than any other route for sedation administration, and intranasal dexmedetomidine is the drug that is leading the way to making this route a preferred option in many situations.  The literature on this method of delivering dexmedetomidine is still in its infancy, and there are very few peer-reviewed reports of its intranasal use when compared to the actual use of the drug by this route.

One of the most quoted papers on intranasal dexmedetomidine use comes from India and is actually a comparison of oral midazolam to intranasal dexmedetomidine for CT scan imaging procedures1. In the study Ghai and colleagues randomized 59 children scheduled to undergo CT imaging under sedation to receive either 0.5 mg/kg of oral midazolam or 2.5 mcg/kg of intranasal dexmedetomidine.  After 20-30 minutes, intravenous cannulation was performed and response to placement was graded using a validated score.   CT imaging was then performed if the patient was adequately sedated (Ramsay score of greater than or equal to four).  If further sedation was needed, ketamine 1mg/kg was added by IV.   The authors found that a significantly higher proportion of children in the dexmedetomidine cohort achieved adequate sedation for CT scan when compared to the midazolam group.   Patients showed less distress at the time of IV cannulation as well.

Another recent study from Miller and colleagues evaluated several methods for sedating children with trisomy 21 for transthoracic echocardiograms2. These methods included general anesthesia with sevoflurane by mask, general anesthesia with sevoflurane followed by propofol infusion, oral pentobarbital, and intranasal dexmedetomidine.   The authors found that intranasal dexmedetomidine at 2.5mcg/kg was an effective sedative as a single dose for TTEcho in 37 of 41 (90%) cases.   Dexmedetomidine given in this way was not associated with a significantly higher risk of bradycardia in patients with trisomy 21 compared with other sedative or anesthetic regimens including pentobarbital or sevoflurane-based general anesthesia.   Bradycardia was much more common in the children over 36 months that were given dexmedetomidine (76%) when compared to those under 24 months (6.7%).   Hypotension was not different in the dexmedetomidine (29%) when compared to the GA group (50%). 

Taken together these two studies add to the small number of peer-reviewed reports of intranasal dexmedetomidine in important ways.  First, these studies begin to establish what appears to be the acceptable, effective dose for this medication when given for non-invasive procedural sedation.  Indeed the success rates reported in both studies are reasonable if not yet ideal.   One can imagine that combinations of this dose of intranasal dexmedetomidine with small doses of oral medication could bring the success rates into the high 90 percent range – which would be on a par with almost any non-IV sedation regimen. 

The studies also establish some baseline safety data for the intranasal use of the drug.  In a group of children who could be considered at high risk for bradycardia (Trisomy 21 patients with congenital heart disease), the Miller study found no higher rate of bradycardia for dexmedetomidine than for standard methods of GA.  Further monitoring of the outcomes of the use of intranasal dexmedetomidine are clearly needed before any conclusions can be made about this sedation technique, but (at least to date) it appears to be no more concerning than the use of intravenous dexmedetomidine which is now growing a significant history of generally safe use. 

The PSRC is currently in the midst of planning and executing a prospective trial of the use of intranasal dexmedetomidine.  The study will look at details of current use of the drug at several PSRC centers and catalog the doses used, procedures it is used for, and the timing of onset and offset of sedation.  Study organizer Daniel Tsze, MD hopes that the data gathered will lead to the appropriate planning of a prospective randomized, multicenter trial on intranasal dexmedetomidine which would add greatly to the current experience and knowledge of the action and capability of the drug when used in this manner. 

References

  1. Ghai B, Jain K, Saxena AK, Bhatia N, Sodhi KS. Comparison of oral midazolam with intranasal dexmedetomidine premedication for children undergoing CT imaging: a randomized, double-blind, and controlled study. Paediatr Anaesth 2017;27:37-44.
  2. Miller J, Ding L, Spaeth J, et al. Sedation methods for transthoracic echocardiography in children with Trisomy 21-a retrospective study. Paediatr Anaesth 2017.

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