Intranasal dexmedetomidine and intranasal ketamine association allows shorter induction time for pediatric sedation compared to intranasal dexmedetomidine and oral midazolam

Abstract

Background Non-painful diagnostic procedures require an inactive state for a prolonged time, so that sedation is often needed in younger children to perform the procedures. Our standard of care in this setting consists of the association between oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (4 mcg/kg). One of the limits of this approach is that the onset of action is quite delayed (up to 55 min) and poorly predictable. We chose to compare this association with intranasal-ketamine and intranasal-dexmedetomidine. Methods This is a “pre-post” study. The study population included the first forty children receiving sedation with the “new” combination intranasal ketamine (3 mg/kg) and intranasal dexmedetomidine (4 mcg/kg) compared to a historical cohort including the last forty children receiving sedation with our standard of care combination of intranasal dexmedetomidine (4mcg/kg) and oral midazolam (0,5 mg/kg). Results The association intranasal dexmedetomidine and intranasal ketamine allowed for a significantly shorter sedation induction time than the combination intranasal dexmedetomidine and oral midazolam (13,5 min versus 35 min). Both group’s cumulative data showed a correlation between age and sedation effectiveness, with younger children presenting a higher success rate and shorter induction time (p 0,001). Conclusions: This study suggests that the ketamine and dexmedetomidine intranasal association may have a shorter onset of action when compared to intranasal dexmedetomidine and oral midazolam.

Using intranasal dexmedetomidine with buccal midazolam for magnetic resonance imaging sedation in children: A single-arm prospective interventional study

“…We have been investigating a convenient and effective sedation regimen to manage anxiety and minimize psychological trauma in children having MRI examinations. Recent advancements in the administration of dexmedetomidine–midazolam combination therapy revealed that these two drugs combination provided an alternative for MRI sedation in children ( 11 – 13 , 21 ). Success rates of 82.5–84% were obtained using intranasal dexmedetomidine combined with oral midazolam ( 11 , 13 ), whereas success rate of 88–95% was observed when utilizing intranasal dexmedetomidine–midazolam combination ( 12 , 22 ).…”

“…Recent advancements in the administration of dexmedetomidine–midazolam combination therapy revealed that these two drugs combination provided an alternative for MRI sedation in children ( 11 – 13 , 21 ). Success rates of 82.5–84% were obtained using intranasal dexmedetomidine combined with oral midazolam ( 11 , 13 ), whereas success rate of 88–95% was observed when utilizing intranasal dexmedetomidine–midazolam combination ( 12 , 22 ). Nevertheless, low pH and undiluted midazolam is associated with unpleasant burning sensation and may eaisly disrupt nasal mucosa and nerves.…”

“…Intranasal dexmedetomidine can be effective in 30 and 70% of children for MRI sedation at doses of 3 and 4 µg•kg −1 , respectively (10). Adding midazolam or ketamine by oral or nasal administration route augments the sedative effect and increases the success rate (11)(12)(13)(14). However, additional administration of these medications is limited by the oral-administration-induced low bioavailability and potential damage to nasal nerves and mucosa by their low pH.…”

Clinical Uses of Ketamine in Children: A Narrative Review

“…It allays preoperative anxiety in children and improves their cooperation during procedures [33]. A study by Cossovel et al suggested that the combination of intranasal dexmedetomidine in the dose of 2μg/kg and oral ketamine in the dose of 3mg/kg can help in satisfactory separation of the child from the caretaker, allow better success rates of venous cannulation, and smooth induction of general anesthesia [34]. According to Darlong et al, the combination of 3 mg/kg oral ketamine and 0.25 mg/kg midazolam has minimal side effects and allows rapid induction of anesthesia when compared to using either of the drugs alone [35].…”

“…It is also the agent of choice for induction in children with reactive airway disease and difficult airways because of its broncho-dilating effect [6]. When ketamine is used as a co-induction agent with propofol, midazolam, or dexmedetomidine, it provides the benefits of hemodynamic stability, reduced pain on injection, and less respiration depression [34,35].…”