Intranasal Dexmedetomidine Plus Ketamine for Procedural Sedation

Intranasal medications may offer a technically easier and pain‐free approach toprocedural sedation (PSA); one that may have widespread applicability in patients withneedle‐phobia, difficult IV access, resource‐limited settings, or when experience placingan IV is limited. Although IN ketamine has been found to be effective for fracture pain,procedural pain, anesthetic pre‐induction, and diagnostic imaging, a recent shortage ofthis agent in the highest concentration of 100 mg/mL has severely limited out ability tostudy its effectiveness and consequent clinical uptake. Our research team conducted threesystematic reviews of randomized trials of IN ketamine and IN dexmedetomidine in childrenundergoing painful procedures. The latter review included 18 trials (n=2128) of childrenage 1 month to 14 years. Our review found that IN dexmedetomidine, dosed from 1‐4 mcg/kg,was well tolerated and superior to conventional sedatives (midazolam and chloral hydrate)in providing adequate sedation to 525/669 (78.5%) children. A number of studies foundthat IN dexmedetomidine was in fact superior to IN ketamine. Surendar et al. found thatIN dexmedetomidine at 1.5 mcg/kg facilitated successful sedation in 18/21 (86%) ofchildren undergoing dental procedures and was more effective than IN ketamine 5 mg/kg.Gyanesh et al. found that the proportion of children with satisfactory IV sedation wasgreater with IN dexmedetomidine 1 mcg/kg compared to IN ketamine 5 mg/kg [47/52 (90%)versus 43/52 (83%), respectively]. Mostafa et al. found that IN dexmedetomidine 1 mcg/kgwas more effective at facilitating caregiver separation than IN ketamine 5 mg/kg or INmidazolam 0.2 mg/kg [30/32 (92%) versus 22/32 (69%) versus 28/32 (88%), respectively].Moreover, a combination of dexmedetomidine and ketamine appeared to be superior thaneither agent alone. Qiao et al. found that IN dexmedetomidine 2 mcg/kg and oral ketamine3 mg/kg in children undergoing IV insertion was superior to both IN dexmedetomidine 2.5mcg/kg and oral ketamine 6 mg/kg alone (80.1% versus 47.6% versus 68.3%, respectively).Bhat et al. found that a combination of IN dexmedetomidine 1 mcg/kg and IN ketamine 2mg/kg versus IN dexmedetomidine 1 mcg/kg alone facilitated greater acceptance of facemask (67% versus 52%, respectively) and greater tolerance of caregiver separation (93%versus 89%, respectively) (38). We also found evidence that higher doses of INdexmedetomidine were more effective. More specifically, at the higher end of the dosingrange (1‐4 mcg/kg), IN dexmedetomidine 3 mcg/kg was superior to IN ketamine 7 mg/kg;providing adequate sedation to 25/29 (86.3%) versus 23/29 (79.4%) of children undergoingIV insertion, respectively. A dose‐finding study of IN dexmedetomidine in children < 3years who were post‐operative from cardiac surgery and were undergoing transthoracicechocardiography found an optimal median effective dose of 3.3 mcg/kg (range 2.72‐3.78mcg/kg). Taken together, our review suggests that the most effective and tolerableintranasal agent for procedural sedation for fracture reduction is a combination of INdexmedetomidine 4 mcg/kg and IN ketamine 2‐3 mg/kg. There is ample and ongoing evidenceof suboptimal management for procedural pain in children, a high frequency of orthopedicinjuries requiring IV placement for PSA, and a lack of evidence to support the use ofstrategies that reduce the pain of IVs. However, there are no studies that have shown theeffectiveness of IN ketamine for fracture reduction in children. In order to providerobust evidence supporting an alternate approach that precludes the need for an IV inchildren undergoing PSA, the investigators propose a study to answer the importantresearch question: In children presenting to the ED with an orthopedic injury requiringPSA, does IN Ketodex provide as effective sedation as IV ketamine?