Intranasal medications may offer a technically easier and pain-free approach to procedural sedation (PSA); one that may have widespread applicability in patients with needle-phobia, difficult IV access, resource-limited settings, or when experience placing an 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 of this agent in the highest concentration of 100 mg/mL has severely limited out ability to study its effectiveness and consequent clinical uptake. Our research team conducted three systematic reviews of randomized trials of IN ketamine and IN dexmedetomidine in children undergoing painful procedures. The latter review included 18 trials (n=2128) of children age 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 found that IN dexmedetomidine was in fact superior to IN ketamine. Surendar et al. found that IN dexmedetomidine at 1.5 mcg/kg facilitated successful sedation in 18/21 (86%) of children 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 was greater 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/kg was more effective at facilitating caregiver separation than IN ketamine 5 mg/kg or IN midazolam 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 than either agent alone. Qiao et al. found that IN dexmedetomidine 2 mcg/kg and oral ketamine 3 mg/kg in children undergoing IV insertion was superior to both IN dexmedetomidine 2.5 mcg/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 2 mg/kg versus IN dexmedetomidine 1 mcg/kg alone facilitated greater acceptance of face mask (67% versus 52%, respectively) and greater tolerance of caregiver separation (93% versus 89%, respectively) (38). We also found evidence that higher doses of IN dexmedetomidine were more effective. More specifically, at the higher end of the dosing range (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 undergoing IV insertion, respectively. A dose-finding study of IN dexmedetomidine in children \< 3 years who were post-operative from cardiac surgery and were undergoing transthoracic echocardiography found an optimal median effective dose of 3.3 mcg/kg (range 2.72-3.78 mcg/kg). Taken together, our review suggests that the most effective and tolerable intranasal agent for procedural sedation for fracture reduction is a combination of IN dexmedetomidine 4 mcg/kg and IN ketamine 2-3 mg/kg. There is ample and ongoing evidence of suboptimal management for procedural pain in children, a high frequency of orthopedic injuries requiring IV placement for PSA, and a lack of evidence to support the use of strategies that reduce the pain of IVs. However, there are no studies that have shown the effectiveness of IN ketamine for fracture reduction in children. In order to provide robust evidence supporting an alternate approach that precludes the need for an IV in children undergoing PSA, the investigators propose a study to answer the important research question: In children presenting to the ED with an orthopedic injury requiring PSA, does IN Ketodex provide as effective sedation as IV ketamine?