 Intranasal IN delivery of analgesic agents provides rapid and convenient drug administration without the need for needles. In children, the placement of an intravenous line often increases anxiety and pain, requires nursing time, and can be very difficult to achieve, so the IN route is particularly advantageous. IN delivery of fentanyl has become increasingly more common in pain management for children in many settings, including pre-hospital and emergency department ED settings. Over the past decade, many studies have demonstrated that intranasal fentanyl is as effective as intravenous morphine to treat acute moderate to severe pain. Intranasal fentanyl has become standard of care in some pediatric EDs with the advantage of avoiding intravenous line placement. However, adverse effects attributed to IN fentanyl are similar to those of other opioid analgesics: hypotension, sedation, and occasionally respiratory depression. Ketamine is a noncompetitive N-methyl D-aspartate NMDA receptor antagonist that blocks the release of the excitatory neurotransmitter glutamate and provides anesthesia, amnesia, and analgesia by decreasing central sensitization and wind-up phenomenon. Due to its high lipid solubility, ketamine rapidly crosses the blood-brain barrier, provides rapid onset of action peak concentration at 1 minute after intravenous push and rapid recovery to baseline duration of action 5-15 minutes after intravenous push. At sub-dissociative doses, either used as an adjunct to opioid analgesics or as a solo agent, ketamine provides effective analgesia while preserving airway patency, ventilation, and cardiovascular stability. 