Pediatric Ketamine Study for Pain Management

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.

Ketamine has been less studied for pain management, however it has been safely used via
different routes of administration in children. Studies dating back to 1990's use ketamine at
doses as high as 6 mg/kg intranasally in children for pre-medication prior to surgery or for
sedation with little or no reported adverse effects. A hospital in Australia is currently
conducting a clinical trial comparing IN fentanyl 1.5 ug/kg to IN ketamine 1mg/kg for the
treatment of pain caused by isolated musculoskeletal injury. The intention of our study is
similar to this, however the investigators will not limit the patients to those with only
musculoskeletal pain and a more simplified pain scale will be used.

To assess pain, the investigators will use the standard pain scale that is currently used in
our Pediatric ED in order to minimize the need to re-train any of our staff with a different
pain scale. The scale incorporates the Numerical rating scale (0-10 scale; NRS) and the
Wong-Baker faces pain scale (6 faces corresponding to 0,2,4,6,8,10; WBS). While prior studies
have used different pain scales, primarily the visual analog scale (VAS), the scales that the
investigator currently use have been validated in children in 2009.

Inclusion Criteria:

- Children aged 3-17,

- weighing less than 50kg

- present to the pediatric ED with moderate-severe acute pain (defined as pain greater
than or equal to 6/10).

- Treating physician determines the patient to require opioid analgesia.

Exclusion Criteria:

- Children with facial trauma or any abnormal nasal anatomy;

- developmentally delayed children;

- children with head trauma/increased intracranial pressure (ICP);

- children with known allergy to fentanyl or ketamine;

- children who are unable to provide pain scale assessment;

- children with chronic pain of greater than 4 weeks;

- Pregnant females;

- and children with a Glasgow Coma Scale (GCS)<15.