IN Sub-Dissociative Ketamine vs IN Fentanyl

Intranasal medications are commonly used in place of parenteral opioids in children. IN
fentanyl is the most commonly used intranasal analgesic medication in the pediatric
population with demonstrated safety and efficacy comparable to IV fentanyl and IV morphine.
IN ketamine, at sub-dissociative doses, offers similar safety and efficacy to IN fentanyl
and the additional advantage of potentially reducing the total use of opioid agents during
the emergency department visit. Ketamine is easily stored and has a wide therapeutic window
with an extremely low risk of cardiorespiratory complications. This study will compare the
safety and efficacy of IN ketamine to IN fentanyl in children with suspected, isolated
extremity fractures in the pediatric emergency department.

The primary aim of the study is to examine the feasibility of future protocol expansion. The
investigators will conclude that additional studies are NOT feasible if the observed rate of
side effects for ketamine that exceeds fentanyl by three-fold or event rate of 5% or more
for ketamine-related SAEs. The primary aim of the study will compare the frequency of
adverse events over 6-hours among children randomized to receive either intranasal
sub-dissociative ketamine (IN ketamine) or intranasal fentanyl (IN fentanyl) for pain
control in the emergency department. The exploratory aim of the study will compare the
efficacy of intranasal ketamine to intranasal fentanyl as measured by a reduction in age
appropriate pain scale scores over 2-hours. The secondary aim of the study will compare the
total dose of opioid pain medication in morphine equivalents/kg/hour required during the ED
evaluation of children with suspected, isolated extremity fractures after randomization and
treatment with IN ketamine or IN fentanyl.

Eighty children ages 3-17 years with a suspected, isolated extremity fracture that requires
analgesia will be randomized to receive IN ketamine or IN fentanyl upon presentation to the
emergency department and will be followed for 2 hours for efficacy and 6 hours for safety.

All participants will be premedicated with acetaminophen or ibuprofen and baseline data,
including pain level, will be collected. The trial consists of two treatment arms. (IN
ketamine 1 mg/kg or IN fentanyl 1.5 mcg/kg). Randomization will follow a 1:1 ratio, with
approximately 40 per group. Randomization will be stratified by ages 3-10 and 11-17. The
participants will be assessed by a research coordinator for adverse events every 5 minutes
using an adverse events checklist for the first fifteen minutes post study medication
administration and every 30 minutes for the first two hours after drug administration. The
vital signs and pain scale assessment will be repeated every 10 minutes for the first 30
minutes and then every 30 minutes for the first two hours after drug administration. A final
assessment will be made 6 hours after the last dose of study drug or at discharge from the
ED to assess for late side effects or adverse events. Study medication may be repeated times
one at a reduced dose after 20 minutes when the full effects of the first dose are known.
The decision to administer additional study medication (0.5 mg/kg ketamine or 0.75 mcg/kg
fentanyl ) will at be at the discretion of the treating physician. Should a second dose of
study medication be required, a new schedule of patient assessments will commence following
the same schedule as for the first dose. Participant assessments will continue until the 2
hour endpoint is reached from the time of the last drug administration, with a final
assessment at 6 hours after the last dose of study drug or at discharge from the ED to
assess for late side effects or adverse events.

Inclusion Criteria:

- single suspected, isolated extremity fracture that requires analgesia

Exclusion Criteria:

- GCS < 15 at ED presentation,

- reported allergy or adverse reaction to ketamine or fentanyl,

- pregnancy,

- intoxication,

- hypotension (less than 70 mmHg +2x age or less than 90 mm Hg for patients greater
than 11 years of age)

- weight > 70 kg

- patients receiving opioid analgesia administered prior to arrival

- multiply injured patients

- aberrant nasal anatomy that precludes IN medications