Pain is typically under-treated in children. Intranasal administration of analgesics has the benefits of rapid, needleless administration and a more rapid onset compared to oral administration. Ketamine is used frequently by the intravenous or intramuscular route for procedural sedation due to its efficacy and safety.

Clinical Question

In children 8-17 years of age presenting to the emergency department with an acute, painful orthopedic extremity injury is Intranasal Ketamine (1.5 mg/kg) non-inferior to Intranasal Fentanyl (1.0 mcg/kg) in reducing pain at 30 minutes from administration?



  • 8-17 years
  • Acute
  • Orthopedic extremity injury
  • Moderate-severe pain (visual analog pain score (VAS) >35 mm)


  • Significant head, chest, abdomen or spine injury
  • GCS <15
  • Nasal trauma, aberrant nasal anatomy, active epistaxis
  • History of psychosis
  • Opioid administration prior to arrival
  • Non-English speaking
  • In police custody
  • Post-menarchal girls without a negative pregnancy test


Intranasal Ketamine 1.5 mg/kg (maximum dose 100 mg)


Intranasal Fentanyl 2.0 mcg/kg (maximum dose 100 mcg)


Primary Outcome:

  • Difference in pain reduction at 30 minutes (DVAS)

Secondary Outcomes:

  • Difference in pain reduction at 15 and 60 minutes (DVAS)
  • Sedation level: University of Michigan Sedation Scale, Capnography levels
  • Change in vital signs defined by PALS guidelines: Baseline, 15, 30 and 60 minutes

Adverse events (Common Terminology Criteria for Adverse Events 4th Ed): ED, 30-days

Rescue Medications required


Interventional: Randomized Clinical Trial (Non-inferiority Hypothesis)

Primary Results

N = 85 (Ketamine 43, Fentanyl 42)


There was a statistical and clinically significant reduction in pain at 15, 30 and 60 minutes for both study Medications. The upper limit for the pain score differences at 15, 30 and 60 minutes (table below) was less than the 10 mm defined by the authors for Ketamine to be considered non-inferior to Fentanyl.

15 minutes -24.4 (-29.3, -19.4) -25.3 (-30.3, -20.3) 0.93 (-6.09, 7.96)
30 minutes -30.6 (-35.8, -25.4) -31.9 (-37.2, -26.6) 1.26 (-6.19, 8.71)
60 minutes -27.7 (-33.8, -21.6) -29.0 (-35.1, -22.8) 1.30 (-7.36, 9.95)
1. Mean Difference (mm) within medication group (95% CI), All significant
2. Mean Difference (mm) between medication groups (95% CI), All non-inferior
A 15 mm decrease in VAS score is considered a clinically significant improvement in pain



  • Adverse events were statistically more common in the Ketamine group
    • Ketamine: 77% (34/44) > 1AE
    • Fentanyl: 31% (13/42) > 1AE
  • Relative Risk: 2.5, 95% CI (1.5, 4.0)
  • All minor ( Grade II) and transient. Drowsiness (Both), dizziness (Both) and unpleasant taste (Ketamine only) were the most common

No difference between the two groups:

  • Vital signs
  • Level of sedation
  • Need for rescue medications


  • Randomized controlled trial: Allocation concealed, blinding of clinicians
  • Non-inferiority hypothesis
  • Similar demographic characteristics, mechanism and type of injury, time to arrival, baseline pain scores and the requirement for reduction and sedation


  • Single center study
  • 30-day follow-up available for 83% limiting conclusion regarding late complications
  • Per protocol analysis without an intention to treat analysis
  • Insufficient power to identify rare outcomes such as laryngospasm

Author's Conclusions

“Intranasal sub-dissociative ketamine provides effective analgesia that is not inferior to intranasal fentanyl for pain associated with acute extremity injuries in children. Ketamine was associated with more adverse events, but all were mild and transient. Ketamine should be considered for pediatric pain management in the emergency setting, especially when opioids are contraindicated or associated with increased risk, such as prior to procedural sedation.”

Our Conclusions

Intranasal, sub-dissociative dosing of Ketamine appears to be an efficacious alternative to intranasal opioids. Mild, transient adverse events (drowsiness, dizziness, unpleasant taste) were more common in the Ketamine group. A larger sample size would be necessary to determine if sub-dissociative dose Ketamine is associated with a higher rate of serious adverse events such as laryngospasm.

Bottom Line

Intranasal Ketamine provides effective analgesia when compared to intranasal Fentanyl. Adverse events are more common but mild and self-limited. It is likely most appropriate for patients in which an opiate is less desirable.

Read More


Graudins A, Meek R, Egerton-Warburton D, Oakley E, Seith R.

The PITCHFORK (Pain in Children Fentanyl or Ketamine) Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine and Fentanyl for the Relief of Moderate to Severe Pain in Children with Limb Injuries.”

Ann Emerg Med. 2015 Mar;65(3):248-254.


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Nisha Narayanan, MD, Elizabeth Haines, MD