This double-blind, double-dummy trial randomised 1,194 adults aged 18 to 65 presenting to the emergency department with moderate to severe pain from acute musculoskeletal trauma to 20 mg of ketamine given either subcutaneously or intranasally.
At 30 minutes the mean fall in numerical rating scale was 3.70 points with the subcutaneous route and 4.42 with the intranasal, a difference of 0.72 (95% CI -0.95 to -0.48). That difference, and those at every other time point from 5 to 120 minutes, sat below the 1.3-point threshold for clinical importance. Secondary outcomes were the same apart from more minor adverse events in the subcutaneous group.
So the choice can be made on grounds other than efficacy. Intranasal delivery needs no needle, no cannula and no sharps disposal, which matters in a child, in a needle-phobic adult, in prehospital care and in any crowded department where a cannula is a delay rather than a given. Subcutaneous dosing is more reliable in a patient with epistaxis, nasal obstruction or facial injury, and is easier to titrate. Both routes reduced pain by roughly four points from baseline, which is a substantial effect for either.
- Pain fell 3.70 points subcutaneously and 4.42 intranasally at 30 minutes
- The 0.72-point difference is below the threshold for clinical importance
- More minor adverse events with the subcutaneous route
- Choose on practicality: intranasal avoids a needle, subcutaneous suits facial injury
The statistics, in plain English
The interval, -0.95 to -0.48, excludes zero, so intranasal is genuinely and reproducibly a little better on the scale. But the entire interval lies inside the 1.3-point band regarded as imperceptible, which means the trial has positively established equivalence in practical terms rather than merely failing to find a difference. That is a stronger and more useful conclusion than a non-significant result would have been.
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