Ketamine at analgesic doses is increasingly used in emergency departments for acute musculoskeletal pain, and the route has largely been decided by habit and by what the department stocks. This randomised, double-blind, double-dummy trial settled the comparison. It enrolled 1,194 adults aged 18 to 65 presenting with acute musculoskeletal trauma and moderate to severe pain, randomised to 20 mg ketamine subcutaneously or 20 mg intranasally, with pain scored at 5, 10, 15, 30, 60, 90 and 120 minutes.
Both worked, and worked well. At 30 minutes the mean fall in numerical rating scale score was 3.70 (SD 1.88) with subcutaneous and 4.42 (2.15) with intranasal — a difference of 0.72 in favour of intranasal (95% CI -0.95 to -0.48). That is statistically significant and clinically irrelevant: the accepted threshold for a difference a patient would notice is 1.3 points, and every timed comparison fell below it. Secondary outcomes matched, except that minor adverse events were more frequent with the subcutaneous route.
The practical consequence is that the route is now a logistical decision, not a clinical one — and once that is true, intranasal has advantages that have nothing to do with pain scores. No needle, no sharps, no injection in a patient who is already frightened and in pain, faster to give at triage, and usable where establishing access is difficult or the patient is combative. For a child, an elderly patient with poor veins, or a crowded department where analgesia waits on a nurse being free to cannulate, that matters.
In Indian emergency practice the argument is stronger still. Analgesia is routinely delayed while access is obtained, and a drug that a triage nurse can give with an atomiser removes a step from that chain. Two limits to note: the trial studied 20 mg fixed doses in adults aged 18 to 65 with musculoskeletal trauma, so it does not speak to weight-based dosing, to children, to the elderly, or to visceral or neuropathic pain. And ketamine remains a controlled drug with the same monitoring requirements whichever way it goes in.
- Treat route as a logistics decision — intranasal and subcutaneous ketamine relieved pain equally.
- Prefer intranasal where access is hard, the patient is needle-averse, or analgesia would otherwise wait on cannulation.
- Minor adverse events were commoner with the subcutaneous route, another small point in favour of intranasal.
- Stock an atomiser and agree a fixed 20 mg adult dose so the option is actually available at triage.
- The trial covered adults 18 to 65 with musculoskeletal trauma only; do not extrapolate to children or visceral pain.
The statistics, in plain English
This is a good example of statistical significance and clinical significance parting company. The 0.72-point difference has a confidence interval of -0.95 to -0.48 that excludes zero, so it is a real difference — but the whole interval sits below 1.3 points, the smallest change patients reliably notice on this scale. So the trial does not just fail to find an important difference; it positively excludes one, which is a stronger statement. The double-dummy design, where every patient got both an injection and a nasal spray with only one active, is what allowed genuine blinding across two very different routes.
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