Written by Jonathan Brewer
Spoon Feed
Intranasal ketamine provided slightly greater pain reduction than subcutaneous administration for acute musculoskeletal trauma, but the difference was not clinically significant. Both routes appear safe, but a fewer minor adverse effects were observed intranasally.
Ketamine works either way—intranasal may have it by a nose
This randomized, double-blinded trial enrolled 1,194 ED patients (18–65 yrs) with moderate to severe traumatic musculoskeletal pain, comparing a fixed 20mg dose of intranasal (IN) vs. subcutaneous (SC) ketamine. The primary endpoint was a numerical reduction score (NRS) of pain at 30 minutes. IN ketamine reduced pain by −4.42 vs. −3.70 with SC, a statistically but not clinically significant difference. This modest advantage persisted across 5–120 minutes. Rates of achieving NRS <3 and need for rescue analgesia were similar.
Minor adverse effects (i.e. fatigue, dizziness, nausea, headache) occurred more frequently in the SC group, but no serious adverse events were reported. The fixed 20mg dose corresponded to ~0.3 mg/kg on average, but this may have overdosed smaller patients in the SC arm, contributing to increased side effects.
How will this change my practice?
Both routes are viable analgesic options when managing acute traumatic pain. Given similar efficacy with fewer adverse effects, I’ll preferentially use intranasal ketamine when rapid, needle-free analgesia is desirable. That said, I’d be interested to see a study with weight-based dosing and with pediatrics (where I already see non-IV ketamine being utilized more) before making the final decision.
Source
Intranasal Versus Subcutaneous Ketamine for the Treatment of Acute Traumatic Pain in the Emergency Department: A Randomized Clinical Trial. Ann Emerg Med. 2025 Oct 17:S0196-0644(25)01233-8. doi: 10.1016/j.annemergmed.2025.09.019. Epub ahead of print. PMID: 41108307.
