STUDY OBJECTIVE: To compare the efficacy and safety of subcutaneous versus intranasal ketamine in controlling pain following acute musculoskeletal trauma.
METHODS: We conducted a randomized, double-blinded, double-dummy prospective study, including adult participants aged 18 to 65 years, presenting to the emergency department (ED) for acute musculoskeletal trauma with moderate to severe pain. Participants were randomly assigned to receive either 20 mg subcutaneous or intranasal ketamine. Our primary outcome was the reduction in the numerical rating scale (NRS) at 30 minutes, with additional measures at 5, 10, 15, 60, 90, and 120 minutes. Other secondary outcomes were the percentage of patients with a NRS score of less than 3 at the end of the protocol, adverse events, and the need for additional pain medications.
RESULTS: We enrolled 599 patients in the subcutaneous group and 595 in the intranasal group. At 30 minutes, the mean NRS decrease from baseline was -3.70 (1.88) in the subcutaneous group and -4.42 (2.15) in the intranasal group, yielding a mean difference of -0.72 (95% confidence interval -0.95 to -0.48). Although statistically significant, this difference, as well as those observed at all other time points, remained below the 1.3 NRS threshold for clinical importance. There was no difference in secondary outcomes except more minor adverse events in the subcutaneous group.
CONCLUSION: For patients presenting to the ED with acute musculoskeletal trauma, we found no clinically important differences in pain reduction between ketamine 20 mg, subcutaneous and ketamine 20 mg, intranasal.
| Discipline Area | Score |
|---|---|
| Physician |  |
Physician rater
Any good quality research on ketamine is very valuable these days. We are all very interested in its comparative benefits and harms vs opioids and NSAIDs.
Physician rater
Essentially a non-inferiority trial without non-inferiority statistics. This supports the inclination to choose between IN and SC options on the basis of cost and convenience considerations.
Physician rater
The opioid crisis has accelerated interest in alternative analgesic strategies for ED settings (http://pmid.us/31040501) including ketamine (http://pmid.us/30019434). The route of ketamine administration is a topic I've not seen evaluated in the past, so this may be newsworthy for clinicians; however, I would wonder what the post-discharge analgesic strategy would be in these patients (http://pmid.us/30228730).
Physician rater
The rationale for comparing with the subcutaneous route is unclear, given its known variability in absorption. A comparison of intravenous to intranasal administration would be more appropriate for evaluating clinical differences.
Physician rater
This RCT shows that both intranasal and subcutaneous ketamine are effective for treating acute traumatic pain in emergency departments. More research is necessary to refine dosing for optimal balance between efficacy and side effects. Intranasal delivery is favoured because of fewer minor side effects.
, McMaster University