Intranasal Versus Subcutaneous Ketamine for the Treatment of Acute Traumatic Pain in the Emergency Department: A Randomized Clinical Trial.

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.