Intranasal ketamine matches subcutaneous injections for traumatic pain relief

Clinical takeaway: For adults presenting to the ED with moderate to severe pain from acute musculoskeletal trauma, 20 mg intranasal ketamine provided pain relief comparable to 20 mg subcutaneous ketamine and was associated with fewer minor adverse events.

Acute musculoskeletal trauma is a common reason for ED visits, and ketamine is increasingly used as an opioid-sparing analgesic, but the optimal route of administration remains uncertain.

In this randomized, double-blind, double-dummy trial, investigators enrolled nearly 1,200 adults aged 18 to 65 years who presented to the emergency department with acute musculoskeletal trauma and moderate to severe pain. Participants were randomized to receive either 20 mg intranasal ketamine (n = 595) or 20 mg subcutaneous ketamine (n = 599), with pain assessed over the following 2 hours.

At the primary endpoint of 30 minutes, pain scores decreased by an average of 4.4 points with intranasal ketamine and 3.7 points with subcutaneous administration. Although the difference statistically favored intranasal delivery, the gap was less than 1 point on the pain scale and remained below the predefined threshold for a clinically meaningful difference. Similar findings were observed at all other measured time points, including 5, 10, 15, 60, 90, and 120 minutes.

Secondary outcomes were also largely comparable. Rates of achieving excellent pain control, defined as a numeric rating scale score below 3 by the end of the study period, and the need for additional analgesia did not differ between groups. However, patients receiving subcutaneous ketamine experienced more minor adverse events.

As the authors concluded, “we found no clinically important differences in pain reduction” between subcutaneous and intranasal ketamine in this population. The findings support intranasal ketamine as an effective, noninvasive alternative for acute traumatic pain management in the ED.

Source: Dhaoui R, et al. (2025 Sep) Ann Emerg Med. Intranasal Versus Subcutaneous Ketamine for the Treatment of Acute Traumatic Pain in the Emergency Department: A Randomized Clinical Trial