Preoperative Intranasal Oxytocin and Probable Acute Stress Disorder After Traumatic Fracture Surgery: A Randomized Clinical Trial.

Summary

In this double-blind randomized clinical trial of 328 adults, a single 40-IU intranasal oxytocin dose before anesthesia induction reduced the 3-day incidence of screening-positive probable acute stress disorder from 30.5% to 15.9%. The risk ratio was 0.52 and the adjusted hazard ratio was 0.45, while no serious adverse events were observed.

Key Findings

• A total of 328 adults were randomized and analyzed by intention to treat, with 164 participants in each group.
• The 3-day incidence of screening-positive probable acute stress disorder was 15.9% with oxytocin versus 30.5% with placebo.
• Oxytocin was associated with a risk ratio of 0.52 and an adjusted hazard ratio of 0.45, with no serious adverse events observed.

Clinical Implications

Preoperative intranasal oxytocin could become a feasible preventive intervention for patients undergoing traumatic fracture surgery, but it should not yet be adopted routinely because the study was single-center, follow-up was short, and the outcome was a screening-positive probable diagnosis rather than a confirmed long-term disorder.

Limitations

• The trial was conducted at a single center, limiting generalizability.
• Follow-up was short and the primary outcome was a screening-positive probable disorder rather than a structured long-term psychiatric diagnosis.

Future Directions

Multicenter trials should assess confirmed acute stress disorder and posttraumatic stress disorder over longer follow-up, examine dose-response relationships, identify patients most likely to benefit, and evaluate interactions with perioperative psychological support and analgesic strategies.