Invited Commentary 

Dexmedetomidine Infusion for Rib Fractures—Still in Search of the Right Indication?

Joshua B. Brown

JAMA Surg 2025;160;(10):1057. doi:10.1001/jamasurg.2025.3235

Dexmedetomidine is an α-2 agonist that garnered significant attention in recent years. Often used for sedation in the intensive care unit (ICU), it has advantages of lighter sedation with less respiratory depression compared with other agents.¹ When studied in critically ill patients and patients receiving mechanical ventilation against other common sedatives such as propofol and midazolam, mortality and ventilator-free days have generally been similar,^2,3 but there are noted increases in adverse effects (namely, bradycardia and hypotension), as well as reports of increased agitation.⁴

Outside of sedation, dexmedetomidine has also been evaluated for a variety of potential indications based on its unique properties. One randomized trial evaluated prophylactic low-dose infusion in older adults undergoing noncardiac surgery, finding a lower incidence of postoperative delirium compared with placebo.⁵ Recent interest in the potential analgesic properties of dexmedetomidine has led to several investigations in perioperative pain control. Dexmedetomidine has been effective in reducing opioid requirements and improving pain scores when used in the preoperative, intraoperative, and postoperative settings.⁶

Based on this, Nahmias and colleagues⁷ hypothesized that dexmedetomidine may be a useful addition to a standardized pain control regimen among trauma patients with rib fractures. Adding an effective nonopioid pain control modality to the toolkit has a significant potential impact on the field. The authors conducted a single-center, randomized, double-blind clinical trial comparing 48 hours of low-dose continuous dexmedetomidine infusion with placebo.⁷ They enrolled injured patients with 3 or more rib fractures admitted to the ICU who were not intubated and evaluated numeric pain score area under the curve over the first 48 hours. They randomized 41 patients, finding no difference in pain scores or opioid requirements between treatment arms.

First, Nahmias and colleagues⁷ should be congratulated on tackling a randomized trial in a trauma population. However, as with all trials, despite the best efforts to control as much as possible, there are limitations that require consideration when interpreting this trial. Because it is a small trial, there is always the concern that it is underpowered to detect smaller but clinically relevant differences, especially for longitudinal pain scores rather than a static difference in means used for sample size calculations. The small size also led to some clinically relevant but statistically nonsignificant differences in patient characteristics, baseline pain, and complications between groups. Several patients did not get the full duration of study drug, and dexmedetomidine dosing may have been lower than necessary to see significant analgesic benefits, albeit almost a third had the infusion stopped for bradycardia or hypotension. Ultimately, dexmedetomidine may still be looking for the right indication in trauma, but several valuable lessons from this trial can inform the design and conduct of larger multicenter trials that may yet find the optimal use of dexmedetomidine among similar or other populations of injured patients.