The introduction of ketamine into a spinal cord ischemia (SCI) protection protocol used during thoracoabdominal aortic aneurysm (TAAA) repairs led to significant reductions in postoperative opiate administration and patient-reported pain scores, a randomized controlled trial (RCT) performed by a team of researchers at the University of Kentucky in Lexington, Kentucky, demonstrated.
The 20-patient doubled-blind RCT showed that among the 10-patient cohort who received ketamine as part of their SCI protection bundle, estimated mean six-hour oral morphine-equivalent use over the first 48 hours was 49mcg (95% confidence interval [CI] 28.7–69.3) vs. 110mcg (95% CI 89.8– 130.3) in the saline placebo cohort (p=0.019). The estimated six-hour mean pain score for the cohort given ketamine, meanwhile, was 1.9 (95% CI 0.4–3.4) vs. 4.2 (95% CI 2.6–5.8) for those who received the placebo.
The data were delivered during the 2025 Southern Association for Vascular Surgery (SAVS) annual meeting in St. Thomas, the U.S. Virgin Islands ( Jan. 22–25) by senior investigator Sam Tyagi, MD, an assistant professor of surgery at the University of Kentucky. Tyagi received the prestigious SAVS Founders’ Award for the paper.
Tyagi and colleagues sought to address the specter of low-dose naloxone, a component of the SCI protection bundle, in worsening perioperative pain scores and increasing the need for postoperative opiate administration.
The study grew out of a previous multidisciplinary retrospective analysis aimed at identifying a pain management strategy to alleviate perioperative pain and reduce opiate reliance alongside, later, an informal conversation in which the potential for the use of ketamine in the mix emerged, Tyagi explained.
That study demonstrated that patients who received a continuous infusion of naloxone with their SCI protection bundle recorded pain scores that were statistically significantly higher and were receiving more morphine-equivalent pain medications when compared to patients who had similar operations but were under no SCI protection protocol.
“So, not only were we giving them much higher doses of opiates, we were also poorly controlling their pain on top of that,” Tyagi explained.
That’s when the suggestion to incorporate ketamine emerged during a holiday season chat with his physician brother. After some investigation, the project was set in motion.
The RCT saw patients randomized by the University of Kentucky pharmacy team before arriving in the operating room for their TAAA procedure, where ketamine administration—or the placebo—was initiated and continued during the time they were on the SCI protection protocol. “Nothing else was changed,” Tyagi said.
Results showed that no patients had adverse outcomes related to the ketamine, though one died from procedural-related complications. Another enrollee withdrew from the study several hours after randomization.
“The amount of morphine equivalents [administered] was essentially half in the ketamine group versus the placebo saline group,” Tyagi told SAVS, with pain scores showing “a 2.3 [point] difference in the ketamine vs. placebo group.”
Among future directions of study, the researchers aim to quantify the impact of incisions on pain scores, explore excitatory amino acids in cerebrospinal fluid in the setting of ketamine, as well as expand on the 20-patient RCT itself.
