Ketamine infusion for pain control in severely injured patients: Results of a randomized controlled trial.
Thomas W Carver, William J Peppard, Jaclyn A Gellings, Rozalin Thapa, Colleen Trevino, Margo Mantz-Wichman, Jacob R Peschman, Aniko Szabo, Yushan Yang, Mary E Schroeder, David J Milia, Anuoluwapo F Elegbede, Marc A de Moya, Terri A de Roon-Cassini
The journal of trauma and acute care surgery June 1, 2025 DOI: 10.1097/TA.0000000000004602 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 78 |
| Population | Severely injured adult trauma patients (Injury Severity Score ≥15) aged 18-64 years admitted to a Level 1 trauma center |
| Interventions | Ketamine 0.9% normal saline |
| Dose | 3 μg/kg/min |
| Duration | 48 hours |
| Topics | Ketamine Esketamine |
| Keywords | Opioids Pain management Severe injury Trauma care Ketamine therapy Opioid alternatives Clinical trials |
| Citations | 3 |
| Key findings | Adjustable-dose ketamine did not reduce opioid use or pain scores compared with placebo in severely injured trauma patients. |
Abstract
Opiate-based pain regimens remain the cornerstone of pain management following traumatic injury, but issues related to opioids have driven research into alternative analgesics. Adjunctive ketamine has been increasingly used to decrease opioid use, but little evidence exists to support its efficacy within the trauma population. A prospective, randomized, double-blind placebo-controlled trial of severely injured (Injury Severity Score [ISS], ≥15) adult patients (aged 18-64 years) admitted to a Level 1 trauma center was conducted. Exclusion criteria included Glasgow Coma Scale score of <14, ISS of <15, pregnancy, and chronic opiate use. All patients were prescribed a patient-controlled analgesia in addition to being randomized to either adjustable dose ketamine starting at 3 μg/kg/min or an equivalent rate of 0.9% normal saline. Study drug and patient-controlled analgesia titration were allowed as part of a treatment algorithm. The primary outcome was reduction in oral morphine equivalent (OME) utilization at 24 hours. We performed a planned interim analysis upon reaching a predetermined enrollment goal. Forty-two of 78 patients (53.8%) were randomized to the experimental arm. Both groups were similar in makeup and had a median ISS of 22 (19, 28.5). The median OMEs in adjustable dose ketamine and placebo groups were 110.6 (55.7, 191.7) and 99.2 (50.6, 172.6), respectively ( p = 0.85). No significant difference in OME was found in 24- to 48-hour or the entire 48-hour study period. Adjustable dose ketamine had no impact on pain scores throughout the study period when compared with placebo (4.9 vs. 4.7, p = 0.95). These findings met the futility cutoff, and enrollment was terminated. Adjustable dose ketamine failed to reduce OME totals or pain scores in a severely injured trauma cohort when compared with placebo at any time point. Additional studies are necessary to determine if there is any benefit for adjuvant ketamine in different trauma subpopulations. Therapeutic/Care Management; Level I.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |