Faculty Collaboration Database

Ketamine infusion for pain control in severely injured patients: Results of a randomized controlled trial. J Trauma Acute Care Surg 2025 Jun 01;98(6):858-866

Date

03/28/2025

Pubmed ID

40152587

DOI

10.1097/TA.0000000000004602

Scopus ID

2-s2.0-105002736919 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

LEVEL OF EVIDENCE: Therapeutic/Care Management; Level I.

Author List

Carver TW, Peppard WJ, Gellings JA, Thapa R, Trevino C, Mantz-Wichman M, Peschman JR, Szabo A, Yang Y, Schroeder ME, Milia DJ, Elegbede AF, de Moya MA, de Roon-Cassini TA

Authors

Thomas W. Carver MD Professor in the Surgery department at Medical College of Wisconsin
David J. Milia MD Professor in the Surgery department at Medical College of Wisconsin
William J. Peppard PharmD Trauma/Surgical Critical Care Pharmacist in the Pharmacy department at Froedtert Hospital
Jacob R. Peschman MD Associate Professor in the Surgery department at Medical College of Wisconsin
Mary Elizabeth Schroeder MD Chief Medical Officer, Associate Professor in the Medical College Physicians Operations department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
Colleen Trevino PhD Associate Professor in the Surgery department at Medical College of Wisconsin
Terri A. deRoon Cassini PhD Center Director, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Analgesia, Patient-Controlled
Analgesics
Analgesics, Opioid
Double-Blind Method
Female
Humans
Infusions, Intravenous
Injury Severity Score
Ketamine
Male
Middle Aged
Pain
Pain Management
Pain Measurement
Prospective Studies
Treatment Outcome
Wounds and Injuries
Young Adult