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Rib fractures occur in up to 40% of trauma patients and are associated with increased mortality. Opiate-based pain regimens remain the cornerstone of rib fracture management; however, concerns around opioids have fostered interest in alternative analgesics. Ketamine is currently being used in lieu of opioids, but little evidence exists supporting its use within the trauma population.A prospective, randomized, double-blind placebo-controlled trial of adult patients with three or more rib fractures admitted to a Level I trauma center was conducted. Exclusion criteria included age older than 64 years, Glasgow Coma Scale score less than 13, and chronic opiate use. The experimental arm received low-dose ketamine (LDK) at 2.5 μg·kg−1·min−1 while the placebo cohort received an equivalent rate of 0.9% normal saline. All infusions were continued for 48 hours. The primary outcome was reduction in numeric pain score (NPS) during the first 24 hours. Secondary outcomes studied included oral morphine equivalent (OME) utilization, length of stay, epidural rates, pulmonary complications, and adverse events.Forty-five (49%) of 91 patients were randomized to the experimental arm. Both groups were similar in makeup. Overall, 74.7% were male, had a median age of 49 years, and an Injury Severity Score (ISS) of 14. Low-dose ketamine was not associated with a significant reduction in 24-hour NPS or OME totals. Subgroup analysis of 45 severely injured patients (ISS, >15) demonstrated that LDK was associated with a significant reduction in OME utilization during the first 24 hours (35.7 vs. 68, p = 0.03), 24 hours to 48 hours (64.2 vs. 96, p = 0.03), and overall (152.1 vs. 198, p = 0.048). No difference in other secondary outcomes or adverse events was noted.Low-dose ketamine failed to decrease NPS or OME within the overall cohort, but a decrease in OME was observed among patients with an ISS greater than 15. Confirmatory studies are necessary to determine if LDK is a useful adjunct among severely injured patients.Therapeutic study, level II.