Does Scheduled Low-Dose Short-Term NSAID (Ketorolac) Modulate Cytokine Levels after Orthopaedic Polytrauma? A Secondary Analysis of a Randomized Clinical Trial

OBJECTIVES:To determine whether scheduled low-dose, short-term ketorolac modulates cytokine concentrations in orthopaedic polytrauma patients.METHODS:Design:Secondary analysis of a double-blinded, randomized controlled trial.Setting:Single Level I trauma center from August 2018 to October 2022.Patient Selection Criteria:Orthopaedic polytrauma patients between 18 and 75 years with a New Injury Severity Score greater than 9 were enrolled. Participants were randomized to receive 15 mg of intravenous ketorolac every 6 hours for up to 5 inpatient days or 2 mL of intravenous saline similarly.Outcome Measures and Comparisons:Daily concentrations of prostaglandin E2 and interleukin (IL)-1a, IL-1b, IL-6, and IL-10. Clinical outcomes included hospital and intensive care unit length of stay, pulmonary complications, and acute kidney injury.RESULTS:Seventy orthopaedic polytrauma patients were enrolled, with 35 participants randomized to the ketorolac group and 35 to the placebo group. The overall IL-10 trend over time was significantly different in the ketorolac group (P = 0.043). IL-6 was 65.8% higher at enrollment compared to day 3 (P < 0.001) when aggregated over both groups. There was no significant treatment effect for prostaglandin E2, IL-1a, or IL-1b (P > 0.05). There were no significant differences in clinical outcomes between groups (P > 0.05).CONCLUSIONS:Scheduled low-dose, short-term, intravenous ketorolac was associated with significantly different mean trends in IL-10 concentration in orthopaedic polytrauma patients with no significant differences in prostaglandin E2, IL-1a, IL-1b, or IL-6 levels between groups. The treatment did not have an impact on clinical outcomes of hospital or intensive care unit length of stay, pulmonary complications, or acute kidney injury.LEVEL OF EVIDENCE:Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.