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

Abstract

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 18-75 years with a New Injury Severity Score greater than 9 were enrolled. Participants were randomized to receive 15 mg of intravenous (IV) ketorolac every 6 hours for up to 5 inpatient days or 2 mL of IV saline similarly. Outcome Measures and Comparisons: Daily concentrations of prostaglandin E2 (PGE2), interleukin (IL)-1a, IL-1b, IL-6, and IL-10. Clinical outcomes included hospital and intensive care unit (ICU) length of stay (LOS), pulmonary complications, and acute kidney injury (AKI). 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 PGE2, 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, IV ketorolac was associated with significantly different mean trends in IL-10 concentration in orthopaedic polytrauma patients with no significant differences in PGE2, IL-1a, IL-1b, or IL-6 levels between groups. The treatment did not have an impact on clinical outcomes of hospital or ICU LOS, pulmonary complications, or AKI. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.