SO28. Safety Profile and Optimal Timing of Perioperative NSAIDs in Breast Reduction Surgery: A Multi-Cohort Analysis

PURPOSE: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for perioperative pain management remains controversial in plastic surgery. While previous research has been limited to animal studies and small human trials, this comprehensive analysis provides robust data on NSAID safety in breast reduction surgery, examining both broad NSAID use and specific ketorolac outcomes while establishing temporal patterns of risk. METHODS: We conducted three complementary retrospective cohort analyses of breast reduction patients using TriNetX data (2019-2023): (1) all NSAID classes within one week of surgery (n=12,537 matched pairs), (2) ketorolac-specific administration (n=5,813 matched pairs), and (3) time-specific NSAID administration at postoperative day 1 (n=2,202 matched pairs) and day 2 (n=1,176 matched pairs). Propensity score matching accounted for age, ethnicity, race, sex, tobacco use, nicotine dependence, and hemoglobin A1C. Primary outcome was hematoma formation. RESULTS: Patients receiving NSAIDs on day 1 showed minimal but significant increased hematoma risk compared to non-NSAID patients (RD=0.007%, p=0.033). By day 2, there was no significant difference in hematoma risk (RD=0.003%, p=0.574). Early general NSAID use showed modest risk increase (RD=0.425%, p=0.001), while ketorolac demonstrated no significant increase in complications. CONCLUSION: This analysis suggests that delaying NSAID administration until postoperative day 2 minimizes hematoma risk, while ketorolac appears safe for earlier use. Though early NSAID use shows statistically significant risks, these modest increases (<1/2%) should be weighed against the substantial risks of opioid use, including significant dependency risk. Clinical judgment and patient-specific risk stratification can further reduce risk when considering NSAID administration before day 2.