Impact of Proton Pump Inhibitor Use on Surgical Outcomes Following Malleolar Fracture Fixation: A Propensity-Matched Analysis

Research Type: Level 3 - Retrospective cohort study, Case-control study, Meta-analysis of Level 3 studies Introduction/Purpose: Proton pump inhibitors (PPIs) are commonly prescribed for acid suppression but have been implicated in impairing bone healing and increasing infection risk. The impact of PPI use on surgical outcomes following malleolar fracture fixation remains unclear. This study evaluates the association between preoperative PPI use and postoperative complications, including wound disruption, infection, thromboembolic events, and delayed healing in patients undergoing open reduction and internal fixation (ORIF) of malleolar fractures. We hypothesize that PPI use may be associated with higher rates of postoperative complications. By utilizing a large multi-center dataset and propensity score matching, we aim to provide robust evidence on whether PPI use should be a consideration in preoperative risk stratification for malleolar surgery. Methods: A retrospective cohort study was conducted using the TriNetX research network, including patients aged 18–65 years who underwent ORIF for medial, lateral, posterior, bimalleolar, or trimalleolar fractures. Patients were categorized into two cohorts: those with documented PPI use prior to surgery (Cohort 1, n=16,105) and those without (Cohort 2, n=70,745). Propensity score matching (1:1) was performed to balance demographics and comorbidities, yielding 11,535 matched pairs. The primary outcomes assessed within 180 days postoperatively included wound disruption, infection, sepsis, deep vein thrombosis (DVT), pulmonary embolism (PE), complex regional pain syndrome (CRPS), stiffness, vessel injury, nerve injury, acute kidney injury (AKI), myocardial infarction (MI), and stroke. Risk ratios, odds ratios, and statistical significance were determined using z-tests and Kaplan-Meier survival analysis. Results: Following propensity matching, PPI use was associated with a significantly increased risk of postoperative infection (3.5% vs. 2.7%, p=0.001), sepsis (1.5% vs. 0.8%, p< 0.001), DVT (2.5% vs. 1.6%, p< 0.001), PE (1.4% vs. 0.9%, p=0.001), stiffness (5.0% vs. 3.9%, p< 0.001), and vessel injury (0.3% vs. 0.1%, p=0.001). No significant differences were observed in wound disruption, nerve injury, AKI, MI, or CRPS. These findings suggest that PPI use may contribute to an increased risk of postoperative complications following malleolar fracture fixation, particularly in relation to thromboembolic events and infections. Conclusion: This study demonstrates an association between preoperative PPI use and increased postoperative complications following malleolar fracture fixation. Specifically, PPI users exhibited higher rates of infection, sepsis, thromboembolic events, and stiffness compared to non-users. These findings highlight the need for clinicians to carefully assess the risks and benefits of PPI use in surgical candidates. Future prospective studies are warranted to further investigate the underlying mechanisms driving these associations and to develop risk mitigation strategies. Surgeons should consider these findings in preoperative planning to optimize patient outcomes following malleolar fracture surgery.