Serotonergic antidepressants are associated with increased acute bleeding events following femur fracture fixation: A nationwide matched cohort analysis of 5,477 patients.

Introduction: Serotonergic antidepressants, including both selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been linked to adverse outcomes following orthopedic procedures. This study aims to evaluate the impact of SSRIs/SNRIs on outcomes in patients following operative fixation of the femur. We hypothesized that perioperative use of SSRIs would be associated with worse outcomes post-surgery.

Methods: A retrospective cohort analysis was conducted using the TriNetX global federated research network. Adult patients (>18 years) with femur fractures treated surgically were identified using Current Procedural Terminology (CPT) and International Classification of Disease (ICD-10) codes. Propensity score matching was performed to create two cohorts: patients using SSRIs/SNRIs and non-users, each consisting of 5,477 matched patients. Outcomes assessed included postoperative bleeding complications, intensive care unit (ICU) requirement, and wound dehiscence.

Results: On the day of surgery, there were no differences in rates of acute post-hemorrhagic anemia (12 % vs 12 %, p = 0.86), hemoglobin <7g/dL (6 % vs 6 %, p = 0.97) or transfusion (4.9 % vs 4.4 %, p = 0.24). From postoperative day 1-7, rates of acute post-hemorrhagic anemia (18 % vs 16 %, p < 0.01), hemoglobin < 7 g/dL (29 % vs 24 %, p < 0.01) and transfusion (9.5 % vs 8.0 %, p < 0.01) were significantly higher in the SSRI/SNRI cohort. From postoperative day 7-30, there were no observed differences in rates for acute post-hemorrhagic anemia, hemoglobin <7g/dL, transfusion and hematoma incision and drainage.

Conclusions: Perioperative use of SSRIs/SNRIs in patients with femur fractures is associated with increased risk of acute bleeding complications (Day 1-7); however, the increased risk of bleeding complications is not observed beyond one week postoperatively. Balancing surgical risk with mental health needs is crucial. These findings underscore the importance of careful management of patients with SSRIs/SNRIs undergoing orthopedic procedures, particularly in terms of postoperative blood loss anemia and the need for transfusion.