Proton pump inhibitors (PPIs) are widely prescribed for gastric acid suppression, but prolonged use has been linked to impaired bone healing and increased fracture risk, raising concern for spinal fusion outcomes. Histamine H2-receptor antagonists (H2RAs) may offer a safer alternative for bone health in this population. This study aims to evaluate and compare the postoperative complication profiles of patients receiving PPI versus H2RA prophylaxis following multi-level lumbar fusion. This retrospective cohort analysis was conducted using data from the TriNetX Research Network (2010–2025). We identified adults undergoing multi-level lumbar fusion with no documented history of PPI or H2RA use prior to surgery. Patients were categorized into postoperative PPI or H2RA cohorts. To minimize selection bias, 1:1 propensity score matching was utilized to balance demographics and clinical comorbidities. Outcomes were assessed at 90 days and 2 years using multivariate logistic regression to estimate risk ratios (RR) and p-values. After matching, 7,360 patients remained per cohort. At 90 days, PPI users had higher rates of pneumonia (1.98% vs. 1.26%; RR = 1.57, p = 0.001), postoperative anemia (15.22% vs. 13.74%; RR = 1.11, p = 0.011), and dural tears (0.88% vs. 0.22%; RR = 4.06, p < 0.001). At 2 years, PPI use was associated with higher rates of revision surgery (9.14% vs. 7.38%; RR = 1.24, p < 0.001), pedicle screw loosening (5.29% vs. 4.29%; RR = 1.23, p = 0.005), and mechanical complications (21.41% vs. 20.00%; RR = 1.07, p = 0.034). Postoperative PPI therapy is associated with significantly increased risks of both short-term medical and long-term surgical complications following lumbar fusion. These findings suggest that H2RAs may represent a more favorable alternative for gastric prophylaxis in this patient population to optimize bone-related outcomes and overall surgical recovery.
Patel et al. (Fri,) studied this question.