Incidence, risk factors, and prediction model of piperacillin/tazobactam-associated hypokalemia in neonates

Background: Maintaining optimal potassium levels is critical in neonates. Piperacillin/tazobactam (TZP) is associated with hypokalemia in adults, but neonatal data are limited. Objectives: This study aimed to investigate the incidence, severity, and determinants of TZP-associated hypokalemia (TAH) in neonates and develop a predictive model for early detection. Design: Retrospective cohort study. Methods: Neonates treated with TZP between January 2019 and December 2024 at Xiamen Women and Children’s Hospital were included. Demographic, laboratory, and medication data were extracted. Naranjo probability scores assessed TAH causality. Multivariate logistic regression identified predictors, and a nomogram predicted TAH occurrence. Nomogram performance was evaluated. Results: Among 1027 neonates initially screened, 358 met the inclusion criteria and were ultimately included in the analysis. The incidence of TAH in this cohort was 20.4% (73/358). Independent predictors included higher baseline serum creatinine ( p = 0.012, OR 1.02, 95% CI 1.00–1.03), dopamine use ( p = 0.002, OR 3.37, 95% CI 1.54–7.36), and lower serum calcium ( p = 0.049, OR 0.31, 95% CI 0.10–0.99) was a protective factor. The nomogram showed good predictive accuracy (AUC = 0.771) and net benefit. High-risk neonates had a higher hypokalemia incidence (log-rank test p < 0.001). Conclusion: Higher baseline serum creatinine, dopamine use, and lower serum calcium are independent predictors of neonatal TAH. The nomogram offers a user-friendly tool for TAH prediction, facilitating early detection and management in clinical practice. This study supports early detection, diagnosis, and intervention for neonatal TAH.