Dosing trajectories of antihypertensive agents among preterm infants: A retrospective, cross-sectional analysis

Introduction: Preterm infants are at an increased risk for hypertension as well as complications from hypertension due to incomplete organogenesis. Due to the lack of guidelines for the treatment of hypertension in this population, clinicians rely on experience to make treatment decisions. However, little is currently known about these treatment decisions. Methods: Our study was a retrospective cross-sectional study of preterm infants (gestational age < 37 weeks) who were treated as inpatients at the University of Alabama at Birmingham Medical Center with an antihypertensive medication and who were infants at discharge (postnatal age < 1 year). The three most common antihypertensive agents were identified and dosing patterns in milligram per kilogram for each agent were plotted over time (hours). The K-means algorithm was used to identify clusters of patients based on these dosing trajectories. Demographic and clinical information was compared across these clusters. Results: The study included 120 patients and 134 patient visits. The three most common antihypertensive agents across patient visits were propranolol (58%), captopril (12%), and esmolol (8.8%). Patients were treated with captopril for an average of 319 hours, propranolol for 275 hours, and esmolol for 55 hours before discontinuation. The average time to dose increase was shortest for patients treated with esmolol at 10 hours, while it was 60 and 118 hours for captopril and propranolol respectively. Esmolol was initiated in the youngest patients with an average postnatal age of 3 days compared to 18 and 87 days for propranolol and captopril. Conclusions: Each of the three agents exhibited different overall dosing trajectories. Captopril was started low and increased over time, likely due to safety concerns in preterm infants. Propranolol was the most prevalent agent and was initiated at target dose, potentially due to its favorable safety/efficacy profile. Esmolol was used acutely and had the most variable dosing trajectories, because of its ability to be easily titrated. The dosing trajectories identified in this study will contribute to the development of prospective comparative effectiveness studies or randomized controlled trials of different antihypertensive dosing strategies in preterm infants.