Comparison of the Effectiveness of Maintenance Doses of Caffeine Citrate on Tracheal Tube Removal and Apnea After it in Premature Infants Hospitalized in the Neonatal Intensive Care Unit: A Randomized Clinical Trial

Background: Respiratory distress ranks among the leading causes of mortality and morbidity in premature infants, with intubation and mechanical ventilation being prominent aggressive treatments. Caffeine citrate, a widely used methylxanthine, treats apnea of prematurity in such infants. However, the efficacy of high caffeine doses remains contentious. Objectives: This study aimed to evaluate the effectiveness and side effects of maintenance doses of caffeine citrate in facilitating tracheal tube removal and reducing subsequent apnea episodes in premature infants in neonatal intensive care units. Methods: Conducted as a randomized clinical trial at Afzalipur Hospital in Kerman, Iran, in 2023, this study involved eighty neonates with gestational ages under 35 weeks. They were divided into two groups: One received an initial caffeine citrate dose of 20 mg/kg followed by a maintenance dose of 5 mg/kg per day until the infant exhibited no apnea for at least 7 days post-extubation, while the other group received a maintenance dose of 10 mg/kg. Variables such as gestational age, sex, weight, and Apgar scores at one and five minutes post-birth were analyzed. The study assessed the effectiveness of caffeine citrate doses in terms of tracheal tube removal and reduction in apnea incidents, with secondary outcomes including patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), feeding intolerance, and tachycardia. Due to data non-normality, non-parametric tests were utilized for mean comparisons and the chi-Square test for qualitative variables and relationships (P-value < 0.05). Results: The findings revealed no significant differences in hospital stay duration, time until separation from the device, Apgar scores at one and five minutes post-birth, or the incidence of PDA, NEC, BPD, and feeding intolerance between the two groups. However, the incidence of tachycardia was notably higher in the group receiving the higher caffeine dose (P-value = 0.026). Conclusions: While the incidence of tachycardia was significantly higher in infants receiving a maintenance dose of 10 mg/kg, there was no observed difference in the efficacy of the two caffeine doses. Therefore, a maintenance dose of 5 mg/kg of caffeine citrate emerges as a more favorable treatment option.