Evaluation of the safety of doxapram in premature neonates born before 28 weeks of gestation.

Abstract

To assess the short-term safety of doxapram for treating apnea of prematurity. This is a retrospective and bicenter study. Eligible children were born before 28 weeks of gestation from January 1, 2020 to December 31, 2021. The association between doxapram treatment and gastrointestinal events was assessed with logistic regression models with adjustment for the main confounding factors: center, sex, intra-uterine growth restriction and gestational age. The main outcome measures are gastrointestinal events (necrotizing enterocolitis or feeding intolerance), the adverse effects of doxapram most frequently reported in the literature. The population consisted of 268 children; 113 (42.2%) received doxapram. As compared with children who did not receive doxapram, those who did had lower gestational age at birth (25.4 vs 26.3 weeks), lower birth weight and more evidence of greater clinical respiratory severity. Doxapram treatment was not associated with increased risk of gastrointestinal events (30.1% and 29.7% in the treated and untreated groups; odds ratio 1.3, 95% CI 0.7-2.4, p = 0.43). More children in the treated than untreated group had high blood pressure (25.7% vs 6.5%).

Conclusion: In children born before 28 weeks of gestation, doxapram treatment for apnea of prematurity was not associated with the occurrence of gastrointestinal events.

What is known: • Doxapram is a well-known second-line treatment for apnea of prematurity. It is a central nervous stimulant that can be used in refractory apnea of prematurity despite continuous positive airway pressure and optimal caffeine therapy. However, its use varies among countries and centers, probably because of suspected adverse effects. Studies suggest that this drug may have potential side effects such as digestive events (necrotizing enterocolitis).

What is new: • We present reassuring data on the digestive safety of doxapram. Use of this drug was not associated with increased rates of digestive events in preterm infants born before 28 weeks of gestation.