Low-dose doxapram therapy for idiopathic apnea of prematurity

Background: Doxapram is contraindicated for newborn infants in Japan because of its serious side effects. However, because of encouraging results of recent studies regarding the efficacy and safety of therapy for apnea of prematurity (AOP) with lower doses of doxapram than those previously proposed, approximately 60% of Japanese neonatologists continue to use doxapram at small doses. Caution is warranted because the sample sizes of the former studies are inadequate to evaluate doxapram for both its beneficial and harmful effects. Therefore, we conducted the present study in order to investigate the efficacy and harmful events of low-dose doxapram therapy for idiopathic AOP in very low-birth weight (VLBW) infants in a larger population. Methods: One hundred and six VLBW infants with idiopathic AOP were treated with doxapram at a dose of 0.2–1.0 mg/kg per h in combination with methylxanthines and the frequency of apnea and secondary outcomes were compared with a group of control infants. Results: An approximate 80% reduction in the frequency of apnea was found with only minimal side effects following low-dose doxapram. Although there were no significant differences in secondary outcomes between the doxapram-treated and control groups, mortality in doxapram-treated infants was significantly lower than that in control infants. Conclusions: Patients with AOP unresponsive to treatment with methylxanthines may benefit from the addition of low-dose doxapram.