[A comparison of the efficacy of aminophylline and doxapram in preventing idiopathic apnea in preterm newborn infants]. A blinded, randomized, placebo-controlled trial to compare theophylline and doxapram for the treatment of apnea of prematurity. Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study.
Doxapram is an analeptic of the respiratory system that has been used in the last few years for the treatment of idiopathic apnea spells in infants who show resistance to methylxantine. In this study we have compared the efficacy of aminophylline and doxapram for the prevention of idiopathic apnea spells in two groups of preterm infants comparable for gestational age, birthweight and postnatal age. The two drugs resulted to be effective in preventing the spells of apnea in 66% and 60% of the cases respectively. In the cases in which there was a partial or negative response, the association of the two substances resulted in a noticeable reduction of the apnea spells. The positive effect of the association of aminophylline and doxapram is probably due to the different action mechanism on the stimulation of the respiratory system. A blinded, randomized, placebo-controlled trial was conducted to evaluate the effectiveness of theophylline and doxapram therapy in 31 infants with significant apnea of prematurity. Of 10 infants, two had a short-term response to placebo, 8 of 10 infants to theophylline, and 7 of 11 infants to doxapram (placebo vs treatment with theophylline or doxapram: p = 0.01). The two infants who initially responded to placebo remained responsive for the duration of the study. Of the eight infants in whom treatment with placebo failed, five were randomly assigned to receive theophylline, for a total of 15 infants treated with theophylline, and two of the eight were randomly assigned to receive doxapram, for a total of 13 infants treated with doxapram; the remaining infant required tracheal intubation. Of the 15 infants randomly assigned to receive theophylline, seven responded for the duration of the study; of the eight infants who did not respond to treatment with theophylline, five responded to doxapram, one responded to a combination of theophylline and doxapram, and two remained resistant to treatment. Of the 13 infants randomly assigned to receive doxapram four responded for the duration of the study; of the nine who did not respond to doxapram, seven responded to theophylline, one responded to a combination of theophylline and doxapram, and one remained resistant to treatment. This study demonstrates that although therapy with theophylline or doxapram is associated with a significant short-term reduction in the incidence of apnea compared with that in placebo-treated infants, the long-term response to treatment is frequently incomplete and is not sustained more than 1 week. A double-blind controlled study, in two parts, was undertaken to compare the effectiveness of aminophylline and doxapram therapy in idiopathic apnea of prematurity. In the first part of this study, eight of 15 infants responded to doxapram therapy with complete cessation of apneic spells and six of 11 infants responded similarly to administration of aminophylline. These differences were statistically insignificant. In the second part of the study, assessment was made of whether the addition of doxapram to aminophylline therapy was effective in treatment of apnea of prematurity that had been unresponsive to aminophylline alone. Of ten infants who continued to have apneic spells during treatment with aminophylline, eight responded to the addition of doxapram with complete cessation of apnea. Nine infants received placebo in addition to aminophylline, and none had a reduction in frequency of apnea.
Intravenous doxapram and intravenous methylxanthine appear to be similar in their short term effects for treating apnea in preterm infants, although these trials are too small to exclude an important difference between the two treatments or to exclude the possibility of less common adverse effects. Long term outcome of infants treated in these trials has not been reported. Further studies would require a large number of infants to clarify whether there might be differences in responses or adverse effects with these two drugs at different ages.