A controlled clinical study comparing doxapram and theophylline in the treatment of apneas of prematurity

The objective of this study was to prove the superiority of doxapram compar ed to theophylline therapy in apneas of prematurity in very low birth weigh t infants. Therefore all VLBW infants (gestational age < 35 weeks) were ran domized if they had in a 2 hours-interval more than 2 apneas, 4 bradycardia s or 4 oxygen desaturations. They received either theophylline (loading dos e 5 mg/kg b. w., 3 mg/kg b. w. bid) or doxapram by continuous infusion of 0 .5 mg/kg/h. Apneas, bradycardias and desaturations were recorded from the t rend analysis of our monitoring system over the first 3-days and a 7 days p eriod and compared statistically (Mann-Whitney U-test). Plasma levels of bo th drugs and a polysomnographic recording were obtained during steady state conditions in parallel to a behavioral observation according to Prechtl. T he recorded events were again compared using the Mann-Whitney U-test. Twent y patients were treated with theophylline, 14 with doxapram. In 9 patients of each group we could perform a polysomnography and behavioral observation . The incidence of apneas, bradycardias and desaturations in a 7 days-inter val was not significantly different between both groups. Analyzing the firs t 3 days of treatment, however, we could detect a significantly lower rate of apneas in the doxapram group (2.5 apneas compared to 7 in the theophylli ne group, p<0.037). In the polysomnographic recording and in our behavioral observations we could not record any significant differences between both groups. Therefore we can conclude that theophylline and doxapram are compar able in the treatment of apneas of prematurity, however, doxapram is superi or to theophylline in reducing the rate of apneas in the first 3 days of tr eatment.