Key messages
– Due to a lack of robust evidence, the benefits and risks of doxapram (a medication used in cases when stimulation of breathing is necessary) in preventing or treating breathing pauses in premature babies are unclear. We found no data on long-term effects of the treatments.
– Doxapram might be slightly better than no treatment in reducing breath-holding episodes with little or no difference in unwanted effects. Doxapram may be of little or no help in having the babies breathing on their own without machine support.
– The studies that we found were written more than 20 years ago. However, there are two studies in progress on this topic that could add information on the use of doxapram.
What is apnea of prematurity?
Apnea of prematurity is a common problem in premature infants. Very small babies sometimes 'forget' to breathe and, when they hold their breath for 20 seconds or more, or when these episodes lead to alterations in their heart beat and oxygen values, it is called apnea. Apnea episodes can have a negative effect on the babies' development during their lives.
How is it usually treated in premature babies?
Doctors usually treat breath-holding episodes with medicines that stimulate the babies' brains to result in breathing. These medicines are called methylxanthines and the most well-known is caffeine.
What did we want to find out?
We wanted to know if doxapram, a stimulating medicine that is different from methylxanthine, could help to treat or prevent breath-holding episodes. We also wanted to find out if doxapram was associated with any unwanted effects.
What did we do?
We searched for studies that compared doxapram, alone or with methylxanthine, to no treatment or alternative treatment in treating or preventing breath-holding episodes or in helping babies to breathe on their own without a machine support.
We compared and summarized their results, and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found eight studies that involved 248 premature babies, from 25 to 32 weeks of gestational age (from the first day of the woman's last period to birth). The biggest study was in 56 babies and the smallest study was in 10 babies. Doxapram and the other medicines were given through infusion in a vein. None of the studies was about prevention of breath-holding events. Three studies focused on medicines used to help babies breathing on their own without machine support, while five were on treatment of breath-holding events.
Doxapram might work slightly better than no treatment in reducing episodes when babies stop breathing for some seconds with little or no difference in unwanted effects when compared to no treatment or to other medicines used for the same purpose. We do not know if doxapram has an effect on the occurrence of breath-holding events when compared to other treatments, or on the need for breathing support by a machine.
When trying to shift ventilated babies to breathing on their own, doxapram may help other commonly used medicines to reduce breath-holding episodes, and it may shorten the duration of oxygen support, even if it might be of little or no help in stopping machine support. The effect of doxapram on unwanted events in this situation is unclear.
What are the limitations of the evidence?
We have little confidence in the evidence because not all the studies provided data about everything of interest. Available data are on few infants with a very low number of events of interest.
How up to date is this evidence?
The evidence is up to date to March 2023.
