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Doxapram Treatment for Apnea of Prematurity: A Systematic Review
Roseanne J S Vliegenthart1, Christine H Ten Hove, Wes Onland
1Department of Neonatology, Emma Childrens' Hospital AMC, Amsterdam, The Netherlands.
Insights
Doxapram may help reduce apnea in preterm infants, but evidence on its safety and effectiveness is limited. More research is needed to determine if doxapram should be routinely used for apnea of prematurity.
Area of Science:
- Neonatal medicine
- Pharmacology
Background:
- Apnea of prematurity (AOP) is a common complication in preterm infants.
- Caffeine is the primary treatment for AOP.
- Doxapram is considered for persistent AOP cases.
Purpose of the Study:
- To evaluate the efficacy and safety of doxapram for AOP in infants born before 34 weeks gestational age.
Main Methods:
- Systematic search of electronic databases and relevant literature.
- Independent assessment of study eligibility and quality by two reviewers.
- Data extraction on study design, patient characteristics, and outcomes.
Main Results:
- Randomized trials showed doxapram reduced apnea versus placebo, but not compared to theophylline.
- Observational studies (n=1,994) suggested positive effects on apnea rate, but with heterogeneity.
- Limited data on long-term outcomes; short-term adverse effects were reported, especially at higher doses.
Conclusions:
- Current evidence is insufficient to confirm doxapram's efficacy and safety for AOP.
- Routine use of doxapram is not recommended at this time.
- A large multicenter randomized controlled trial is necessary for conclusive evidence.
Background:
Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been advocated as an additional therapy.
Objective:
To identify and appraise all existing evidence regarding efficacy and safety of doxapram use for AOP in infants born before 34 weeks of gestational age.
Methods:
All studies reporting on doxapram use for AOP were identified by searching electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research. Two reviewers independently assessed study eligibility and quality, and extracted data on study design, patient characteristics, efficacy and safety outcomes.
Results:
The randomized controlled trials showed less apnea during doxapram treatment when compared to placebo, but no difference in treatment effect when compared to theophylline. No serious adverse effects were reported. We identified 28 observational studies consisting mainly of cohort studies and case series (n = 1,994). There was considerable heterogeneity in study design and quality. Most studies reported a positive effect of doxapram on apnea rate. A few studies reported on long-term outcomes with conflicting results. A range of possible doxapram-related short-term adverse effects were reported, sometimes associated with the use of higher doses.
Conclusion:
Based on the limited number of studies and level of evidence, no firm conclusions on the efficacy and safety of doxapram in preterm infants can be drawn. For this reason, routine use cannot be recommended. A large multicenter randomized controlled trial is urgently needed to provide more conclusive evidence.
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