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Caffeine versus theophylline for apnea of prematurity: a randomised controlled trial
Maria Skouroliakou1, Flora Bacopoulou, Sophia L Markantonis
1IASO Maternity Hospital, Harokopio University, Athens, Greece.
Insights
Caffeine showed an advantage over theophylline for treating apnea of prematurity in infants under 33 weeks gestation during the first week. Routine drug monitoring is not typically needed for either medication within the first three weeks.
Area of Science:
- Neonatal Medicine
- Pharmacology
- Pediatric Pulmonology
Background:
- Apnea of prematurity is a common respiratory challenge in preterm infants.
- Theophylline and caffeine are commonly used methylxanthines for managing apnea of prematurity.
- Assessing the comparative efficacy and monitoring needs of these agents is crucial for optimizing treatment.
Purpose of the Study:
- To compare the efficacy of standard doses of theophylline and caffeine in reducing apnea frequency in preterm infants.
- To evaluate the necessity of therapeutic drug monitoring for both agents during the initial treatment period.
Main Methods:
- A randomized, open-label study involving 70 neonates (<33 weeks gestation) with apnea.
- Infants were assigned to receive either theophylline or caffeine for treatment or prevention of apnea.
- Apnea frequency was the primary outcome; serum methylxanthine levels were monitored periodically.
Main Results:
- Both theophylline and caffeine significantly reduced apnea events.
- Caffeine demonstrated a greater benefit in controlling apnea, particularly for prophylaxis, during the first week of therapy.
- Serum concentrations for both drugs generally remained within therapeutic ranges and did not strongly correlate with apnea events.
Conclusions:
- Caffeine offers a therapeutic advantage over theophylline in preterm infants (<33 weeks gestation) within the initial week of treatment.
- Routine serum concentration monitoring for theophylline and caffeine is generally not required in the first three weeks of therapy for apnea of prematurity, unless clinically indicated.
Aim:
To compare standard doses of theophylline and caffeine for apnea of prematurity in terms of apnea frequency and assess the need for therapeutic drug monitoring.
Methods:
Seventy neonates less than 33 weeks gestation, breathing spontaneously, were randomly assigned (open-label) to receive either theophylline or caffeine for treatment or prevention of apnea. The primary outcome measure was the difference in apnea frequency between theophylline and caffeine patient groups. Methylxanthine serum levels were measured on the 1st, 3rd and 7th days of therapy and every 7 days thereafter.
Results:
Thirty-seven neonates received theophylline (T) and 33 caffeine (C) for treatment (8 T/10 C) or prevention of apnea (29 T/23 C). Treatment with either methylxanthine significantly decreased apnea events (T, P= 0.012; C, P= 0.005) while only C prophylaxis appeared to control apnea in infants at risk. Analysis of combined (treatment plus prophylaxis) data showed a significant decrease in apnea frequency only in those infants receiving caffeine (P= 0.001). However, there was no sustained benefit of C over T beyond the first week of therapy. T and C concentrations (2.2-13.9 mg/L; 5.5-23.7 mg/L, respectively) in the majority of cases fell within the recommended therapeutic ranges and were not significantly associated with apnea events.
Conclusions:
This study shows an advantage of C over T for premature infants <33 weeks gestation during the first week of therapy. Standard regimens of both methylxanthines do not seem to require routine concentration monitoring in the first 3 weeks of treatment unless indicated by clinical effect.
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