Caffeine versus theophylline for apnea in preterm infants

Steer, Peter A. and Henderson-Smart, David J. (2000) Caffeine versus theophylline for apnea in preterm infants. Cochrane Database of Systematic Reviews, 2000 2: CD000273.

Author Steer, Peter A.
Henderson-Smart, David J.
Title Caffeine versus theophylline for apnea in preterm infants
Journal name Cochrane Database of Systematic Reviews
ISSN 1464-780X
Publication date 2000
Sub-type Critical review of research, literature review, critical commentary
Volume 2000
Issue 2
Start page CD000273
Total pages 1
Place of publication London, U.K.
Publisher BMJ Publishing Group
Language eng
Subject C3
321019 Paediatrics
730204 Child health
Formatted abstract
Background: Recurrent apnea is common in preterm infants, particularly at very early gestational ages. These episodes of loss of effective breathing can lead to hypoxemia and bradycardia which may be severe enough to require resuscitation including use of positive pressure ventilation. Two forms of methylxanthine (caffeine and theophylline) have been used to stimulate breathing and so prevent apnea and its consequences.

Objectives: In preterm infants with recurrent apnea, does caffeine treatment compared to theophylline treatment lead to a clinically important reduction in apnea and use of mechanical ventilation without clinically important side effects?

Search strategy: Standard strategies of the Neonatal Review Group were used. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (see main text for strategy), previous reviews including cross references, abstracts conferences and symposium proceedings, expert informants, journal handsearching mainly in the English language. Also an expert informant's search in the Japanese language was made by Prof Y. Ogawa.

Selection criteria: All trials utilising random or quasi-random patient allocation in which caffeine was compared with theophylline for the treatment of apnea were eligible. Trial quality and eligibility were assessed independently by each author. There must have been an effort to exclude specific causes of apnea. Measures of the severity of apnea as well as the response to treatment must have been consistent with an evaluation of 'clinical apnea' as defined by the American Academy of Pediatrics (Nelson 1978).

Data collection and analysis: Standard method of Neonatal Review Group was used. Each author assessed eligibility, trial quality and extracted data separately, then compared and resolved differences. Results are expressed as relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) was calculated.

Main results: There is no difference in the failure rate (< 50% reduction in apnea/bradycardia) of treatment with caffeine or theophylline at 1-3 (two studies) or 5-7 days (one study). There is a higher mean rate of apnea in the standard caffeine group at 1-3 days [three studies, mean diff. 0.398 (0.334,0.463) /100min] but not at 5-7 days (two studies). Side effects, as indicated by tachycardia or feed intolerance leading to change in dosing, are lower in the caffeine group [typical RR 0.17 (0.04,0.72), RD -0.285 (-0.467,-0.104), NNT 3.5 (2.1, 9.6)]. This was consistent across the three studies. No trial reported the use of IPPV and no data are available to assess effects on growth and development.

Author's conclusions: Caffeine appears to have similar short term effects on apnea/bradycardia to theophylline. In view of the other therapeutic advantages of caffeine (a higher therapeutic ratio, more reliable enteral absorption and a longer half life) this is the preferred treatment for apnea in preterm infants. The possibility that higher doses of caffeine might be more effective in extremely preterm infants needs further evaluation in randomized clinical trials.
Q-Index Code C3
Additional Notes Revised, updated in: Cochrane Database Syst Rev. 2010;(1):CD000273.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: School of Medicine Publications
Version Filter Type
Citation counts: Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Tue, 10 Jun 2008, 13:21:56 EST