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Cochrane Database Syst Rev. 2001;(4):CD000048.

Prophylactic caffeine to prevent postoperative apnea following general anesthesia in preterm infants.

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NSW Centre for Perinatal Health Services Research, Queen Elizabeth II Institute for Mothers and Infants, Building DO2, University of Sydney, Sydney, NSW, Australia, 2006.



Growing ex-preterm infants who undergo general anesthesia for surgery at about term-equivalent age may have episodes of apnea, cyanosis and bradycardia during the early postoperative period. A breathing stimulant such as caffeine, given at the time of operation, might prevent these episodes.


In ex-preterm infants who undergo general anesthesia for surgery, does the prophylactic use of caffeine prevent episodes of apnea, cyanosis and bradycardia during the postoperative period without clinically important side effects?


The standard strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, MEDLINE (1966 - July 2001), EMBASE 1980 - July 2001), CINAHL (1982 - July 2001) and Cochrane Library Issue 2, 2001. Search terms included text 'apnea', 'caffeine' and MeSH 'infant, premature'. Searches were also made of previous reviews including cross references. Abstracts of the Society for Pediatric Research were hand searched for the years 1996 - 2001 inclusive.


All trials utilising random or quasi-random patient allocation, in which treatment was compared with placebo or no treatment, were included.


The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to select trials, evaluate quality and to extract data. The methodological quality of each trial was reviewed by the second author blinded to trial authors and institution(s). Each author extracted data separately, compared and resolved differences. Meta-analysis used relative risk and risk difference.


Three eligible trials were found. In each trial apnea/bradycardia occurred in fewer treated than control infants. The typical estimate for relative risk reduction was 91%, 95% CI 66%, 98%. Absolute risk reduction was 58%, indicating that fewer than two infants have to be treated with caffeine to expect to prevent one with postoperative apnea. In two trials continuous recordings of oxygen saturation detected hypoxaemic episodes (<90 %) in fewer treatment than control infants. No infant in any trial required intubation and mechanical ventilation. No adverse effects were reported.


Implications for practice. Caffeine can be used to prevent postoperative apnea/bradycardia and episodes of oxygen desaturation in growing preterm infants if this is deemed clinically necessary. In view of the small numbers of infants studied in these trials and uncertainty concerning the clinical significance of the episodes, caution is warranted in applying these results to routine clinical practice. Implications for research. There is a need to determine which infants might benefit most by this treatment. Studies confined to those most at risk of apnea (prior history, younger postmenstrual age) and those that might require mechanical ventilation (chronic lung disease) would be of value.

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