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

Background

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.

Objectives

To determine the effect of the prophylactic use of caffeine to prevent episodes of apnea, cyanosis and bradycardia during the postoperative period in ex-preterm infants who undergo general anesthesia for surgery.

Search strategy

The standard strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal Trials, MEDLINE (1966 - July 2008), EMBASE 1980 - July 2008), CINAHL (1982 - July 2008) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2008. Search terms included text words 'postoperative', 'apnea or apnoea', 'caffeine' and MeSH heading '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 - 2008 inclusive.

Selection criteria

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

Data collection and analysis

The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to select trials, evaluate trial 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, and then compared and resolved any differences. Meta-analysis used relative risk and risk difference.

Main results

Three eligible trials were found. In each trial apnea/bradycardia occurred in fewer infants treated with caffeine. The typical estimate for relative risk is 0.09 (95% CI 0.02, 0.34). The typical estimate for absolute risk difference is -0.58 (95% CI -0.74, -0.43) indicating that fewer than two infants have to be treated with caffeine to expect to prevent one with postoperative apnea. In two trials (Welborn 1989; LeBard 1989), continuous recordings of oxygen saturation detected hypoxaemic episodes (< 90 %) in fewer treatment than control infants [typical RR 0.13 (95% CI 0.03, 0.63)]. No infant in any trial required intubation and mechanical ventilation. No adverse effects were reported.

Authors' conclusions

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.