Doxapram treatment for apnea in preterm infants.

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. Doxapram has been used to stimulate breathing and so prevent apnea and its consequences.

OBJECTIVES

In preterm infants with recurrent apnea, does treatment with doxapram lead to a clinically important reduction in apnea and use of intermittent positive airways pressure (IPPV), without clinically important side effects?

SEARCH STRATEGY

Searches were made of the Oxford Database of Perinatal trials, the Cochrane Collaboration Clinical Trials Register, MEDLINE 1966 - July 2001, Embase 1980 - July 2001, CINAHL 1982 - July 2001 (using text words 'doxapram', 'apnea or apnoea' and MeSH term 'infant, premature'), previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, mainly in the English language. Abstracts of the Society for Pediatric Research were searched from 1996 - 2001 inclusive. Also an expert informant's search in the Japanese language was made by Prof. Y. Ogawa in 1996.

SELECTION CRITERIA

All trials utilising random or quasi-random patient allocation, in which doxapram was used for the treatment of apnea in preterm infants were included.

DATA COLLECTION AND ANALYSIS

Each author evaluated the papers for quality and inclusion criteria. Independent data extraction was carried out.

MAIN RESULTS

Only one trial, which randomized 11 infants to intravenous doxapram and 10 infants to placebo, was found. There were fewer treatment failures after 48 hours in the group of preterm infants treated with doxapram (4/11) compared with the group treated with placebo (8/10). The wide confidence intervals made this result non-significant [RR 0.45 (0.20, 1.05)]. Only one infant, who was from the placebo group, was given IPPV. Of the seven responders by 48 hours in the group of 11 who received doxapram, five failed to respond between 48 hours and seven days after commencement of therapy. This gives a late failure rate of 9/11, similar to the short term failure rate in the placebo group of 8/10. It is not possible to evaluate the late responses of all those in the placebo group since they crossed over to a treatment arm.

REVIEWER'S CONCLUSIONS: Although intravenous doxapram might reduce apnea within the first 48 hours of treatment, there are insufficient data to evaluate the precision of this result or to assess potential adverse effects. No longterm outcomes have been measured. Further studies are needed to determine the role of this treatment in clinical practice.