displasia broncopulmonar

Manejo del niño con Displasia Broncopulmonar

Marzo 2009

Posnatal corticosteroids for bronchopulmonary dysplasia

Alan H. Jobe, MD,PhD

Clin Perinatol 36 (March 2009) 177–188

There really are only two core questions that need to be asked about the use of postnatal corticosteroids for bronchopulmonary dysfunction (BPD): do they work, and do they have clinically concerning adverse effects? The challenge is to define what ‘‘work’’ means, what adverse effects are of concern, and what ‘‘they’’ are, because multiple corticosteroids are used in different doses at different postnatal ages for different treatment durations.

The use of postnatal corticosteroids for BPD has been widely evaluated by randomized, controlled trials, but these trials have multiple treatment schedules and have produced limited and inconsistent information about outcomes. Ultimately, the clinician must weigh the statistical and population-based evidence and decide if corticosteroids might help a particular infant and if the risks are acceptable.

In 1990, about 17% of very low birth weight (VLBW) infants cared for in the Vermont Oxford Network received postnatal corticosteroids, and the rate of use was 7% for VLBW infants in the National Institute for Child Health and Human Development Neonatal Research Network. The peak rate of use was 28% for Vermont Oxford Network and 23% for the Neonatal Research Network in 1997. As follow-up information about adverse effects of corticosteroids on neurodevelopment began to appear, the American Academy of Pediatrics and the Canadian Pediatric Association strongly recommended against the use of corticosteroids to prevent or treat BPD in 2002.2 Since then, use has decreased. In 2006 8% of VLBW infants overall in the Vermont Oxford Network registry and 23% of the infants in the group at highest risk (those with birth weights between 501 and 750 g) received postnatal corticosteroids (R. Soll, personal communication, 2008). Therefore, postnatal corticosteroids continue to be used selectively in infants. Infants also receive corticosteroids for indications other than BPD. In 62 neonatal ICUs in California in 2003, 19% of VLBW infants received postnatal steroids, but only 3.6% received steroids for BPD alone; the other uses were for treatment of hypotension, airway management after extubation, or a combination of indications.3 Some ICUs also use aerosolized corticosteroids. Thus the risks and benefits of corticosteroid use remain a concern. Corticosteroids are used preferentially in the smaller and earlier gestational age infants because those infants are at highest risk for developing severe BPD.

There are justified concerns about the use of postnatal corticosteroids for any indication, but especially for BPD. Those concerns, however, must be balanced against the clear acute physiologic effects on lung function that can allow infants to come off mechanical ventilation. Shinwell and colleagues52 recently reported for the Israel Neonatal Network that a decreased use of postnatal corticosteroids in VLBW infants, from 23.5% in 1997 and 1998 to 11% in 2002 and 2003, was associated with an increase in BPD (oxygen use at 36 weeks) from 12.9% to 18.7%. This report suggests that the price one pays for decreased corticosteroid use is more BPD. The author considers the critical analysis to be the meta-regression analysis reported by Doyle and colleagues, 53 which shows that postnatal corticosteroids decrease the risk of death or cerebral palsy in populations of infants who have a 50% or greater risk of BPD . Treatment of low-risk populations may increase the risk of adverse outcomes.

The DART trial demonstrated acute effects on the lungs of ventilated infants progressing toward BPD with an initial dose of 0.15 mg/kg/d.9 The general clinical experience is that some infants respond quickly to corticosteroids and others do not. Considering the information available, the author favors corticosteroid treatment of a ventilator- dependent infant who is 14 to 28 days of age and who is progressing toward BPD. An initial dose of dexamethasone of 0.1 to 0.2 mg/kg/d for 3 days may achieve the goal of extubation. If extubation can be achieved or is likely to be accomplished, the dose can be tapered over 3 to 6 days (total treatment, 6–9 days). If extubation is not possible after the initial 3 days of treatment, the treatment should be stopped. This approach is not evidence based; it is an attempt to maximize benefit and minimize the risk of postnatal corticosteroids. Betamethasone or hydrocortisone might be better choices than dexamethasone, but neither has been evaluated in trials for this indication.

The follow-up data are particularly confusing, because bad or good outcomes have been reported with early or late treatment and with higher or lower exposures. Other aspects of care may interact with corticosteroids and contribute to these inconsistent outcomes. Clearly, the use of corticosteroids and indomethacin together soon after birth increases gastrointestinal perforations. For example, good nutrition might blunt adverse effects of postnatal corticosteroids. Following the lead of Doyle and colleagues, the very selective use a low-dose (but what dose?) corticosteroid (but which one?) for as short a duration as possible (presently undefined) in the infants at highest risk is the best treatment that can be offered now. The recommendation to limit postnatal corticosteroid use should not discourage careful studies of postnatal corticosteroids in high-risk VLBW infants.