High-Dose Dexamethasone
The recommendation: Don't prescribe high-dose dexamethasone (0.5 mg/kg per day) for the prevention or treatment of bronchopulmonary dysplasia (BPD) in the preterm infant.
The rationale: High-dose dexamethasone (0.5 mg/kg per day) does not appear to confer additional therapeutic benefit over lower doses and is not recommended. High doses also have been associated with numerous short- and long-term adverse outcomes, including neurodevelopmental impairment.
Medscape spoke with Kristi L. Watterberg, MD, Professor of Pediatrics in the Division of Neonatology at the University of New Mexico. Dr. Watterberg is also Chair of the Committee on Fetus and Newborn at AAP.
Medscape: Can you review the guidelines for appropriate use of dexamethasone in preterm infants?
Dr. Watterberg: To begin the discussion with what is appropriate is difficult. We can comfortably say: "Don't use high-dose dexamethasone because it has a lot of bad side effects including neurodevelopmental compromise." But we don't have a lot of information about lower doses for shorter periods of time. The meta-analyses show that dexamethasone decreases BPD. There have been some small, randomized, controlled trials that suggest that a lower dose, like 0.15 mg/kg per day, is not associated with the kind of risk that occur with higher doses. The studies are too small to say that with any certainty. The trouble is that, on the other side of this equation, BPD itself is also associated with side effects and compromised neurodevelopmental outcome. So we have to try to weigh the problems of both sides -- the disease and the treatment for the disease.
Based on the research we have to date, if a little tiny baby is still on mechanical ventilation after 1-2 weeks of age, the clinician might consider using a corticosteroid in order to try to help that baby get off the ventilator and to decrease both the incidence and severity of BPD.
Medscape: How common is the practice of using higher doses of dexamethasone?
Dr. Watterberg: I believe that there is far less use of high-dose dexamethasone than there was 10 years ago when AAP issued its first statement on use of postnatal corticosteroids to prevent and treat BPD.[1] (Editor's note: An updated policy was released by AAP in 2010). That statement noted that high doses of dexamethasone were proven to be harmful to babies and should not be used except under very unusual clinical circumstances. This recommendation was confirmed by subsequent meta-analyses[2,3] that documented clearly that high doses of dexamethasone for prolonged periods of time are not good for little babies. In response to that, most people who are using dexamethasone where they think it's appropriate are using much lower doses. There are, however, still some places that continue to use the higher dose.
Medscape: Is the neurodevelopmental outcome of infants treated with lower and higher doses comparable?
Dr. Watterberg: That's probably an unanswered question, although 2 small studies of babies receiving lower-dose dexamethasone showed developmental outcomes similar to babies who received placebo.[4,5] Historically, in response to those meta-analyses and guidelines cautioning against the routine use of dexamethasone or other corticosteroids, clinicians became very nervous about using steroids at any dose and in any baby. However, for some babies who are still on the ventilator, the failure to use corticosteroids may be more harmful to them than getting a lower dose of steroids and getting off the ventilator. So we are in a flux in terms of studying dexamethasone and hydrocortisone. It is surprising. The initial reports suggesting that steroids could get babies off the ventilator and provide short-term benefit were first published in the 1980s. Even back then, researchers noted that we really need to study this more before we adopt this therapy. But as it was being studied, it was also being adopted.
What we are pretty sure we know is that high doses of dexamethasone, particularly given for long periods of time, are harmful. Children exposed to these drugs are shorter, they have smaller heads, their neurodevelopment is not as good, and the incidence of cerebral palsy is higher. So it's not something to use at that dose. However, we do think that steroids probably have a place in the management of babies who are on the ventilator. It's just that we think we need to use lower doses and probably for shorter periods of time. But that still needs additional study. So we can't make those positive recommendations as well as we can say: "Don't use high-dose dexamethasone."
From Medscape