Minidex: The efficacy and safety of very low dose dexamethasone used to facilitate the extubation of ventilator dependent preterm babies who are at high risk of bronchopulmonary dysplasia

Summary

Bronchopulmonary dysplasia (BPD) or chronic lung disease is one of the ongoing problems of neonatal medicine. It affects approximately 35% of babies born at less than 30 weeks’ gestation who survive to discharge from neonatal care. In the UK this equates to about 1,450 affected babies a year. BPD prolongs hospitalisation and is associated with a significant long term respiratory and neurodevelopmental healthcare burden.

One of the few interventions that have been proven to reduce the incidence or severity of BPD are corticosteroids. Corticosteroids facilitate the extubation of preterm babies and reduce the incidence of BPD, and they became a mainstay of neonatal care throughout the 1990’s. However, their popularity declined sharply in the early 2000’s when a meta-analysisfound that babies treated with high dose regimens of postnatal corticosteroids have an increased risk of long-term adverse neurodevelopmental outcomes. This decline in the popularity of corticosteroids has been associated with an increase in BPD.

Further investigation of the association between corticosteroids and adverse long-term neurodevelopmental outcomes revealed that the likelihood of a poor outcome is modified by both the baby’s postnatal age at treatmentand their underlying risk of developing BPD. Increased risk of adverse outcomes is seen in those babies treated at less than 8 days of age, but not in babies with signs of evolving BPD treated at over 7 days of age. Once the baby’s risk of developing BPD rises above about 50% corticosteroid treatment may actually reduce the risk of the composite outcome of death or cerebral palsy.

Many clinicians now use low or very low dose regimens after 7 days of life to improve pulmonary function in babies at high risk of BPD in the hope that it will be possible to maximize the pulmonary benefits while minimizing the neurodevelopmental risks. While this seems to be a reasonable standpoint there is no good evidence to support it.

In a retrospective cohort study Yates found that babies at risk of BPD who received a very low dose corticosteroid regimen extubated significantly faster than controls who did not receive corticosteroids. This regimen, Minidex (50 mcg/kg/day of dexamethasone for 10 days followed by alternate days for 6 days) was derived from the physiological corticosteroid replacement dose. It now needs to be carefully evaluated in a randomised controlled trial to assess its efficacy at improving lung function and clinical acceptability.

94 ventilator dependent preterm babies of less than 30 weeks’ gestation will be randomized to either a course of Minidex or placebo. The primary outcome will be time to extubation as a proxy measure of short–term improvement in lung function. Secondary outcomes will include morbidity and respiratory outcomes to 36 weeks PMA, safety data, measures of the parent/family involvement in their baby’s care and (in Leeds and Bradford babies only) changes to the inflammatory cytokine profile.