Consulting Parents About the Use of Dexamethasone

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Dexamethasone is a powerful steroid that has traditionally been used in neonatal care for the treatment of Chronic Lung Disease (CLD). Like all steroids it has side effects. Perhaps the most serious is the increased risk of Cerebral Palsy (CP). However, CLD itself increases the risk of Cerebral Palsy (Marlow et al 2005). As with many treatments in neonatal care it can be difficult to define whether the disease or the treatment has caused the adverse effects. This paper aims to consider the risk/benefit of using dexamethasone, how we make the decision to use dexamethasone and how we involve parents in that decision. These considerations will provide the background to the description of a discussion with parents about using dexamethasone, a reflection on that consultation and suggested changes to improve our practice. This will reflect many components of the Framework for Decision Making about Medications (Appendix 1). The proposed aetiology of CLD is that the initiation of inflammatory mediators causes impairment of alveolarization and vasculogenisis. The lack of anti-inflammatory mediators in preterm infants can result in an inundation of the body by a pro-inflammatory cascade. Inflammatory mediators are activated by interuterine or post natal infection, ventilator trauma, oxidents, or pulmonary oedema, all of which damage the immature lung (Gupta et al 2012). Although dexamethasone has been used for its anti-inflammatory effects in CLD since the 1970s, the mechanism of its action is not completely understood. The primary anti-inflammatory effect appears to be the mediation of annexin1 synthesis. Annexin1 suppresses phospholipase A2 expression, thus blocking eicosanoids (prostaglandins/thromboxanes/prostacyclines/leukotrines) and thus blocking the subsequent leukotriene inflammatory events including adhesion and migration. Glucocorticoids inhibit the two main products of inflammation – prostaglandins and leukotrines. They also inhibit cyclooxygenase in a similar action to NSAIDS. They reduce the influx of neutrophils into the lungs by decreasing micovascular permeability. They reduce pulmonary oedema (Gupta et al 2012

There have been multiple studies of the use of dexamethasone in CLD, examining the efficacy of treatment, which treatment regimens are most beneficial and the incidence of adverse outcomes. Although there have been many trials, the multiple treatment schedules used, the relatively small size of the trials and the inconsistent outcome information has made them very difficult to evaluate. In 2003 a Cochrane Database Analysis (Haliday et al) reviewed 21 randomised controlled studies involving 3072 babies. Its conclusions were that there were significant benefits in earlier extubation and less CLD at 28 days and 36/40, but there was an increased risk of adverse neurological outcome and CP. It noted however that no single study had sufficient power to detect important adverse effects definitively. It recommended more long term studies. In 2005 Doyle published the results of a partial trial using low dose dexamethasone. This became known as the DART trial. It found that the use of dexamethasone facilitated extubation and reduced CLD. A review of the outcomes of these babies at two years of age found no significant increase in risk of adverse neurological outcome or of C.P. Unfortunately, there were only 70 babies in this evaluation. Once again it was too small to definitively answer the question of whether long term outcomes outweighed the benefits of use. However having moved away from using steroids for CLD, many neonatologists now use this protocol. In 2009 the Cochrane review of the use of post natal dexamethasone for treatment of CLD was revisited and updated (Haliday et al). The conclusions were that there was significant benefit in earlier extubation and less CLD at 28/7 and 36/40. Bleeding and intestinal perforation were significant adverse effects. Side effects included...
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