Anemia of Prematurity - Portal Neonatal

treat acute bronchospasm; however, it may be used as an agent to prevent
bronchospasm from occurring. With current aerosol administration strategies, exactly
how much medication is delivered to the airways and lungs of infants with BPD
(especially if they are ventilator dependent) is unclear. Because significant smooth
muscle relaxation does not appear to occur within the first few weeks of life, do not
initiate aerosol therapy before this time unless profound respiratory illness exists.
o Systemic bronchodilators
� Methylxanthines are used to increase respiratory drive, decrease apnea, and improve
diaphragmatic contractility. These substances may also decrease pulmonary VR and
increase lung compliance in infants with BPD, probably through direct smooth muscle
relaxation. They also exhibit diuretic effects.
� All of the above effects may increase success at weaning from mechanical ventilation.
Synergy between theophylline and diuretics has been demonstrated. Theophylline
has a half-life of 30-40 hours, is metabolized primarily to caffeine in the liver, and may
include adverse effects, such as increase in heart rate, gastroesophageal reflux,
agitation, and seizures. Caffeine has a longer half-life than theophylline
(approximately 90-100 h) and is excreted unchanged in the urine. Both are available
in intravenous and enteral formulations. Caffeine has fewer adverse effects than
theophylline.
� Long-term comparison studies of these 2 agents are needed. Oral albuterol and
subcutaneous terbutaline have also been used to treat infants with BPD but appear to
offer no therapeutic advantage when compared to the methylxanthines.
o Corticosteroids: These are produced by the adrenal gland. Mineralocorticoids are
produced in the adrenal medulla and primarily affect fluid and electrolyte balance.
Glucocorticoids possess strong anti-inflammatory properties and affect the metabolism of
many tissues. Systemic and inhaled corticosteroids have been studied extensively in
preterm infants to prevent and treat BPD.
� Seven studies have evaluated the effect of dexamethasone versus placebo during the
first 2 weeks of life to prevent BPD. Original work by Cummings et al in 1989 revealed
that a 42-day course of dexamethasone resulted in a decrease need for oxygen and
improved neurologic outcome compared to control subjects aged 6 and 15 months. In
1998, Papile et al reported on the effects of dexamethasone treatment at 2 weeks
versus 4 weeks in 371 preterm infants.
� Dexamethasone treatment initiated at 14 days reduced 28-day mortality and oxygen
requirement at 1 month; however, Koroco et al found no difference in CLD at 36
weeks corrected age in 60 infants who received systemic and inhaled corticosteroids
or saline placebo beginning at 7 days of life. In 1999, Garland et al reported findings
on very early use of a 3-day course of dexamethasone begun within 48 hours of life to
prevent BPD. He found that infants treated with dexamethasone had less BPD but
noticed an increase in early intestinal perforations. The difference in intestinal
perforations between groups prompted a dosage adjustment after the first interim
analysis.
� Dexamethasone has also been administered to preterm infants older than 3 weeks to
treat presumed CLD (ie, 28-d oxygen requirement). The largest collaborative
dexamethasone trial revealed a decrease in ventilator requirements but no difference
in supplemental oxygen usage. Outcomes at age 3 years were similar.
� Dexamethasone is the primary systemic synthetic corticosteroid that has been studied
in preterm neonates. Dexamethasone has many pharmacologic benefits but
significant adverse effects. Dexamethasone stabilizes cell and lysosomal membranes,
increases surfactant synthesis, increases serum vitamin A concentration, inhibits
prostaglandin and leukotriene, decreases PE, breaks down granulocyte aggregates,
and improves pulmonary microcirculation. The adverse effects are hyperglycemia,
hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy,
adrenal suppression, and death.
� Approximately 30 randomized trials have been performed examining strategies to
prevent or treat BPD. An excellent on-line review of most of Professor Halliday's
studies is available at the National Institute of Child Health and Human Development.
The dexamethasone trials may be grouped by time of dexamethasone administration;
for example, early administration may be considered within 2 days of birth or within
the first 2 weeks of life, and late administration may be considered after 2 weeks of