Bronchopulmonary Dysplasia Medication

Updated: Mar 28, 2014
  • Author: Namasivayam Ambalavanan, MD, MBBS; Chief Editor: Ted Rosenkrantz, MD  more...
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Medication

Medication Summary

Many drug therapies are used to treat infants with severe bronchopulmonary dysplasia (BPD). The efficacy, exact mechanisms of action, and potential adverse effects of these drugs have not been definitively established. A study group from the NICHD and US Food and Drug Administration (FDA) reviewed many of the drugs used to prevent and treat bronchopulmonary dysplasia. Walsh and colleagues concluded that detailed analyses of many of these treatments, as well as long-term follow-up, are needed. [18]

Vitamin A supplementation

Seven trials of vitamin A supplementation in preterm neonates to prevent bronchopulmonary dysplasia were analyzed for the Cochrane Collaborative Neonatal review. Vitamin A supplementation reduced bronchopulmonary dysplasia and death at 36 weeks' postmenstrual age.

Diuretics

Furosemide (Lasix) is the treatment of choice for fluid overload in infants with bronchopulmonary dysplasia. It is a loop diuretic that improves clinical pulmonary status and function and decreases pulmonary vascular resistance. Daily or alternate-day furosemide therapy may facilitate weaning from positive pressure ventilation (PPV), oxygenation, or both. Adverse effects of long-term therapy are frequent and include hyponatremia, hypokalemia, contraction alkalosis, hypocalcemia, hypercalciuria, renal stones, nephrocalcinosis, and ototoxicity. Careful parenteral and enteral nutritional supplementation is required to maximize the benefits instead of exacerbating the adverse effects.

Thiazide diuretics plus aldosterone inhibitors (eg, spironolactone [Aldactone]) have also been used in infants with bronchopulmonary dysplasia. In several trials of infants with bronchopulmonary dysplasia, thiazide diuretics combined with spironolactone increased urine output with or without improvement in pulmonary mechanics. Hoffman et al reported that spironolactone did not reduce the need for supplemental electrolytes in preterm infants with bronchopulmonary dysplasia. [19] To the present authors' knowledge, long-term studies to compare the efficacy of furosemide with those of thiazide and spironolactone therapy have not been performed.

Bronchodilators

Albuterol is a specific beta2-agonist used to treat bronchospasm in infants with bronchopulmonary dysplasia. Albuterol may improve lung compliance by decreasing airway resistance by relaxing smooth muscle cell. Changes in pulmonary mechanics may last as long as 4-6 hours. Adverse effects include increased blood pressure (BP) and heart rate. Ipratropium bromide is a muscarinic antagonist that is related to atropine; however, it may have bronchodilator effects more potent than those of albuterol. Improvements in pulmonary mechanics were demonstrated in patients with bronchopulmonary dysplasia after they received ipratropium bromide by inhalation. Combined therapy with albuterol and ipratropium bromide may be more effective than either agent alone. Few adverse effects are noted.

Methylxanthines are used to increase respiratory drive, decrease apnea, and improve diaphragmatic contractility. These substances may also decrease pulmonary vascular resistance and increase lung compliance in infants with bronchopulmonary dysplasia, probably by directly causing smooth muscle to relax. Methylxanthines also have diuretic effects. All of these effects may increase success in weaning patients from mechanical ventilation.

Synergy between theophylline and diuretics has been demonstrated. Theophylline has a half-life of 30-40 hours. It is metabolized primarily to caffeine in the liver and may result in adverse effects such as increase in heart rate, gastroesophageal reflux, agitation, and seizures. The half-life of caffeine is approximately 90-100 hours, and caffeine is excreted unchanged in the urine. Both agents are available in intravenous and enteral formulations. Caffeine has fewer adverse effects than theophylline. Schmidt and colleagues reported that the early use of caffeine to treat apnea of prematurity appeared to reduce ventilatory requirements and that it may decrease the incidence of bronchopulmonary dysplasia. [20]

Corticosteroids

Systemic and inhaled corticosteroids have been studied extensively in preterm infants to prevent and treat bronchopulmonary dysplasia.

Dexamethasone is the primary systemic synthetic corticosteroid studied in preterm neonates. Dexamethasone has many pharmacologic benefits but clinically significant adverse effects. This drug stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, inhibits prostaglandin and leukotriene, decreases pulmonary edema (PE), breaks down granulocyte aggregates, and improves pulmonary microcirculation. Its adverse effects are hyperglycemia, hypertension, weight loss, GI bleeding or perforation, cerebral palsy, adrenal suppression, and death.

Many researchers have evaluated the effects of early administration of dexamethasone to prevent bronchopulmonary dysplasia, often demonstrating short-term improvements in clinical outcome. However, Papile and associates reported that early use of dexamethasone during the first 2 weeks of life did not prevent bronchopulmonary dysplasia and may worsen neurologic outcome. [21] Infants who received a combination of dexamethasone and indomethacin were at increased risk of spontaneous intestinal perforation. Neurodevelopmental follow-up studies of infants treated with prolonged and high-dose dexamethasone suggest that, though this therapy improves short-term pulmonary outcome, long-term outcome appears to considerably worsen.

Studies of inhaled glucocorticoid therapy have suggested that the only beneficial effect was a reduction in the use of systemic corticosteroids in infants receiving inhaled steroids. However, concerns about systemic absorption (hypertension), associated complications, drug delivery, and current restrictions on systemic dexamethasone use may eliminate the need for this therapeutic approach. The routine use of dexamethasone in infants with bronchopulmonary dysplasia is not currently recommended. The American Academy of Pediatrics and the Canadian Society of Pediatrics do not advocate the routine use of corticosteroids in preterm neonates to treat bronchopulmonary dysplasia. [22, 23] Despite these recommendations, dexamethasone is still used in carefully selected patients who have substantially increased ventilatory requirements at about 1 month of age.

Vasodilators

Inhaled NO (iNO) is a short-acting gas that relaxes the pulmonary vasculature. It may also act as an anti-inflammatory agent at low concentrations.

Multiple randomized controlled trials of iNO in preterm infants have been performed using varying entry criteria and outcomes. The results are mixed. Although certain selected subgroups may benefit, whether the sickest and smallest infants at greatest risk of bronchopulmonary dysplasia benefit from iNO remains unclear.

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Diuretics

Class Summary

Diuretics promote excretion of water and electrolytes by the kidneys. They are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention results in edema or ascites.

Furosemide (Lasix)

DOC for fluid overload in infants with BPD. Loop diuretic. Therapy qd or qod improves respiratory function and may facilitate weaning from PPV, oxygen, or both. Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.

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Bronchodilators

Class Summary

Bronchodilators decrease muscle tone in both the small and large airways in the lungs, increasing ventilation. This category includes beta-adrenergic agents, methylxanthines, and anticholinergics.

Albuterol (Proventil, Ventolin)

Specific beta2-agonist used to treat bronchospasm in infants with BPD. May improve lung compliance by decreasing airway resistance secondary to smooth muscle cell relaxation. With current strategies for aerosol administration, exactly how much is delivered to airways and lungs of infants with BPD (especially if ventilator dependent) is unclear. Because clinically significant smooth muscle relaxation does not appear to occur in first few weeks of life, do not start aerosol therapy before this time unless patient has profound respiratory illness.

Caffeine citrate (Cafcit)

CNS stimulant used to treat infants with apnea of prematurity and infants with BPD. Caffeine may facilitate weaning from ventilator.

Theophylline (Elixophyllin, Theo-Dur)

Systemic bronchodilator. Used to treat apnea of prematurity. May improve contractility of skeletal muscle and decrease diaphragmatic fatigue in infants with BPD. May facilitate weaning infant with BPD from continuous mechanical ventilation.

Monitor serum levels and adjust on basis of infant's response; therapeutic levels approximately 5-12 mcg/mL. IV dose based on theophylline equivalent.

Ipratropium bromide (Atrovent)

Muscarinic antagonist with potent bronchodilating effects. May improve pulmonary mechanics in infants with BPD. Inhaled drug poorly absorbed systemically.

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Corticosteroids

Class Summary

Corticosteroids 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.

Dexamethasone (Decadron)

Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, inhibits prostaglandin and leukotriene, breaks down granulocyte aggregates, and improves pulmonary microcirculation. Has many pharmacologic benefits but clinically significant adverse effects: hyperglycemia, hypertension, weight loss, GI bleeding or perforation, cerebral palsy, adrenal suppression, and death.

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Vitamin

Class Summary

Preterm infants are deficient in vitamin A.

Vitamin A (Palmitate-A 5000)

Intramuscular vitamin A supplementation reduces incidence of BPD. Firm dosing guidelines not established.

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