BRONCHOPULMONARY DYSPLASIA MEDICATION

bronchopulmonary dysplasia medication :
Many different drug therapies are employed to treat infants with severe BPD. The efficacy, exact mechanisms of action, and potential adverse effects of these medications have not been definitively established. Thiazide diuretics with inhibitors of aldosterone have been used in infants with BPD. Several trials of thiazide diuretics combined with spironolactone have shown increased urine output with or without improvement in pulmonary mechanics in infants with BPD. In 2000, Hoffman reported that spironolactone administration does not reduce the need for supplemental electrolyte administration in preterm infants with BPD. Long-term efficacy studies comparing furosemide to thiazides plus spironolactone therapy have not been performed.

Bronchodilators are typically prescribed. Ipratropium bromide is a muscarinic antagonist that is related to atropine but may have more potent bronchodilator effects. Improvements in pulmonary mechanics have been demonstrated in BPD after ipratropium bromide inhalation. Combination therapy of albuterol and ipratropium bromide may be more efficacious than either agent alone. Few adverse effects are noted.

Systemic bronchodilators include methylxanthines, which are used to increase respiratory drive, decrease apnea, and improve diaphragmatic contractility. Methylxanthines are routinely used in preterm infants to treat BPD and apnea of prematurity. Methylxanthines have been shown to improve diaphragmatic contractility, improve lung compliance, and decrease pulmonary resistance in infants with BPD, probably through direct smooth muscle relaxation. They 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 h, is metabolized primarily to caffeine in the liver, and may produce adverse effects (eg, increased heart rate, gastroesophageal reflux, agitation, seizures). Caffeine has a longer half-life than theophylline (approximately 90-100 h) and is excreted unchanged in the urine. Both are available in IV and parenteral 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 they appear to offer no therapeutic advantage when compared to the methylxanthines.

Systemic and inhaled corticosteroids have been studied extensively in preterm infants to prevent and treat BPD. Dexamethasone is the primary systemic synthetic corticosteroid that has been studied in preterm neonates. In 1999, Banks and colleagues studied the effect of inhaled nitric oxide in 16 preterm infants with severe BPD. Eleven of 16 infants had improved oxygenation after 1 hour of inhalation, an effect that persisted in some infants. Further controlled studies are necessary to define nitric oxide use in the prevention and treatment of BPD.
Cromolyn sodium inhibits release of inflammatory mediators from mast cells. Some studies have shown a decrease in inflammatory mediators in tracheobronchial aspirates of infants with BPD who were treated with this drug.

Drug Category: Diuretics -- Promote excretion of water and electrolytes by the kidneys. Used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites.

Drug Category: Bronchodilators -- These act to decrease muscle tone in both the small and large airways in the lungs, thereby increasing ventilation. This category includes subcutaneous medications, beta-adrenergic agents, methylxanthines, and anticholinergics.

Drug Category: Corticosteroids -- 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.

Drug Category: Pulmonary vasodilators -- NO was recently approved for treatment of pulmonary hypertension. NO is an important mediator of vascular tone.

bronchopulmonary dysplasia Further Outpatient Care:
• Infection
o Increased susceptibility to respiration infections is frequent in infants with BPD in the first 2 years of life.
o Respiratory syncytial virus (RSV) infection in infants with BPD may cause severe illness and even death.
o RSV immunoglobulin infusion and RSV antibody injection administered on a monthly basis may prevent or reduce risk of rehospitalization of infants with BPD and may mitigate illness severity.
o The AAP has published guidelines on the use of these medications during RSV season (November-March) in preterm infants discharged from the NICU.

• Growth and development
o Poor growth and delayed development are frequently observed in infants with BPD. Secondary to abnormal pulmonary function, increased energy requirements are noted. In addition, many of these infants may have worsening pulmonary function with liberalization of fluid intake. Use of diuretics, high-energy formulas and breast milk additives, or both are the mainstays of treatment in and out of the hospital.
o In 1981, Markestad et al found the degree of catch-up growth correlated directly with respiratory function. Long-term survivors are at increased risk for neurodevelopmental disabilities.
o Vohr and Singer et al found no difference in full-scale IQ scores between infants with BPD and control preterm infants.
o Therapies used to treat BPD as well as other perinatal and postnatal events may impair neurodevelopmental outcome. In 1992, O'Shea et al reported on the outcome of infants with BPD who were treated with a 42-day course of dexamethasone. A 42-day course of dexamethasone was associated with an increased risk of cerebral palsy. Cummings' 1989 study refutes these findings.

bronchopulmonary dysplasia Deterrence/Prevention:
• The multifactorial etiology of BPD compounds its prevention.
• Prenatal steroid therapy and postnatal surfactant use has improved survival and perhaps redirected severity of BPD.
• Postnatal corticosteroid use may facilitate ventilator weaning but is fraught with many adverse effects. Reconsider standard of care therapy with postnatal dexamethasone, weighing the risk-to-benefit ratio in each case.
• Use of exogenous surfactant has improved neonatal survival but may increase the prevalence of BPD in preterm infants.
• Meticulous attention to oxygen and PPV may modify BPD.
• Maximizing nutritional support, careful monitoring of fluid intake, and judicious diuretic use helps promote lung healing.
• Conclusive evidence of HFV use to prevent BPD is not currently available.
• Inhaled NO may improve oxygenation in some infants with BPD, but synergistic toxicity of hyperoxia and NO on pulmonary and surfactant systems has been demonstrated in vitro.
• Davis in 2000 and Rosenfeld et al in 1986 completed human studies of recombinant SOD supplementation to prevent BPD in preterm infants. In preliminary studies, prophylactic use of recombinant SOD revealed that it is safe and may modify disease severity. Results of the most recent phase III efficacy trial are soon to be forthcoming. Effective prevention of BPD has yet to be found.

bronchopulmonary dysplasia Complications:
• Chorioamnionitis, PVL, severe intraventricular hemorrhage, ventriculomegaly, sepsis, and severe retinopathy of prematurity all are important confounding variables that can greatly affect infant outcome.

bronchopulmonary dysplasia Prognosis:
• Most neonates with BPD ultimately survive; however, these infants are at increased risk for serious infections, airway hyperreactivity, cardiac dysfunction, and neurologic impairments.
o Since the routine use of surfactant replacement has begun, survival of the most immature infants has improved. Along with other advances in technology and improved understanding of neonatal physiology, infants with BPD today appear to have less disease severity as compared to infants in years past. Infants with severe BPD remain at high risk for pulmonary morbidity and mortality during the first 2 years of life.

o Fortunately, pulmonary function slowly improves in most survivors with BPD, likely secondary to continued lung and airway growth and healing. Northway followed the cases of patients with BPD to adulthood. Northway reported in 1992, that these patients had airway hyperreactivity, abnormal pulmonary function, and hyperinflation noted on chest radiography. Rehospitalization for impaired pulmonary function is most common during the first 2 years of life. In 1990, Hakulinen et al found a gradual decrease in symptom frequency in children aged 6-9 years as compared to the first 2 years of life. Bader in 1987 and Blayney et al in 1991 found persistence of respiratory symptoms and abnormal PFT results in children aged 7 and 10 years, respectively. High-resolution chest CT scanning or MRI studies in children and adults with a history of BPD reveal lung abnormalities that correlate directly with the degree of pulmonary function abnormality. Postsurfactant studies of infants with BPD have yielded similar results of improved pulmonary function with time. Northway reported cor pulmonale in 36% of survivors. Oxygen supplementation at home is not infrequently required, and failure to relieve pulmonary hypertension with oxygen may be associated with a poor prognosis.

o Persistent right ventricular hypertrophy or fixed pulmonary hypertension unresponsive to oxygen supplementation on cardiac catheterization portends a poor prognosis.