Pharmacology Review

Abstract

Bronchopulmonary dysplasia (BPD) continues to be a major morbidity in preterm infants, especially among the most immature neonates. Although BPD is a multifactorial disease, persistent inflammation is believed to be the final common pathway in its evolution. BPD initially presents with an exudative phase primarily in the immature preterm neonate still receiving respiratory support around 7 to 10 days of age. During this phase, pulmonary edema develops due to proinflammatory cytokine-induced increased alveolar-capillary membrane permeability. Persistence of a patent ductus arteriosus (PDA) with left-to-right shunting or administration of excessive intravenous fluids during this period also promotes pulmonary overcirculation, thus contributing to the pulmonary edema. The associated increased lung water content results in decreased lung compliance both in evolving and established BPD. Diuretics are administered to prevent or treat the pulmonary edema and control total body sodium content. The most commonly used diuretics are furosemide (a loop diuretic), chlorothiazide, and spironolactone. Loop diuretics primarily exert their effects by inhibiting the 2Cl−,Na+-K+ cotransporter in the kidney and the lungs, resulting in diuresis and decreased pulmonary edema formation, respectively. Treatment with diuretics is associated with decreased pulmonary edema and airway resistance as well as improvements in lung compliance. However, diuretics have potentially significant adverse effects, including fluid and electrolyte imbalance, osteopenia, nephrocalcinosis, hearing impairment, and growth failure. There is no evidence that the use of diuretics has an effect on the long-term pulmonary or nonpulmonary outcomes in infants who have BPD.