Bronchopulmonary Dysplasia Treatment & Management

Updated: Jan 13, 2020
  • Author: Namasivayam Ambalavanan, MD, MBBS; Chief Editor: Muhammad Aslam, MD  more...
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Medical Care

Mechanical ventilation

In most cases of bronchopulmonary dysplasia (BPD), respiratory distress syndrome is diagnosed and treated. The mainstay for treating RDS has been surfactant replacement with oxygen supplementation, continuous positive airway pressure (CPAP), and mechanical ventilation. The treatment necessary to recruit alveoli and prevent atelectasis in the immature lung may cause lung injury and activate the inflammatory cascade.

Trauma secondary to positive pressure ventilation (PPV) is generally referred to as barotrauma. With the recent focus on a ventilation strategy involving low versus high tidal volume, some investigators have adopted the term volutrauma. Volutrauma suggests the occurrence of lung injury secondary to excessive tidal volume from PPV.

The severity of lung immaturity, the fetal milieu, and the effects of surfactant deficiency determine the need for PPV, surfactant supplementation, and resultant barotrauma or volutrauma. With severe lung immaturity, the total number of alveoli is reduced, increasing the positive pressure transmitted to distal terminal bronchioles. In the presence of surfactant deficiency, surface tension forces are increased. Some compliant alveoli may become hyperinflated, whereas other saccules with increased surface tension remain collapsed. With increasing PPV to recruit alveoli and improve gas exchange, the compliant terminal bronchiole and alveolar ducts may rupture, leaking air into the interstitium, with resultant pulmonary interstitial emphysema (PIE). The occurrence of PIE greatly increases the risk of bronchopulmonary dysplasia.

Many modes of ventilation and many ventilator strategies have been studied to potentially reduce lung injury, such as synchronized intermittent mechanical ventilation (SIMV), high-frequency jet ventilation (HFJV), and high-frequency oscillatory ventilation (HFOV). Results have been mixed, although some theoretical benefits are associated with these alternative modes of ventilation. Although shorter duration of mechanical ventilation has been demonstrated in some trials of SIMV, most trials have not had a large enough sample size to demonstrate a reduction in bronchopulmonary dysplasia. Systematic reviews suggest that optimal use of conventional ventilation may be as effective as HFOV in improving pulmonary outcomes. Regardless of the high-frequency strategy used, avoidance of hypocarbia and optimization of alveolar recruitment may decrease the risk of bronchopulmonary dysplasia and associated of neurodevelopmental abnormalities.

PPV with various forms of nasal CPAP has been reported to decrease injury to the developing lung and may reduce the development of bronchopulmonary dysplasia. In general, centers that use "gentler ventilation" with more CPAP and less intubation, surfactant, and indomethacin had the lowest rates of bronchopulmonary dysplasia.

Oxygen and PPV frequently are life-saving in extremely preterm infants. However, early and aggressive CPAP may eliminate the need for PPV and exogenous surfactant or facilitate weaning from PPV. Some recommend brief periods of intubation primarily for the administration of exogenous surfactant quickly followed by extubation and nasal CPAP to minimize the need for prolonged PPV. This strategy may be most effective in infants without severe RDS, such as many infants with birth weights of 1000-1500 g. In infants who require oxygen and PPV, careful and meticulous treatment can minimize oxygen toxicity and lung injury. Optimal levels include a pH level of 7.2-7.3, a partial pressure of carbon dioxide (pCO2) of 45-55 mm Hg, and a partial pressure of oxygen (pO2) level of 50-70 mm Hg (with oxygen saturation at 87-92%).

Assessment of blood gases requires arterial, venous, or capillary blood samples. As a result, indwelling arterial lines are often inserted early in the acute management of RDS. Samples obtained from these lines provide the most accurate information about pulmonary function. Arterial puncture may not provide completely accurate samples because of patient agitation and discomfort. Capillary blood gas results, if samples are properly obtained, may be correlated with arterial values; however, capillary samples may widely vary, and results for carbon dioxide are poorly correlated. Following trends in transcutaneous PO2 and pCO2 may reduce the need for frequent blood gas measurements.

Weaning from mechanical ventilation and oxygen is often difficult in infants with moderate-to-severe bronchopulmonary dysplasia, and few criteria are defined to enhance the success of extubation. When tidal volumes are adequate and respiratory rates are low, a trial of extubation and nasal CPAP may be indicated. Atrophy and fatigue of the respiratory muscles may lead to atelectasis and extubation failure. A trial of endotracheal CPAP before extubation is controversial because of the increased work of breathing and airway resistance.

Optimization of methylxanthines and diuretics and adequate nutrition may facilitate weaning the infant from mechanical ventilation. Meticulous primary nursing care is essential to ensure airway patency and facilitate extubation. Prolonged and repeated intubations, as well as mechanical ventilation, may be associated with severe upper airway abnormalities, such as vocal cord paralysis, subglottic stenosis, and laryngotracheomalacia. Bronchoscopic evaluation should be considered in infants with bronchopulmonary dysplasia in whom extubation is repeatedly unsuccessful. Surgical interventions (cricoid splitting, tracheostomy) to address severe structural abnormalities are used less frequently today than in the past.

Oxygen therapy

Oxygen can accept electrons in its outer ring to form free radicals. Oxygen free radicals can cause cell-membrane destruction, protein modification, and DNA abnormalities. Compared with fetuses, neonates live in a relatively oxygen-rich environment. Oxygen is ubiquitous and necessary for extrauterine survival. All mammals have antioxidant defenses to mitigate injury due to oxygen free radicals. However, neonates have a relative deficiency in antioxidant enzymes.

The major antioxidant enzymes in humans are superoxide dismutase, glutathione peroxidase, and catalase. Activity of antioxidant enzymes tend to increase during the last trimester of pregnancy, similar to surfactant production, alveolarization, and development of the pulmonary vasculature. Increases in alveolar size and number, surfactant production, and antioxidant enzymes prepare the fetus for transition from a relatively hypoxic intrauterine environment to a relatively hyperoxic extrauterine environment. Preterm birth exposes the neonate to high oxygen concentrations, increasing the risk of injury due to oxygen free radical.

Animal and human studies of supplemental superoxide dismutase and catalase supplementation have shown reduced cell damage, increased survival, and possible prevention of lung injury. Evidence of oxidation of lipids and proteins has been found in neonates who develop bronchopulmonary dysplasia. Supplementation with superoxide dismutase in ventilated preterm infants with RDS substantially reduced in readmissions compared with placebo-treated control subjects. Further trials are currently under way to examine the effects of supplementation with superoxide dismutase in preterm infants at high risk for bronchopulmonary dysplasia.

Ideal oxygen saturation for term or preterm neonates of various gestational and postnatal ages has not been definitively determined. Many clinicians have adopted oxygen saturation target ranges of 90-95% following results of the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) trial [25] and more recent similar trials, which indicate an increased risk of mortality in infants with target oxygen saturation of 85-89% compared with 91-95%.

In SUPPORT, the rate of oxygen use at 36 weeks was reduced in the lower-oxygen-saturation group compared with the higher-oxygen-saturation group (P = 0.002), but the rates of bronchopulmonary dysplasia among survivors, as determined by the physiological test of oxygen saturation at 36 weeks, and the composite outcome of bronchopulmonary dysplasia or death by 36 weeks did not differ significantly between the treatment groups. A delicate balance to optimally promote neonatal pulmonary (alveolar and vascular) and retinal vascular homeostasis is noted.

In the Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP) trial to reduce severe retinopathy of prematurity (ROP), oxygen saturations of more than 95% minimally affected retinopathy but increased the risk for pneumonia or bronchopulmonary dysplasia.

The normal oxygen requirement of a preterm infant is unknown. Pulmonary hypertension and cor pulmonale may result from chronic hypoxia and lead to airway remodeling in infants with severe bronchopulmonary dysplasia. Oxygen is a potent pulmonary vasodilator that stimulates the production of nitric oxide (NO). NO causes smooth muscle cells to relax by activating cyclic guanosine monophosphate. Currently, pulse oximetry is the mainstay of noninvasive monitoring of oxygenation.

Repeated episodes of desaturation and hypoxia may occur in infants with bronchopulmonary dysplasia receiving mechanical ventilation as a result of decreased respiratory drive, altered pulmonary mechanics, excessive stimulation, bronchospasm, and forced exhalation efforts. Forced exhalation efforts due to infant agitation may cause atelectasis and recurrent hypoxic episodes. Hyperoxia may overwhelm the neonate's relatively deficient antioxidant defenses and worsen bronchopulmonary dysplasia. The patient's oxygen requirements are frequently increased during stressful procedures and feedings. Caregivers are more likely to follow wide guidelines for ranges of oxygen saturation than narrow ones. Some infants, especially those living at high altitudes, may require oxygen therapy for many months.

Transfusion of packed RBCs may increase oxygen-carrying capacity in preterm infants who have anemia (hematocrit < 30% [0.30]), but transfusion may further increase complication rates. The ideal hemoglobin level in critically ill neonates is not well established. Hemoglobin levels are not well correlated with oxygen transport, although it has been shown that oxygen content and systemic oxygen transport increased and that oxygen consumption and requirements decreased in infants with bronchopulmonary dysplasia after blood transfusion.

The need for multiple transfusions and donor exposures can be minimized by using iron supplementation, a reduction in phlebotomy requirements, and by use of erythropoietin administration.

Treatment of inflammation

Chorioamnionitis is associated with a higher risk of development of bronchopulmonary dysplasia. [1] Elevated levels of interleukin-6 and placental growth factor in the umbilical venous blood of preterm neonates are associated with increased incidence of bronchopulmonary dysplasia. This inflammation likely affects alveolarization and vascularization of the pulmonary system of the second-trimester fetus.

Fetal sheep exposed to inflammatory mediators or endotoxin develop inflammation and abnormal lung development. Activation of inflammatory mediators has been demonstrated in humans and animal models of acute lung injury. Activation of leukocytes after cell injury caused by oxygen free radicals, barotrauma, infection, and other stimuli may begin the process of destruction and abnormal lung repair that results in acute lung injury then bronchopulmonary dysplasia.

Radiolabeled activated leukocytes have been recovered by means of bronchoalveolar lavage (BAL) in preterm neonates receiving oxygen and PPV. These leukocytes, as well as lipid byproducts of cell-membrane destruction, activate the inflammatory cascade and are metabolized to arachidonic acid and lysoplatelet factor. Lipoxygenase catabolizes arachidonic acid, resulting in the production of cytokines and leukotrienes. Cyclooxygenase may also metabolize these byproducts to produce thromboxane, prostaglandin, or prostacyclin. All of these substances have potent vasoactive and inflammatory properties. levels of these substances are elevated in the first days of life, as measured in tracheal aspirates of preterm infants who subsequently develop bronchopulmonary dysplasia.

Metabolites of arachidonic acid, lysoplatelet factor, prostaglandin, and prostacyclin may cause vasodilatation, increase capillary permeability with subsequent albumin leakage, and inhibit surfactant function. This effects increase oxygenation and ventilation requirements and potentially increase rates of bronchopulmonary dysplasia Activation of transcription factors such as nuclear factor-kappa B in early postnatal life is associated with death or bronchopulmonary dysplasia.

Collagenase and elastase are released from activated neutrophils. These enzymes may directly destroy lung tissue because hydroxyproline and elastin (breakdown products of collagen and elastin) have been recovered in the urine of preterm infants who develop bronchopulmonary dysplasia.

Alpha1-proteinase inhibitor mitigates the action of elastases and is activated by oxygen free radicals. Increased activity and decreased function of alpha1-proteinase inhibitor may worsen lung injury in neonates. A decrease in bronchopulmonary dysplasia and in the need for continued ventilator support is found in neonates given supplemental alpha1-proteinase inhibitor.

All these findings suggest the fetal inflammatory response effects pulmonary development and substantially contributes to the development of bronchopulmonary dysplasia. The self-perpetuating cycle of lung injury is accentuated in the extremely preterm neonate with immature lungs.

Management of infection

Maternal cervical colonization and/or colonization in the neonate with Ureaplasma urealyticum has been implicated in the development of bronchopulmonary dysplasia. Viscardi and colleagues found that persistent lung infection with U urealyticum may contribute to chronic inflammation and early fibrosis in the preterm lung, leading to pathology consistent with clinically significant bronchopulmonary dysplasia. [2]

Systematic reviews have concluded that infection with U urealyticum is associated with increased rates of bronchopulmonary dysplasia. Infection—either antenatal chorioamnionitis and funisitis or postnatal infection—may activate the inflammatory cascade and damage the preterm lung, resulting in bronchopulmonary dysplasia. In fact, any clinically significant episode of sepsis in the vulnerable preterm neonate greatly increases his or her risk of bronchopulmonary dysplasia, especially if the infection increases the baby's requirement for oxygen and mechanical ventilation.

Future management

Future management of bronchopulmonary dysplasia will involve strategies that emphasize prevention. Because few accepted therapies currently prevent bronchopulmonary dysplasia, many therapeutic modalities (eg, mechanical ventilation, oxygen therapy, nutritional support, medication) are used to treat bronchopulmonary dysplasia. Practicing neonatologists have observed reduced severities of bronchopulmonary dysplasia in the postsurfactant era. Maintaining PPV and oxygen therapy for longer than 4 months and discharging patients to facilities for prolonged mechanical ventilation is now unusual.



Infants with bronchopulmonary dysplasia have multisystem involvement. Therefore, various pediatric subspecialists should be consulted: cardiologist, pulmonologist, gastroenterologist, developmentalist, ophthalmologist, neurologist, physical therapist, and nutritionist.

Pharmacists who have specialized in pediatrics and neonatal care are invaluable in guiding therapy and providing in-patient and outpatient support for these fragile infants. They may also assist with ongoing care after patients are discharged from the hospital.



Infants with bronchopulmonary dysplasia have increased energy requirements. Early parenteral nutrition is often used to ameliorate the catabolic state of the preterm infant, although excessive fluid administration (and failure to lose weight) in the first week of life may increase the risk for patent ductus arteriosus (PDA) and bronchopulmonary dysplasia. Maximizing the patient's intake of protein, carbohydrates, fat, vitamins, and trace metals is critical to prevent further lung injury and augment tissue repair. However, excessive administration of non-nitrogen calories should be avoided because this may lead to excessive formation of carbon dioxide and complicate weaning.

Antioxidant enzymes may protect the lung and help prevent or mitigate bronchopulmonary dysplasia. In preterm neonates, deficiency of trace element such as copper, zinc, and manganese may predispose them to lung injury, and supplementation may provide protection.

Vitamins A and E are nutritional antioxidants that may help prevent lipid peroxidation and maintain cell integrity. However, supplementation of vitamin E in preterm neonates does not prevent bronchopulmonary dysplasia. Preterm neonates may be deficient in vitamin A, and many trials of vitamin A supplementation to prevent bronchopulmonary dysplasia in preterm infants have been completed. Data from meta-analyses reported in a Cochrane Database review of vitamin A supplementation indicate that vitamin A supplementation reduces the risk of bronchopulmonary dysplasia in premature neonates.

Extremely preterm infants may require large amounts of free water because of increased insensible water loss through their thin, immature skin. Excessive administration of fluid increases the risk of symptomatic PDA and pulmonary edema (PE). The increased ventilator settings and oxygen requirements necessary to treat PDA and PE may worsen pulmonary injury and increase the risk of bronchopulmonary dysplasia. Early PDA treatment may improve pulmonary function but does not affect the incidence of bronchopulmonary dysplasia. A retrospective study by Oh et al revealed that lowered fluid intake soon after birth helped reduce the risk of death and oxygen requirement at 36 weeks' corrected gestational age. [26]

Protein and fat supplementation is progressively increased to provide approximately 3-3.5 g/kg/day. Rapid and early administration of high concentrations of lipids may possibly worsen bronchopulmonary dysplasia by depleting pulmonary vascular lipid. Excessive glucose loads may increase oxygen consumption, the respiratory drive, and glucosuria. Calcium and phosphorus requirements are greatly increased in preterm infants. Most mineral stores in the fetus are collected during the third trimester, leaving the extremely preterm infant deficient in calcium and phosphorus and at increased risk of rickets. Furosemide therapy and limited intravenous administration of calcium may worsen bone mineralization and cause secondary hyperparathyroidism.

Vitamin A supplementation decreases the incidence of bronchopulmonary dysplasia. Supplementation of trace minerals (eg, copper, zinc, manganese) are needed because they are essential cofactors in antioxidant enzymes.

Early insertion of percutaneous central venous lines may aid the administration of parenteral nutrition.

Early enteral feeding of small amounts (even if umbilical lines are in place) followed by slow, steady increases in volume appears to optimize tolerance of feeds and nutritional support. The most immature and unstable preterm infant often has a difficult transition to complete enteral nutrition. Frequent interruption of feedings because of intolerance or illness can complicate the care of patients. Enteral feedings of breast milk provides the best nutrition while preventing feeding complications (eg, sepsis, necrotizing enterocolitis). The energy content of expressed breast milk and formulas can be enhanced to increase energy intake while minimizing fluid intake. Infants may require 120-150 kcal/kg/day to gain weight.

Diuretics are often used to treat fluid overload, but initially avoiding excessive fluid administration is preferred.

Postnatal growth failure is common and may have considerable effects on long-term developmental outcomes. Strategies to optimize postnatal weight gain are important to improve pulmonary, retinal, and neurologic development.



The multifactorial etiology of bronchopulmonary dysplasia complicates its prevention. Note the following:

  • Prenatal steroid therapy and postnatal surfactant has improved survival and mitigated the severity of bronchopulmonary dysplasia. Prevention of preterm birth and chorioamnionitis should reduce the incidence of bronchopulmonary dysplasia.

  • Meticulous attention to optimal oxygenation, ventilation (early extubation, increased use of continuous positive airway pressure [CPAP]), and fluid management may decrease the incidence and severity of bronchopulmonary dysplasia.

  • Maximizing nutritional support, careful monitoring of fluid intake, and judicious use of diuretics promote lung healing.

  • Evidence regarding the use of high-frequency ventilation, inhaled nitric oxide (iNO), and antioxidants (other than vitamin A) to prevent bronchopulmonary dysplasia is inconclusive.


Long-Term Monitoring


Infants with bronchopulmonary dysplasia (BPD) are at high risk of respiratory infections in the first 2 years of life. Note the following:

  • In infants with bronchopulmonary dysplasia, infection with a respiratory syncytial virus (RSV) may cause severe illness and even death.

  • Monthly injections of RSV antibody may prevent or reduce the risk of rehospitalization in infants with bronchopulmonary dysplasia and may mitigate the severity of illness.

  • The American Academy of Pediatrics (AAP) has issued a policy statement about the use of RSV antibody injections during RSV season (November to March) in preterm infants discharged from the NICU.

Growth and development

Poor growth and delayed development are frequently observed in infants with bronchopulmonary dysplasia, especially those with markedly abnormal pulmonary function. In addition, many infants may have worsening pulmonary function with liberalization of fluid intake and repeated pulmonary infections. Use of diuretics, high-energy formulas, and breast-milk additives are the mainstays of treatment in and out of the hospital.

Infants with bronchopulmonary dysplasia are at high risk for abnormal neurodevelopment.

At 18-22 months' corrected age in extremely low birth weight infants, abnormal growth occurred in 50-60% of infants with bronchopulmonary dysplasia. The risk of neurodevelopmental impairment, cerebral palsy, and low intelligent quotient (IQ) more than doubled in infants with severe bronchopulmonary dysplasia compared with infants with mild bronchopulmonary dysplasia.