Bronchopulmonary dysplasia: Management

INTRODUCTION — Bronchopulmonary dysplasia (BPD),also known as neonatal chronic lung disease (CLD), is an important cause of respiratory morbidity in preterm newborns. Day-to-day care is mostly directed towards improving symptoms, with many common interventions having little impact on long-term outcome. Most patients with BPD gradually improve as healing occurs and lung growth continues, but the time required for improvement varies widely. Management is also directed at minimizing further injury, providing an optimal environment to support growth and recovery, and detecting complications associated with BPD.

The management of established BPD is reviewed here. Pathogenesis and clinical features, prognosis, and potential strategies to prevent BPD are discussed separately. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features" and "Outcome of infants with bronchopulmonary dysplasia" and "Bronchopulmonary dysplasia: Prevention".)

TERMINOLOGY

Prematurity — Different degrees of prematurity are defined by gestational age (GA), which is calculated from the first day of the mother's last period, or birth weight (BW). Data on BPD are often based upon the following classification of preterm infants categorized by BW or GA (table 1).

These terms are used throughout this discussion.

Bronchopulmonary dysplasia — It has been challenging to maintain a consistent definition of BPD because of changes in the population at risk (ie, greater number of patients at earlier GAs) and advances in neonatal management (ie, surfactant and antenatal glucocorticoid therapy, and less aggressive mechanical ventilation) have altered the pathology and clinical course of BPD and led to revisions in its definition (table 2).

When evaluating the literature, it is important to have an appreciation of the definitions used and their limitations, especially if comparing data across different studies and to ensure that results are applicable to the clinical setting at hand [1,2]. Most of the evidence cited in this topic have used one of the following definitions:

●Oxygen requirement either at 28 postnatal days or 36 weeks postmenstrual age (PMA) [3-5].

●2001 National Institute of Child Health and Human Development (NICHD) definition, which added criteria that included GA, severity of disease, and timing of assessment based on GA [6]. Further revisions were suggested at a subsequent 2016 NICHD workshop that renamed categories and added newer modes of noninvasive ventilation (eg, nasal cannula flow) not included in the previous definition, radiologic evidence of disease as a criterion, and a new category (IIIA) of early lethal BPD [7].

The discussion that reviews the ongoing challenge of establishing a consensus definition is reviewed separately. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features", section on 'Definitions'.)

APPROACH TO BPD MANAGEMENT — The management goals for established BPD consist of promotion of growth to enhance lung development and repair, minimization of further lung damage, optimization of lung function with improved gas exchange, and detection and management of acute pulmonary decompensations and complications.

During hospitalization, general measures provided to all patients with established BPD include adequate nutrition to promote growth and modest fluid restriction. The administration of other interventions vary based on the severity of the BPD and are directed towards maintaining a target goal of pulse oximetry saturation (SpO₂) between 90 and 95 percent while minimizing further lung injury (table 2):

●Mild BPD (class I) – Patients with mild BPD require minimal respiratory support including low concentration of oxygen delivered by nasal cannulae or hood or noninvasive pressure support without oxygen supplementation. These patients are managed with general measures focused on providing adequate nutrition and fluid restriction of 140 to 150 mL/kg per day.

●Moderate BPD (class II) – Patients with moderate BPD require more respiratory support but oxygen supplementation does not typically exceed fraction of inspired oxygen (FiO₂) >0.30, and infants are not ventilator dependent. In addition to the general measures, management may include the addition of diuretic therapy for those infants who receive positive airway pressure (PAP) despite modest fluid restriction.

●Severe BPD (class III) – Patients with severe disease receive respiratory support that typically includes mechanical ventilation and/or FiO₂ >0.30; both of which may cause additional lung injury. In our practice, SpO₂ is targeted between 90 and 95 percent, and partial pressure of carbon dioxide (PaCO₂) between 55 and 65 mmHg as long as pH remains in the normal range (ie, 7.3 to 7.4).

For patients who are mechanically ventilated, we recommend small tidal volume ventilation to minimize further pulmonary injury. However, airway dilation and dead space to tidal volume ratio increase with chronic mechanical ventilation in extremely low birth weight (ELBW) infants (BW <1000 g); over time, higher tidal volumes are often needed to maintain effective ventilation. (See 'Respiratory support' below.)

Additional pharmacologic interventions focused on improving lung function with a goal of weaning respiratory support include diuretics, systemic and inhaled corticosteroids, and bronchodilators:

●We suggest a trial of diuretic therapy for patients who remain ventilator-dependent or dependent on PAP despite modest fluid restriction. (See 'Diuretics' below.)

●We suggest a trial of corticosteroids for patients who cannot be weaned from maximal ventilatory and oxygen support. (See 'Corticosteroids' below.)

●We do not routinely use bronchodilators but reserve their use for episodes of acute pulmonary decompensation due to severe airway reactivity. (See 'Bronchodilators' below.)

Comprehensive in-hospital care also entails:

●Evaluation and treatment of any acute pulmonary decompensation (see 'Acute exacerbations' below)

●Screening and managing complications associated with BPD (systemic hypertension, pulmonary artery hypertension, and neurodevelopmental impairment) (see 'Complications' below)

●Planning for post-discharge care (see 'Post-discharge' below)

GENERAL MEASURES — In-hospital general measures that are applied to all infants with established BPD include ensuring adequate nutrition for growth that promotes lung repair and development and moderate fluid restriction to improve lung function (air-gas exchange). (See "Bronchopulmonary dysplasia: Prevention", section on 'Fluid management'.)

Nutrition — Nutrition is provided to meet the increased total energy needs of infants with BPD and ensure appropriate lung growth and repair. Total energy needs in some infants may increase to 150 kcal/kg per day, and protein intake of 3.5 to 4 g/kg per day is needed. Because fluid intake is often restricted, the desired nutrients may need to be contained in a reduced volume of feeding. In all cases of BPD, the nutritional intake should meet the caloric needs of the infant and include all major and trace nutrients.

In our centers, fortified human milk that is supplemented to meet their needs for adequate growth is given to infants with BPD. Mother's milk is preferred, but if not available, donor milk should be used. If fluid restriction below 140 mL/kg is needed, commercially available human milk fortifier can be added to increase caloric density to 24, 27, or 30 kcal/oz as needed. An alternative option is to alternate feeds between fortified human milk and preterm formula with a higher nutrient density [8]. (See "Human milk feeding and fortification of human milk for premature infants", section on 'Fortification of human milk' and "Growth management in preterm infants", section on 'Bronchopulmonary dysplasia'.)

The nutritional intake is revised based upon the growth of the infants and the results of laboratory evaluation as discussed below. A dietitian experienced in the management of chronically ill infants should monitor dietary profile and growth parameters, and recommend revisions as needed.

Infants with BPD may have oral motor dysfunction and feeding disorders that adversely affect growth, and require specific intervention. Consultation with an experienced clinician (occupational and/or speech therapist) is useful to assess and manage these feeding difficulties. The evaluation and management of these patients are discussed separately. (See "Neonatal oral feeding difficulties due to sucking and swallowing disorders".)

Growth and nutritional monitoring — Patients should be weighed two to three times per week while in the hospital, and length and head circumference should be measured weekly (figure 1 and figure 2). Nutritional monitoring includes measurements of blood urea nitrogen, calcium, phosphorus, and alkaline phosphatase concentrations. Serum electrolyte concentrations should be monitored in infants on diuretic therapy. (See "Growth management in preterm infants" and 'Diuretics' below.)

Fluid restriction — Based upon our clinical experience, fluid intake is restricted for infants with BPD to improve pulmonary function by preventing excess pulmonary fluid (eg, pulmonary edema), thereby improving air-gas exchange. Most infants can be managed with modest fluid restriction of 140 to 150 mL/kg per day. However, in severely affected infants, fluid restriction to 110 to 120 mL/kg per day may be necessary.

Although data based upon clinical trials comparing restrictive versus liberal intake are limited, there appears to be a trend towards better outcome with a more restrictive fluid management in reducing the risk of BPD and decreasing mortality [9,10]. However, data are insufficient to show that fluid restriction is beneficial for infants with established BPD [11].

As noted above, adequate nutrition must be provided to ensure proper growth regardless of the decision to restrict fluid intake. The caloric density of feeds may need to be increased in patients who are managed with a more restrictive fluid intake.

Screening — Comprehensive in-hospital care includes monitoring for complications for BPD:

●Weekly blood pressure measurements to detect systemic hypertension. (See 'Systemic blood pressure' below.)

●Echocardiographic assessment for patients at risk for pulmonary arterial hypertension (PAH) (algorithm 1). (See 'Pulmonary artery hypertension' below and "Pulmonary hypertension associated with bronchopulmonary dysplasia".)

●Neurodevelopmental screening. (See 'Development' below.)

RESPIRATORY SUPPORT — Respiratory care is supportive and should minimize additional injury. Respiratory support includes noninvasive continuous pressure support (eg, nasal continuous positive airway pressure [nCPAP]) and mechanical ventilation. (See "Approach to mechanical ventilation in very preterm neonates", section on 'Indications for invasive MV' and "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Respiratory support devices'.)

Mechanical ventilation — In patients with established BPD who require mechanical ventilation, the use of low tidal volumes (4 to 6 mL/kg) is preferred to minimize volutrauma that contributes to mechanical lung injury (see "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features", section on 'Mechanical ventilation' and "Approach to mechanical ventilation in very preterm neonates" and "Overview of mechanical ventilation in neonates", section on 'Volume-targeted ventilation'). However, airway dilation and dead space to tidal volume ratio increase with chronic mechanical ventilation in extremely low birth weight (ELBW) infants (BW <1000 g) [12]. As a result, infants with severe BPD may require higher tidal volumes over time to maintain effective ventilation [13]. In our centers, we target pulse oximetry saturation (SpO₂) between 90 and 95 percent and allow permissive hypercapnia (partial pressure of carbon dioxide [PaCO₂] 50 to 55 mmHg) as long as pH remains in the normal range (ie, 7.3 to 7.4). In patients with severe disease, PaCO₂ values up to 70 mmHg may be tolerated on occasion to avoid further escalation of ventilator support [14].

Based on our clinical experience, a slightly prolonged inspiratory duration of 0.4 to 0.5 seconds sometimes is needed to promote uniform lung inflation in patients who develop uneven airway obstruction. In addition, maintaining a positive end-expiratory pressure (PEEP) of 5 to 7 cm H₂O generally minimizes atelectasis and counters the development of pulmonary edema in infants with BPD. However, infants with bronchomalacia (narrowing of the bronchi due to diminished cartilage airway support) may require higher levels of PEEP to keep airways open during exhalation. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features", section on 'Mechanical ventilation'.)

Suctioning is associated with tracheal and bronchial injury. Suctioning is limited to only when it is needed, and ensuring that the passage of the suction catheter does not go beyond the distal tip of the endotracheal tube ("calibrated suctioning") is recommended to avoid injury and protect the airway mucosa.

Monitoring and weaning — Ongoing assessment of ventilator-dependent infants includes continuous pulse oximetry to monitor oxygenation, and intermittent blood gas sampling to monitor pH and PaCO₂. We initially obtain daily or every other day blood gas samples to monitor PaCO₂ and pH. Frequency of sampling decreases as the clinical condition stabilizes with fewer ventilator changes. Blood gas sample and chest radiograph are obtained to evaluate any episode of respiratory decompensation. (See 'Acute exacerbations' below.)

With growth and improving lung function, periodic attempts should be made to wean ventilator support as tolerated. Infants who can maintain acceptable PaCO₂ levels with minimal ventilator support and without increased respiratory effort or tachypnea can be extubated and weaned to continuous positive airway pressure (CPAP) and then, if needed, to only supplemental oxygen alone based on SpO₂ values.

Prolonged ventilation and tracheostomy — In addition to ongoing lung injury, prolonged ventilation and intubation may be associated with acquired subglottic stenosis and laryngeal injury, especially in infants who require multiple intubations. Tracheostomy placement provides a stable and reliable airway, and diminishes acute events due to endotracheal tube displacement or obstruction [13]. The appropriate timing and indications of tracheostomy placement in infants requiring chronic ventilation remains poorly defined, as information is based on retrospective data [13,15,16]. In our practice, tracheostomy is considered in infants who are 40 to 42 weeks postmenstrual age and are expected to need continued ventilator support. However, it is clear more information is needed to determine the optimal timing and indications of tracheostomy in infants with BPD.

In a multicenter cohort study of 8683 infants born at <30 weeks gestational age (GA) and surviving to at least 36 weeks, tracheostomy was performed in 3.5 percent (n = 304) [16]. After adjustment, primary outcome of death or neurodevelopmental impairment (NDI) occurred more frequently among those receiving tracheostomy (odds ratio [OR] 3.3, 95% CI 2.4-4.6). However, the risk of death alone was lower in the group of infants who underwent tracheostomy (OR 0.4, 95% CI 0.3-0.7). The composite outcome of death or NDI before 120 days of life was lower for infants who had tracheostomies performed before 120 days of life compared with those receiving tracheostomies after 120 days (OR 0.5, 95% CI 0.3-0.9).

Predictors for tracheostomy in a smaller multicenter study of 868 infants (mean GA 26 weeks) with severe BPD, in which 12 percent of the cohort underwent tracheostomy, included the presence of clinical pulmonary hypertension/cor pulmonale, ongoing mechanical ventilation, age at the time of referral, and increasing GA at birth [15]. The unexpected finding of increased GA as a predictor may reflect death before referral for tracheostomy of the most immature infants or different underlying physiology in more mature infants with severe disease.

Oxygen — The use of supplemental oxygen is challenging in preterm infants with BPD, because of the competing needs of avoiding hypoxia versus exposure to excess oxygen. Based upon the available evidence, we recommend an oxygen saturation target range of 90 to 95 percent for preterm infants. Once an infant with BPD reaches term and achieves mature retinal vascularization (as documented by ophthalmologic examination), target SpO₂ values may be increased to 100 percent [14]. Further discussion of oxygen use and the impact on pulmonary artery hypertension is discussed below. (See "Neonatal target oxygen levels for preterm infants", section on 'Oxygen target levels' and 'Pulmonary artery hypertension' below.)

Supplemental oxygen is used to ensure adequate tissue oxygenation and avoid alveolar hypoxia, which increases pulmonary vascular resistance and may lead to cor pulmonale [17,18]. Hypoxemia also may increase airway resistance in infants with BPD [19,20]. However, increases in inspired oxygen concentrations, even small changes, may have a negative impact on the clinical course, such as increasing the risk of retinopathy of prematurity or exacerbating pulmonary inflammation or pulmonary edema. (See "Bronchopulmonary dysplasia: Definition, pathogenesis, and clinical features", section on 'Oxygen toxicity'.)

Guidelines for neonatal targeted oxygen saturation goals continue to evolve with the accumulation of new evidence and is an ongoing active area of research. The challenges, including a description of the available data in determining oxygen target levels, are discussed separately. (See "Neonatal target oxygen levels for preterm infants", section on 'Oxygen target levels'.)

PHARMACOLOGIC INTERVENTIONS FOR MORE ADVANCED BPD — Pharmacologic therapy is focused on improving lung function so that respiratory support can be weaned. It is typically reserved for infants with severe disease who are ventilator-dependent with the exception of diuretic therapy, which may be used in patients with moderate disease.

Diuretics — Although diuretic therapy has been shown to improve short-term pulmonary mechanics, there is little evidence that the long-term use of diuretics improves clinical outcome of infants with BPD [21]. Nevertheless, we use diuretics in infants with BPD to improve pulmonary function in patients who remain ventilator-dependent or require positive end-expiratory pressure (PEEP) despite modest fluid restriction.

Agents — Two classes of diuretic agents used in infants with BPD are:

●Thiazide diuretics – Acute and chronic administration of diuretics that act on the distal renal tubule (thiazide and/or spironolactone) produce short-term improvement in lung mechanics in preterm infants with BPD [22]. However, in a systematic review, data were inadequate to show that distal diuretic administration improved long-term clinical outcome in infants with established or developing BPD [22]. Further clinical trials are needed to determine whether there is a role for chronic use of thiazide diuretics.

●Loop diuretics – The loop diuretic most commonly used and best studied in the management of BPD is furosemide. In a systematic review, chronic administration of furosemide either enterally or intravenously to infants with BPD older than three weeks of age improved pulmonary mechanics and oxygenation [23]. Pulmonary mechanics were also improved after a single intravenous dose of furosemide (1 mg/kg). However, no benefit was demonstrated in clinical outcomes, including need for ventilator support, length of hospital stay, survival, or long-term outcome. No consistent effects were found when intravenous furosemide was given to preterm infants younger than three weeks of age with developing BPD.

In a large retrospective study of 3252 preterm infants (GA <32 weeks) cared for in 43 neonatal intensive care units in children's hospitals, there was a six-fold difference in the proportion of days of loop diuretic exposure for infants with severe BPD between the lowest-use and highest-use centers (7.3 versus 49.4 percent) [24]. However, despite this marked variation in loop diuretic usage, mortality rates were similar between low- and high-use centers (9.7 versus 9.5 percent, adjusted odds ratio (aOR) 0.98. 95% CI 0.62-1.53) as was the median discharge postmenstrual age (44.8 versus 45 weeks, aOR 47.3, 95% CI 46.8-47.9 for the low-use center versus 47.4, 95% CI 46.9-47.9 for high-use centers). This study was limited by the lack of data on dose amount and frequency as well of the possibility of other unidentified center-specific factors that may have an impact on mortality and the postmenstrual age at discharge. Nevertheless, these data do question the long-held use of loop diuretics in this population and point out the need for further research to determine whether loop diuretics are beneficial in the care of infants with severe BPD.

Our approach — Although there is lack of beneficial outcome data, we use chronic diuretic therapy for infants who, despite modest fluid restriction (140 to 150 mL/kg per day), remain ventilator-dependent or require PEEP provided either by continuous positive pressure (CPAP) or high-flow nasal cannulae (HFNC). In these cases, we generally begin with a thiazide diuretic agent, such as chlorothiazide (oral dose of 20 to 40 mg/kg per day divided into two doses) or hydrochlorothiazide (oral dose of 3 to 4 mg/kg per day divided into two doses [maximum dose of 37.7 mg per day]). The published oral maximum dose of chlorothiazide is 375 mg; however, in our experience, we have never approached this maximum dose. In addition, intravenous administration of chlorothiazide can be given as a dose of 2 to 8 mg/kg per day in two divided doses. We do not routinely use a combination of spironolactone with thiazide as spironolactone does not add any further benefit in our experience [25]. However, other centers will add spironolactone as a potassium-sparing diuretic.

In our centers, furosemide is used in the following settings. We do not recommend combination therapy of furosemide and a thiazide diuretic. So, if chronic thiazide therapy is used, it is discontinued when furosemide is administered:

●For acute pulmonary exacerbation attributed to pulmonary edema, intermittent or single dose of furosemide (1 mg/kg per dose intravenously or 2 mg/kg per dose orally) is administered. In infants with more severe respiratory decompensation, a trial of furosemide may be continued for two to three days.

●During or following a red blood cell transfusion, a single intravenous dose of furosemide (1 mg/kg) is often given.

●A longer course of furosemide is considered for ventilator-dependent infants with severe BPD who had a short-term positive response to furosemide during an acute exacerbation, or for infants who remain unstable after modest fluid restriction and the administration of daily thiazide diuretics. The duration of furosemide therapy is dependent on the individual's response. However, we avoid the chronic use of furosemide, if possible, because of its potential complications of ototoxicity and nephrocalcinosis.

We typically continue diuretic therapy until infants are no longer receiving positive airway pressure (PAP) and have a fraction of inspired oxygen () <30 percent. Weaning strategies include decreasing the daily diuretic dose in a step-wise fashion every 3 to 4 days, or not adjusting the dose for growth.

Serum electrolytes should be measured one to two days after initiating diuretic therapy, with an increase in diuretic dosing, and at least weekly with chronic use. Electrolyte supplements should be administered to compensate for increased urinary loss. We usually start with 2 to 4 mEq/kg per day of potassium chloride, and adjust as needed based on laboratory values and changes in diuretic dosing.

Complications — Electrolyte abnormalities (hyponatremia, hypokalemia, and hypochloremic alkalosis) are common because diuretic use increases urinary loss of sodium, potassium, and chloride [21,26]. Dietary supplementation with potassium chloride usually is needed to prevent these abnormalities. As noted above, some centers will add spironolactone as a potassium-sparing diuretic.

Little data are available regarding effect of diuretics on long-term bone growth and mineralization.

Other complications associated with loop diuretics (eg, furosemide) include:

●Nephrocalcinosis and/or nephrolithiasis due to increased urinary calcium excretion [27,28]. (See "Nephrocalcinosis in neonates", section on 'Loop diuretics'.)

●Ototoxic, especially high-dose, intravenous therapy. (See "Loop diuretics: Dosing and major side effects", section on 'Ototoxicity'.)

Bronchodilators — Inhaled or subcutaneous administration of beta-2 agonists (eg, albuterol or levalbuterol) acutely decreases airway resistance and increases compliance [28-30]. However, we do not recommend routine or chronic use of inhaled B2 bronchodilators in infants with BPD because of lack of evidence of long-term efficacy and their known adverse effects (tachycardia, hypertension, and possibly arrhythmias). In our practice, we reserve their use for infants with severe BPD during acute episodes of bronchoconstriction. (See 'Management' below.)

In a trial of preterm infants (gestational age [GA] <31 weeks) who were ventilator-dependent at 10 days of age, there were no significant differences in regards to survival, developing and severity of BPD, or duration of ventilator support or oxygen therapy among the four groups of patients assigned treatment for 28 days with placebo, salbutamol and placebo, beclomethasone and placebo, or salbutamol and beclomethasone [31].

However, in some infants with severe BPD (table 2), especially older infants who remain ventilator-dependent, acute episodes of bronchoconstriction can occur. In this setting, inhaled beta-2 agonists (eg, albuterol or levalbuterol) may improve short-term function [30,32]. However, it is important to differentiate bronchoconstriction from bronchomalacia with large airway collapse also seen in infants with BPD [33]. (See "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Bronchomalacia'.)

An initial trial of beta-2 agonists is administered through a metered-dose inhaler with a spacer. The infant should be observed for clinical benefit, as evidenced by improved gas exchange (improved pulse oximetry saturation [SpO₂] values and/or decrease in partial pressure of carbon dioxide [PaCO₂]), decreased respiratory effort, or fewer episodes of respiratory decompensation. If beneficial, the beta-2 agents can be used up to a 48-hour period, then progressively weaned. If no benefit is seen, treatment should be discontinued. (See 'Acute exacerbations' below.)

Corticosteroids — Corticosteroids may reduce inflammation and improve lung function in infants with evolving or established BPD. In our practice, we do not routinely use systemic dexamethasone to treat BPD due to concerns of serious adverse effects [34]. We reserve this treatment for the exceptional infant with severe BPD who remains ventilator-dependent and/or has an oxygen requirement of >50 percent.

Although systemic corticosteroids improve lung mechanics and reduce the need for assisted ventilation in infants with established BPD, concerns about long-term neurologic sequelae have led to the recommendations of restrictive use of systemic glucocorticoid therapy in the preterm infant by both the American Academy of Pediatrics and the Canadian Paediatric Society (AAP/CPS) [34].

It is uncertain whether inhaled glucocorticoid therapy is beneficial in the management of infants with BPD. We do not recommend routine use of inhaled glucocorticoid therapy. We may consider the use of inhaled glucocorticoid only in selected older infants with severe BPD who are dependent upon substantial pulmonary support (eg, mechanical ventilation and high concentrations of supplemental oxygen) or who have demonstrated airway reactivity.

Glucocorticoid therapy and its adverse effects in the treatment of BPD are discussed in greater detail separately. (See "Prevention of bronchopulmonary dysplasia: Postnatal use of corticosteroids".)

ACUTE EXACERBATIONS — Infants with BPD may have acute episodes of pulmonary decompensation, most often noted by a decrease in pulse oximetry saturation (SpO₂). These may be associated with infections, severe airway reactivity, pulmonary air leak, increased pulmonary edema, displacement of endotracheal tube in ventilator-dependent patients, or the development of symptomatic tracheobronchomalacia. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Acquired tracheobronchomalacia'.)

Evaluation — The evaluation of an episode of acute pulmonary deterioration should include:

●Assessment of fluid status – Is there a recent weight gain that may be evidence of excessive fluid retention in the lung, which contributes to pulmonary decompensation?

●Respiratory assessment – The evaluation should assess prolonged expiratory phase and increased work of breathing during both inspiration and expiration. If the infant requires ventilatory support, the lung findings should be described as either in the context of ventilator-produced breaths or spontaneous breaths. Specific findings on lung auscultation may be a clue to an underlying pulmonary complication:

•Wheezing or decreased air movement may be indicative of bronchoconstriction.

•Rhonchi or decreased breath sounds are suggestive of a consolidated process, such as pneumonia.

•Rales may indicate pulmonary edema.

•Absent breath sounds may be due to pneumothorax, or displaced endotracheal tube in ventilator-dependent infants.

●Chest radiography – A chest radiograph should be obtained to detect pulmonary parenchymal changes, which may be suggestive of infection or increased pulmonary interstitial fluid, or detect pulmonary air leak or displacement of the endotracheal tube (see "Pulmonary air leak in the newborn"). The chest film may also detect hyperinflation or collapse, diaphragm position, and any changes in heart size.

●Laboratory testing

•Complete blood count to detect leukocytosis, which may indicate an infectious process.

•Capillary or arterial blood gas sample to monitor partial pressure of carbon dioxide (PaCO₂) and pH levels, and to decide if changes in respiratory support are needed: ventilator changes in ventilator-dependent patients, increased pressure support in patients dependent on continuous airway pressure, or intubation and ventilation in infants who are not intubated.

●Evaluation for possible ventilator-associated pneumonia (VAP) – Although there is a lack of consensus on the definition of VAP in infants with BPD, acquired pulmonary infection is always a concern in ventilated patients. In our practice, a tracheal aspirate for culture and Gram stain should be obtained if secretions have become purulent, changed in volume or quality, or a new consolidated area (suggestive of an infectious process) is detected on chest radiography. If bacterial pneumonia is suspected, blood culture should also be obtained. Rapid tests for viral pathogens may be considered, followed by viral culture, depending on season and possible exposures.

●Evaluation for tracheobronchomalacia – Tracheobronchomalacia is characterized by abnormally compliant and collapsing trachea and bronchi presumably due to barotrauma, prolonged intubation, or injury from infection. Infants with tracheobronchomalacia will have episodes of apnea with absent airflow and chronic wheezing that does not improve with bronchodilators. In these infants, the diagnosis is made by dynamic airway endoscopy. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Acquired tracheobronchomalacia'.)

Management — Management is directed towards the suspected underlying cause of acute exacerbations:

●Infection – If bacterial infection is suspected, antibiotic treatment is initiated while awaiting culture results. Clinical findings suggestive of infection include a new localized consolidation on chest radiography or physical examination, leukocytosis, or the presence of fever.

●Pulmonary air leak – Management of the various forms of pulmonary air leak in the neonate is discussed separately. (See "Pulmonary air leak in the newborn".)

●Displaced endotracheal tube – The endotracheal tube is correctly repositioned above the carina of the trachea.

●Airway reactivity – Episodes of severe airway reactivity in infants with BPD should be treated immediately in a step-wise approach. The goal is to re-establish adequate airflow and ventilation before severe deterioration results in a life-threatening situation. Therapy is initiated with the least toxic measures to limit, as much as possible, adverse effects. Management of acute bronchospasm is based upon guidelines for asthma therapy published by the National Asthma Education and Prevention Program; however, many medications and doses cited do not apply to infants younger than one year of age [32]. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management".)

•We begin treatment with levalbuterol (45 mcg per puff), administered as one to two puffs by metered dose inhaler with a spacer (MDI-S) every four to six hours. If there is severe airway obstruction, levalbuterol can be initially given as one to two puffs every 20 minutes for three doses. Albuterol therapy is weaned by decreasing the dosing frequency as airflow improves and is withheld if the heart rate exceeds 200 beats per minute. The infant should be observed for clinical benefit as evidenced by improved gas exchange (improved SpO₂ values and/or decrease in PaCO₂), decreased respiratory effort, or fewer episodes of respiratory decompensation.

•If acute bronchospasm occurs in an infant already receiving inhaled corticosteroids, the dose is doubled for five to seven days. If treatment with a beta-adrenergic agent and inhaled corticosteroids fails to re-establish stable pulmonary function, we consider a short (7 to 10 days) tapering course of systemic hydrocortisone (initial dose 5 mg/kg). However, we try to limit this treatment to ventilator-dependent infants who are older than 40 weeks postmenstrual age (PMA) because of concern of adverse effects on long-term developmental outcome. (See "Prevention of bronchopulmonary dysplasia: Postnatal use of corticosteroids", section on 'Systemic corticosteroids'.)

●Large airway patency – We manage infants with tracheobronchomalacia by providing high positive end-expiratory pressure (PEEP) to maintain airway patency during expiration. In severe cases of tracheobronchomalacia that require long-term high PEEP (9 to 14 cm H₂O) to maintain an open airway, tracheostomy may be considered. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Tracheostomy'.)

COMPLICATIONS

Systemic blood pressure — Systemic hypertension is common in infants with BPD [35-37]. It is usually a transient finding in the first year of life and lasts approximately four months [35,38-41]. Approximately one-half of patients with BPD will have received medical therapy for blood pressure control. In our practice, blood pressure is monitored at least weekly in infants who remain hospitalized and at each outpatient visit after discharge. If blood pressure is elevated, an evaluation to determine the underlying cause should be performed. Persistent elevations may require treatment. (See "Etiology, clinical features, and diagnosis of neonatal hypertension" and "Management of hypertension in neonates and infants".)

The pathogenesis for hypertension is uncertain and may be caused by increased levels of catecholamines, angiotensin, or antidiuretic hormone, or altered neurohumoral regulation [42]. Hypertension is also associated with glucocorticoid treatment.

Pulmonary artery hypertension — PAH is a serious sequela of BPD, affecting 12 to 25 percent of infants with BPD, which may present as early as the first two weeks of age [43-45]. It may develop due to structural disruption of the pulmonary circulation associated with alveolar injury, chronic alveolar hypoxia, and/or inadvertent periods of hypoxemia. Because it is a common and serious complication of infants with severe BPD, we screen at-risk infants with an echocardiogram.

Screening, evaluation, and management of PAH in infants with BPD are discussed separately. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Pulmonary hypertension' and "Pulmonary hypertension associated with bronchopulmonary dysplasia", section on 'Epidemiology and natural history'.)

Development — Neurodevelopmental outcome is poorer in infants with BPD than in unaffected infants of similar GA and birth weight (BW). An appropriate environment that minimizes noise, discomfort, and exposure to bright light should be identified for each patient as it is important to try to minimize the adverse impact of prolonged hospitalization upon infant development. Primary nursing should be encouraged to allow the infant to be cared for by a small group of individuals. The clinical team should work closely with parents to promote infant-parent bonding and provide a friendly, play-oriented environment using the infant's own toys and possessions.

Developmental assessment should begin during the infant's hospital stay and continue after the infant is discharged. (See "Outcome of infants with bronchopulmonary dysplasia" and "Care of the neonatal intensive care unit graduate", section on 'Screening'.)

Ventricular hypertrophy — Left ventricular hypertrophy (LVH) may be associated with BPD, although the incidence of this complication is uncertain and likely small. The few published reports include data from cardiac catheterization and autopsy findings as well as some echocardiographic observations and do not reflect contemporary practice. Although the pathophysiology is unclear, the etiology is likely multifaceted. LVH may cause an elevation in left atrial (LA) pressure and increase pulmonary congestion and edema, which may impact pulmonary function [46].These abnormalities are usually found during screening for PAH and may be associated with systemic hypertension. Patients with persistent LVH or those with signs of LV dysfunction should be evaluated by a pediatric cardiologist.

By contrast, there is no evidence of changes in echocardiographic measurements of the right ventricle with the possible exception of the eccentricity index, which, if elevated, suggests right ventricular overload [47].(See "Echocardiographic assessment of the right heart", section on 'Interventricular septal shape'.)

Surgery — Infants with severe BPD are more likely to undergo one or more surgical procedures [48]. The most common operations include gastrostomy insertion, fundoplication, herniorrhaphy, and tracheostomy.

POST-DISCHARGE

Planning — Infants with moderate to severe BPD typically have a prolonged and complicated birth hospitalization and require considerable supportive management after discharge to home. Optimal discharge planning is provided by a multidisciplinary team that includes a neonatologist, pediatric pulmonologist, nurses, respiratory therapists, a social worker, a child life specialist, a nutritionist, physical and occupational therapists, and an audiologist [13,49]. The team should meet regularly to monitor the patient's clinical course and to review and refine goals and criteria for discharge. The transition from hospital to home may require substantial preparation. In many cases, a step-down unit or rehabilitation facility is an intermediate step before discharge home. (See "Discharge planning for high-risk newborns", section on 'Neonatal discharge planning'.)

Discharge criteria for oxygenation include having a stable oxygen requirement with mean pulse oximetry measurements of 95 percent or greater and without frequent episodes of desaturation. At discharge, cardiorespiratory parameters (respiratory and heart rate, blood pressure, oxygen requirement, chest radiograph, and most recent echocardiogram to assess for pulmonary hypertension) should be communicated to the primary care provider responsible for the care of the infant.

Training of the parents (or the individual who will be the primary care provider) is important. Prior to discharge, the parents need to demonstrate competency in the daily care of their infant, ability to recognize signs of respiratory distress and acute illnesses, and in some cases, the skills needed for complex medical care (use of medical equipment, tracheostomy care, and drug administration). Parents and other potential caregivers should learn cardiopulmonary resuscitation. Arrangements should be made for the necessary equipment for home care and nursing support, if needed. Education of the parents about the use of this equipment should begin well before anticipated discharge. (See "Discharge planning for high-risk newborns", section on 'Family discharge planning'.)

Care — As is true for all infants discharged from the neonatal intensive care unit (NICU), comprehensive continuity of care that addresses the needs of the NICU graduates and their families is required. The neonatal team should communicate to the identified primary care provider who will be responsible for the medical management of the infant after discharge. In some cases, this includes ongoing care by a subspecialist (eg, infants with pulmonary hypertension or tracheostomy) and other health care professionals.

The initial visit is scheduled within 48 to 72 hours after discharge from the hospital, during which the infant's hospital course is reviewed, current medical status is evaluated, and parental/caregiver questions and concerns are addressed. (See "Care of the neonatal intensive care unit graduate", section on 'Role of the primary care provider' and "Care of the neonatal intensive care unit graduate", section on 'Initial visit' and "Pulmonary hypertension associated with bronchopulmonary dysplasia", section on 'Management after hospital discharge'.)

Subsequent visits focus on routine primary care (eg, immunization and growth), general care targeted for NICU graduates (ie, hearing, vision, and neurodevelopment screening), and specific management issues for infants with BPD [13]. These include prevention of respiratory syncytial virus (RSV) infection, ongoing assessment for pulmonary hypertension, and management of chronic complications, including systemic hypertension. (See "Care of the neonatal intensive care unit graduate" and "Care of the neonatal intensive care unit graduate", section on 'Subsequent visits'.)

Prevention of RSV infection — Severe respiratory failure may occur in patients with BPD who develop infection with respiratory syncytial virus (RSV). Prophylaxis should be provided with palivizumab for infants younger than two years of age who have required medical therapy for BPD within six months of the RSV season. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Palivizumab immunoprophylaxis'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchopulmonary dysplasia".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Bronchopulmonary dysplasia (The Basics)")

SUMMARY AND RECOMMENDATIONS — The management goals for infants with established BPD entail promotion of growth to enhance lung development and repair, minimization of further lung damage, optimization of lung function with improved gas exchange, and detection and management of acute pulmonary decompensations and complications. (See 'Approach to BPD management' above.)

●During birth hospitalization, general measures for all patients with established BPD include adequate nutrition to promote growth, modest fluid restriction, and screening for complications associated with BPD. (See 'General measures' above.)

•Dietary management includes monitoring of growth and revision of dietary intake to ensure adequate caloric intake for growth based upon growth and laboratory evaluation. Fortified human milk is used whenever possible because of the intrinsic benefits of human milk. (See 'Nutrition' above and "Infant benefits of breastfeeding".)

•Fluid intake restriction is thought to enhance pulmonary function by preventing excess pulmonary fluid (eg, pulmonary edema), thereby improving air-gas exchange. For infants with BPD, we suggest modest fluid restriction of 140 to 150 mL/kg per day (Grade 2C). In some cases, caloric density of feeds may need to be increased to maintain fluid restriction. (See 'Fluid restriction' above.)

•Screening includes weekly blood pressure measurements, neurodevelopmental screening, and echocardiographic assess for pulmonary arterial hypertension (PAH). (See 'Screening' above.)

●Administration of other interventions are primarily reserved for patients with severe disease who typically require mechanical ventilation and/or fraction of inspired oxygen (FiO₂) >0.30. (See 'Approach to BPD management' above.)

●In patients who require mechanical ventilation (see 'Respiratory support' above):

•We suggest the use of low tidal volumes (4 to 6 mL/kg) to minimize mechanical pulmonary injury (Grade 2C).

•We suggest allowing for mild permissive hypercapnia targeting partial pressure of carbon dioxide (PaCO₂) between 55 and 65 mmHg as long as pH remains in the normal range (ie, 7.3 to 7.4) versus targeting for normal values of PaCO₂ (Grade 2C).

•We suggest using a positive end-expiratory pressure (PEEP) between 5 to 7 cm H₂O to minimize atelectasis and reduce the risk of pulmonary edema (Grade 2C).

•Targeted oxygen saturation based upon pulse oximetry (SpO₂) is set initially between 90 and 95 percent to avoid hypoxemia and exposure to excess oxygen, which is associated with retinopathy of prematurity. As the preterm infants reach term age, target SpO₂ is increase to 100 percent as the infant achieves term age. (See 'Oxygen' above and "Neonatal target oxygen levels for preterm infants", section on 'High versus low SpO2 targets'.)

•During hospitalization, oxygen saturation is monitored continuously by pulse oximetry and ventilation by intermittent blood gas sampling (eg, PaCO₂ and pH).

●We suggest not using chronic routine diuretic therapy in all patients with BPD (Grade 2C). We reserve chronic diuretic therapy for patients who are ventilator-dependent or receive positive airway pressure (PAP) despite modest fluid restriction. In these patients, we start with a thiazide rather than a loop diuretic because of the increased risk of complications associated with loop diuretics. We use loop diuretics (eg, furosemide) intermittently in episodes of acute pulmonary decompensation and during blood transfusions, and on a longer-term basis in ventilator-dependent or PAP-dependent patients who fail to respond to fluid restriction and thiazide diuretics. (See 'Diuretics' above.)

●We suggest not using routine administration of bronchodilators (Grade 2B). Bronchodilators are reserved for episodes of acute pulmonary decompensation due to severe airway reactivity for infants with severe BPD. (See 'Bronchodilators' above and 'Acute exacerbations' above.)

●We suggest not using routine systemic glucocorticoid therapy due to concerns of adverse side effects (Grade 2C). We reserve this treatment for the infant with severe BPD who cannot be weaned from mechanical ventilation and/or receives oxygen supplementation >50 percent. (See 'Corticosteroids' above and "Prevention of bronchopulmonary dysplasia: Postnatal use of corticosteroids", section on 'Systemic corticosteroids'.)

●We suggest not using routine inhaled glucocorticoid therapy (Grade 2C). We use this as short-term therapy only in ventilator-dependent patients who require high oxygen and have signs of airway obstruction or reactive airway disease. (See 'Corticosteroids' above.)

●Infants with BPD may have acute episodes of pulmonary decompensation due to infections, severe airway reactivity, pulmonary air leak, pulmonary edema, displacement of endotracheal tube in ventilator-dependent patients, or large airway collapse (tracheobronchomalacia). Management of these exacerbations is dependent upon the underlying etiology. (See 'Acute exacerbations' above.)

●Assessing for complications of BPD includes monitoring for PAH, systemic hypertension, left ventricular hypertrophy, and neurodevelopmental impairment. (See 'Complications' above.)

●Infants with moderate to severe BPD typically have a prolonged and complicated birth hospitalization, and require considerable supportive management after discharge to home. Optimal discharge planning is provided by a multidisciplinary team that regularly monitor the patient's clinical course, reviews and refines goals and criteria, and ensures continuity of care following discharge by identifying and communication with a designated primary care provider. (See 'Post-discharge' above and "Discharge planning for high-risk newborns".)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge James Adams, Jr., MD, who contributed to an earlier version of this topic review.