Bronchopulmonary Dysplasia is chronic lung disease ,it is categorised into mild, moderate,severe based upon the condition

Bronchopulmonary Dysplasia in paediatric studies

1. Bronchopulmonary Dysplasia (BPD) Dr.A.Sagar PG 1 st year Moderator: Dr.keziah mam

2. Definition Bronchopulmonary dysplasia is a pathologic process leading to signs and symptoms of chronic lung disease that originates in the neonatal period. The currently accepted definition includes an oxygen requirement for 28 days postnatally and the disorder is graded as mild, moderate or severe on the basis of supplemental oxygen requirement and gestational age.

3. Mild BPD : Infants who have been weaned from any supplemental oxygen. Moderate BPD : Infants who continue to need upto 30% oxygen (2-3L/min). Severe BPD : Infants whose requirements exceed 30% oxygen (2-3L/min) and/or include continuous positive airway pressure or mechanical ventilation.

4. Etiology The etiology of BPD is multifactorial and affects both the lungs and the heart. Prematurity. Atelectrauma & Volutraum. Prolonged oxygen exposure. Pulmonary interstitial emphysema. Chorioamnionitis.

5. Sepsis. Symptomatic PDA. Malnutrition. Vitamin-A deficiency. Fluid overload. Family history of atopy or asthma.

6. Pathophysiology BPD is a multifactorial disease caused by a combination of antenatal and postnatal factors leading to arrested lung development inflammation,and injury. Antenatal Factors: Intrauterine events affect lung growth even before birth. Infection/Cytokines cause inflammation and damage to developing lungs. Antenatal glucocorticoids may help lung maturation,but imbalance can affect alveolar growth. Intrauterine growth restriction/ poor nutrition leads to impaired alveolar and vascular development.

7. 2. Perinatal and Postnatal Factors : Initiation of ventilation (mechanical ventilation, oxygen exposure)Cause barotrauma/ volutraum (injury from high pressure and volume).Leads to oxidative stress and free radical damage due to high oxygen. Inflammation – Inflammatory cells and Cytokines are activated, worsening lung injury. Over distension – Positive pressure ventilation stretches immature alveoli leads to alveolar rupture, air leaks, pulmonary interstitial emphysema). Infection - both prenatal and Postnatal infections worsen lung damage.

8. 3. Arrested Lung Development : In BPD injury inflammation of normal sequence of saccular to alveolar stage of lung development leads to interruption of alveolarisaication. This results fewer large alveoli with abnormal vascular growth leads to impaired gas exchange. Chronic lung disease with alveolar hypoplasia, vascular remodelling, fibrosis and impaired lung function.

9. These changes lead to abnormalities of lung function, the most important of which includes- Interstitial oedema. Increased work of breathing. Reactive airway disease and Pulmonary hypertension.

10. Pathophysiology

11. Pulmonary pathophysiologic changes in infants with BPD : Decreased pulmonary compliance. Increased pulmonary resistance. Tracheobronchial airflow abnormalities. Increased work of breathing. Air trapping and lung volume changes. Reactive airway disease. Pulmonary hypertension. Interstitial oedema.

12. Clinical presentation : Infants affected are usually immature and have very low birth weight . The most common clinical scenario is of a 23-26-weeks of gestation baby who over a period of 4-10 weeks progresses from needing ventilation to CPAP through to requiring supplemental oxygen. Most babies have initial RDS and require respiratory support in the form of ventilation or CPAP.

13. They respond well to initial surfactant and ventilation, with improvement in the respiratory distress. However, in some there may be an increase in their oxygen and ventilatory requirements in the first two weeks of life. This dependence on respiratory support tends to continue and, although many will come off the ventilator or CPAP, the oxygen dependence continues .

14. Many of these babies will continue to have tachypnea, tachycardia and signs of respiratory distress, such as intercostal recession and nasal flaring. Bronchial hyper-reactivity and wheezing can also occur. Some babies can develop pulmonary hypertension.

15. Diagnosis Diagnostic criteria : Gestational age <32 wks >32 wks Time point of assessment 36 wk postmenstrual age or discharge home, whichever comes first. >28 days but <56 days postnatal age or discharge home, whichever comes first. Treatment with oxygen >21% for at least 28 days >21% for at least 28 days Mild BPD Breathing room air at 36 wk PMA or discharge home, whichever comes first. Breathing room air by 56 days PNA or discharge home, whichever comes first. Moderate BPD Need for <30% oxygen at 36 wk PMA or discharge home, whichever comes first. Need for <30% oxygen at 56 days PNA or discharge home, whichever comes first. Severe BPD Need for >30% oxygen and/or positive pressure ventilation at 36 wk PMA or discharge home, whichever comes first. Need for >30% oxygen and/or positive pressure ventilation at 56 days PNA or discharge home, whichever comes first.

16. (B) Physical Examination: Tachypnea . Intercostal retractions. Mouth breathing. Diffuse fine rales on auscultation. Wheezing or prolongation of expiration may also be present.

17. (C) Laboratory Studies: Arterial blood gas analysis : Arterial blood gases may show acidosis, hypercapnea and relative hypoxia (for the inspired oxygen concentration). Serum electrolytes : Abnormalities of electrolytes may reveal from chronic CO2 retention (Increased serum HCO3), Diuretics therapy (Hyponatremia, Hypokalemia), or fluid restriction (Increased serum creatinine) or all 3.

18. Complete blood count : To diagnose neutropenia or increased WBC count in sepsis. Urinalysis : Microscopic examination may reveal the presence of RBC indicating a possible nephrocalcinosis as a result of prolonged diuretics therapy.

19. (D) Imaging & Other Studies : Chest X-ray : Shows streaky interstitial markings, patchy atelectasis intermingled with cystic area and severe overall lung hyperinflation.

20. Figure : Bronchopulmonary Dysplasia

21. More recently, Computerised Tomography (CT) scanning has provided insights into the pathophysiology of BPD. Electrocardiography & Echocardiography : Indicated in non-improving and worsening BPD. ECG and Echo could detect cor pulmonale and/or pulmonary hypertension, manifested by pulmonary artery pressure with right axis elevation, thickening of right ventricular wall.

22. Management : Prevention of BPD : Prevention of prematurity and RDS by delaying delivery beyond 30 wks would decrease BPD by 75% and antenatal corticosteroid. Reducing exposure to risk factors : Minimizing exposure to oxygen by limiting SPO2 to 90-95%. Ventilation strategies that minimize the use of excessive tidal volume.

23. Fluid restriction. Aggressive closure of PDA. Adequate nutrition. Vitamin A supplementation : 5000 IU administered intramuscularly 3 times/week for 4 weeks, significantly reduces the rate of BPD. Caffeine : Methylxanthine such as caffeine increase respiratory drive, improve diaphragmatic contractility,

24. decreases the frequency of apnea & allow for shorter duration of mechanical ventilation, leading to a reduced rate of BPD. Inhaled Nitric Oxide : Its use to BPD remains controversial. Animal studies shows reduce pulmonary vascular tone & prevent lung inflammation. Recent studies have not shown inhaled nitric oxide to be effective in preventing BPD.

25. (B) Treatment of BPD : Once BPD is present, the goal of management is to prevent further lung injury by- Minimizing respiratory support. Improving pulmonary function. Preventing cor pulmonale. Emphasizing growth & nutrition.

26. Respiratory support: Supplemental oxygen : Reduction of FiO2 as early as possible to avoid oxygen toxicity, while maintaining PO2 at a level to maintain tissue oxygenation and avoid pulmonary hypertension & cor pulmonale. Maintain PO2 in between 50-70mmHg and saturation in between 90-95%.

27. Nasal CPAP : Nasal CPAP is increasingly used at birth rather than ventilation even for the very preterm babies. A recent randomized controlled trial has shown that 50% of babies of 25-28 weeks of gestation can manage on CPAP without ever requiring intubation and ventilation. There is no increase in risk of death or BPD in this group and they are less likely to be oxygen-dependent at 28 days of age.

28. Mechanical ventilation: If the baby does need intubation and ventilation it is important to minimize ventilation-associated lung injury. Strict monitoring and maintaining of tidal volumes along with use of synchronized ventilation modes is recommended. Use lowest PIP(Peak inspiratory pressure) to deliver adequate tidal volume (3-5ml/kg), short inspiratory time (0.3-0.5 sec), PEEP(Positive end expiratory pressure)(2-6 cm H2O).

29. A Cochrane review has confirmed that early surfactant replacement therapy with extubation to nasal CPAP compared with later selective surfactant administration with continued ventilation is associated with less need for ventilation and lower incidence of BPD.

30. (2) Improving lung function: Fluid restriction : Restricted fluid to 120 ml/kg/d is often required. It can be accomplished by concentrating proprietary formulas to 24 cal/oz. Diuretic therapy : Furosemide and other diuretics such as chlorothiazide and spironolactone are used to treat fluid overload and are effective short-term therapy for ventilated babies.

31. Bronchodilator: Studies have revealed that inhaled bronchodilators, most commonly beta-adrenergic agonists, can aid with short-term improvement in lung function and may be helpful to infants who have BPD during acute exacerbations.

32. Corticosteroid: Dexamethasone (corticosteroid) is effective in achieving short-term clinical improvement in ventilated babies as well as reducing the long-term risk of developing BPD. However, there is evidence that its use in the first week of life is associated with an increased risk of short-term adverse effects (gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure) and cerebral palsy.

33. A Cochrane review of postnatal corticosteroid treatment initiated after 7 days of age suggests that late therapy may reduce neonatal mortality without significantly increasing the risk of adverse long-term neurodevelopmental outcome. However, it concludes that the current evidence is limited so the use of late corticosteroids should be reserved for babies who cannot be weaned off the ventilator.

34. (3 ) Growth & Nutrition : Because growth is essential for recovery from BPD, adequate nutritional intake is crucial. Infants with BPD frequently have high calorie needs (120-150 kcal/kg/d or more) because of increased metabolic expenditures. In addition, antioxidant therapy may also enhance pulmonary & nutritional status.

35. ( C) Discharge Planning : Oxygen can often be discontinued before discharge from the neonatal intensive care unit. However, home oxygen therapy can be a safe alternative to a long term hospitalization. The need for home respiratory rate, heart rate & oxygen monitoring must be decided on an individual basis but is generally recommended for infants discharged home on oxygen.

36. Synagis ( Pralivizumab , humanized monoclonal antibodies against respiratory syncytial virus) should be given monthly (15mg/kg administered intramuscularly) throughout the RSV season. All parents should be instructed on cardiopulmonary resuscitation.

37. ( D) General Care : Care plans for older infants with BPD should include adopting their routine for home life and involving the parents in their care. Immunization should be given at the appropriate chronological age. Periodic screening for chemical evidence of Rickets and Echocardiographic evidence of pulmonary hypertension is recommended.

38. Sequelae & Prognosis : There is increased risk of poor neuro -developmental outcome. Infants with birth weight of <1500gm who have BPD have greater language delay as well as increased fine and gross motor impairment. The first two years are the 'danger' period for airways disease. Affected infants can remain oxygen-dependent for many months and frequently require hospital re-admission in the first two years after birth.

39. Chronic respiratory morbidity is a common adverse outcome in preterm infants with BPD. Recurrent respiratory symptoms requiring admission to hospital are common, particularly in those with respiratory syncytial virus (RSV)-associated lower respiratory tract infections (LRTIs). Although pulmonary function improves with age, air flow abnormalities may persist. The most severely affected may remain symptomatic and have evidence of airway obstruction even as adults.

40. Infants with BPD are at an increased risk of developing serious pulmonary infection, particularly due to RSV. There is evidence that use of RSV monoclonal antibody injections (palivizumab) in the winter months reduces the risk of serious infection and hospitalization. Recent study suggests that prophylaxis of RSV infection is cost-effective for the NHS. P alivizumab prophylaxis in preterm infants with BPD during the RSV season. Vaccination against influenza should be considered.

41. Summarizes the steps of preventing and treating BPD in preterm VLBW infants Antenatal period – Antenatal corticosteroids At birth – If resuscitation required, avoid excessive pressure and volume (i.e. avoid excessive chest rise); delay cord clamping and ensure optimal FRC. Birth to 24 hours – Early CPAP, try to avoid intubation If surfactant is to be used, use early surfactant Fluids : 60-80 ml/kg/d Nutrition : Oral feeds- breast milk (MEN/full feeds) to be initiated in stable infants If on ventilator early rescue surfactant and early extubation Settings : Rapid rates(50-60/min), moderate PEEP(4-6cm H2O), Short Ti (0.25-0.4 s). Consider volume targeted ventilation (4-5 ml/kg) Target values – SpO2: 91-95%;PaCO2 45-55 mmHg; pH 7.25-7.35 Use methylxanthines to facilitate extubation

42. 24 hours to 1 week - Fluids: Daily increment of 15 -20ml/kg/d to reach a maximum of 140-150ml/kg/d by day 7. Nutrition : Parenteral: TPN for ELBW infants till full enteral feeds are achieved. Enteral : Gradually increase feed volume by 20-30 ml/kg/d if accepting well: give only breast milk; fortify with HMF after reaching 100 mg/kg/d If on ventilator : Settings and target values as above,extubate to CPAP/NIPPV as early as possible methylamines to facilitate extubation.

43. 2-4 weeks - Fluids :150-160 ml/kg/d Nutrition : Fortify breast milk with HMF; Increase calorie intake to 120-150kcal/kg/d If on ventilator: Settings : PTV mode slow rates (25-40/min), moderate PEEP (4-5 cm H2O), moderate Ti (0.35-0.45 s),low tidal volume (4-6 ml/kg) Target values : SpO2 91-95%,PaCo2 45-55 mm/Hg, pH 7.25-7.35 Steroids : Consider in ELBW infants on ventilator support even after 10-14 days of age Diuretics for features of pulmonary edema Bronchodilators for bronchospasm Diagnose and treat pulmonary hypertension, gastroesophageal reflux .

44. >4 Weeks – Fluids : 150-160 ml/kg/d Nutrition : Fortify breast milk HMF, add more colories of needed If on ventilator : mild / moderate BPD Settings : PTV mode ,slow rates (20-40/min), moderate PEEP (6-8 cm H2O),Ti(0.35-0.45 s), tidal volume (5-8ml/kg), Target values : SpO2 92-98%,PaCO2 45-60 mm Hg ,pH>7.25 Severe chronic BPD Setting : PTV mode ,slow rates (15-30/min),high PEEP ( upto (8-10 cm H2O), longer Ti (0.5-1.0 s),large tidal volume (6-12ml/kg) Target values : SpO2,92-98%,PaCO2 50-60 mm Hg,pH > 7.25 Bronchodilators for bronchospasm Sedation and muscle relaxation for BPD spells Consider sildenafil for established pulmonary arterial hypertension.

45. Conclusion: Advances in neonatal care have resulted in increased rates of survival of extremely premature infants leading to both a new set of management challenges as well as an emerging population of long-term survivors of BPD. Non-invasive ventilation is preferred over invasive ventilation. During invasive ventilation- volume controlled, patient triggered ventilation with moderate PEEP,

46. low tidal volume and and slightly high Ti is used to minimize ventilator induced lung injury. Interdisciplinary care to manage the complex pulmonary, nutritional and developmental needs of these patients is critical and may itself influence outcomes of severe BPD. Subclinical right ventricular dysfunction, obstructive lung disease, exercise intolerance and asthma like symptoms in survivors are frequent and should be evaluated and managed accordingly.

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