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Ppt bpd

  1. 1. Bronchopulmonary dysplasia( chronic lung disease) Dr prathik
  2. 2. <ul><li>First defined by northway in 1967 </li></ul><ul><li>Incidence </li></ul><ul><li>In 1970 s----30-40% of neonates who received mechanical ventilation </li></ul><ul><li>Recently incidence is increased – increased survival of VLBW babies </li></ul><ul><li>Acc to NICHD database(2003) incidence is about </li></ul><ul><li>< 1000 grams---23.2% </li></ul><ul><li>1000-1249 g---8.4% </li></ul><ul><li>1250-1499 g---5.4% </li></ul>
  3. 3. <ul><li>No indian database </li></ul><ul><li>Study from PGI </li></ul><ul><li>< 1000 grams---50% </li></ul><ul><li>1000-1249 g---8.1% </li></ul><ul><li>1250-1499 g---2.3% </li></ul>
  4. 4. DEFINITION <ul><li>Initially defined as continous oxygen dependency for first 28 days with compatible clinical and radiologic findings </li></ul><ul><li>Bronchopulmonary dysplasia:clinicalpresentation. J Pediatr 1979 </li></ul><ul><li>Later, it was proposed to use the need for supplemental oxygen at 36 weeks postmenstrual age (PMA) as the diagnostic criterion especially in preterm very low birth weight (VLBW) infants </li></ul><ul><li>Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988 </li></ul>
  5. 5. NIH DEFINITION < 32 weeks > 32 weeks Time point of assessment 36 weeks PMA or discharge* > 28 days but < 56 days postnatal age or discharge* Treatment with oxygen > 21% for at least 28 days > 21% for at least 28 days Mild Breathing room air at 36 weeks PMA or discharge Breathing room air at 56 days postnatal age or discharge* Moderate Need for <30% oxygen at 36 weeks PMA or discharge Need* for <30% oxygen at 56 days postnatal age or discharge Severe Need for > 30% oxygen and/or positive pressure (IMV/CPAP) at 36 weeks PMA or discharge Need for > 30% oxygen and/or positive pressure (IMV/CPAP) at 56 days postnatal age or discharge
  6. 6. Etiology <ul><li>Multifactorial </li></ul><ul><li>The major risk factors include </li></ul><ul><li>prematurity </li></ul><ul><li>oxygen therapy, </li></ul><ul><li>mechanical ventilation, </li></ul><ul><li>infection( u urealyticum) </li></ul><ul><li>patent ductus arteriosus (PDA) </li></ul><ul><li>Excessive early intravenous fluid administration </li></ul>
  7. 7. <ul><li>genetic predisposition ( inadequate activity of antioxidant enzymes sod, catalase, glutathione peroxidase and ceruloplasmin --- predisposes to o2 toxicity) </li></ul><ul><li>Familial airway hyperreactivity </li></ul><ul><li>Increased inositol clearance </li></ul>
  8. 8. pathogenesis <ul><li>The most important factor in the pathogenesis of CLD is prematurity </li></ul><ul><li>Exposure of immature lungs to high O2 concentrations and positive pressure ventilation results in oxidative stress and ventilator induced lung injury (barotrauma/volutruma) </li></ul>
  9. 9. Infection <ul><li>Intrauterine infection (chorioamnionitis) </li></ul><ul><li>Inflammatory cytokines(IL-1,IL6 and TNF alfa) </li></ul><ul><li>Lung injury and arrest of lung growth </li></ul>
  10. 10. <ul><li>U urealyticum is most commonly implicated </li></ul><ul><li>Several large clinical studies have found a strong correlation between the presence of BPD and the development of late-onset sepsis, usually with organisms such as staphylococcus epidermidis </li></ul>
  11. 11. Barotrauma/Volutrauma <ul><li>The most immediate and frequent cause of BPD is the lung injury imposed by mechanical ventilatory support. </li></ul><ul><li>positive-pressure mechanical ventilation </li></ul><ul><li>Immature lung </li></ul><ul><li>Surfactant def </li></ul><ul><li>Injury to endothelium </li></ul>
  12. 12. <ul><li>increased permaebility of serum protiens </li></ul><ul><li>Inhibition of surfactant </li></ul><ul><li>Increased surface tension, unequal areation, collapse of alveoli </li></ul><ul><li>Increased pressure to distend saccules->lung injury, PIP ,pneumothorax. </li></ul>
  13. 13. <ul><li>Studies have shown that overdistension of the lung (not increased pressure) is responsible for lung injury in the surfactant-deficient lung </li></ul><ul><li>volutrauma and not barotrauma is the primary determinant of VILI. </li></ul>
  14. 15. Inflammation <ul><li>oxygen free radicals, pulmonary barotrauma, infectious agents </li></ul><ul><li>attraction and activation of leukocytes. </li></ul><ul><li>excessive oxygen free radicals ,tumour necrosis factor, interleukin-1, interleukin-8 (IL-8), and transforming growth factor (TGF)-1 </li></ul><ul><li>breakdown of capillary endothelial integrity and leakage of macromolecules (e.g., albumin) into alveolar spaces. </li></ul>
  15. 16. <ul><li>Albumin leakage and pulmonary edema inhibit surfactant function </li></ul><ul><li>The release of elastase and collagenase from activated neutrophils directly destroys the elastin and collagen framework of the lung. </li></ul>
  16. 17. Genetics <ul><li>neonates were more likely to develop BPD if there was a strong family history of atopy and asthma </li></ul><ul><li>Nickerson found a positive family history of asthma in 77% of infants with RDS who subsequently developed BPD, compared with only 33% who did not . </li></ul><ul><li>Clark and associates found that only infants with HLA-A2 developed BPD. </li></ul>
  17. 18. Clinical and radiologic features <ul><li>Respiratory signs in infants with CLD include fast but shallow breathing, retractions, and paradoxical breathing. Rales and coarse rhonchi are usually heard on auscultation </li></ul><ul><li>Old BPD, as originally described by Northway, had four distinct stages: </li></ul>
  18. 19. Stage I <ul><li>Hyaline membrane. </li></ul><ul><li>Alveolar and interstitial oedema. </li></ul><ul><li>Necrosis of bronchial mucosa. </li></ul>
  19. 20. Stage II <ul><li>Areas of emphysema </li></ul><ul><li>Atelectasis </li></ul><ul><li>Areas of necrosis and repair of bronchial mucosa . </li></ul>
  20. 21. Stage III <ul><li>Cystic areas with hyperinflation. </li></ul><ul><li>Bronchial metaplasia and hyperplasia. </li></ul><ul><li>Interstitial oedema. </li></ul>
  21. 22. Stage IV <ul><li>Hyperinflation, </li></ul><ul><li>Interstitial streak densities </li></ul><ul><li>Flatter chest </li></ul>
  22. 23. <ul><li>Infants with new BPD show only haziness reflecting diffuse loss of lung volume or increased lung fluid. </li></ul><ul><li>Occasionally they have dense areas of segmental or lobar atelectasis or pneumonic infiltrates, but they do not show severe over inflation. </li></ul>
  23. 24. Old vs New BPD <ul><li>OLD BPD is seen in infants who received aggressive ventilation and were exposed to high inspired oxygen concentration from birth </li></ul><ul><li>emphysema, atelectasis and fibrosis, and marked epithelial metaplasia and smooth muscle hypertrophy in the airways and in the pulmonary vasculature. </li></ul>
  24. 25. <ul><li>NEW BPD occurs in infants who had only mild respiratory failure requiring shorter duration of ventilation and or oxygen therapy immediately after birth. </li></ul><ul><li>Seen in VLBW infants, earlier stages of gestation , before alveolarization has been completed and associated with antenatal infection. </li></ul><ul><li>Due to ARREST IN ALVEOLAR DEVELOPMENT </li></ul>
  25. 26. Histo-Pathologic characteristics of the ‘New BPD’ <ul><li>Decreased, large and simplified alveoli (alveolar hypoplasia) </li></ul><ul><li>Decreased number and dysmorphic capillaries </li></ul><ul><li>Variable interstitial fibroproliferation </li></ul><ul><li>Negligible airway epithelial lesions </li></ul><ul><li>Variable airway smooth muscle hyperplasia </li></ul>
  26. 27. Prevention of BPD <ul><li>BEFORE BIRTH </li></ul><ul><li>Prenatal antibiotics and infection prevention </li></ul><ul><li>Prompt treatment of chorioamnionitis with antibiotics. </li></ul>
  27. 28. Prevention of bpd <ul><li>Antenatal steroids </li></ul><ul><li>Use of antenatal steroids in mothers at risk for delivering a premature infant reduces the incidence of neonatal deaths and RDS but does not reduce the incidence of CLD. </li></ul><ul><li>Antenatal thyrotropin-releasing hormone (TRH) has not been effective in prevention of BPD. </li></ul><ul><li>Cochrane Database Syst Rev 2004; </li></ul>
  28. 29. Practices in delivery room <ul><li>The goal in babies being resuscitated at birth,whether born at term or preterm, should be an oxygen saturation value in the interquartile range of preductal saturations </li></ul><ul><li>These targets may be achieved by initiating resuscitation with air or a blended oxygen and titrating the oxygen concentration to achieve an SpO2 in the target range using pulse oximetry </li></ul><ul><li>If blended oxygen is not available, resuscitation should be initiated with air </li></ul><ul><li>If the baby is bradycardic (HR 60 per minute) after 90 seconds of resuscitation------ increase to 100 % o2. </li></ul><ul><li>Use lower target inflation pressure range between 20- 25 cm h2o </li></ul>
  29. 30. Ventilatory strategies <ul><li>Continuous positive airway pressure (CPAP ): </li></ul><ul><li>Early initiation of nasal CPAP has been shown to reduce the need for intubation and mechanical ventilation </li></ul>
  30. 31. Nasal intermittent positive pressure ventilation (NIPPV) <ul><li>NIPPV is a method of augmenting NCPAP by delivering ventilator breaths via the nasal prongs. </li></ul><ul><li>Improves the tidal and minute volumes and decrease the inspiratory effort required by neonates as compared to nCPAP </li></ul><ul><li>The Cochrane review that included three RCTs found a trend towards reduction in rates of chronic lung disease. </li></ul><ul><li>Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database of Systematic Reviews </li></ul>
  31. 32. Patient-triggered ventilation (PTV): <ul><li>Patient triggered modes (SIMV, assist-control, and pressure support ventilation) improve the infant-ventilator asynchrony. </li></ul><ul><li>The Cochrane review concluded that though PTV is associated with shorter duration of ventilation, it does not reduce the incidence of BPD. </li></ul><ul><li>Synchronized mechanicalventilation for respiratory support in newborn infants. Cochrane Database of SystematicReviews2008 </li></ul>
  32. 33. High-frequency ventilation (HFV): <ul><li>Animal studies indicate that HFV could lead to less lung injury when compared to conventional ventilation </li></ul><ul><li>A recent meta-analysis that included 17 RCTs of conventional versus high frequency ventilation found no significant difference in the incidence of BPD </li></ul><ul><li>Ventilation strategies and outcome in Randomised Trials of High Frequency Ventilation Arch Dis Child. 2005 </li></ul>
  33. 34. Volume targeted ventilation <ul><li>The Cochrane review that included four RCTs found significant reduction in the duration of ventilation and pneumothorax rates but only a borderline reduction in the incidence of BPD. </li></ul><ul><li>Volume-targeted versus pressure-limited ventilation in the neonate. Cochrane Database of Systematic Reviews 2005 </li></ul>
  34. 35. <ul><li>PERMISSIVE HYPERCAPNIA : </li></ul><ul><li>Hypocapnia that occurs during assisted ventilation is an independent risk factor for BPD </li></ul><ul><li>Co2 targets of 45-55 mm hg are now recommended in order to reduce the days of ventilation. </li></ul>
  35. 36. <ul><li>Permissive hypoxemia: A ccepting lower oxygen saturation values is associated with decreased incidences of CLD and ROP </li></ul><ul><li>BOOST-trial and STOP-ROP trial indicate that maintaining higher oxygen saturation (>95%) is associated with increased need for oxygen at 36 weeks PMA and greater use of postnatal steroids and diuretics in premature infants (when compared to maintaining lower oxygen saturation of 89-94%). </li></ul><ul><li>Spo2 b/w 85-93% ---- < 32 wks </li></ul><ul><li>87-94%---->32 wks </li></ul>
  36. 37. Fluid restriction <ul><li>The systematic review of studies on fluid restriction has not found any significant reduction in the incidence of BPD </li></ul><ul><li>The amount of fluid restriction in VLBW infants is not definitely known. </li></ul><ul><li>Fluid restriction for treatment of preterm babies with chronic lung disease. (Protocol) Cochrane Database of Systematic Reviews 2005; </li></ul>
  37. 38. Nutrition <ul><li>Aggressive parenteral nutrition and early enteral feeding decreases the incidence of BPD in VLBW infants </li></ul><ul><li>( The role of nutrition in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 2006 ) </li></ul><ul><li>Enteral feeding is often delayed in these infants due to gastrointestinal immaturity, parenteral nutrition with proteins and lipids should be initiated as soon as possible after birth. </li></ul><ul><li>. </li></ul>
  38. 39. <ul><li>Metabolic rate and energy expenditure are elevated in BPD </li></ul><ul><li>Infants developing BPD require 20 to 40% more calories than their age-matched healthy controls . </li></ul><ul><li>caloric requirement varies from 120 to 150 Kcal/kg/day </li></ul><ul><li>More calories– lipids( mct oil)> carbohydrates, lowers respiratory quotient and decreases co2 production. </li></ul>
  39. 40. <ul><li>When enteral feeding is started --- give only EBM. </li></ul><ul><li>Addition of HMF will also increase the calories and make up the deficiencies of protiens and minerals. </li></ul><ul><li>Mct oil and glucose polymers can also be added. </li></ul>
  40. 41. Pharmacological strategies <ul><li>Exogenous surfactant </li></ul><ul><li>Prophylactic surfactant therapy in infants born before 30 weeks of gestation has not been shown to reduce the incidence of BPD. However, surfactant treatment for established RDS ( ‘rescue therapy’) in infants born at or after 30 weeks of gestation is associated with significant reduction in the incidence of BPD </li></ul><ul><li>American Academy of Pediatrics Committee on Fetus and Newborn.Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics 2008; </li></ul>
  41. 43. Role of vit A <ul><li>Vitamin A ---integrity of respiratory tract epithelial cells. </li></ul><ul><li>Very preterm infants are relatively deficient in vitamin A which has been shown to associated with CLD. </li></ul><ul><li>large dose of intramuscular vitamin A (5000 units three times a week for 4 weeks from birth) decreases the incidence of CLD. </li></ul><ul><li>(Cochrane Database Syst Rev 2007) </li></ul><ul><li>All ELBW infants with respiratory distress requiring supplemental oxygen or mechanical ventilation at 24 hours of age should recieve vit A </li></ul><ul><li>Vit E – antoxidant, no role in prevention of bpd </li></ul>
  42. 44. <ul><li>Role of superoxide dismutase : </li></ul><ul><li>sod antioxidant --eliminates the free radicles </li></ul><ul><li>Preterms – deficient in antioxidant enzymes and sucesptible to oxidant injury. </li></ul><ul><li>A RCT enrolled around 300 infants proved the safe nature of the drug CuZnSOD, </li></ul><ul><li>But did not find any difference in the primary outcome of BPD at 36 weeks PMA. </li></ul>
  43. 45. <ul><li>SOD treated infants-- fewer episodes of respiratory illness at I year of age. </li></ul><ul><li>Cochrane review on this subject conclude that “The use of superoxide dismutase to prevent chronic lung disease of prematurity is not recommended” </li></ul>
  44. 46. Methylxanthines <ul><li>caffeine – reduced incidence of BPD . </li></ul><ul><li>In a multicenter trial , infants < 1,250 g who received caffeine had lower BPD rates than infants who did not receive it. </li></ul><ul><li>Duration of ventilaton, need for CPAP, and supplemental oxygen were reduced by caffeine administration. </li></ul><ul><li>( Adjunctive therapies in chronic lung disease:examining the evidence. Semin Fetal Neonatal Med 2008) </li></ul>
  45. 47. <ul><li>Another large RCT that used caffeine for these indications in infants with birth weights of 500-1250g has shown a significant decrease in the incidence of BPD. </li></ul><ul><li>Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnoea of prematurity. N Engl J Med 2006 </li></ul><ul><li>The authors attributed this rather unexpected finding to reduced duration of mechanical ventilation in the caffeine treated group </li></ul>
  46. 48. Indomethacin / Ibuprofen therapy for PDA: <ul><li>Patent ductus arteriosus is one of the major risk factors for BPD. </li></ul><ul><li>prevention or treatment of PDA should ideally reduce its risk. </li></ul><ul><li>However, prophylactic use of indomethacin in very low birth weight infants has failed to show any reduction in the incidence of BPD despite a significant reduction in the incidence of PDA </li></ul><ul><li>(Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001) </li></ul>
  47. 49. <ul><li>Similar results are obtained with ibufrofen. </li></ul><ul><li>Treatment of symptomatic PDA could possibly reduce the incidence of BPD . </li></ul><ul><li>Recommendations for the postnatal use of indomethacin: an analysis of four </li></ul><ul><li>separate treatment strategies. J Pediatr. 1996 </li></ul>
  48. 50. ROLE OF STEROIDS <ul><li>inflammation ----pathogenesis of BPD </li></ul><ul><li>Early : During the first 96 hrs after birth </li></ul><ul><li>Moderately early :Between postnatal days 7 and 14. </li></ul><ul><li>Delayed :After 3 weeks of age </li></ul><ul><li>Most commonly used steroid is :dexamethasone </li></ul><ul><li>AMERICAN ACADEMY OF PEDIATRICS Committee on Fetus and Newborn </li></ul>
  49. 51. Systemic Early Postnatal Corticosteroid Therapy <96 Hours <ul><li>preterm, respiratory distress syndrome, and required mechanical ventilation with oxygen at the time of enrollment </li></ul><ul><li>Corticosteroids (dexamethasone)intravenously within 96 hours after birth. </li></ul><ul><li>The most commonly used dosages were 0.5 mg/kg of body weight per day for 3 days, followed by a tapering course </li></ul>
  50. 52. <ul><li>The combined outcome of death or CLD at 28 days PNA or at 36 weeks’PMA was significantly decreased by early corticosteroid treatment </li></ul><ul><li>Weaning from mechanical ventilation was more successful in infants treated with dexamethasone. </li></ul><ul><li>incidences of hypertension, hyperglycemia, insulin therapy for hyperglycemia, gastrointestinal bleeding or perforation, and hypertrophic obstructive cardiomyopathy were increased by early corticosteroid treatment. </li></ul><ul><li>Borderline increased risk of PVL in steroid group </li></ul>
  51. 53. Moderately Early Postnatal Corticosteroid Therapy (7–14 Days PNA) <ul><li>The combined outcome of death or CLD was decreased at 28 days’ PNA and at 36 weeks’ PMA. </li></ul><ul><li>There was increase in incidence of hyperglycemia, gastrointestinal bleeding, hypertrophic obstructive cardiomyopathy, and infection. </li></ul><ul><li>AMERICAN ACADEMY OF PEDIATRICS Committee on Fetus and Newborn </li></ul>
  52. 54. Systemic Delayed Postnatal Corticosteroid Therapy (>3 Weeks) <ul><li>The incidence of CLD at 36 wks PMA was decreased by steroid therapy. </li></ul><ul><li>Same side effects. </li></ul><ul><li>AMERICAN ACADEMY OF PEDIATRICS Committee on Fetus and Newborn </li></ul>
  53. 55. <ul><li>The use of inhaled steroids, as well as the use of systemic steroids cannot be recommended as a part of standard practice for ventilated preterm infants to prevent CLD </li></ul><ul><li>( Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm Neonates Cochrane Database of Systematic Reviews 2008) </li></ul>
  54. 56. Inhaled nitric oxide <ul><li>pulmonary vasodilatation ,reduces lung inflammation and promotes lung growth </li></ul><ul><li>iNO as rescue therapy for the very ill preterm infant does not appear to be effective. </li></ul><ul><li>Early routine use of iNO in preterm infants with respiratory disease does not improve survival without BPD </li></ul><ul><li>Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database of Systematic Reviews 2010, Issue 12 </li></ul>
  55. 57. Diuretic therapy: <ul><li>MOA: decreases interstitial and peribronchial fuid--- dec resistance and improves compliance </li></ul><ul><li>Response: acute response – 1 hr, max clinical response– 1 wk </li></ul><ul><li>Indication: clinical/radiographic features of pulmonary edema in an infant with evolving or established BPD Pharmacological strategies in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 2006 </li></ul>
  56. 58. <ul><li>Dose: 0.5-1 mg/kg, stop after 24- 48 hours if no improvement in clinical condition. </li></ul><ul><li>no effects on mortality or the incidence of BPD </li></ul>
  57. 59. Mast cell stabilizers <ul><li>Cromolyn sodium </li></ul><ul><li>decrease neutrophil migration and activation ----minimizes inflammation in the lungs </li></ul><ul><li>Dose: 10-20 mg 6-8 hr , nebulization. </li></ul><ul><li>2 trials– no benefit in prevention and treatment. </li></ul><ul><li>Cromolyn sodium for the prevention of chronic lung disease in preterm infants. Cochrane Database Syst Rev. 2001 </li></ul>
  58. 60. Associted complications <ul><li>Cor pulmonale </li></ul><ul><li>Systemic hypertension </li></ul><ul><li>Systemic to pulmonary shunting </li></ul><ul><li>Metabolic imbalance– sec to diuretics </li></ul><ul><li>Infection-- urealasma and mycoplasma----rx with erythromycin </li></ul><ul><li>Viral infections and fungal infections are also common </li></ul>
  59. 61. <ul><li>Cns dysfunction: a neurologic syndrome presenting with EPS signs has been described </li></ul><ul><li>Hearing loss </li></ul><ul><li>ROP </li></ul><ul><li>Nephrocalcinosis </li></ul><ul><li>Growth failure </li></ul>
  60. 62. Discharge planning <ul><li>Spo2 maintained > 92-94% </li></ul><ul><li>No significant period of desaturation during feeding or sleep </li></ul><ul><li>Good weight gain </li></ul><ul><li>Stable respiratory status </li></ul>
  61. 63. Immmunization <ul><li>In addition to standard immunization , infants with CLD should receive penumocoocal, influenza and palivizumab </li></ul><ul><li>AAP RECOMMENDATIONS FOR PALIVIZUMAB </li></ul><ul><li>Administer monthly beginning in early november for 5 months </li></ul><ul><li>Dose: 15mg/kg IM </li></ul>
  62. 64. OUTCOME <ul><li>MORTALITY: 10-20% in first year of life (infection) </li></ul><ul><li>Morbidity: increased risk of reactive airway disease , bronchiolitis and pneumonia </li></ul><ul><li>Rehospitalization rate is twice that of matched controls in first 2 yr of life </li></ul><ul><li>Growth failure: delayed growth in 1/3 to 2/3 of these infants at 2 years. </li></ul>