Bronchopulmonary Dysplasia(BPD)

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Bronchopulmonary Dysplasia(BPD)

• Kumari Weeratunge M.D.
• PL - 2

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Back ground

• Develops in neonates treated with O2 PPV .
• Originally described by Northway in 1967 using
  clinical , radiographic histologic criteria .
• Bancalari refined definition using ventilation
  criteria , O2 requirement _at_ 28days to keep
  PaO2gt50mmhg abnormalities in chest x ray .

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Back ground

• Shennan proposed in 1988 criteria of O2
  requirement _at_ 36 weeks corrected GA .
• Antenatal steroids , early surfactant Rx gentle
  modes of ventilation minimize severity of lung
  injury .

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Pathophysiology

• Multifactorial
• Major organ systems - lungs heart
• Alveolar stage of lung development - 36wks GA to
  18 months post conception
• Mechanical ventilation O2 interferes with
  alveolar pulmonary vascular development in
  preterm mammals .
• Severe BPD ?Pulmonary HT abnormal pulmonary
  vascular development .

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Stages of BPD

• Defined by Northway in 1967
• Stage 1 - similar to uncomplicated RDS
• Stage 2 - pulmonary parenchymal opacities with
  bubbly appearance of lungs
• Stage 3 4 areas of atelectasis ,
  hyperinflation fibrous sheaths
• Recently CT MRI of chest reveals more details
  of lung injury

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Frequency of BPD

• Dependent on definition used in NICU .
• Using criteria of O2 requirement _at_ 28 days
  frequency range from 17 - 57 .
• Survival of VLBW infants improved with surfactant
  ?Actual prevalence of BPD has increased .

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Mortality/Morbidity of BPD

• Infants with severe BPD?Increased risk of
  pulmonary morbidity mortality within the first
  2 years of life .

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Pulmonary Complications of BPD

• Increased resistance airway reactivity evident
  in early stages of BPD along with increased FRC .
  
• Severe BPD? Significant airway obstruction with
  expiratory flow limitations further increased
  FRC secondary to air trapping hyperinflation

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Volume trauma Barotrauma

• Rx of RDS surfactant replacement , O2 , CPAP
  mechanical ventilation .
• Increased PPV required to recruit all alveoli to
  Px atelectasis in immature lungs?Lung
  injury?Inflammatory cascade .
• Trauma secondary to PPV-?Barotrauma
• Volumetrauma?Lung injury secondary to excess TV
  from increased PPV .

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Volume trauma Barotrauma

• Severity of lung immaturity effects of
  surfactant deficiency ?determines PPV .
• Severe lung immaturity?Alveolar number is
  reduced?increased PP transmitted to distal
  bronchioles .
• Surfactant deficiency?some alveoli collapse while
  others hyper inflate .

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Volume trauma Barotrauma

• Increased PPV to recruit all alveoli?Compliant
  alveoli terminal bronchioles rupture?leaks air
  in to interstium?PIE?Increase risk of BPD
• Using SIMV compared to IMV in infants lt1000g
  showed less BPD .

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O2 Antioxidants

• O2 accept electrons in its outer ring?Form O2
  free radicals?Cell membrane destruction
• Antioxidants(AO)?Antagonise O2 free radicals
• Neonates-Relatively AO deficient
• Major antioxidants super oxide dismutase ,
  glutathione peroxidase catalase

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O2 Antioxidants

• Antioxidant enzyme level increase during last
  trimester .
• Preterm birth?Increased risk of exposure to O2
  free radicals

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Inflammation

• Activation of inflammatory mediators?In acute
  lung injury
• Activation of leukocytes by O2 free radicals ,
  barotrauma infection?Destruction abnormal
  lung repair?Acute lung injury?BPD
• Leukocytes lipid byproducts of cell membrane
  destruction?Activate inflammatory cascade

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Inflammation

• Lipoxigenase cyclooxigenase pathways are
  involved in the inflammatory cascade
• Inflammatory mediators are recovered in tracheal
  aspirate of newly ventilated preterm who later
  develops BPD
• Metabolites of mediators?vasodilatation?increased
  capillary permeability?albumin leakage
  inhibition of surfactant function?risk of
  barotrauma

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Inflammation

• Neutrophils release collegenase
  elastase?destroy lung tissue
• Hydroxyproline elastin recovered in urine of
  preterms who develops BPD
• Di2ethylhexylphthalate(DEHP) degradation product
  of used ET tubes?lung injury
• A study in 1996 found that increased interleukin
  6 in umbilical cord plasma

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Infection

• Maternal cervical colonization/ preterm neonatal
  tracheal colonization of U.urealyticum associated
  with high risk of BPD

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Nutrition

• Inadequate nutrition supplementation of preterm
  compound the damage by barotrauma , inflammatory
  cascade activation deficient AO stores
• Acute stage of CLD?increased energy expenditure
• New born rats?nutritionally deprived?decreased
  lung weight

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Nutrition

• Cu , Zn , Mn deficiency?predispose to lung injury
• Vit A E prevent lipid peroxidation maintain
  cell integrity
• Extreme prematurity large amounts of H2O needed
  to compensate loss from thin skin

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Nutrition

• Increased fluid administration ?increased risk of
  development of PDA pulmonary edema(PE)
• High vent settings high O2 needed to Rx PDA
  PE
• Early PDA Rx improve pulmonary function but no
  effect on incidence of BPD

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Genetics

• Strong family history of asthma atopy increase
  risk of development severity of BPD

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CVS Changes

• Endothelial cell proliferation
• Smooth muscle cell hypertrophy
• Vascular obliteration
• Serial EKG right ventricular hypertrophy
• Echocardiogram abnormal right ventricular
  systolic function left ventricular hypertrophy

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CVS Changes

• Persistent right ventricular hypertrophy/ fixed
  pulmonary hypertension unresponsive to
  supplemental O2 leads to poor prognosis

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Airway

• Trachea main stem bronchi - abnormalities
  depend on duration frequency of intubation
  ventilation
• Diffuse or focal mucosal edema ,
  necrosis/ulceration occur
• Earliest changes from light microscopy?loss of
  cilia in columnar epithelium , dysplasia/necrosis
  of the cells

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Airway

• Neutrophils , lymphocyte infiltrate goblet cell
  hyperplasia?increased mucus production
• Granulation tissue upper airway scarring from
  deep suctioning repeated ET intubation results
  in laryngotracheomalacia , subglottic stenosis
  vocal cord paralysis

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Airway

• Necrotizing bronchiolitis results from edema ,
  inflammatory exudate necrosis of epithelial
  cells .
• Inflammatory cells , exudates cellular debris
  obstruct terminal airways
• Activation proliferation of fibroblasts?peribron
  chial fibrosis obliterative fibroproliferative
  bronchiolitis

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Radiologic Findings

• Decreased lung volumes
• Areas of atelectasis
• Hyperinflation
• Lung haziness
• PIE

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Histologic Findings

• In 1996 Cherukupalli colleagues described 4
  pathologic stages
• Acute lung injury
• Exudative bronchiolitis
• Proliferative bronchiolitis
• Obliterative fibroproliferative bronchiolitis

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Medical care in BPD

• Prevention
• Mechanical ventilation
• O2 therapy
• Nutritional support
• Medications

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Mechanical Ventilation

• O2 PPV life saving
• Aggressive weaning to NCPAP eliminate need of PPV
• Intubation primarily for surfactant therapy
  quickly extubation to NCPAP decrease need for
  prolong PPV
• If infant needs O2 PPV gentle modes of
  ventilation employed to maintain pH 7.28 7.40 ,
  pCo2 45 65 , pO2 50- 70

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Mechanical Ventilation

• Pulse oximetry transcutaneous Co2 mesurements
  provide information of oxygenation ventilation
  with minimal patient discomfort
• SIMV provide information on TV minute volumes
  which minimize O2 toxicity barotrauma/volumetra
  uma
• SIMV allow infant to set own IT rate

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Mechanical Ventilation

• When weaning from vent O2 difficult when
  adequate TV low FiO2 achieved?trial of
  extubation NCPAP
• Commonly extubation failure?secondary to atrophy
  fatigue of respiratory muscles
• Optimization of nutrition diuretics
  contribute to successful weaning from vent
• Meticulous nursing care essential to ensure
  airway patency facilitate extubation

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O2 Therapy

• Chronic hypoxia airway remodeling?pulmonary HT
  cor pulmanale
• O2?stimulate production of NO?smooth muscle
  relaxation?vasodilatation

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O2 Therapy

• Repeated desats secondary to hypoxia results
  from- decreased respiratory drive
• - altered pulmonary
  mechanics
• - excessive stimulation
• - bronchospasm
• Hyperoxia?worsen BPD as preterms have a relative
  deficiency of AO

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O2 Therapy

• O2 requirement increase during stressful
  procedures feedings?therefore wean O2 slowly
• Keep sats 88 - 92
• High altitudes?may require O2 many months
• PRBC transfusion?increase O2 carrying capacity in
  anemic(hctlt30) preterms

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O2 Therapy

• Study in 1988 found increased O2 content
  systemic O2 transport , decreased O2 consumption
  requirement after blood Tx
• Need for multiple Tx donor exposures decreased
  by?erythropoetin , iron supplements decreased
  phlebotomy requirements

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Nutritional Support

• Infant with BPD- increased energy requirements
• Early TPN compensate for catabolic state of
  preterm
• Avoid excessive non N calories? increase CO2
  complicate weaning
• Early insertion of central lines?maximize
  calories in TPN

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Nutritional Support

• Rapid early administration of increased
  lipids?worsen hyperbillirubinemia BPD through
  billirubin displacement from albumin pulmonary
  vascular lipid deposition respectively .
• Excessive glucose load?increase O2 consumption ,
  respiratory drive glucoseuria.

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Nutritional Support

• Cu , Mn , Zn essential cofactors in AO defenses
• Early initiation of small enteral feeds with EBM
  , slow steady increase in volume?facilitate
  tolerance of feeds
• Needs 120 150 Kcal/kg/day to gain weight

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Medical Therapy

• Diuretics
• Systemic bronchodilators

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Diuretics

• Furesemide (Lasix) Rx of choice
• Decrease PIE pulmonary vascular resistance
• Facilitate weaning from PPV , O2 /both
• Adverse effects hyponatremia , hypokalemia ,
  hypercalciuria , cholelithiasis ,
  nephrocalcinosis ototoxicity

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Diuretics

• Careful parenteral enteral supplements?
  compensate adverse effects
• Thiazide spiranolactone for long term Rx

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Systemic Bronchodilators

• Methylxanthines increase respiratory drive ,
  decrease apnea , improve diaphragmatic
  contractility
• Smooth muscle relaxation decrease pulmonary
  vascular resistance increase lung compliance
• Exhibit diuretic effects

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Systemic Bronchodilators

• Theophyline metabolized primarily to caffeine
  in liver
• Adverse effects increase heart rate , GER ,
  agitation seizures

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Prognosis

• Pulmonary function slowly improves ?secondary to
  continued lung airway growth healing
• Northway- Airway hyperactivity , abnormal
  pulmonary functions , hyperinflation in chest x
  ray persists in to adult hood
• A study in 1990 found gradual decrease in symptom
  frequency in children 6 9 yrs