Bronchopulmonary Dysplasia

Bronchopulmonary Dysplasia(BPD) Kumari Weeratunge M.D. PL - 2 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 @ 28days to keep PaO2>50mmhg & abnormalities in chest x –ray . Back ground   Shennan proposed in 1988 criteria of O2 requirement @ 36 weeks corrected GA . Antenatal steroids , early surfactant Rx & gentle modes of ventilation minimize severity of lung injury . 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 . 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 Frequency of BPD    Dependent on definition used in NICU . Using criteria of O2 requirement @ 28 days frequency range from 17% - 57% . Survival of VLBW infants improved with surfactant Actual prevalence of BPD has increased . Mortality/Morbidity of BPD  Infants with severe BPDIncreased risk of pulmonary morbidity & mortality within the first 2 years of life . 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 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 . 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 . 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 <1000g showed less BPD . O2 & Antioxidants     O2 accept electrons in it’s 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 O2 & Antioxidants   Antioxidant enzyme level increase during last trimester . Preterm birthIncreased risk of exposure to O2 free radicals 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 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 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 Infection  Maternal cervical colonization/ preterm neonatal tracheal colonization of U.urealyticum associated with high risk of BPD 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 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 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 Genetics  Strong family history of asthma & atopy increase risk of development & severity of BPD 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 CVS Changes  Persistent right ventricular hypertrophy/ fixed pulmonary hypertension unresponsive to supplemental O2 leads to poor prognosis 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 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 Airway    Necrotizing bronchiolitis – results from edema , inflammatory exudate & necrosis of epithelial cells . Inflammatory cells , exudates & cellular debris obstruct terminal airways Activation & proliferation of fibroblastsperibronchial fibrosis & obliterative fibroproliferative bronchiolitis Radiologic Findings      Decreased lung volumes Areas of atelectasis Hyperinflation Lung haziness PIE Histologic Findings      In 1996 Cherukupalli & colleagues described 4 pathologic stages Acute lung injury Exudative bronchiolitis Proliferative bronchiolitis Obliterative fibroproliferative bronchiolitis Medical care in BPD      Prevention Mechanical ventilation O2 therapy Nutritional support Medications 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 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/volumetrauma SIMV – allow infant to set own IT & rate 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  O2 Therapy   Chronic hypoxia & airway remodelingpulmonary HT & cor pulmanale O2stimulate production of NOsmooth muscle relaxationvasodilatation 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 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(hct<30%) preterms 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 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 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. 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 Medical Therapy   Diuretics Systemic bronchodilators 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 Diuretics   Careful parenteral & enteral supplements compensate adverse effects Thiazide & spiranolactone for long term Rx Systemic Bronchodilators    Methylxanthines – increase respiratory drive , decrease apnea , improve diaphragmatic contractility Smooth muscle relaxation – decrease pulmonary vascular resistance & increase lung compliance Exhibit diuretic effects Systemic Bronchodilators   Theophyline – metabolized primarily to caffeine in liver Adverse effects – increase heart rate , GER , agitation & seizures 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