Bronchopulmonary Bronchopulmonary Dysplasia(BPD)Dysplasia(BPD)

Kumari Weeratunge M.D.

PL - 2

Back groundBack 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 groundBack 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 .

PathophysiologyPathophysiology

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 BPDStages 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 BPDFrequency 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 BPDMortality/Morbidity of BPD

Infants with severe BPDIncreased risk of pulmonary morbidity & mortality within the first 2 years of life .

Pulmonary Complications of Pulmonary Complications of BPDBPD

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 & Volume trauma & BarotraumaBarotrauma

Rx of RDS – surfactant replacement , O2 , CPAP & mechanical ventilation .

Increased PPV required to recruit all alveoli to Px atelectasis in immature lungsLung injuryInflammatory cascade .

Trauma secondary to PPV-Barotrauma VolumetraumaLung injury secondary to

excess TV from increased PPV .

Volume trauma & Volume trauma & BarotraumaBarotrauma

Severity of lung immaturity & effects of surfactant deficiency determines PPV .

Severe lung immaturityAlveolar number is reducedincreased PP transmitted to distal bronchioles .

Surfactant deficiencysome alveoli collapse while others hyper inflate .

Volume trauma & Volume trauma & BarotraumaBarotrauma

Increased PPV to recruit all alveoliCompliant alveoli & terminal bronchioles ruptureleaks air in to interstiumPIEIncrease risk of BPD

Using SIMV compared to IMV in infants <1000g showed less BPD .

O2 & AntioxidantsO2 & Antioxidants

O2 accept electrons in it’s outer ringForm O2 free radicalsCell membrane destruction

Antioxidants(AO)Antagonise O2 free radicals

Neonates-Relatively AO deficient Major antioxidants – super oxide dismutase ,

glutathione peroxidase & catalase

O2 & AntioxidantsO2 & Antioxidants

Antioxidant enzyme level increase during last trimester .

Preterm birthIncreased risk of exposure to O2 free radicals

InflammationInflammation

Activation of inflammatory mediatorsIn acute lung injury

Activation of leukocytes by O2 free radicals , barotrauma & infectionDestruction & abnormal lung repairAcute lung injuryBPD

Leukocytes & lipid byproducts of cell membrane destructionActivate inflammatory cascade

InflammationInflammation

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 mediatorsvasodilatationincreased capillary permeabilityalbumin leakage & inhibition of surfactant functionrisk of barotrauma

InflammationInflammation

Neutrophils – release collegenase & elastasedestroy lung tissue

Hydroxyproline & elastin recovered in urine of preterms who develops BPD

Di2ethylhexylphthalate(DEHP) degradation product of used ET tubeslung injury

A study in 1996 found that increased interleukin 6 in umbilical cord plasma

InfectionInfection

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

NutritionNutrition

Inadequate nutrition supplementation of preterm compound the damage by barotrauma , inflammatory cascade activation & deficient AO stores

Acute stage of CLDincreased energy expenditure

New born ratsnutritionally depriveddecreased lung weight

NutritionNutrition

Cu , Zn , Mn deficiencypredispose 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

NutritionNutrition

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

GeneticsGenetics

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

CVS ChangesCVS 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 ChangesCVS Changes

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

AirwayAirway

Trachea & main stem bronchi - abnormalities depend on duration & frequency of intubation & ventilation

Diffuse or focal mucosal edema , necrosis/ulceration occur

Earliest changes from light microscopyloss of cilia in columnar epithelium , dysplasia/necrosis of the cells

AirwayAirway

Neutrophils , lymphocyte infiltrate & goblet cell hyperplasiaincreased mucus production

Granulation tissue & upper airway scarring from deep suctioning & repeated ET intubation results in laryngotracheomalacia , subglottic stenosis & vocal cord paralysis

AirwayAirway

Necrotizing bronchiolitis – results from edema , inflammatory exudate & necrosis of epithelial cells .

Inflammatory cells , exudates & cellular debris obstruct terminal airways

Activation & proliferation of fibroblastsperibronchial fibrosis & obliterative fibroproliferative bronchiolitis

Radiologic FindingsRadiologic Findings

Decreased lung volumes Areas of atelectasis Hyperinflation Lung haziness PIE

Histologic FindingsHistologic Findings

In 1996 Cherukupalli & colleagues described 4 pathologic stages

Acute lung injury Exudative bronchiolitis Proliferative bronchiolitis Obliterative fibroproliferative bronchiolitis

Medical care in BPDMedical care in BPD

Prevention Mechanical ventilation O2 therapy Nutritional support Medications

Mechanical VentilationMechanical 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 VentilationMechanical 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 VentilationMechanical Ventilation

When weaning from vent & O2 difficult – when adequate TV & low FiO2 achievedtrial of extubation & NCPAP

Commonly extubation failuresecondary 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 TherapyO2 Therapy

Chronic hypoxia & airway remodelingpulmonary HT & cor pulmanale

O2stimulate production of NOsmooth muscle relaxationvasodilatation

O2 TherapyO2 Therapy

Repeated desats secondary to hypoxia results from- decreased respiratory drive

- altered pulmonary mechanics

- excessive stimulation

- bronchospasm Hyperoxiaworsen BPD as preterms have

a relative deficiency of AO

O2 TherapyO2 Therapy

O2 requirement increase during stressful procedures & feedingstherefore wean O2 slowly

Keep sats 88% - 92% High altitudesmay require O2 many

months PRBC transfusionincrease O2 carrying

capacity in anemic(hct<30%) preterms

O2 TherapyO2 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 byerythropoetin , iron supplements & decreased phlebotomy requirements

Nutritional SupportNutritional 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 linesmaximize calories in TPN

Nutritional SupportNutritional Support

Rapid & early administration of increased lipidsworsen hyperbillirubinemia & BPD through billirubin displacement from albumin & pulmonary vascular lipid deposition respectively .

Excessive glucose loadincrease O2 consumption , respiratory drive & glucoseuria.

Nutritional SupportNutritional Support

Cu , Mn , & Zn essential cofactors in AO defenses

Early initiation of small enteral feeds with EBM , slow & steady increase in volumefacilitate tolerance of feeds

Needs 120 – 150 Kcal/kg/day to gain weight

Medical TherapyMedical Therapy

Diuretics Systemic bronchodilators

DiureticsDiuretics

Furesemide (Lasix) Rx of choice Decrease PIE & pulmonary vascular

resistance Facilitate weaning from PPV , O2 /both Adverse effects – hyponatremia ,

hypokalemia , hypercalciuria , cholelithiasis , nephrocalcinosis & ototoxicity

DiureticsDiuretics

Careful parenteral & enteral supplements compensate adverse effects

Thiazide & spiranolactone for long term Rx

Systemic BronchodilatorsSystemic Bronchodilators

Methylxanthines – increase respiratory drive , decrease apnea , improve diaphragmatic contractility

Smooth muscle relaxation – decrease pulmonary vascular resistance & increase lung compliance

Exhibit diuretic effects

Systemic BronchodilatorsSystemic Bronchodilators

Theophyline – metabolized primarily to caffeine in liver

Adverse effects – increase heart rate , GER , agitation & seizures

PrognosisPrognosis

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