Care of the Child with Bronchopulmonary Dysplasia and Pulmonary - PowerPoint PPT Presentation

Care of the Child with Bronchopulmonary Dysplasia and Pulmonary Hypertension Peter Mourani Has documented that he has no Peter M. Mourani, MD financial relationships to disclose or Associate Professor of Pediatrics Section of Critical Care Conflicts of Interest (COIs) to Pediatric Heart Lung Center University of Colorado Denver resolve. The Children’s Hospital Pulmonary Hypertension (PH) in Bronchopulmonary Dysplasia (BPD) • Strongly associated with morbidity and mortality Unapproved or Off Label • PH is one manifestation of pulmonary vascular Disclosures for disease (PVD) Peter Mourani • Lung disease, cardiac shunts, and cardiac dysfunction may exacerbate PVD and PH in BPD Presenter: Dr. Mourani has documented that his presentation involves • High clinical suspicion and comprehensive comments or discussion of unapproved or off-label, experimental or investigational use of inhaled nitric oxide and sildenafil evaluations are required to identify the factors contributing to PVD and PH • Advances in basic pulmonary vascular biology have directly led to novel therapies 1

PH is Associated with High Pulmonary Vascular Disease Mortality in BPD in BPD 1 0.9 Decreased Growth 0.8 Probability of Survival • Angiogenesis 0.7 • Alveolarization Prolonged oxygen 0.6 All PH Patients therapy 0.5 Severe PH Altered redistribution Abnormal Function 0.4 Mild PH Surface area • High vascular tone of blood flow in 0.3 • Altered vasoreactivity response to infection for 0.2 • Impaired metabolic function gas exchange 0.1 Exercise intolerance 0 Abnormal Structure 0 10 20 30 40 Pulmonary • SMC proliferation Hypertension Months After Diagnosis • Altered extracellular matrix Adapted from Khemani E, et al, Pediatrics 2007 Mourani PM, Curr Opin Pediatr. 2013 Jun;25(3):329-37 Persistent Controversies Regarding The Pulmonary Circulation in BPD PH in BPD • What is the definition of PH in BPD? • What is the incidence of PH in BPD? • What is the contribution of PH to outcomes in BPD? • What is the best approach to identify BPD infants with PH? • What are the optimal treatment strategies for PH in context of BPD? Mourani , Abman. In Bronchopulmonary Dysplasia , 2009. 2

Incidence of PH in BPD Two Center Prospective Study of PVD in Preterm Infants ● University of Colorado and Indiana University An HS, et al. Korean ● Inclusion Criteria: Circulation Journal 2010 ● Birthweight: 500 - 1250 grams ● Gestational age < 34 weeks Bhat R et al. Pediatrics ● Less than 7 days old at enrollment 2012 ● Echocardiograms performed at 36 wks PMA in conjunction with physiologic assessment for BPD according NIH criteria. ● Subjects followed until 2 years of age Echo PH Criteria Lung Disease Heart Disease • Hypoxemia • RV dysfunction • All Echocardiograms read by a single cardiologist • Hyperinflation • Impaired LV blinded to clinical status • Atelectasis contractility • Hypercarbia • LV diastolic dysfunction • PH Criteria 1: • L>R shunt lesions Pulmonary – R>L or bidirectional Cardiac Level Shunt Hypertension – Estimated RVSP >40 mm Hg, or RVSP/Sys BP >0.5 in BPD • PH Criteria 2: – Inclusive Criteria 1, or Pulmonary Vascular Disease – Moderate or severe septal wall flattening • High tone and reactivity • Hypertensive vascular remodeling • PH Criteria 3: • Decreased vascular growth • Systemic-pulmonary collateral vessels – Inclusive of Criteria 1 and 2, or • Pulmonary vein stenosis Mourani , Abman. – Mild septal wall flattening In Bronchopulmonary 11 Dysplasia , 2009. 3

Role of Cardiac Diagnostic Approach to Pulmonary Catheterization in BPD Hypertension in BPD • Assess severity of PH • Screening echocardiograms (ECHO) for: • Anatomic heart disease/ shunt lesions – Severe BPD at 36 weeks • Structural vascular abnormalities (eg, arterial – infants with prolonged ventilator and/or oxygen requirements – cyanotic episodes stenosis, pulmonary venous obstruction, systemic – marked hypercarbia to pulmonary collateral vessels, others) – persistent pulmonary edema, diuretic dependence • Catheter-based interventions – poor growth, IUGR, oligohydramnios • Assess cardiac function (LV diastolic dysfunction) • General evaluation and treatment for factors contributing • Acute vasoreactivity/hypoxia testing for selection of to persistent respiratory disease and PH chronic therapy • Consider cardiac catheterization Patients with Neonatal CLD Pulmonary Vascular Effects of Inhaled Receiving Sildenafil Exhibited NO and Oxygen in Children with BPD Improved Pulmonary Pressures Hyperoxia Calcium Channel Hyperoxia + iNO Blocker 0 1 2 3 Percent change in PAP from Baseline -5 -10 -15 -20 c -25 -30 -35 -40 Mourani PM et al J. Pediatrics 2008 Mourani PM et al, AJRCCM 2004 4

Sildenafil use is Associated with Longitudinal Evaluation of PH in BPD Hemodynamic Improvement • Serial monitoring: 1.00 – echocardiogram Percent of Patients Showing Hemodynamic Improvement – BNP and pro-BNP 0.75 – Respiratory course – Growth and activity 0.50 • Patients who fail to improve/deteriorate: – Repeat extensive respiratory evaluation 0.25 – Consider repeat cardiac catheterization Censored Observations • Additional Therapies: 0.00 0 100 200 300 400 500 600 – Endothelin receptor blockers, prostacyclin analogues Days on Sildenafil Therapy • Weaning of drug therapies Mourani PM et al J. Pediatrics 2008 Acknowledgements Summary: PH in BPD University of Colorado/ Indiana University Children’s Hospital Colorado • Brenda Poindexter • PH contributes to worse outcomes in BPD, but • Steve Abman • David Ingram limited data exist regarding the natural history of • Marci Sontag • Howard Edenberg PH in BPD • Joshua Miller • Leslie Dawn Wilson • Chris Baker Colorado Clinical Translational • Cardiopulmonary interactions contribute • John Kinsella Science Institute significantly to PVD in BPD • Adel Younoszai • Lucy Fashaw • Donna Parker • Cardiac catheterization plays an important • Christine Reed • Neil Makrham diagnostic role for PVD in BPD (PH severity, • Kathy Hale • Sharon Ryan • Barbara Pruckler anatomic abnormalities) • Greg Seedorf • Amy Martin • More data are needed to define the utility, timing, • James Thorpe St. Joseph’s Hospital, Denver and duration of drug treatments for PH in BPD • KC Clevenger • Ellina Liptsen • Erin Hughes • Alfonso Pantoja 5