Best Practices in Bronchopulmonary

Transcription

1 Best Practices in Bronchopulmonary Dysplasia a (BPD) Prevention e Matthew M. Laughon, MD, MPH Professor of Pediatrics The University of North Carolina at Chapel Hill

2 I receive support from the U.S. government for work in pediatric i and neonatal clinical i l pharmacology (Government Contract HHSN C, PI: Benjamin), from NICHD (K23HL092225), and from NHLBI (R34 HL124038). I h i d t f Pfi A t ll d Abb i I have received support from Pfizer, Astellas, and Abbvie for work on DSMBs and consulting.

3 What are evidence-based practices that influence risk of BPD? How much is BPD determined by clinical management (i.e., post-natal factors) versus gestational age and other biologic variables? 3

4 BPD Variation: CPQCC, ,779 infants, weeks GA Lapcharoensap JAMA Peds

5 Best Practices 1. Use consistent definition of BPD 2. Avoid mechanical ventilation 3. Use vitamin A, caffeine 4. Reserve dexamethasone for infants at high risk 5

6 Best Practices 1. Use consistent definition of BPD 2. Avoid mechanical ventilation 3. Use vitamin A, caffeine 4. Reserve dexamethasone for infants at high risk 6

7 Old BPD vs. New BPD Definitions of BPD Oxygen dependency at 28 postnatal days Oxygen dependency at 36 weeks PMA Physiologic definition: test of oxygen dependency at 36 weeks PMA NIH Consensus definition: none, mild, moderate, severe BPD 7

8 NICHD Consensus NICHD severity-based definition of BPD for premature infants at 36 weeks post-menstrual age No BPD Mild BPD Moderate BPD Severe BPD All BPD categories require treatment with >21% oxygen for first 28 postnatal days 21% oxygen 21% oxygen <30% oxygen* 30% oxygen and/or (no positive positive pressure* pressure) Not treated with oxygen for 28 days NCPAP or mechanical ventilation, FiO NC 0.5 LPM, 100% FiO 2 Oxygen at 36 1/7 weeks, no oxygen on 36 6/7 weeks Transfer/discharge 8

9 Definitions of BPD across Trials Definition # RCTs O 2 at 28 days 14 O 2 at 36 weeks PMA 19 O 2 at 28 days and 36 weeks PMA 4 Physiologic BPD 2 Severity based 2 Swan JAMA Peds

10 Best Practices 1. Use consistent definition of BPD 2. Avoid mechanical ventilation 3. Use vitamin A, caffeine 4. Reserve dexamethasone for infants at high risk 10

11 Explanatory Modeling Day 1 Day 3 Day 7 Day 14 Day 21 Day 28 Var. AUC Var. AUC Var. AUC Var. AUC Var. AUC Var. AUC BW BW Vent. Type Vent. Type Vent. Type Vent. Type FiO Vent BW BW FiO FIO Type GA Center Center Center Center Center Center Male FiO FiO BW BW Vent. Type FiO Male Male Male Male Male GA GA Race/ Ethn. Race/ Ethn. PDA Tx Laughon AJRCCM website: neonatal.rti.org

12 NRN Estimator: MV vs. NCPAP Typical risk of moderate, severe BPD, or death by postnatal day and respiratory support in premature infants weeks gestation 1 Postnatal t day Mechanical ventilation NCPAP Laughon AJRCCM website: neonatal.rti.org 12

13 How to provide gentle ventilation? DR management» Room air vs. 100% oxygen for resuscitation» NCPAP vs. surfactant Ventilator strategies» High frequency vs. conventional» Permissive hypercapnia» Oxygen targeting Fluid restriction 13 Tan 2010 Cochrane; Bell 2014 Cochrane; SUPPORT NEJM 2010; Schmidt JAMA 2013; BOOST NEJM 2013; Thome Lancet Resp Med 2015; COIN Trial NEJM 2008

14 Volume targeted vs. Pressure Limited: Death or BPD (36 weeks) Wheeler 2010 Cochrane 14

15 Best Practices 1. Use consistent definition of BPD 2. Avoid mechanical ventilation 3. Use vitamin A, caffeine 4. Reserve dexamethasone for infants at high risk 15

16 Neonatal Drug Development: BPD Infants Enrolled Preliminary Prevents Favorable # IND/ in RCTs Data BPD RCTs, # RCTs N/total (%) ± Vitamin A 856 Y Y 1/2 (50) 0/2 Caffeine 2006 Y Y 1/1 (100) 0/1 Dexamethasone 1513 Y Y 4/8 (50) 0/8 Inositol 233 Y Y 1/1 (100) 0/1 Clarithromycin 68 Y Y 1/1 (100) 0/1 Surfactant 1647 Y N 4/8 (50) 0/8 Inhaled nitric oxide 2712 Y N 2/7 (28) 0/7 Selenium 529 N N 0/1 (0) 0/1 Hydrocortisone 411 Y N 0/3 (0) 0/3 Allopurinol 400 N N 0/1 (0) 0/1 N-acetylcysteine 391 Y N 0/1 (0) 0/1 Inhaled beclomethasone 313 Y N 0/2 (0) 0/2 Azithromycin 220 Y N 0/1 (0) 0/1 Estrogen/progesterone 85 Y N 0/1 (0) 0/1 Alpha-1-antitrypsin 106 N N 0/1 (0) 0/1 Inhaled salbutamol 87 Y N 0/1 (0) 0/1 Superoxide dismutase 33 Y N 0/1 (0) 0/1 Cromolyn sodium 26 Y N 0/1 (0) 0/1 Inhaled fluticasone 53 Y N 0/1 (0) 0/1 Thyroxine 49 N N 0/1 (0) 0/1 Total 11, /44 (32%) 0/44 Swan JAMA Peds

17 Best Practices 1. Use consistent definition of BPD 2. Avoid mechanical ventilation 3. Use vitamin A, caffeine 4. Reserve dexamethasone for infants at high risk 17

18 Dexamethasone Doyle JPeds

19 Pediatrix Data Warehouse Verkud PAS

20 Best Practices 1. Use consistent definition of BPD 2. Avoid mechanical ventilation 3. Use vitamin A, caffeine 4. Reserve dexamethasone for infants at high risk 20

21 Questions? 21