1. Physiologic Basis for the Management of Acute Respiratory Disorders in the Newborn Marc Collin, MD 18 November 2003

2. Developmental Anatomy Alveoli-developed by 25th week -increase in # until 8 yr. -from 20 to 300 million -surface area: 2.8 m2 @ birth 32 m2 @ 8 yr. 75 m2 @ adulthood -diameter: 150- 300 um(NB-Adult)

3. Developmental Anatomy Airways- cartilaginous - relatively weak in infancy - dynamic compression - bronchiolitis (RSV) - RAD - crying!

4. Developmental Anatomy –airways enlarge in diameter/length –distal airways lag in first 5 yr. –high peripheral resistance in infancy –Resistance = 1/R4

5. Pulmonary Physiology Compliance = Change in Volume Change in Pressure

6. Static Lung Volumes

7. Mechanics of Infant v. Adult Lung

8. Pulmonary Physiology Alveoli at birth fluid-filled v. air-filled v. air-liquid interface pressures up to 80 cm H2O @ birth alveolar rupture

9. Pressure-Volume Curves after Air v. Liquid Lung Expansion

10. Pulmonary Physiology LaPlace relationship: P = 2T/R P= distending pressure T= wall tension R= radius (alveolar)

12. Pressure-Volume Curves of First 3 Breaths

13. Developmental Biochemistry of Alveoli History: Avery & Mead-1959 - RDS secondary to surfactant deficiency - Treatment: CPAP

14. Surfactant Phospholipids - phosphatidylcholine - phosphatidylglycerol Surfactant proteins - A, B, C

15. Surfactant Components

16. Surfactant Type II alveolar epithelial cells -responsible for synthesis, storage, secretion, and reuptake Lamellar bodies -intracellular storage form of surfactant -secreted via exocytosis -forms tubular myelin in extracellular space

17. Surfactant and Type II Cells

20. Surfactant Inactivation by: - alveolar-capillary leak - pulmonary edema - hemorrhage (hemoglobin) - alveolar cell injury - meconium

21. Surfactant Recycling - spent forms taken up/reused by Type II cells. - process facilitated by SP-A, B, and C - half-life = 3.5 days

22. RDS US incidence: 30,000/yr. Inversely related to gestational age Onset-shortly after birth Signs-grunting, flaring,retracting Duration-1 week

23. RDS

24. Progressive atelectasis V/Q mismatch Decreased FRC Impaired ventilation (weak respiratory m’s, compliant chest wall) Increased PVR due to hypoxia, acidosis

25. RDS Right to left shunting leading to further hypoxemia Left to right shunting leading to pulmonary edema

26. Exogenous Surfactants Replacement therapy/Fujiwara, Japan, 1980 Human (from C/S) Artificial (Exosurf) Bovine (Survanta) Calf (Infasurf) Pig (Curosurf)

27. Compliance Before and After Surfactant Before surfactant After surfactant VOLUME PRESSURE

28. Air Leaks Pulmonary interstitial emphysema (PIE) Pneumomediastinum Pneumothorax Pneumopericardium Pneumoperitoneum

29. Subtle left pneumothorax

30. Left pneumothorax now more obvious

31. Left pneumothorax?

32. pneumothorax

33. Transillumination of left pneumothorax

34. pneumomediastinum

37. Pneumopericardium (note air under heart)

38. Air Leaks initiating factor: PIE (alveolar rupture into perivascular and peribronchial spaces) dissection into mediastinum further dissection into pleural, pericardial space rupture from surface blebs direct lung rupture-VERY rare

39. Air Leak Risk Factors RDS: 12-26% MAS/other aspirations Spontaneous

40. Air Leak Management early recognition (esp. in preterms) nitrogen wash-out (term/near-term) needle aspiration v. tube thoracotomy limit barotrauma HFOV positioning selective ET intubation

41. Meconium Aspiration Syndrome (MAS) GI secretions, cellular debris, bile, pancreatic juice, mucus, lanugo hairs, vernix; blood. incidence: ~15% (30% @ >42 wks) cause v. result of ‘asphyxia’

42. MAS Asphyxia  intestinal ischemia  anal sphincter relaxation  meconium passage

43. MAS Asphyxia  fetal gasping  enhanced meconium entry into respiratory tract

44. MAS-Presentation Respiratory distress - tachypnea - prolonged expiratory phase - hypoxemia Increased A-P diameter (‘barrel’ chest) Pulmonary hypertension

45. MAS-Radiographic Findings coarse alveolar infiltrates consolidation/hyperaeration pleural effusion (30%) pneumothorax/pneumomediastinum

46. Meconium aspiration syndrome

48. MAS-Pathophysiology Acute small airway obstruction -increased expiratory resistance -increased FRC -regional atelectasis -V/Q mismatching

49. MAS-Pathophysiology Surfactant inactivation -decreased compliance -hypoxia Pulmonary hypertension

50. MAS-Treatment Intubation/tracheal suction @ delivery Saline lavage? Surfactant therapy

51. MAS-Ventilatory Support CPAP/PEEP (be careful) Air leak due to ball-valve phenomenon Decreased I/E ratio (more E time) Hyperventilation (CMV) HFOV iNO ECMO

52. Persistent Pulmonary Hypertension of the Newborn (PPHN) Etiology: Primary v. Secondary Failure of transition from high to low PVR after birth PFO and PDA right  left shunting Intrapulmonary shunting, esp. w/ pulmonary parenchymal disease

53. PPHN PVR decreases secondary to: -mechanical distention of pulmonary vascular bed improved oxygenation of pulmonary vascular bed prostacyclin and NO production

54. PPHN Remodeling of pulmonary vascular musculature Normally, fully muscularized preacinar arteries extend to terminal bronchiolar level. Muscularization begins to decrease w/in days, complete w/in months. Regression process delayed by hypoxia Chronic hypoxia stimulates further muscularization

55. PPHN Differential Diagnosis: - Primary (chronic hypoxia) - Parenchymal disease (MAS, pneumonia, RDS, hemorrhage) - Cyanotic heart disease (TGV, critical PS, HLHS, severe coarctation) - Pulmonary hypoplasia (Potter’s S., Oligohydramnios, CDH, CCAM)

56. Congenital cystic adenomatoid malformation

58. Congenital diaphragmatic hernia

59. Thoracic hypoplasia

60. Hypoplastic right lung

61. Hypoplastic lungs

62. PPHN-Treatment/Medical Intravascular volume Correct metabolic acidosis Pressors (be careful!) Sedation (for lability) v. paralysis

63. PPHN-Treatment/Respiratory induction of respiratory alkalosis pressure support/barotrauma risk depending on etiology (compliance) very labile….SLOW wean (maintain relative HYPERoxia, if possible) iNO ECMO