Oxygenation of the Neonate

1. Oxygenationof the Neonate

2. Abbreviations • O2- oxygen • FiO2- inspired O2 concentration • PO2- partial pressure of O2 • PaO2- arterial O2 tension • SaO2- arterial oxygen saturation

3. What is oxygen?

4. Most widely occurring element on Earth Considered by some to be a air pollutant Catalyst for free radical formation contains one or more unpaired electrons superoxide theory of oxygen toxicity toxicity (oxidative stress) is due to excess formation of superoxide radical (reduction product of O2) effects are countered by superoxide dismutase (antioxidant enzymes)

5. Oxidative Stress occurs when generation of reactive oxygen species exceed the ability of the cell to remove them produces physiologic, inflammatory and histologic changes produces injury in proteins (amino acids, DNA), membrane lipids, carbohydrates

6. Protective Forces Compartmentalize processes which create free radicals Superoxide dismutase and other enzymes Vitamin E- most abundant antioxidant Vitamin C Bilirubin and other antioxidants

7. Why is oxygen important?

8. Mitochondria (power house of the cell) is oxygen dependent Oxygen is necessary for aerobic metabolism (breakdown of glucose) ATP limited storage capacity

9. Fetal Oxygenation • Umbilical venous blood from placenta to fetus has a PaO2 20-30 mm Hg. • Fetus able to survive secondary to low metabolic demands (placenta/mother provide support) • In fetus low PaO2 causes pulmonary vasoconstriction and ductus arteriosus vasodilation

11. Introduction of oxygen to body • Regulated by the oxygen pressure gradient • Convection of air into the lungs • Diffusion of oxygen into the blood • Convection flow of blood to the tissue • Diffusion of oxygen into the cells • Diffusion of oxygen into the mitochondria

12. Oxygen transport is dependent on availability of oxygen oxygen carrying capacity of blood rate of blood flow

13. Factors affecting oxygen carrying capacity and delivery to tissue respiratory status hemoglobin level and configuration cardiac output blood pressure heart rate tissue ischemia/edema disease state

14. Oxygen in the blood is found dissolved in plasma small quantity linear relationship to PO2 ~ 10% FiO2 equals 1% of blood’s O2 content bound to hemoglobin larger quantity fully saturated- one gram hemoglobin will bind 1.34ml of oxygen nonlinear relationship to PO2 oxygen dissociation curve

16. Oxygen Dissociation Curve • At low PO2 levels, O2 binds quickly to hemoglobin • Between 40-80mm Hg, binding slows • Above 100mm Hg, binding is relatively static (hemoglobin is saturated) • Levels above 50-80mm Hg have the potential to cause harm

17. Shifting of Curve To the left (increased affinity of hemoglobin to O2) hemoglobin saturation can be achieved at lower PO2 levels greater percentage of fetal hemoglobin decrease in 2,3-diphosphoglycerate content occurs in premature infants with RDS alkalemia hypocapnia hypothermia

18. To the right (decreased affinity of hemoglobin to O2) hemoglobin saturation is achieved at higher PO2 levels reduction in fetal hemoglobin increased 2,3-DPG acidemia hypercapnia hyperthermia

19. Hemoglobin is ~ 1/3 of hematocrit Hemoglobin levels are important Hgb 15 X 1.34 ml = 20.1 ml O2 (if 100% saturated) Hgb 10 x 1.34 ml = 13.4 ml O2 (if 100% saturated) Hgb 7 x 1.34 ml = 9.38 ml O2 (if 100% saturated)

20. Adequate Oxygenation PO2 necessary to deliver an amount of oxygen to the tissues for effective metabolism without creating a toxic effect Variable among individuals Continuous fluctuations

21. What is 21% FiO2? Total pressure in the atmosphere at sea level is 760mm Hg • Water vapor 47mm Hg • 21% of remaining pressure (760- 47) is exerted by oxygen- 150mm Hg (which means PaO2 of room air is 150mm Hg) • Nitrogen makes up the majority of the remaining air • Carbon dioxide is miniscule (0.001 %)

22. First breaths • Arterial-alveolar oxygen tension ratio • Normal term infant • Initial PCO2 60-80mm Hg • Inhales room air (150mm Hg) • Mixing causes dilution of oxygen diffusing into blood • At ~ 20 minutes of age PCO2 30-40mm Hg • Ultimately PO2 diffusing into blood is ~80-100mm Hg

23. Lung Development • Individual variations • Stages overlap

24. Prematurity: Interrupts Lung Development Premature Term Pseudoglandular Period (7 to 16 weeks GA) Alveolar Period (36 to 41 weeks GA) Saccular Period (26 to 36 weeks GA) Canalicular Period (16 to 26 weeks GA) • The lungs of premature infants are underdeveloped at birth • Although alveoli are present in some infants as early as 32 weeks GA, they are not uniformly present until 36 weeks GA *Pictures are artistic renditions of lung development and are designed to emphasize terminal acinus development & not the entire conducting airway system Behrman: Nelson Textbook of Pediatrics, 16th ed., 2000. Langston C, et al. Am Rev Respir Dis. 1984;129:607-13

25. Normal Lung Development Canalicular Period 16 to 26 weeks Saccular Period 26 to 36 weeks Alveolar Period 36 to 41 weeks ( Non-human primate lung sections) Presented by K Stenmark, MD: ICRV, 2003

26. Embryonic (0-7 weeks) lung buds form, blood vessels connect to heart Pseudoglandular (6-17 weeks) pre-acinar airways and blood vessels develop

27. Canalicular (16-27 weeks) respiratory regions develop peripheral epithelium and mesenchyme thin type I and II pneumonocytes develop

28. Alveolar (27 weeks to term) saccules develop and produce alveoli Post natal alveoli and small blood vessels multiple

29. Complications of hyperoxia

30. Individual variations Must keep in mind that all disease states are multifactorial Controlling oxygen exposure is critical but other complicating factors must also be addressed

31. Retinopathy of Prematurity Proliferative vascular disease

33. Vitreous gel clear gel that fills the inside of the eye Optic nerve bundle of more than 1,000,000 nerve fibers that carry visual messages from the retina to the brain Macula small sensitive area of the retina that gives central vision Fovea center of macula, gives sharpest vision

34. Retina light sensitive tissue lining the back of the eye, converts light into electrical impulses that are sent to the brain via the optic nerve Iris colored part of eye, regulates amount of light entering the eye Cornea clear outer part of eye’s focusing system

35. Pupil opening at center of the iris, adjusts the size of the pupil to control amount of light entering the eye Lens clear part of eye behind iris that helps focus light on retina Iris colored part of eye, regulates the amount of light entering the eye

36. Normal Eye Development • Eye starts development at ~ 16 weeks • blood vessels of retina begin to form at the optic nerve • grow towards the edge of the retina, supplying oxygen and nutrients • Last trimester • eye develops rapidly • Term • eye growth is almost complete (vessels have reached the edge of the retina)

37. Risk factors for ROP • Prematurity • Low birth weight • Complicated hospital course • Co-morbidities • Oxygen exposure (toxicity)

38. Preterm Eye Development • Preterm eye • blood vessels have not reached edges of the retina • vessel growth may be arrested • vessel growth is resumed and continues to periphery unless abnormalities occur

39. ROP • Pathogenesis • any factor causing vasoconstriction of immature retinal vessels • interruption of migration of blood vessels from the optic nerve to the ora serrata • retina sends out signals to induce renewal of growth • abnormal vessels may develop (fragile, weak) • leads to scarring which can lead to pulling on retina

41. Stage I mild abnormal blood vessel growth (demarcation line) Stage II moderately abnormal blood vessels growth (ridge)

42. Stage III severely abnormal blood vessel growth (extraretinal fibrovascular proliferation) blood vessel growth is towards the center of the eye instead of along surface of retina Plus Disease blood vessels of the retina are enlarging and twisting “tortuosity”

43. Stage IV partially detached retina caused by traction from scarring and abnormal vessel growth Stage V complete retina detachment end stage of disease

44. Zone I most posterior, near optic nerve Zone II extends to ora serrata Zone III extends to periphery

45. Oxygen’s implication retinal vessels form in an environment of low PaO2 (20-30mm Hg) at birth, dramatic increase in PaO2 (even RA creates significant increase) retinal vessels constrict in response to increased PaO2, diminishing flow and nutrients down regulation of vascular endothelial growth factor (secondary to hyperoxia)

46. as metabolic demands of growing eye increase, nonvascularized areas of the eye become hypoxic eye sends signals for help neovascularization and increased levels of VEGF occurs cycles of hyperoxia and hypoxia

47. Treatment prevention surgical intervention laser or cryotherapy- burns away periphery of retina where abnormal vessels abound (loss peripheral vision) (stage III with plus dz) scleral buckle- banding the eye to prevent vitreous gel from pulling on scar tissue, releases pressure from retina (stage IV, V) vitrectomy- replacing vitreous gel with saline in order to remove scar tissue (stage V)

48. Oxygen toxicity in the Lung

49. Incomplete development and inadequate responsiveness of pulmonary antioxidant enzyme system Cessation of transplacental substrates Lungs are susceptible due to large surface area of type I and II cells coming into direct contact with FiO2

50. Increased production of cytotoxic oxygen free radicals Overwhelms the antioxidant defenses in the capillary endothelial and alveolar cells Radicals react with intracellular constituents producing chain reaction