Purpose and Goal: CNEP # 2029

  • Understand the effects of oxygen in the neonate.
  • Learn about the effects of oxygen toxicity in the neonate.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for successful completion:

  • Successfully complete the post-test
  • Complete the evaluation form

Date

  • November 2015 – November 2017

Learning Objectives

  • Describe the harmful effects of oxygen therapy.
  • Describe the effects of oxygen free radical formation.
  • Identify 2 approaches for the prevention of oxygen toxicity

Introduction

  • Supplemental use of oxygen is common in the NICU
  • Excessive or inappropriate use of oxygen may be harmful
    • It has been associated with cell injury
    • It has been shown to cause complications
  • The most common negative effect is chronic lung disease

The History of Oxygen

  • 1774 Discovery
    • Discovered by Joseph Priestly
    • He heated mercuric oxide
  • 1778 First Therapeutic Use
    • Antoine Lavoisier coined the term “oxygen”
    • First use for a “blue baby”
  • 1799 The Pneumatic Institution
    • Founded to administer oxygen to adults
      • Consumption
      • Asthma
      • Palsy
      • Dropsy
      • King’s Evil
  • 1900 Modern Medicine
    • First use of continuous oxygen
    • A 46 year old woman with pneumonia
  • 1917 Seminal Work
    • Scott Haldane published guidelines
    • “The Therapeutic Administration of Oxygen”
  • 1917 Oxygen Therapy and WWI
    • Used to treat phosgene poisoning
  • 1950s Consequences of Unlimited Use
    • Widely accepted as a panacea for everything
    • First used in infants with respiratory failure
    • Results in severe consequences
      • Retinopathy of Prematurity
  • 1960s Higher Rates of Mortality
    • A more conservative approach
    • Resulted in higher rates of mortality
      • Despite prevention of blindness
  • 1980s Advent of Pulse Oximetry
    • Developed to monitor oxygen saturations
    • American Academy of Pediatrics
      • Developed guidelines for use
      • Significantly ↓ risks of complications
  • 1992 The Formation of ILCOR
    • International Committee on Resuscitation
    • Facilitated consensus recommendations
  • 2000 ILCOR Publishes Guidelines
    • First set of guidelines for CPR
  • 2010 ILCOR Updates CPR Recommendations
    • Current guidelines reflect evidence based practice

Oxygen Use in the Neonate

  • Oxygen (O2) is commonly used in the NICU
  • The therapeutic use of oxygen
    • Requires a delicate balance
    • Maximizing and minimizing risks
  • Recent studies show O2 can be toxic
    • Too little oxygen
    • Too much oxygen
    • Wide swings in O2 saturations

The Harmful Effects of Oxygen

  • Too much O2 can have negative effects
    • Developing brain
    • Developing eyes
    • Developing lungs
  • O2 toxicity means lung injury due to O2
  • All NICU infants are at risk for O2 toxicity
    • Due to increased exposure to O2
    • Due to reduced antioxidant defenses
  • Antioxidant systems are important
    • Do not develop until third trimester
    • Prevent overproduction of O2 free radicals
  • Underdeveloped antioxidant systems
    • Places infants at risk for:
      • Retinopathy of Prematurity (ROP)
      • Necrotizing Enterocolitis (NEC)
      • Bronchopulmonary Dysplasia (BPD)
      • Chronic Lung Disease (CLD)

Retinopathy of Prematurity

  • Retinopathy is also known as ROP
    • Previously known as RFP
    • RFP = Retrolental Fibroplasia
  • ROP is a vascular disorder of the eyes
  • Recognized as causing blindness in 1940
  • It is associated with:
    • Low birth weight
    • Low gestational age
    • Supplemental O2 therapy
  • Evidence suggests the cause of ROP
    • Is associated with retinal immaturity
    • Is associated with ↑ retinal arterial O2
  • Wide fluctuation in O2 saturations
    • Affect the developmental of ROP
    • Affect the progression of ROP
  • Controlled administration of O2
    • Decreases the incidence of ROP
  • Laser or cryotherapy treatments
    • Can have complications
    • Can lead to strabismus
    • Can lead to future myopia
  • Prevention of ROP is the best approach

Chronic Lung Injury

  • Chronic lung injury is multifactorial
    • Underventilation
      • ↓ alveolar recruitment
      • Loss of alveolar recruitment
    • Overventilation
      • Barotrauma
      • Volutrama
  • The fetal lung develops in a low O2 environment
  • Exposure to a high neonatal O2 environment
    • Causes lung damage
      • ↑ production of free radicals
      • Damages airways and lungs
    • Leads to BPD or CLD
  • Underdeveloped antioxidant systems
    • Interfere with normal lung development
    • Lead to O2 free radical lung injury
      • Inflammation
      • Diffuse alveolar damage
      • Progressive pulmonary dysfunction

Oxygen Free Radicals

  • O2 free radicals are derived from O2
  • They are highly reactive chemical molecules
    • Produced by cell metabolism
    • Made up of unpaired electrons
    • Very unstable and short lived
  • Free radical are essential for growth
  • Excess free radicals → oxidative stress
  • The neonatal period is a time of oxidative stress
    • Excess free radicals
      • Can result from hypoxia
      • Can result from hyperoxia
        • Progressive ↑ free radicals
        • Increased cell damage
      • Can lead to inflammation
        • Increased tissue damage
        • Increased cell death
  • Normally there is a balance in the body
    • Between free radical formation
    • Between defense mechanisms
  • Antioxidants are defense mechanisms
    • Prevent formation of free radicals
    • Delay formation of free radicals
  • There are many well know antioxidants
    • Intracellular
      • Catalase
      • Glutathione
      • Superoxide dismutase
    • Extracellular
      • Bilirubin
      • Transferrin
      • Vitamin A
      • Vitamin C
      • Vitamin E
      • Betacarotene
  • Antioxidant systems are limited in the neonate
    • They develop in the third trimester
    • Preterm infants are at highest risk
      • Immature antioxidant systems
      • Decreased antioxidant enzymes
      • Decreased defense mechanisms
      • Increased risk of O2 toxicity

Clinical Approach to Limiting Toxicity

  • O2 should be treated like a drug
  • The most important strategy is to limit O2
  • Current standards of care:
    • Using room air for resuscitation
    • Using an O2 blender at delivery
    • Using an O2 blender in the NICU
    • Limiting invasive ventilation
      • Increased use of CPAP
      • Noninvasive Minute Ventilation
      • High Flow Nasal Cannula
    • Use of pulse oximetry to titrate O2
      • Oxygen saturations
        • 88-93% < 34 weeks
        • 90-95% > 34 weeks
        • > 95% only as needed
    • Prone positioning
    • Decreasing free radical production
      • Preventing infection
      • Preventing inflammation
      • Using fresh breastmilk
      • Protecting TPN from light
        • Decreases photo-oxidation
      • Decreasing blood transfusions
        • Decreases oxidant load
      • Limiting medications
        • Analgesics
        • Antibiotics
        • Anticonvulsants
      • Supplemental antioxidants
  • Possible future standards of care:
    • Immune modulators
      • Interleukin-11

Summary

  • Supplemental O2 is common in the NICU
  • Negative effects of O2 have been identified
    • The safest duration of O2 is not known
    • The safest O2 concentration is not known
  • Infants should always be provided minimal O2

References

  1. Malhotra, A., Schwartz, D.R, and Schwartzstein, R.M. 2015. Oxygen Toxicity. Up-To-Date.
  2. Clark, R.H., Gerstmann, D.R., Jobe, A.H., Moffitt, S.T., Slutsky, A.S. and Yoder, B.A. 2001. Lung Injury in Neonates: Causes, Strategies for Prevention, and Long-Term Consequences. The Journal of Pediatrics, 139 (4), p. 478-486.
  3. Johnson, K., Scott, S.D. and Fraser, K.D. 2011. Oxygen Use for Preterm Infants: Factors That May Influence Clinical Decisions Surrounding Oxygen Titration. Advances in Neonatal Care, 11 (1), p. 8-14.
  4. Baba, L. & McGrath, J.M. 2008. Oxygen Free Radicals. Advances in Neonatal Care, 8 (5), p. 256-264.

Evaluation

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