Inhaled Nitric Oxide in preterm infants

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Inhaled Nitric Oxide in preterm infants

• Oommen Mathew MD
• Medical College of Georgia
• Augusta, GA

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Nitric oxide properties

• Clear, odorless gas
• Generally considered an environmental pollutant
• Cigarette smoke 400-1000 ppm
• Free radical
• Diffuses easily across cell membrane
• Intracellular messenger
• High affinity for hemoglobin
• Short half-life(3-5 s) and unstable
• Potent vasodilator

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Nitric oxide properties

• NO is a gas with no known cellular storage
  mechanism
• NO is the lowest molecular weight human cell
  product
• Widely distributed CNS, Epithelial cells of
  lung, kidney, stomach, pancreas, uterus

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iNO metabolism

• Combines with HgB to form Met HgB
• Reacts with oxygen to form Nitrites (NO-2)
• and Nitrates (NO-3)
• Nitrates are excreted by the kidneys (gt70 of
  iNO)
• Loss in exhaled air

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Why use iNO in preterm infants?

• NO mediates normal lung growth
• Anti-inflammatory effects
• Improves early pulmonary function
• Modifies lung growth and elastin deposition
• Pulmonary NO production is decreased in BPD
• iNO decreases PPHN in patients with BPD
• Surfactant dysfunction in BPD is improved by iNO
• Decreases protein leak in BPD
• Low dose iNO is an antioxidant

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Potential risks of iNO in preterm infants

• Increases bleeding time intracranial
  hemorrhage
• Oxidant lung injury with prematurity
• Low PVR left to right shunting
• Pulmonary edema,
  pulmonary hemorrhage,
  systemic hypoperfusion

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Skimming 1997
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Van Meurs 1997
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Cheung 1998
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Cheung 1998
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Banks 1999
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Subhedar 1997
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Mercler et al 1999
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Kinsella et al 1999
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Schreiber et al 2003
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Schreiber et al 2003
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Van Meurs 2005
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Van Meurs 2005
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Field 2005
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Hascoet et al 2005
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Mestan 2005
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iNO for respiratory failure in preterm infants

• 7 randomized trials
• Short term improvement in oxygenation
• No difference in BPD or mortality

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Kinsella 2006
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Kinsella 2006
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Ballard 2006
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No differences in PDA, NEC, ROP, Sepsis
Ballard 2006
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When to say No to iNO

• Patients with TAPVR (obstructed)
• Patients with pulmonary veno occlusive disease
• Neonates dependent on R to L shunt
• Severe L ventricular failure
• Significant bleeding diathesis
• Severe thrombocytopenia
• Severe IVH

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iNO in Preterm Infants

• Where do we go from here?
• iNO appears to be effective in less sick infants,
  noncaucasian infants and more mature infants
  (gt1000g)
• Rescue treatment improves oxygenation but not
  outcomes
• iNo may be neuroprotective in a subset of preterm
  infants
• Should we consider prophylactic or early
  rescue iNo in preterm infants at risk for
  adverse outcomes?
• Should we combine with surfactant treatment?