Use of Blended Oxygen for Delivery Room Resuscitation of Very Low Birth Weight Infants
Condition: Prematurity; Oxidant Injury
MeSH terms: Premature Birth
Study type: Interventional

Summary: 
      We propose a preliminary trial to evaluate the safety and efficacy of using more restricted
      oxygen during resuscitation for VLBW infants than is utilized currently in an effort to
      reduce the oxidant stress of such treatment, and to possibly reduce associated multi-system
      organ related dysfunction.

      In attempting to design a trial comparing higher versus lower oxygen during neonatal
      resuscitation with the potential for benefit to the enrolled infants, and a minimal level of
      risk, and acknowledging that the use of Room Air may be considered premature in view of the
      lack of any safety data in this population, we are proposing to utilize an oxygen blender and
      a pulse oximeter in the delivery room in the treated group. The treated group will have their
      fraction of inspired oxygen increased from 21%, as necessary, to achieve a target oxygen
      saturation of 85 to 90% at 5 minutes of life, compared with the standard of care group who
      will receive 100% oxygen without the use of a blender, which is the current approach in most
      centers in this country. The targeted saturation of 85% will provide enough oxygen to treat
      any ventilation/perfusion mismatch, while exposing the infants to significantly less inspired
      oxygen.

      Hypothesis: We hypothesize that the use of restricted inspired oxygen during resuscitation
      will result in a significant reduction in oxidant stress without any harmful clinical
      effects.
    

Detailed description: 
      We propose to study the preterm infant (gestational age 23-32 weeks) as these infants are the
      most vulnerable to the acute and chronic possible toxicities of excess oxygen and the
      associated oxygen free radicals. We will study 40 infants.

      Infants will be randomized following parental consent obtained prior to delivery to initially
      be placed on a pulse oximeter and receive blended oxygen to a targeted oxygen saturation of
      85 to 90% at 5 minutes of life, or 100% oxygen for a minimum of 5 minutes without the use of
      a blender. The inspired oxygen will be increased using the blender if the infant's SaO2
      remains less than 60% at two minutes, less than 70% at 3 minutes, and/or if bradycardia with
      a heart rate of less than 100 bpm persists after 2 minutes of resuscitation.

      Cord blood will be obtained following our usual procedures and a portion will be saved for
      later analysis of lipid peroxides, oxidized and reduced glutathione and total antioxidant
      status. Similar assays will be performed at 1 hour, week and at 1 month for all surviving
      infants.

      Intervention:

      Prior to the infant's delivery, the randomization will be drawn from double sealed envelopes
      randomized by blocks of 10. A blender will be in place in the delivery room area and provide
      the source of oxygen to the resuscitation device. Following randomization and before the
      delivery, the blender will be turned to either 21% or 100%. The respiratory therapist will
      increase the blender immediately to 100% oxygen under the following conditions:

        1. Need for chest compressions or medication administration

        2. Heart rate is less than 100 at 2 minutes of life

        3. Heart rate less than 60 for 30 seconds at any time of life.

      Oxygen will be incrementally increased in the room air group by the following protocol:

      If O2 Sat: Blender:

      < 70 at 3 min, increase to 50% x30 sec No Response: increase to 75% x30 sec No Response:
      increase to 100%

      < 85 at 5 min, increase to 50% x30 sec No Response: increase to 75% x30 sec No Response:
      increase to 100%

      A pulse oximeter will be placed on the infant's extremity, preferably the right hand. The
      data stored in the oximeter will be retrieved and the data points kept as a file. These data
      points represent the SaO2 every 2 seconds during the monitored period. The resuscitation
      teams will utilize the pulse oximeter to determine if additional oxygen is required and to
      evaluate the effectiveness of resuscitation. In addition, we will review the data collected
      by the pulse oximeter to observe the change in SaO2 with delivery and resuscitation.

      We have the capability to perform video recordings and will follow the methodology of Carbine
      et al. A video camera is mounted on the overhead warmer, loaded with a blank Mini-DV tape.
      The camera will be turned to record mode just prior to the initiation of the resuscitation.
      Following completion of the resuscitation, the recorder will be turned off, and the tape
      removed and placed in a secure location till reviewed and scored. All collected videotapes
      will be centrally reviewed by the research team to ensure consistency of scoring. All tapes
      will be erased following review, and the scoring sheets completed during the video reviews
      will be maintained as research data, and stored for as long as required.

      Protocol Violations

      We anticipate that there will be occasional protocol violations. These may be as follows:

      Failure to complete resuscitation using the randomized Oxygen level. Failure to increase the
      FiO2 as required by protocol ( presence of bradycardia (HR< 100 bpm for 2 minutes), and/or
      poor color or an SaO2 < 70% at 3 minutes by SaPO2)

      Adverse Events:

      As this will be a very vulnerable population, we expect that there will be serious adverse
      events including death.

      Adverse events which may be related to the study maneuver would include:

        1. Prolonged hypoxia and/or failure to respond to resuscitation

        2. The need for chest compressions, and/or epinephrine These will be noted from the video
           review and chart documentation

      Measures of Oxidant Stress: Blood from the Cord and subsequent specimens from the infant at 1
      hour, 1 week and 1 month will be obtained, 400 microlitres, 4/10th of an ml for a total of
      1.2 ml from the infant, spun and frozen and run at our basic science laboratory for
      measurement of lipid peroxides, oxidized and reduced glutathione and total antioxidant
      status. Lipid peroxides will be measured using the K-ASSAY kit from the Kamiya Biomedical
      company. Total antioxidant status will be measured using the Randox Total Antioxidant status
      kit.
    

Intervention name(s): Titration of oxygen in delivery room
Intervention type(s): Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Prematurity; Resuscitation; Room Air