Automatic Oxygen Control for Reducing Extremes of Oxygen Saturation (AreOS): A Randomised Control Trial
Condition: Prematurity
MeSH terms: Premature Birth
Study type: Interventional

Summary: 
      Oxygen treatment is common in babies born early (preterm) and requiring intensive care.
      Having too much or too little oxygen can increase the risk of damage to the eyes and lungs,
      and contribute to death or disability. Preterm infants because of their immaturity experience
      episodes of low oxygen levels. The low oxygen episodes are primarily due to pauses in their
      breathing (Apnoea of prematurity) and immaturity of their lung. These episodes persist for
      weeks. The lower the gestation at birth the longer the duration of these events. Studies have
      shown that these episodes of low oxygen saturations especially if frequent and prolonged is
      associated with poor developmental outcome, severe eye disease and lung disease.

      Traditionally, the oxygen delivery is manually adjusted when infant has low oxygen
      saturation. However previous studies have shown despite the best efforts the oxygen level can
      only be maintained less than half of the time and nearly a one-fifth of the time infant
      spends in low oxygen levels and nearly one third of the time in high oxygen levels. Now it is
      possible to maintain oxygen level in target range by using automatic control of oxygen
      delivery. With the proposed study, we would like to study the efficacy of automatic control
      of oxygen delivery in reducing the time spent in low oxygen levels.
    

Detailed description: 
      Supplemental oxygen remains by far the most commonly used 'drug' in neonatal intensive care
      units. The goal of oxygen therapy is to maintain normal oxygenation while minimizing
      hypoxemia and hypoxemia. Preterm infants are particularly vulnerable to oxygen toxicity and
      oxidative stress leading to retinopathy of prematurity (ROP), bronchopulmonary dysplasia
      (BPD), and periventricular leukomalacia (PVL)[1]. It's also well known that preterm infants
      experience hypoxic events which are primarily linked to cardiovascular instability and apnea
      of prematurity. These events vary as the infant matures. Martin R et al showed in their study
      that these hypoxic events peaked around 2-4 weeks and decreases by 6-8 weeks in preterm
      infants (2). Exposure to prolonged and frequent hypoxemic episodes has been associated with
      increased morbidity and mortality [3-5]. Prolonged hypoxic events (Saturation less than 80%
      for more than 1 minute) have been associated with severe ROP and impaired neurodevelopmental
      outcome in survivors (2, 5).

      Peripheral oxygen saturation monitoring is standard of care in preterm infants. Traditionally
      oxygen saturation (SpO2) targeting is carried out by manual adjustment of fraction of
      inspired oxygen (FiO2) by the caregiver based on the monitored oxygen saturation. However, in
      practice this is only partially achieved during routine care[6]. Hagadorn et al conducted a
      study in 14 centers and showed that preterm infants under 28 weeks' gestation receiving
      oxygen spent on average only 48% of the time with SpO2 within the prescribed target range,
      about 36% of the time above and 16% of the time with SpO2 below the target range [7].

      Preterm infants have frequent fluctuations in SpO2 due to their cardio-respiratory
      instability requiring frequent adjustments of FiO2 [7]. Consequently, these particularly
      vulnerable infants spend significant time with SpO2 outside intended range and are often
      exposed to extremes of hypoxemia and hyperoxaemia. It is now possible to have automated
      control of inspired oxygen using a device (CLiO2™) incorporated in Avea® ventilator. The
      device continuously monitors the oxygen saturation and adjusts the oxygen delivery to
      maintain oxygen saturation within the target range. The safety, feasibility and efficacy of
      this device have already been established [9-14]. There has been further improvement in the
      algorithm of the pulse oximeter incorporated in Avea® ventilator to achieve a better
      normative distribution around the median SpO2 value[15]. Automated control of FiO2
      significantly improves compliance of oxygen saturation targeting and significantly reduces
      exposure to hypoxemia as well as hyperoxaemia [9-14, 16,]. Automatic control of oxygen
      delivery is available in both invasive and non-invasive mode of ventilation (17). The Avea
      ventilators are equipped with Automatic Oxygen control with invasive as well as non-invasive
      mode of ventilation.

      Previous studies looking at the efficacy of automated oxygen control mostly have been a
      crossover model and the study duration less than 48 hours. As previously mentioned, preterm
      infants experience hypoxic events for few weeks before cardiopulmonary maturation is
      established. Hence, it's important to study these events over a longer period of time. The
      objective of this randomised controlled trial is to evaluate the efficacy of the automatic
      oxygen control function in reducing the time spent in extremes of oxygen saturations (less
      than 80%), in preterm infants for the entire period of their respiratory support on invasive
      or non-invasive mode of ventilation.
    

Intervention name(s): Automatic Oxygen control; Manual Oxygen Control
Intervention type(s): Device; Other
Intervention description(s): The CLiO device is integral to the Avea infant ventilator and allows automated OXYGEN adjustment aiming to maintain SpO2 within assigned target range using neonatal pulse oximeter. When first started it adopts the FiO2 previously set by the clinician as the initial 'Baseline FiO2' level. Thereafter, the changes to the FiO2 and their frequency depend on whether SpO2 is below, above or within the target range, the trend in SpO2 and all changes are proportionate to the 'Baseline FiO2' level.; In the manual arm the oxygen is adjusted manually by the clinical team.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Preterm Infants; Automatic oxygen control; Respiratory support