Comparison of Automated Oxygen Control (Closed Loop Inspired Oxygen:CLiO2™) With and Without Automated Pressure Control (Volume Guarantee®) in Preterm Ventilated Infants: A Crossover Study (CLIO-VG Study)

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 hyperoxaemia 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]. Similarly, exposure to hypoxemic episodes can lead to increased mortality [2, 3]. Traditionally oxygen saturation (SpO2) targeting is carried out by manual adjustment of fraction of inspired oxygen (FiO2) by the caregiver. However, in practice this is only partially achieved during routine care[4]. Hagadorn et al conducted a study in 14 centres 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 There was a wide and significant variation in SpO2 target range compliance between the participating centres[5].

Preterm infants have frequent fluctuations in SpO2 due to their respiratory instability requiring frequent adjustments of FiO2 [6]. Consequently, these particularly vulnerable infants spend significant time with SpO2 outside intended range and are often exposed to extremes of hypoxemia and hyperoxaemia. To this end, it is now possible to have automated control of inspired oxygen using a device (CLiO2™) incorporated in Avea® ventilator. The safety, feasibility and efficacy of this device have already been established [7-12]. 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[13]. Automated control of FiO2 significantly improves compliance of oxygen saturation targeting and significantly reduces exposure to hypoxemia as well as hyperoxaemia [7-12, 14].

Another mechanism of respiratory instability and hypoxemia is wide fluctuation in tidal volume in ventilated preterm infants. Volume-targeted modes of ventilation have been used for several years to aim to more accurately control the tidal volumes delivered to ventilated infants. Jain et al showed a reduction in duration of hypoxaemic events when using volume targeted ventilation as compared to pressure controlled ventilation[15]. Avea ventilators can deliver several types of volume-targeted ventilation, including Volume Guarantee® (VG) and volume controlled ventilation (VCV). VCV aims to deliver a set volume of gas irrespective of the lung compliance whereas VG® uses a servo-controlled feedback loop to automatically adjust inspiratory pressures to aim to control tidal volume delivery.

There is no data available currently on whether automatic control algorithm adjustment of inspired oxygen and tidal volume together leads to further improvements in maintaining SpO2 profile within prescribed target range and more importantly to reduce episodes of prolonged hypoxemia and hyperoxaemia in preterm ventilated infants. Hence the investigators propose this study.

The aim of this study is to examine whether automatic control of inspired oxygen and tidal volume together leads to further improvements in maintaining SpO2 profile within the prescribed target range in preterm, ventilated infants.