Prolonged administration of closed-loop inspired oxygen support in preterm infants
A randomised clinical trial

Preterm infants often require supplemental oxygen to prevent hypoxemia, a
condition that has been associated with organ damage and an increased
mortality. However, too much oxygen supplementation resulting in hyperoxemia
may lead to systemic oxidative damage and long-term complications such as
retinopathy of prematurity (ROP). For these reasons, oxygen saturation is
continuously measured in preterm infants with pulse oximetry (SpO2) aiming to
keep it within a safe target range (TR) by manually titrating the fraction of
inspired oxygen (FiO2). However, studies in preterm infants have shown that
SpO2 targeting is a clinical challenge with patients spending only 50% of the
time within their SpO2 TR, due to clinical instability and the limited time
nurses have to adjust the amount of oxygen. Newly developed techniques
incorporated in the ventilator provide the opportunity of automated FiO2
control (A-FiO2). Only short term studies (days) have investigated the A-FiO2
function and long term effects need to be evaluated. The short term studies
indicate that this closed-loop A-FiO2 reduces time outside the TR, decreases
number and duration of hypo- and hyperoxemic episodes, and reduces caregivers*
workload compared to manual FiO2 control (M-FiO2).

To assess the effectiveness of continuous, long term (weeks) use of a
closed-loop FiO2 control system in comparison with M-FiO2 control in preterm
infants with non-invasive respiratory support.

Randomised controlled trial.

In order to study the effectiveness over a longer period of time of the A-FiO2
function of the ventilator, preterm infants will be set at random to either
continuous use of the A-FiO2 function or to continuous use of M-FiO2 control
from first week of life till the 28th day of life.

Benefit and risks: Previous studies have shown that using A-FiO2 function to
keep the patient within preset saturation ranges is feasible and safe. This
study will evaluate the efficacy of such a tool over a longer period. Avoiding
hyperoxemia and hypoxia by tight control of the saturation ranges could be a
potential benefit for the included patients, as there is now a considerable
body of evidence showing that both hypoxia and hyperoxemia can damage multiple
organ systems in the preterm infant.
There are no additional known risks to the infant other than those experienced
routinely by the premature infants who require supplemental oxygen while in the
newborn intensive care nursery.
There are specific alarms and user alerts built in the A-FiO2 function to
improve patient safety in addition to the standard alarms of the pulse
oximeter. These alarms will alert the routine caregivers of conditions that
require assessment and possible intervention.
Group relatedness: Respiratory instability for which supplemental oxygen is
required is a complication occurring exclusively in preterm infants. Any
intervention aiming to reduce the risk of hyperoxemia or hypoxemia therefore
needs to be studied in this specific population at risk.