1. Preterm infants who receive automated oxygen delivery probably spend more time in the desired oxygen saturation range compared to those who receive routine manual oxygen delivery. However, it is unclear whether this effect reduces their risk of death, severe eye disease, or brain development problems.
2. We were unable to draw firm conclusions on the effectiveness of automated oxygen delivery compared with enhanced manual oxygen delivery, or of one automated delivery system compared with another.
3. There is a need for further studies to assess the effects of automated oxygen delivery on important long-term clinical outcomes such as death and major lung, eye, brain, and gut problems.
What is automated oxygen delivery?
Automated oxygen delivery refers to a system that automatically adjusts the amount of oxygen delivered to a patient in response to changes in oxygen readings. It is an alternative to manual adjustment of oxygen delivery by nursing or medical staff.
What did we want to find out?
We wanted to find out whether automated control of oxygen delivery works better than manual control of oxygen delivery, or whether any automated oxygen delivery system works better than any other, in infants with breathing problems who are cared for in the neonatal intensive care unit.
What did we do?
We searched for studies that evaluated:
1. automated oxygen delivery compared with manual oxygen delivery; or
2. one automated oxygen delivery system compared with another.
We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and number of participants.
What did we find?
We included 18 trials involving 457 preterm infants who required breathing support. Sixteen of these trials used a cross-over design (infants switched their assigned intervention halfway through the trial). The biggest study included 80 infants and the smallest study included five infants. The studies were mostly conducted in Europe (particularly Germany and the UK) and the USA. Most studies were conducted in very short periods of time (less than 24 hours). Six trials were funded by the manufacturer or distributors of the automated oxygen delivery devices.
Among preterm infants who require breathing support, automated oxygen delivery probably increases percentage time in the desired oxygen saturation range (oxygen saturation reading range that is considered optimal for the infant and that the doctors and nurses try to achieve) compared to routine manual oxygen delivery, with an average increase of 13.5%. However, it is unclear whether automated oxygen delivery improves other outcomes such as death, severe eye disease, or brain development problems.
It is also unclear whether automated oxygen delivery is better than enhanced manual oxygen delivery (manual control with better staffing), and whether one automated oxygen delivery systems is more effective and safer than another.
What are the limitations of the evidence?
We have moderate confidence in our finding that automated oxygen delivery compared with routine manual oxygen delivery increases time in the desired oxygen saturation range. However, we have little confidence in most of our other findings. Three main factors reduced our confidence in the evidence. First, most cross-over studies did not provide separate data for each study period (before and after the infants changed oxygen delivery system) as recommended. As a result, we could not compare the effects of automated oxygen delivery before and after the cross-over. Second, a few studies with very few participants provided most of the usable data, and most studies did not assess important clinical outcomes such as death and major conditions affecting the infants' guts and long-term brain development. Third, there were inconsistent findings between the studies in some outcomes.
How up to date is this evidence?
Our search is current to January 2023.
Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO2 ranges in preterm infants on respiratory support. However, it is unclear whether this translates into important clinical benefits. The evidence on clinical outcomes such as severe retinopathy of prematurity are of low certainty, with little or no differences between groups.
There is insufficient evidence to reach any firm conclusions on the effectiveness of automated oxygen delivery compared to enhanced manual oxygen delivery or CLACfast compared to CLACslow.
Future studies should include important short- and long-term clinical outcomes such as mortality, severe ROP, bronchopulmonary dysplasia/chronic lung disease, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, and long-term neurodevelopmental outcomes. The ideal study design for this evaluation is a parallel-group randomised controlled trial. Studies should clearly describe staffing levels, especially in the manual arm, to enable an assessment of reproducibility according to resources in various settings. The data of the 13 ongoing studies, when made available, may change our conclusions, including the implications for practice and research.
Many preterm infants require respiratory support to maintain an optimal level of oxygenation, as oxygen levels both below and above the optimal range are associated with adverse outcomes. Optimal titration of oxygen therapy for these infants presents a major challenge, especially in neonatal intensive care units (NICUs) with suboptimal staffing. Devices that offer automated oxygen delivery during respiratory support of neonates have been developed since the 1970s, and individual trials have evaluated their effectiveness.
To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy.
We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials.
We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation).
We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO2) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence.
We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over).
Automated oxygen delivery versus routine manual oxygen delivery
Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO2 range (MD 13.54%, 95% CI 11.69 to 15.39; I2 = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes.
Automated oxygen delivery versus enhanced manual oxygen delivery
There may be no clear difference in time (%) in the desired SpO2 range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI −1.63 to 16.19; I2 = 0%; 2 studies, 19 infants; low-certainty evidence).
No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes.
Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow)
CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO2 range compared to CLACslow (MD 3.00%, 95% CI −3.99 to 9.99; 1 study, 19 infants; low-certainty evidence).
No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes.
OxyGenie compared to CLiO2
Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis.