Eur J Pediatr
DOI 10.1007/s00431-015-2643-0
REVIEW
Compliance in oxygen saturation targeting in preterm infants:
a systematic review
Henriëtte A. van Zanten 1 & Ratna N. G. B. Tan 1 & Agnes van den Hoogen 2 &
Enrico Lopriore 1 & Arjan B. te Pas 1
Received: 11 July 2015 / Revised: 24 September 2015 / Accepted: 28 September 2015
# The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract During oxygen therapy in preterm infants, targeting
oxygen saturation is important for avoiding hypoxaemia and
hyperoxaemia, but this can be very difficult and challenging
for neonatal nurses. We systematically reviewed the qualitative and quantitative studies investigating the compliance in
targeting oxygen saturation in preterm infants and factors that
influence this compliance. We searched PubMed, Embase,
Web of Science, Cochrane, CINAHL and ScienceDirect from
2000 to January 2015. Sixteen studies were selected, which
involved a total of 2935 nurses and 574 infants. The studies
varied in methodology, and we have therefore used a narrative
account to describe the data. The main finding is that there is a
low compliance in oxygen targeting; the upper alarm limits
are inappropriately set, and maintaining the saturation (SpO2)
below the upper limit presented particular difficulties.
Although there is little data available, the studies indicate that
training, titration protocols and decreasing workload could
improve awareness and compliance. Automated oxygen
Communicated by Patrick Van Reempts
regulations have been shown to increase the time that SpO2
is within the target range.
Conclusion: The compliance in targeting oxygen during
oxygen therapy in preterm infants is low, especially in maintaining the SpO2 below the upper limit.
What is Known:
• The use of oxygen in preterm infants is vital, but the optimal strategy
remains controversial.
• Targeting SpO2 during oxygen therapy in preterm infants has been
shown to reduce mortality and morbidity.
What is New:
• Review of the literature showed that the compliance in targeting SpO2
and alarm settings is low.
• Creating awareness of risks of oxygen therapy and benefits in targeting,
decreasing nurse/patient ratio and automated oxygen therapy could
increase compliance.
Keywords Preterm infant . Targeting oxygen . Compliance .
Alarm limits . Hyperoxaemia . Hypoxaemia . Automated
oxygen
* Henriëtte A. van Zanten
h.a.van_zanten@lumc.nl
Ratna N. G. B. Tan
r.n.g.b.tan@lumc.nl
Agnes van den Hoogen
ahoogen@lumc.nl
Enrico Lopriore
e.lopriore@lumc.nl
Abbreviations
CPAP Continuous positive airway pressure
NICU Neonatal intensive care unit
PO
Pulse oximetry
SpO2 Oxygen saturation
TRs
Target ranges
Arjan B. te Pas
a.b.te_pas@lumc.nl
1
Department of Pediatrics, Division of Neonatology, Leiden
University Medical Center, J6-S, PO Box 9600, 2300
RC Leiden, The Netherlands
2
Utrecht Medical Center, Utrecht, The Netherlands
Introduction
Supplemental oxygen is often administered to preterm infants for hypoxemic episodes during respiratory distress or
Eur J Pediatr
apnoeas. It is important to prevent hypoxaemia (defined as
a decrease in arterial blood saturation (SpO2) of ≤80 %
for ≥10 s), as frequent episodes could lead to an increased
risk of morbidities, including retinopathy of prematurity
(ROP), impaired growth, longer term cardio-respiratory instability and adverse neurodevelopmental outcome [12, 15,
30]. In extreme cases, it can even lead to death [12, 15].
Hyperoxaemia (SpO2 of >95 % for ≥10 s) also needs to
be prevented, as administering supplemental oxygen can
potentially lead to high oxygen levels. High concentration
of oxygen is toxic to living cells and is known to be an
important pathogenic factor for bronchopulmonary dysplasia (BPD) and ROP [31] and is correlated with cerebral
palsy [3].
Pulse oximetry (PO) is most commonly used for continuous monitoring of oxygen saturation (SpO2) in a noninvasive manner [26]. To prevent hypoxaemia and
hyperoxaemia, nurses usually titrate oxygen manually to
maintain SpO 2 between the prescribed target ranges.
However, maintaining the SpO2 within this range can be
challenging, and compliance—defined as the nurse’s behaviour that follows the clinical guidelines—[13] is influenced
by several factors [40]. This compliance is important, as it
can largely influence the effect of a certain SpO2 target
range. The optimal range of SpO2 for preterm infants remains undefined, but recent trials have shown that aiming
for 91–95 % has decreased mortality but increased incidence of ROP [36]. However, in these trials, oxygen was
titrated manually, which caused a large overlap in the distribution of SpO2 between the two groups and may have
decreased the observed differences in outcome.
Although comparison of SpO2 target ranges has been subject to systemic review [19], a review in the compliance in
SpO2 target ranges is not available but equally important as
which target range is optimal. The purpose of this study is to
systematically review the available literature in compliance—
and the factors influencing this compliance—in targeting
SpO2 in preterm infants.
Methods
We performed a systematic review, following PRISMA
guidelines where possible (Fig. 1) [28]. The aim of the
PRISMA statement is to help authors improve the
reporting of systematic reviews and meta-analyses, which
made it a particularly useful framework for this report.
Eligible studies were identified by searching online databases from January 1965 to January 2015 in PubMed,
Embase, Web of Science, Cochrane, CINAHL and
ScienceDirect (keywords in Table 1). After selecting the
eligible studies, we manually searched the reference lists
of the selected studies to identify additional references.
The criteria for inclusion limited the selection to articles
published in English or Dutch which referred to preterm
infants, (nursing) compliance, SpO2 monitoring by PO and
targeting oxygen saturation during NICU admission. Both
qualitative and quantitative designs were included, but
publications that were not primary research studies, i.e.
letters, abstracts, reviews and editorials, were not (Fig. 1).
Three authors (HvZ, RT, AH) independently graded
the selected studies using the QualSyst tool for quantitative and qualitative studies [21]. In case of disagreement, consensus was reached through discussion or consultation of a fourth co-author (AtP). The QualSyst tool
for quantitative studies is a validated generic checklist
consisting 14 items with scores from zero to two and
the possibility to score ‘not applicable’. Items rated not
applicable were excluded from the calculation of the
summary score. The maximum total score is 28. The
summary score was calculated by summing the total
score obtained across the relevant items and dividing
that by the total possible score.
The QualSyst tool for qualitative studies is a validated generic checklist consisting of ten items with scores from zero to
two, with the maximum total score of 20. A summary score
was calculated for each study by summing the total score
across the ten items and dividing them by the total possible
score of 20 [21].
Data from selected studies were extracted using a data
extraction form. The following study characteristics were extracted: author, year, design, sample, time points, length of
measurement, target range and key results.
Results
Sixteen articles met the inclusion criteria for this review
(Fig. 1), detailing studies that included a total of 574 infants
and 2935 nurses. Fourteen of these studies used a quantitative design [1, 7–10, 17, 18, 22, 25, 27, 34, 38, 39, 41]
while the remaining two used qualitative methods [2, 29].
There was no homogeneity in the study designs, so pooling
the data for meta-analysis was not possible. We therefore
discuss the studies and their results using a narrative format
organized under thematic headings and summarized in
tables.
Quality assessment
The studies varied in quality, but none was excluded
because of low-quality scores. One observed weakness
was the lack of power analysis in four of the studies [10,
17, 27, 39], and all studies were unclear in the reasoning
behind the timing and duration of SpO2 data collection [1,
Eur J Pediatr
Idenficaon
Fig. 1 Flow diagram selection
studies
Records idenfied through database searching
(PubMed, Embase, Web of Science , COCHRANE,
CINAHL, ScienceDirect
(n = 295)
Addional records idenfied through other sources
(n =0)
Records screened
(n = 192)
Records excluded
(n = 174)
Arcles did not meet inclusion criteria
Full-text arcles assessed for eligibility
(n = 18)
Full-text arcles excluded
(n =2)
Arcles did not meet inclusion criteria
Eligibility
Screening
Records aer duplicates removed
(n = 195)
Included
Studies included in qualitave synthesis
(n=16)
2, 7, 10, 17, 18, 22, 25, 27, 29, 34, 38, 39, 41] (Tables 2
and 3).
Study designs
The designs of the quantitative studies varied and were composed of the following: one efficacy study [9], two pilot clinical trials [6, 41], three randomized clinical trials [7, 18, 38]
and eight observational studies, of which six had a prospective
design [1, 10, 17, 22, 25, 27] and two were retrospective [34,
39] (Table 4). Both qualitative studies employed a descriptive
design [2, 29] (Table 4).
Studies included in quantave
synthesis (n=16)
Time points and length of measurements
All studies were conducted in the period that the infants needed
supplemental oxygen, but the starting time points and duration
of data collection differed between studies. The starting time
point varied between the first day of life [1, 2] and 33 days [8]
(Table 4). In one study, the postnatal age was not described [27].
The duration of data collection also varied widely, the shortest
covering only 4 h [9] and the longest the entire period between
admission and discharge [10]. The data were collected continuously in eight studies [1, 7–9, 18, 34, 38, 39, 41] and intermittently in the remaining studies [10, 17, 22, 27] (Table 4).
Compliance in TR
TRs of SpO2
The lower limit of the target ranges (TRs) varied between
studies from 80 to 92 % [17, 18], and upper limits of TR
varied from 92 to 96 %, respectively [1, 9, 10, 17, 25, 27,
34] (Table 4).
Twelve studies investigated how often SpO2 values were in or
outside the TR, expressed as the percentage of monitored time
[1, 7–9, 17, 18, 22, 25, 34, 38, 39, 41]. In a multicentre study,
Hagadorn et al. observed that SpO2 was below, within or above
TR in 16 (0–47 %), 48 (6–75 %) and 36 (5–90 %), respectively,
of the monitored time [17]. Van der Eijk et al. reported similar
Eur J Pediatr
Table 1
Keywords in different databases
Database
Keywords (including MeSH) terms
PubMed
Hyperoxiaa, Hyperoxia*, hyperoxygenation, Hyperoxias, Hyperoxie, Hyperoxic, Hyperox*, hyperoxemic episode,
hyperoxemic episodes, hypoxia, hypox*, hypoxemic episode, hypoxemic episodes, cyanosis
cyanoses pulse oximetry, pulse oximeter, pulse oximeters, Infanta, Prematurea, prematurity, prematur*,
Pre-mature, pre-maturity, preterm, preterm*, low birth weight infant, low birth weight infants, Oxygen
Inhalation Therapya, Hyperbaric Oxygenationa, Oxygen/administration and dosagea, oxygen/therapeutic
use + Oxygen/therapya, Oxygen/Consumptiona, oxygen consumption, oxygen, oxygenation, FiO2, FiO 2,
FiO(2), FiO, increas*, fraction* exposure*, increase oxygen, increased oxygen, oxygen supplementation,
oxygen therapy, supplemental oxygen, Automated closed loop control, FIO2 automatic, FIO2 adjustment
closed-loop, FIO2 control, Oxygen Inhalation Therapy/instrumentationa, Respiration,
Artificial/instrumentationa
complia*, nursing compliance, Adherence, adher*, Guideline Adherencea, Advance Directive Adherencea,
Goalsa, nursing procedures
CINAHL
Hyperoxia, hyperoxias, Hyperoxia* hyperoxygenation, hyperoxie, hyperoxic, hyperox* cyanosis,
cyanoses, hypoxia*, pulse oximetry, pulse oximeter, pulse oximeters, prematur*, Prematurity, pre-mature,
pre-maturity, preterm, preterm*, pre-term, low birth weight infant, low birth weight infants, Oxygen*,
FiO2, FiO 2, FiO(2), FiO, increas*, fraction, fractions, fraction*, exposure, exposures, exposure*, increase
oxygen, increased oxygen, oxygen supplementation, supplemental oxygen, oxygen saturation, oxygen
administration, oxygen therapy, Automated closed loop control, FIO2 automatic, FIO2 adjustment
closed-loop, FIO2 control, compliance, complia*, nursing compliance, Adherence, adher*
Hyperoxia, Hyperoxias, Hyperoxia*, Hyperoxie, Hyperoxic, hyperoxygenation, Hyperox*, cyanosis,
cyanoses pulse oximetry, pulse oximeter, pulse oximeters, hypoxia*, hypoxemic episodes, hyperoxemic
episodes, hypoxemic episode, hyperoxemic episode, cyanosis, cyanoses, premature, Prematurity, prematur*,
pre-mature, pre-maturity, preterm, preterm*, pre-term, elbw infant*, low birth weight infant*, Oxygen*, FiO2,
FiO 2, FiO(2), FiO, increas*, fraction, fractions, fraction*, exposure, exposures, exposure*, increase oxygen,
increased oxygen, oxygen supplementation, supplemental oxygen, oxygen saturation, oxygen administration,
oxygen therapy, Automated closed loop control, FIO2 automatic, FIO2 adjustment closed-loop, FIO2 control,
compliance, complia*, nursing compliance, Adherence OR adher*
Hyperoxia/, pulse oximetry/, exp Hypoxia/, Hyperoxia, Hyperoxias, Hyperoxia*, Hyperoxie, Hyperoxic,
hyperoxygenation, Hyperox*, pulse oximetry, pulse oximeter, pulse oximeters, hypoxia, hypoxemic
episodes, Bhyperoxemic episodes^ hypoxemic episode, hyperoxemic episode, cyanosis/, cyanosis, cyanoses,
prematurity/, premature, Prematurity, prematur*, pre-mature, pre-maturity, preterm, preterm*, pre-term, low
birth weight infant, low birth weight infants, Oxygen*, FiO2, FiO 2, FiO(2), FiO) increas*, fraction, fractions,
fraction*, exposure, exposures, exposure*, increase oxygen, increased oxygen, oxygen supplementation,
supplemental oxygen, oxygen saturation, oxygen administration, oxygen therapy, exp oxygen therapy/,
oxygen saturation/, Automated closed loop control, FIO2 automatic, FIO2 adjustment closed-loop, FIO2
control, oxygen delivery device/, exp *patient compliance/ compliance, complia*, nursing compliance,
Adherence, adher* Bnursing procedures^
Hyperoxia, Hyperoxias, Hyperoxia*, Hyperoxie, Hyperoxic, hyperoxygenation, Hyperox*, pulse oximetry,
pulse oximeter, pulse oximeters, hypoxia*, cyanosis, cyanoses, premature, Prematurity, prematur*, pre-mature,
pre-maturity, preterm, preterm*, pre-term, low birth weight infant, low birth weight infants, Oxygen*, FiO2,
FiO 2, FiO(2), FiO, increas*, fraction, fractions, fraction*, exposure, exposures, exposure*, increase oxygen,
increased oxygen, oxygen supplementation, supplemental oxygen, oxygen saturation, oxygen administration,
oxygen therapy, Automated closed loop control, FIO2 automatic, FIO2 adjustment closed-loop, FIO2 control,
compliance OR complia* OR nursing compliance OR Adherence OR adher*
Hyperoxia, Hyperoxias, Hyperoxia*, Hyperoxie, Hyperoxic, hyperoxygenation, Hyperox*, pulse oximetry,
pulse oximeter, pulse oximeters, hypoxia*, premature, Prematurity, prematur*, pre-mature, pre-maturity,
preterm, preterm*, pre-term, low birth weight infant, low birth weight infants, Oxygen*, FiO2, FiO 2, FiO(2),
FiO, increas*, fraction, fractions, fraction*, exposure, exposures, exposure*, increase oxygen, increased
oxygen, oxygen supplementation, supplemental oxygen, oxygen saturation, oxygen administration, oxygen
therapy,
Automated closed loop control, FIO2 automatic, FIO2 adjustment closed-loop, FIO2 control, compliance,
complia*, nursing compliance, Adherence, adher*
Web of Science
Embase
ScienceDirect
Cochrane
a
Keywords that were MeSH terms
values, finding that SpO2 was below TR for 16 % of the time and
above it for 30 % [39]. In contrast, Lim et al. only studied infants
receiving supplemental oxygen during CPAP and SpO2 was
below TR for 9 % and above it for 58 % of the time [25].
Education and training
Two studies demonstrated the impact of an educational program in targeting SpO2. Laptook et al. observed that training
Eur J Pediatr
Table 2
Quality appraisal of included quantitative studies
Quality assessment quantitative studies
Studies
Question 2.
Study design
Claure, N. et al. (2001)
1
1
Claure, N. et al. (2009)
1
1
Claure, N. et al. (2011)
2
2
Clucas, L. et al. (2007)
2
2
Hagadorn, J.I. et al. 2006)
2
2
Laptook, A.R. et al. (2006)
1
1
Mills, B.A. et al. (2010)
2
2
Sink, D.W. et al. (2011)
2
1
Urschitz, M.S. et al. (2004)
2
2
Van der Eijk, A.C. et al. (2012) 1
2
Zapata, J. et al. (2014)
2
2
Lim, K. et al. (2014)
2
2
Arawiran, J. et al. (2014)
2
2
Hallenberger, A. et al. (2014)
2
2
3.
Selection
1
1
2
1
1
1
1
1
2
2
2
2
2
2
4.
Subject characteristics
2
2
2
2
2
2
2
1
2
2
2
2
2
2
5.
Random allocation
1
1
1
0
1
0
1
0
2
0
2
n/a
n/a
2
6.
Blinding investigator
0
0
0
0
0
0
0
0
0
0
0
n/a
n/a
0
7.
Blinding subjects
n/a
n/a
0
0
0
0
0
n/a
0
0
0
n/a
n/a
0
8.
Outcome
1
1
2
2
1
1
1
1
1
1
2
2
1
2
Quality assessment quantitative studies
Studies
9.
Sample size
10.
Analytic methods
11.
Estimate of variance
12.
Confounding
13.
Results
14.
Conclusion
Summary
score
Claure, N. et al. (2001)
n/a
2
2
1
1
1
14/24=0.58
Claure, N. et al. (2009)
2
2
2
1
1
1
16/26=0.62
Claure, N. et al. (2011)
2
2
2
1
2
2
22/28=0.79
Clucas, L. et al. (2007)
0
2
2
1
2
2
18/28=0.64
Hagadorn, J.I. et al. 2006)
0
2
2
1
1
1
16/28=0.57
Laptook, A.R. et al. (2006)
2
2
2
1
1
1
15/28=0.54
Mills, B.A. et al. (2010)
0
2
2
1
1
2
17/28=0.61
Sink, D.W. et al. (2011)
n/a
2
0
1
1
1
11/24=0.46
Urschitz, M.S. et al. (2004)
2
2
2
1
2
2
22/28=0.79
Van der Eijk, A.C. et al. (2012)
0
2
1
1
1
1
14/28=0.5
Zapata, J. et al. (2014)
1
2
2
1
2
2
22/28=0.79
Lim, K. et al. (2014)
n/a
2
2
2
2
2
20/20=1
Arawiran, J. et al. (2014)
1
2
2
1
2
1
18/22=0.82
Hallenberger, A. et al. (2014)
2
2
2
1
1
1
21/28=0.75
2 = yes; 1 = partial; 0 = no; n/a = not applicable
did not change the time that SpO2 was below (26.9 vs. 26.6 %;
not significant (ns)) or above TR (15.4 vs. 14.0 %; ns) [22].
Interestingly, Arawiran et al. even observed that training
had an adverse effect and that the time that SpO2 was
within TR decreased after training (44.5±14.4 vs 40.4±
12.8 %) with an increase in time above TR (from 36.9±
17.2 vs 41.9±15.6 %) [1].
third or fourth patient was added to the nurse’s workload [34].
The high percentage of time above TR was probably due to
the use of a lower upper limit (92 %) in comparison with other
studies [7–9, 22, 38, 39]. Lim et al. also confirmed that more
than one infant per nurse was associated with an increase in
the time when SpO2 was above TR (Table 4) [25].
Automated regulation of inspired oxygen
Nurse/patient ratio
Sink et al. studied the influence of the nurse/patient ratio on
compliance in SpO2 targeting. They observed that the proportion of time that SpO2 was below TR decreased from 0.06 to
0.03 and time above TR increased from 0.56 to 0.82 when a
Six recent studies reported that, when compared to manual
titration, the use of automated regulation of inspired oxygen
increased the time that SpO2 spent within TR [7–9, 18, 38,
41]. In a multicenter crossover study of ventilated preterm
infants, Claure et al. (2011) observed that the time that SpO2
15/20=0.75
2
2
0
0
2
2
2 = yes; 1 = partial; 0 = no
2
2
2
1
0
2
2
1
2
2
3.
Context
2.
Study design
1.
Question/objective
Studies
The wide variation in study methodologies made it necessary
to use narrative reporting when discussing the results of this
systematic review. Although the power of some of the studies
was limited and the quality varied, all were considered eligible
for inclusion. Moreover, they focused on different aspects of
compliance in targeting SpO2. The design, TR of SpO2, time
points and duration of each study differed.
The central finding is that compliance in targeting SpO2
was low, as were the alarm settings. All studies in compliance
Quality assessment qualitative studies
Discussion
Table 3
Armbruster et al. interviewed nurses who stated that the following would improve their compliance: further education,
prompt response to alarm limits, a favourable patient to staff
ratio, root cause analyses at the bedside and high priority
given to control oxygen therapy [2]. Nghiem et al. reported
that 63 % of the nurses were aware of the local oxygen saturation guidelines and 57 % of them correctly identified the
target limits specified by their NICU guidelines (Table 4) [29].
Quality appraisal of included qualitative studies
Nurses’ perception and awareness
2
4.
Theoretical framework
5.
Sampling strategy
6.
Data collection
7.
Data analysis
Two studies investigated nursing compliance in setting the
appropriate alarm limits for PO in preterm infants [10, 27].
The actual SpO2 values were not reported, but Clucas et al.
observed that the lower and upper alarm limit was set correctly
in 91 and 23 % of monitored time, respectively [10]. Mills
et al. compared compliance in alarm settings of SpO2 according to whether or not infants participated in a trial. When
infants were participating in the BOOST II trial, the lower
and upper alarm limit for SpO2 was set correctly in 94 %
(88–100 %) and 80 % (71–88 %) of the monitored time period. However, this decreased to 87 % (75–99 %) and 29 %
(17–40 %) when infants were not participating in the trial [27]
(Table 4).
2
Compliance in alarm limit setting
Nghiem, T.H. et al. 2
(2008)
Armbruster, J.
1
et al.
(2010)
8.
Verification procedure
9.
Conclusion
10.
Reflexivity
Summary
score
was within TR increased significantly during the automated
period compared with the manual period (40 % (14) vs 32 %
(13) (mean (SD) p<0.001). The time periods with SpO2
>93 % or >98 % were thus significantly reduced during the
automated period [7]. Although most studies observed that the
time that SpO2 was above TR decreased [7–9, 38, 41] while
the time below TR increased [7, 8, 38, 41], Hallenberger et al.
found different results. They observed no change in time
above TR (16 (0.0–60) vs 15.9 (1.9–34.8) p=0.108) during
automatic control of inspired oxygen and, therefore, no difference with manual control [18] (Table 4).
16/20=0.8
Eur J Pediatr
Summery of included studies
Author
Year
Design
Study objects
Timing of measurement
Target range
Key results
Armbruster, J. et al.
2010
Qualitative study with individual
open-ended interviews
41 nurses
First 3 days of life while infants
were receiving supplemental oxygen
88–92 %
Claure, N. et al.
2009
Pilot clinical trial
16 premature infants,
GA 24.9±1.4
weeks receiving
mechanical
ventilation and FiO2
4-h period with FiO2 adjustment by
clinical staff members (manual)
and 4-h period with automated FiO2
adjustments (automated)
PNA 33 days (SD±15)
88–95 %
Claure, N. et al.
2001
Efficacy study
14 infants, GA 25 weeks
(SD ±1.6) receiving
mechanical ventilation
and FiO2
2 h in manual FiO2 mode and 2 h in
automatic FiO2 mode in
random sequence.
PNA 26 days (SD±11)
88–96 %
Saturations of infants in the Canadian Oxygen
Trial (COT) study were in the intended range
in 68–79 % of time.
Nurses identified education, prompt
response to alarm limits and a favourable
patient to staff ratio as important determinants
of good compliance
In automated mode:
• % of time within SpO2 target range was 58 %
• % of time that SpO2 >95 % was 9 %
• % of time that SpO2 <88 % was 33 %
In manual mode:
• % of time within SpO2 target range was 42 %
• % of time that SpO2 >95 % was 31 %
• % of time that SpO2 <88 % was 27 %
In automatic FiO2 mode
• % of time within SpO2 target range was 74.9 %
• The percentage of time that saturations were <
88 % was 16.5 % and
• >96 % in 9.9 % of the time.
In manual FiO2 mode
• % of time within SpO2 target range was 66.3 %
• The percentage of time that saturations <88 %
was 18.7 % and
• >96 % in 14.9 % of time.
Claure, N. et al.
2011
Clinical trial
32 premature infants
GA 25 weeks (24–27)
receiving mechanical
ventilation and FiO2
24-h period with FiO2 adjustment by
clinical staff members (manual) and
24-h period with automated FiO2
adjustments (automated)
PNA 27 days (range 17–36)
87–93 %
Clucas, L. et al.
2007
Prospective cohort study
80 infants with receiving
supplemental oxygen
Mean GA of 28.4 weeks
(SD ±2.4)
1073 lower and upper
alarm limit values
Daily during weekdays, when the
infant was on oxygen until discharge
PNA 5 days (IQR 2–34.5)
88–92 %
Hagadorn, J.I. et al.
2006
Prospective multicentre cohort study
84 infants
GA 26.3
Median:
(29.4–27.4) 14 centres from
three counties
307 monitor periods of median duration
of 67.3 h
Saturation for 72 h each week for
the first 4 weeks of life
Laptook, A.R. et al.
2006
Prospective observational study
Group 1:
23 infants GA 27 weeks
(±2) receiving continuous
supplemental oxygen
(with or without ventilator)
Group 2:
49 infants, GA 26 weeks (±2) receiving
continuous supplemental
24 h of data twice a month
during 6 months when the
author was available
PNA group 1, 23 days (±21)
PNA group 2, 23 days (±19)
Centre-specific intended TR
92–96 %
90–95 %
88–95 %
88–97 %
88–92 %
87–94 %
92–96 %
90–96 %
85–98 %
88–94 %
85–94 %
88–92 %
83–93 %
Group 1: target range 90–95 %,
Group 2: target range 88–94 %
In automated mode:
• % of time within SpO2 target range was 40 %
• % of time that SpO2 >93 % was 28 %
• % of time that SpO2 <87 % was 32 %
In manual mode:
• % of time within SpO2 target range was 32 %
• % of time that SpO2 >93 % was 43 %
• % of time that SpO2 <87 % was 23 %
The lower alarm limit was set correctly in 91.1 %
of the time, 6.3 % was set lower, and 2.7 %
was set higher than intended; upper
alarm limit was set correctly in
23.3 % of the time, 0.2 % was set lower,
and 76.5 % was set higher
than intended.
Overall, infants spent 16 % below intended
range and 36 % above their NICU’s
intended range
Group 1:
SpO2 values were under target range in 26.9 %
and above the target range in 15.4 % of time
Group 2:
SpO2 values were under target range in 26.6 %
and above the target range in 14.0 % of time
Eur J Pediatr
Table 4
Table 4 (continued)
Author
Year
Design
Mills, B.A. et al.
2010
Prospective cohort study
Nghiem, T.H. et al.
2008
Survey
Sink, D.W. et al.
2011
Urschitz, M.S. et al.
Study objects
Timing of measurement
Target range
Key results
Daily during weekdays, when the
infant was on oxygen until discharge
88–92 %
Lower alarm limits:
In BOOST II trial; 94.2 % was set correctly;
Not in BOOST II; 87.3 % was set correctly.
Upper alarm limits:
In BOOST II trial; 79.8 % was set correctly;
Not in BOOST II; 28.8 % was set correctly
59 NICUs
2805 nurses who submitted surveys
First 4 weeks of life of preterm infants
68 % of included NICUs, had
policy specified SpO2 target
limits; not exactly defined
Retrospective observational study
14 infants GA <26.6 weeks
(SD±1.6) with oximeter data
87 nurses
Every 2 s during routine bedside
oximetry monitoring
PNA 31.6 weeks (mean range
24.1–40.7 weeks)
85–92 %
Of 1957 nurses at NICUs with policies,
64 % of nurses were aware that policy
for SpO2 was present in their NICU.
715 (37 %) nurses correctly identified the
SpO2 limits specified by their NICU policy
Oxygen saturations in infants <28 GA were 61 %
above intended range and 6 % under
de intended range.
Infants of 28–31 weeks of gestation were 70 %
above intended range and 7 % under
de intended range.
Hyperoxic time increased from 48 to 71 %
with assignment of a second patient to
the infant’s nurse and to 82 % with
assignment of a third patient to the
infant’s nurse
2004
Randomized controlled clinical
trial (validation and efficacy trial)
Validation trial:
12 preterm infants
GA; median (IQR) 24.5
(24–28) receiving
ventilator support and FiO2
Efficacy trial;
12 preterm infants
GA; median (IQR) 25.5 (24–33)
receiving ventilator support and FiO2
1 day during five periods of
different modes, 90 min in each mode
• Baseline 1,
• Routine manual control,
• Optimal manual control,
• Closed-loop control,
• Baseline 2
Validation trial:
PNA 21 days (median range 8–57)
Efficacy trial:
PNA 20.5 days (median range 4–78)
87–96 %
Van der Eijk, A.C. et al.
2012
Observational cohort study
Recording started when FiO2 was >
21 % in the first 2 weeks of life
PNA 4 days (range 2–12)
88–94 %
Zapata, J. et al.
2014
Pilot clinical trial
12 infants, median GA
26 2/7 weeks
(range 24 2/7–28) with
a need for supplemental oxygen
20 infants,
mean GA 27.3±1.7 vs 27.7±1.7 weeks
receiving supplemental oxygen
by nasal cannula
12-h study period
PNA 5–14 days
85–93 %
oxygen (with or without
ventilator)
56 infants mean GA 26.7
weeks (SD 2.0)
receiving supplemental oxygen
22 infants in BOOST II trial
Number of recordings=454
Validation trial:
% of time within SpO2 target range was
• Baseline 1, 75.3 %
• Routine manual control, 79.7 %
• Optimal manual control, 85.8 %
• Closed-loop control, 82.1 %
• Baseline 2, 79.4 %
No information over hypoxaemic and
hyperoxaemic periods
Efficacy trial:
% of time within SpO2 target range was
• Baseline 1, 82.9 %
• Routine manual control, 81.7 %
• Optimal manual control, 91 %
• Closed-loop control, 90.5 %
• Baseline 2, 81.2 %
Duration of hypoxic episodes
• Baseline 1, 20.2 s (11.3 %)
• Routine manual control, 19 s (10.7 %)
• Optimal manual control, 16.4 s (9.2 %)
• Closed-loop control, 12.4 s (7 %)
• Baseline 2, 19.1 s (10.7 %)
Duration of hyperoxic episodes
• Baseline 1, 24.7 s (6.7 %)
• Routine manual control, 19.3 s (5.2 %)
• Optimal manual control, 16.4 s (5 %)
• Closed-loop control, 10.1 s (2.7 %)
• Baseline 2, 17.4 s (4.7 %)
SpO2 <88 % in 16 % of the time and >94 %
in 30 % of the time
Eur J Pediatr
With automixer:
• % of time within SpO2 target range was 58 %
• % of time that SpO2 >95 % was 26.5 %
• % of time that SpO2 <85 % was 14 %
In manual routine care:
• % of time within SpO2 target range was 33.7 %
• % of time that SpO2 >95 % was 54.8 %
Author
Year
Design
Study objects
Timing of measurement
Target range
Hallenberger, A. et al.
2014
Multicenter randomized
controlled crossover
clinical trial
34 infants median GA
(range) 26.4 (23.0–35.3)
receiving mechanical
ventilation or nasal CPAP
and supplemental oxygen
24-h period with routine manual
control (RMC) and 24-h period
with closed-loop automated control (CLAC)
PNA 29.9 weeks (26.0–35.6) (median (range))
Four centre-specific TRs
90–95 %
80–92 %
83–93 %
85–94 %
Arawiran, J. et al.
2014
Prospective observational
cohort study
71 premature infants GA
<31 weeks
Pre-intervention phase:
41 infants: 25±1.6 weeks
(mean±SD)
Postintervention phase:
30 infants: 25±1.9 weeks (mean±SD)
Study period from first day of life as long as
they received supplemental oxygen or
were taken off the Masimo
monitors or reached 31 weeks postconceptual
age, whichever occurred first
85–92 %
Lim, K. et al.
2014
Multicenter prospective
observational
cohort study
45 premature infants GA 30
(IQR 27–32 weeks)
2971 h receiving supplemental oxygen
Age at first recording was at day
1 (IQR 0–8 days)
88–92 %
Key results
• % of time that SpO2 <85 % was 11.5 %
In closed-loop automated control (CLAC):
• % of time within SpO2 target range
was 72.1 (13.6) (mean(SD))
• % of time that SpO2 above TR was 15.9
(1.9–34.8)
(median (range))
• % of time that SpO2 below TR was 9.1
(1.9–24.2) (median (range))
In routine manual control (RMC):
• % of time within SpO2 target range was
61.0 (15.2) (mean(SD))
• % of time that SpO2 above TR was 16.0
(0.0–60.0) (median (range))
• % of time that SpO2 below TR was 15.0
(0.5–39.6) (median (range))
Pre-intervention phase:
• Proportion of time spent per 12-h shift in
which individual babies were
(mean (%)±SD (%))
• <70 % was 3.4±2.6
• 70–74 % was 1.6±1.3
• 75–79 % was 4.0±2.9
• 80–84 % was 9.6±5.63
• 85–92 % was 44.5±14.4
• 93–100 % was 36.9±17.2
Postintervention phase:
• Proportion of time spent per
12-h shift in which individual babies
were (mean (%)±SD (%))
• <70 % was 3.3±2.5
• 70–74 % was 1.6±1.1
• 75–79 % was 3.9±2.3
• 80–84 % was 8.9±4.3
• 85–92 % was 40.4±12.8
• 93–100 % was 41.9±15.6
Median proportion of time in % ((IQR))
• % of time within SpO2 target
range was 31 % (19–39)
• % of time that SpO2 >93 % was
59 % (36–74)
• % of time that SpO2 <87 % was 9 %
(4.3–18)
More than one infant per nurse was
associated with a greater frequency
of significant hyperoxaemia (SpO2
>98 %) when infants
were in supplemental oxygen, and
a trend towards
less normoxaemia
Eur J Pediatr
Table 4 (continued)
Eur J Pediatr
in oxygen targeting reported that maintaining the SpO2 below
the upper limit was the most difficult to adhere to [1, 6, 7, 10,
17, 18, 25, 27, 34, 39, 41]. The analysis of the large clinical
trials comparing lower- vs higher-oxygen-saturation TR was
based on the intention to treat principle. However, the larger
proportion of the SpO2 was either below or above the intended
TR and there was also an overlap between the two TRs [4, 32,
36]. Although compliance was audited [27], it is possible that
this has influenced the outcome of the trials. This underlines
the importance in improving compliance in SpO2 targeting, as
improved compliance could have influenced the results.
According to the studies
Several factors may play a role in low compliance in targeting
oxygen saturation: lack of awareness of the TR settings, limited
knowledge of the effects of hypoxaemia and hyperoxaemia and
an increased nurse/patient ratio [2, 23, 25, 29, 34]. Many caregivers were unaware of the appropriate SpO2 limits [29]. In
addition, nurses tend to rely on subjective observations for
oxygen titration, such as skin colour and chest excursions, as
well as PO and blood gases [35]. So far, studies indicate that the
effects of education and training in improving the compliance
targeting SpO2 are disappointing [1, 23].
On the other hand, the use of automated FiO2 regulation,
which eliminates the need for the nurses’ compliance, has
been shown to improve the time that SpO2 remains within
TR [7–9, 38, 41]. The increase in time within TR was small,
but it is possible that the effect of automated FiO2 regulation
has been underestimated. A Hawthorne effect could have increased the nurses’ compliance during the short study period,
thus decreasing the difference between the manual and automated periods. The effectiveness of automated regulation on
oxygenation variability, and whether this results in an improved outcome, remains to be investigated [5].
It has been suggested that the absence of a FiO2 titration
protocol would lead to saturations which would frequently
exceed or fall below the TR [24]. Manual adjustments of
FiO2 can vary widely in frequency and step size, so standardization of these adjustments could decrease large fluctuations
in SpO2 [39]. After implementing an oxygen titration protocol
for reducing the incidence of severe ROP, Lau et al. observed
that the period during which SpO2 was above TR decreased
significantly [24].
Although fewer studies investigated this, compliance with
alarm settings appeared to be low as well, especially the upper
alarm limit [10, 27]. In addition, even when alarm limits are
appropriately set, caregivers seem to have a preference for
SpO2 close to the upper alarm limit [4, 20]. This was also
demonstrated in the large trials comparing TR of SpO2 [36].
It is possible that caregivers are more accustomed to
preventing hypoxaemia than hyperoxaemia. It is also possible
that infants are more stable in SpO2 when kept at the higher
end of the TR. A regular check of alarm limit settings each
shift could increase awareness of this issue.
Educational programs on hyperoxaemia improved knowledge levels [11, 16] but did not lead to better compliance.
Earlier research has shown that after education in risks related
to hyperoxaemia, the nurses’ performance was still variable
and only 51 % of nurses were successful in minimizing exposure of their infants to hyperoxaemia [37]. Nurses usually take
care of more than one patient and perform multitasking [14],
and an increased workload decreases their compliance in TR
[25, 34]. Also, nurses frequently have to deal with alarms, but
a large proportion of the alarms are false [33]. The common
occurrence of false alarms or Bcry wolf^ phenomenon could
lead to no or delayed response of caregivers.
The decision not to limit inclusion criteria in terms of study
design and methodology led to a high level of variety within
the chosen studies, necessitating a narrative review. The advantage of this method, however, is that it enabled us to have a
complete overview of a range of different aspects related to
compliance in SpO2 targeting. However, the review was restricted to recent studies published in English and Dutch; similar studies published in other languages may have been
missed. In addition, the selection process was conducted by
the first author only and selection bias could have occurred.
However, in any case of doubt of including a publication,
peers were approachable for discussion and were resolved
by consensus to avoid bias in the selection process.
In conclusion, the main finding of this literature review is
that there is a low compliance in SpO2 targeting and alarm
settings during oxygen therapy in preterm infants, especially
in maintaining the SpO2 below the upper limit and in setting
the upper alarm limit. Although there is little data available, it
is likely that training, titration protocols and decreasing the
nurses’ workload could improve awareness and compliance.
Automated oxygen regulations have been shown to increase
the time that SpO2 remains within the TR. Improving the
compliance in SpO2 targeting and automated control has the
potential to improve the outcome in preterm infants. The effect of training, implementing protocols and automated
oxygen regulators needs further investigation.
Authors’ contribution Mrs Henriëtte van Zanten was the executive
researcher of the study. She performed literature search, graded the selected studies, wrote and submitted the report. Mrs Ratna Tan was involved in grading the selected studies. Mrs Agnes van den Hoogen was
involved in grading the selected studies. Mr Enrico Lopriore was involved in editing of the manuscript. Mr Arjan te Pas was involved in
writing and editing of the manuscript.
Compliance with ethical standards
Conflict of interest All authors declare that they have no conflict of
interest to disclose.
Eur J Pediatr
Ethical approval This article does not contain any studies with human
participants performed by any of the authors, as this is a systematic review
wherefore no ethical approval is required.
Informed consent No informed consent was obtained, as this is a
systematic review wherefore no informed consent is required.
13.
14.
15.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
16.
17.
References
18.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
Arawiran J, Curry J, Welde L, Alpan G (2014) Sojourn in excessively high oxygen saturation ranges in individual, very lowbirthweight neonates. Acta Paediatr (Oslo, Norway: 1992). doi:
10.1111/apa.12827
Armbruster J, Schmidt B, Poets CF, Bassler D (2010) Nurses compliance with alarm limits for pulse oximetry: qualitative study. J
Perinatol 30:531–534. doi:10.1038/jp.2009.189
Askie LM, Brocklehurst P, Darlow BA, Finer N, Schmidt B,
Tarnow-Mordi W (2011) NeOProM: neonatal oxygenation prospective meta-analysis collaboration study protocol. BMC Pediatr
11:6. doi:10.1186/1471-2431-11-6
Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR,
Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS,
Ambalavanan N, Frantz ID 3rd, Piazza AJ, Sanchez PJ, Morris BH,
Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP,
Duara S, Narendran V, Sood BG, O’Shea TM, Bell EF, Ehrenkranz
RA, Watterberg KL, Higgins RD (2010) Target ranges of oxygen
saturation in extremely preterm infants. N Engl J Med 362:1959–
1969. doi:10.1056/NEJMoa0911781
Claure N (2007) Automated regulation of inspired oxygen in preterm infants: oxygenation stability and clinician workload. Anesth
Analg 105:S37–41. doi:10.1213/01.ane.0000268714.51303.a5
Claure N, Bancalari E (2009) Automated respiratory support in
newborn infants. Semin Fetal Neonatal Med 14:35–41
Claure N, Bancalari E, D’Ugard C, Nelin L, Stein M, Ramanathan
R, Hernandez R, Donn SM, Becker M, Bachman T (2011)
Multicenter crossover study of automated control of inspired oxygen in ventilated preterm infants. Pediatrics 127:E76–E83
Claure N, D’Ugard C, Bancalari E (2009) Automated adjustment of
inspired oxygen in preterm infants with frequent fluctuations in
oxygenation: a pilot clinical trial. J Pediatr 155(640–645):e641–
642. doi:10.1016/j.jpeds.2009.04.057
Claure N, Gerhardt T, Everett R, Musante G, Herrera C, Bancalari E
(2001) Closed-loop controlled inspired oxygen concentration for
mechanically ventilated very low birth weight infants with frequent
episodes of hypoxemia. Pediatrics 107:1120–1124
Clucas L, Doyle LW, Dawson J, Donath S, Davis PG (2007)
Compliance with alarm limits for pulse oximetry in very preterm
infants. Pediatrics 119:1056–1060. doi:10.1542/peds.2006-3099
Deuber C, Abbasi S, Schwoebel A, Terhaar M (2013) The toxigen
initiative: targeting oxygen saturation to avoid sequelae in very
preterm infants. Adv Neonatal Care: Off J Natl Assoc Neonatal
Nurses 13:139–145. doi:10.1097/ANC.0b013e31828913cc
Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu
VK, Walsh M, Finer N, Martin RJ (2010) A higher incidence of
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr 157:69–73
Dracup KA, Meleis AI (1982) Compliance: an interactionist approach. Nurs Res 31:31–36
Edworthy J, Meredith C, Hellier E, Rose D (2013) Learning medical alarms whilst performing other tasks. Ergonomics 56:1400–
1417. doi:10.1080/00140139.2013.819448
Finer N, Leone T (2009) Oxygen saturation monitoring for the
preterm infant: the evidence basis for current practice. Pediatr Res
65:375–380. doi:10.1203/PDR.0b013e318199386a
Ford SP, Leick-Rude MK, Meinert KA, Anderson B, Sheehan MB,
Haney BM, Leeks SR, Simon SD, Jackson JK (2006) Overcoming
barriers to oxygen saturation targeting. Pediatrics 118(Suppl 2):
S177–186. doi:10.1542/peds.2006-0913P
Hagadorn JI, Furey AM, Nghiem TH, Schmid CH, Phelps DL,
Pillers DA, Cole CH (2006) Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks’ gestation: the
AVIOx study. Pediatrics 118:1574–1582. doi:10.1542/peds.20050413
Hallenberger A, Poets CF, Horn W, Seyfang A, Urschitz MS (2014)
Closed-loop automatic oxygen control (CLAC) in preterm infants:
a randomized controlled trial. Pediatrics 133:e379–385. doi:10.
1542/peds.2013-1834
Hummler H, Fuchs H, Schmid M (2014) Automated adjustments of
inspired fraction of oxygen to avoid hypoxemia and hyperoxemia in
neonates - a systematic review on clinical studies. Klin Padiatr 226:
204–210. doi:10.1055/s-0034-1375617
Kaufman DA, Zanelli SA, Gurka MJ, Davis M, Richards CP, Walsh
BK (2014) Time outside targeted oxygen saturation range and retinopathy of prematurity. Early Hum Dev 90(Suppl 2):S35–40. doi:
10.1016/s0378-3782(14)50010-2
Kmet LM (2004) Standard quality assessment criteria for evaluating primary research papers from a variety of fields. vol HTA #13.
Alberta Heritage Foundation for Medical Research (AHFMR),
Edmonton
Laptook AR, Salhab W, Allen J, Saha S, Walsh M (2006) Pulse
oximetry in very low birth weight infants: can oxygen saturation be
maintained in the desired range? J Perinatol: Off J Calif Perinat
Assoc 26:337–341. doi:10.1038/sj.jp.7211500
Laptook AR, Salhab W, Allen J, Saha S, Walsh M (2006) Pulse
oximetry in very low birth weight infants: can oxygen saturation be
maintained in the desired range? J Perinatol 26:337–341
Lau YY, Tay YY, Shah VA, Chang P, Loh KT (2011) Maintaining
optimal oxygen saturation in premature infants. Permanente J 15:
e108–113
Lim K, Wheeler KI, Gale TJ, Jackson HD, Kihlstrand JF, Sand C,
Dawson JA, Dargaville PA (2014) Oxygen saturation targeting in
preterm infants receiving continuous positive airway pressure. J
Pediatr 164:730–736.e731. doi:10.1016/j.jpeds.2013.11.072
Martin RJ, Wang K, Koroglu O, Di Fiore J, Kc P (2011)
Intermittent hypoxic episodes in preterm infants: do they matter?
Neonatology 100:303–310
Mills BA, Davis PG, Donath SM, Clucas LM, Doyle LW (2010)
Improving compliance with pulse oximetry alarm limits for very
preterm infants? J Paediatr Child Health 46:255–258. doi:10.1111/j.
1440-1754.2009.01680.x
Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred
reporting items for systematic reviews and meta-analyses: the
PRISMA statement. J Clin Epidemiol 62:1006–1012. doi:10.
1016/j.jclinepi.2009.06.005
Nghiem TH, Hagadorn JI, Terrin N, Syke S, MacKinnon B, Cole
CH (2008) Nurse opinions and pulse oximeter saturation target
limits for preterm infants. Pediatrics 121:e1039–1046. doi:10.
1542/peds.2007-2257
Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader
D, Bairam A, Moddemann D, Peliowski A, Rabi Y, Solimano A,
Eur J Pediatr
Nelson H (2015) Association between intermittent hypoxemia or
bradycardia and late death or disability in extremely preterm infants. JAMA 314:595–603. doi:10.1001/jama.2015.8841
31. Saugstad OD, Aune D (2011) In search of the optimal oxygen
saturation for extremely low birth weight infants: a systematic review and meta-analysis. Neonatology 100:1–8. doi:10.1159/
000322001
32. Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi
Y, Solimano A, Roberts RS (2013) Effects of targeting higher vs
lower arterial oxygen saturations on death or disability in extremely
preterm infants: a randomized clinical trial. JAMA 309:2111–2120
33. Siebig S, Kuhls S, Imhoff M, Gather U, Scholmerich J, Wrede CE
(2010) Intensive care unit alarms—how many do we need? Crit
Care Med 38:451–456. doi:10.1097/CCM.0b013e3181cb0888
34. Sink DW, Hope SA, Hagadorn JI (2011) Nurse:patient ratio and
achievement of oxygen saturation goals in premature infants. Arch
Dis Child Fetal Neonatal Ed 96:F93–98. doi:10.1136/adc.2009.
178616
35. Solberg MT, Hansen TW, Bjork IT (2011) Nursing assessment
during oxygen administration in ventilated preterm infants. Acta
Paediatr (Oslo, Norway: 1992) 100:193–197. doi:10.1111/j.16512227.2010.02094.x
36. Stenson BJ, Tarnow-Mordi WO, Darlow BA, Simes J, Juszczak E,
Askie L, Battin M, Bowler U, Broadbent R, Cairns P, Davis PG,
Deshpande S, Donoghoe M, Doyle L, Fleck BW, Ghadge A, Hague
W, Halliday HL, Hewson M, King A, Kirby A, Marlow N, Meyer
M, Morley C, Simmer K, Tin W, Wardle SP, Brocklehurst P (2013)
Oxygen saturation and outcomes in preterm infants. N Engl J Med
368:2094–2104. doi:10.1056/NEJMoa1302298
37. Sun SC, Stefen E, Vangvanichyakorn K (2004) Validation of prescribed target SpO(2) range in ELBW infants: a reality check of
nurses’ practice. Pediatr Res 55:528A–528A
38. Urschitz MS, Horn W, Seyfang A, Hallenberger A, Herberts T,
Miksch S, Popow C, Muller-Hansen I, Poets CF (2004)
Automatic control of the inspired oxygen fraction in preterm infants: a randomized crossover trial. Am J Respir Crit Care Med
170:1095–1100. doi:10.1164/rccm.200407-929OC
39. van der Eijk AC, Dankelman J, Schutte S, Simonsz HJ, Smit BJ
(2012) An observational study to quantify manual adjustments of
the inspired oxygen fraction in extremely low birth weight infants.
Acta Paediatr (Oslo, Norway: 1992) 101:e97–e104. doi:10.1111/j.
1651-2227.2011.02506.x
40. van Zanten HA, Tan RN, Thio M, de Man-van Ginkel JM, van
Zwet EW, Lopriore E, Te Pas AB (2014) The risk for hyperoxaemia
after apnoea, bradycardia and hypoxaemia in preterm infants. Arch
Dis Child Fetal Neonatal Ed. doi:10.1136/archdischild-2013305745
41. Zapata J, Gomez JJ, Araque Campo R, Matiz Rubio A, Sola A
(2014) A randomised controlled trial of an automated oxygen delivery algorithm for preterm neonates receiving supplemental oxygen without mechanical ventilation. Acta Paediatr (Oslo, Norway:
1992) 103:928–933. doi:10.1111/apa.12684