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Original article
Effect of a smaller target range on the compliance in targeting and distribution of oxygen saturation in preterm infants
  1. Henriëtte Anje van Zanten1,
  2. Steffen C Pauws1,2,
  3. Ben J Stenson3,
  4. Frans J Walther1,
  5. Enrico Lopriore1,
  6. Arjan B te Pas1
  1. 1 Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
  2. 2 TiCC, Tilburg University, Tilburg, Noord-Brabant, The Netherlands
  3. 3 Neonatal Unit, Simpson Centre for Reproductive Health, Edinburgh Royal Infirmary, Edinburgh, UK
  1. Correspondence to Henriëtte Anje van Zanten, Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, J6-S, PO Box 9600, 2300 RC Leiden, The Netherlands; h.a.van_zanten{at}lumc.nl

Abstract

Background Following recent recommendations, the oxygen saturation (SpO2) target range for preterm infants in our nursery was narrowed towards the higher end from 85%–95% to 90%–95%. We determined the effect of narrowing the SpO2 target range on the compliance in target range and distribution of SpO2 in preterm infants.

Methods Before and after changing the target range from 85%–95% to 90%–95%, infants <30 weeks of gestation receiving oxygen were compared during their admission on the neonatal intensive care unit. For each infant, distribution of SpO2 was noted by collecting SpO2 samples each minute, and the percentage of time spent with SpO2 within 90%–95% was calculated. Oxygen was manually adjusted. Hypoxaemic events (SpO2 <80%) where oxygen was titrated were analysed.

Results Data were analysed for 104 infants (57 before and 47 after the range was narrowed). The narrower range was associated with an increase in the median (IQR) SpO2 (93% (91%–96%) vs 94% (92%–97%), p=0.01), but no increase in median time SpO2 within 90%–95% (49.2% (39.6%–59.7%) vs (46.9% (27.1%–57.9%), p=0.72). The distribution of SpO2 shifted to the right with a significant decrease in SpO2 <90%, but not <80%. The count of minute values for Sp02 <80% decreased, while the frequency and duration of hypoxaemic events and oxygen titration were not different.

Conclusion Narrowing the target range from 85%–95% to 90%–95% in preterm infants was associated with an increase in median SpO2 and a rightward shift in the distribution, but no change in time spent between 90% and 95%.

  • preterm infant
  • supplemental oxygen
  • target range
  • hypoxaemia
  • hyperoxaemia

https://doi.org/10.1136/archdischild-2016-312496

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    What is already known on this topic?

    • Titrating oxygen manually to maintain oxygen saturation (SpO2) within intended target range can be challenging.

    • A higher SpO2 target range (91%–95%) leads to a lower mortality but more retinopathy of prematurity when compared with a lower SpO2 target range (85%–89%).

    What this study adds?

    • Implementing a narrower target range from 85%–95% to 90%–95% was not associated with a change in duration of SpO2 level between 90% and 95%.

    • The distribution of SpO2 shifted to the right, with a decrease in SpO2 <95%, but no effect on hypoxaemia (ie, SpO2 <80%).

    Introduction

    Oxygen therapy in preterm infants is routinely monitored by pulse oximetry during their admission in a neonatal intensive care unit (NICU). In order to prevent the risk for hypoxaemia and hyperoxaemia, neonatal caregivers in most units titrate fraction of inspired oxygen (FiO2) manually in order to stay within the set oxygen saturation (SpO2) target range (TR). Recent randomised trials in evaluating lower SpO2 TR (85%–89%) versus higher SpO2 TR (91%–95%) in preterm infants1–3 have shown that using a higher SpO2 TR led to a reduced mortality but increased the rate of retinopathy of prematurity (ROP) when compared with a lower SpO2 TR.1 3 Although the groups in the studies1–3 had a substantial overlap in SpO2 levels and the optimal TR remains undefined, European and Dutch guidelines now recommend a SpO2 TR of 90%–95% for preterm infants.4

    Maintaining SpO2 within TR during oxygen therapy requires compliance with alarm limit settings, prompt responses and careful oxygen titration of caregivers, which can be a difficult task to perform.5–7 Hyperoxaemia can easily occur, especially when extra oxygen is given after hypoxaemic events.8 The workload of caregivers, education and awareness about the hazards of hypoxaemia and hyperoxaemia, and appropriate alarm settings, can also influence the caregivers’ compliance in SpO2 targeting.5 9 10

    Following the recommendation of European and Dutch guidelines, our TR for SpO2 was recently changed from 85%–95% to 90%–95%. This could lead to more intrinsic stability in infants,11 but we also recognised that complying with this smaller range could be challenging for the NICU nurses.5 11 12 We studied the effect of narrowing TR towards the higher end on the distribution of SpO2 and compliance in SpO2 targeting during oxygen therapy.

    Methods

    A prospective designed pre–post implementation study was performed in the NICU of the Leiden University Medical Center (LUMC), which is a tertiary level perinatal centre with a traditional open-bay NICU architecture and an average of 550 intensive care admissions per year. In the Netherlands, no ethical approval is required for anonymised studies with medical charts and patient data that were collected and noted for standard care. The LUMC Medical Ethics Committee provided a statement of no objection for obtaining and publishing the anonymised data. All preterm infants <30 weeks of gestation admitted to the NICU in LUMC between February 2014 and October 2014 (SpO2 TR 85%–95%) and November 2014 and March 2015 (SpO2 TR 90%–95%) receiving respiratory support (endotracheal and non-invasive ventilation) were included. Data were collected until infants were transferred out of the intensive care area in our unit or to a regional hospital. Preterm infants with major congenital heart disease were excluded. All infants received caffeine therapy, and doxapram was added in case of refractory apnoeas.

    The characteristics of each infant, as well as clinical parameters and ventilator settings (including FiO2 and SpO2), were sampled every minute and routinely collected in the patient data management system (PDMS) (MetaVision; iMDsoft, Tel Aviv, Israel). During both periods the heart rate and SpO2 were collected using a Masimo pulse oximeter (Masimo Radical, Masimo, Irvine, California, USA) integrated in a Philips bedside IntelliVue monitor (Philips Healthcare Nederland, Eindhoven, The Netherlands) with an averaging time set at 8 s. During both periods caregivers titrated the supplemental oxygen manually following local guidelines (figure 1). In our NICU the average nurse:patient ratio was 1:2. During both periods the alarm was activated when SpO2 was directly below or above the set TR, when FiO2 >0.21. When no supplemental oxygen was required, no upper alarm limit was activated. We considered a washout period around changing TR setting not necessary. Before the TR was changed, all caregivers were fully informed. In addition, before the start of each shift, the TR and alarm settings were checked by the nurse if they were set appropriate, which is standard care in our NICU.

    Figure 1
    Figure 1

    Oxygen titration guideline. bpm, beats per minute; FiO2, fraction of inspired oxygen; SpO2, oxygen saturation.

    We were interested in the extent to which nurses were able to comply with the narrower TR, and compared the percentage of time spent with SpO2 between 90% and 95% when FiO2 >0.21. Additionally, the percentage of time spent with SpO2 90%–95%, >95%, >98%, <90%, <85% and<80% was calculated. To evaluate whether the SpO2 distribution changed when no oxygen therapy was given to the infant, the percentage of time that SpO2 was <90%, <85% and <80% when infants were breathing air was also calculated.

    In addition, all hypoxaemic events during non-invasive ventilation were identified in PDMS and analysed from the occurrence of SpO2 <80% accompanied with bradycardia (<80 beats per minutes (bpm)), until the administered oxygen returned to the baseline oxygen before the hypoxaemic event occurred. As data are sampled every minute, every hypoxaemic event (ABC) where extra oxygen was titrated was evaluated by documenting the following characteristics: lowest stored minute value (depth) and count in low minute values (duration) of HR <80 bpm, lowest stored minute value (depth) and the count in low minute values (duration) of SpO2 <80%, ∆FiO2 (maximum additional FiO2 minus baseline FiO2), the count in minute values with additional oxygen, and occurrence and count in minute values with SpO2 >95%. Hypoxaemia was defined as SpO2 <80% and hyperoxaemia as SpO2 >95%.

    Statistical analyses

    For this study a convenience sample was used. For the first period, infants were included who were born 1 month after the implementation of staff training and an oxygen titration guideline13 until the TR was changed. For the second period, infants were included after implementing the new TR, until the time point automated oxygen control was implemented. Quantitative data are presented as median (IQR), mean (SD) or number (percentage) where appropriate. The total duration of SpO2 levels within various ranges for FiO2 >21% was collected for each infant individually before and after implementation of a narrowed TR and was aggregated as a percentage of recorded time (median (IQR)). The Mann-Whitney U test for non-parametric comparisons for continuous variables was used to compare patients’ characteristics and the hypoxaemic event characteristics. A Χ2 test was used to analyse discrete variables. If one of the cells had an expected count of less than five, the Fisher’s exact test was used. p Values <0.05 were considered to indicate statistical significance. Statistical analyses were performed using IBM SPSS Statistics V.23 and R V.3.2.0 (R Core Team (2015); R: A language and environment for statistical computing, R Foundation for Statistical Computing, Vienna, Austria, https://www.R-project.org/).

    Results

    During the study period of 13 months, a total number of 104 infants born <30 weeks of gestation were admitted to our NICU. Of these infants, 57 were born before changing the SpO2 TR, and 47 infants after this change. No infants were excluded. There were no differences in median (IQR) weeks of gestation (28+3 (26+4–29) vs 27+5 (26+1–29) weeks; p=0.25) and birth weight (1000 (855–1206) vs 900 (740–1153) g; p=0.17) or other characteristics (table 1).

    View this table:
    Table 1

    Patient characteristics

    Effect on compliance and SpO2 distribution

    During the TR 85%–95% period 630.244 data points were collected and during the TR 90%–95% period 402.993 data points of SpO2 measurements were collected during oxygen therapy. The median (IQR) number of data points per infant was not different (2359 (377–14129) vs 3082 (1352–15024) data points; p=0.42).

    After changing the TR, there was a slight but significant increase in median (IQR) SpO2 (93% (91%–96%) vs 94% (92%–97%); p<0.02) (figure 2), while the FiO2 slightly decreased (28% (25%–32%) vs 26% (24%–30%); p=0.01). Narrowing TR was not associated with an increase in median (IQR) time SpO2 was within 90%–95% (49.2% (39.6%–59.7%) vs (46.9% (27.1%–57.9%); p=0.72). The time SpO2 was >95% and >98% increased, but did not reach statistical significance. Changing the TR was associated with a significant decrease in both SpO2 <90% (15.7% (7%–21%) vs 10.7% (8.4%–13.7%); p<0.05) and SpO2 <85% (6.2% (2.5%–8.0%) vs 3.5% (2.6%–5.3%); p<0.05), but SpO2 <80% was similar (table 2, figure 2).

    Figure 2
    Figure 2

    Time with oxygen saturation (SpO2) within various ranges collated over all infants and aggregated as total proportion of recorded time.

    View this table:
    Table 2

    Time in different saturation ranges when breathing oxygen

    During the TR 85%–95% period 471.642 data points were collected and in the TR 90%–95% period 424.700 data points of SpO2 measurements were collected when infants were breathing in air. The median (IQR) number of data points per infant was not different (5722 (3112–10395) vs 8102 (3635–13363) data points; p=0.24). Changing the TR was not associated with significant changes in SpO2 distribution, and SpO2 <90% was similar when infants were breathing in air (table 3, figure 3).

    Figure 3
    Figure 3

    Time with oxygen saturation (SpO2) within various ranges collated over all infants and aggregated as total proportion of recorded time.

    View this table:
    Table 3

    Time with SpO2 within various ranges when breathing in air

    Effect on hypoxaemic events and how oxygen was titrated

    During non-invasive respiratory support, 168 hypoxaemic events requiring extra oxygen occurred in 28/57 (49%) infants before and 204 events in 32/47 (68%) infants after the TR was changed. There was no difference in lowest minute value and the count in minute values with bradycardia and SpO2 <80% (table 4). The median (IQR) count of minute values for Sp02 <80% decreased, while the mean (SD) was not different. There was a non-significant increase in hyperoxaemia after the TR was changed (63% (106/168) vs 73% (148/204); p=0.05) (table 4), while there was no difference in ∆FiO2, duration of titrating oxygen down to the baseline and count in minute values with hyperoxaemia (table 4).

    View this table:
    Table 4

    Hypoxaemic events: apnoea, bradycardia, cyanosis characteristics requiring oxygen therapy

    Discussion

    Our study demonstrated the effect of narrowing the SpO2 TR of 85%–95% towards the higher end to 90%–95% on SpO2 distribution of preterm infants when oxygen is supplied. We observed that the new, more narrow TR was associated with a small increase in median SpO2 and a rightward shift in the distribution. While this was associated with a decrease in the prevalence of SpO2 <90%, it had no effect on hypoxaemia (ie, SpO2 <80%). Changing TR did not affect the duration at which SpO2 was 90%–95%. However, it was associated with a non-significant increase in the occurrence of hyperoxaemia (figure 2). These results could indicate that the nurses attempted to comply with the new TR, but found it difficult to titrate oxygen sufficiently to stay within the narrow TR. Nevertheless, as we managed to decrease the exposure to SpO2 less than 90%, narrowing the TR in our unit could lead to similar beneficial effects shown in the recent trials.1–3

    A similar effect was observed around hypoxaemic events. There was no change in occurrence and duration of hypoxaemic events and how oxygen titration was performed, but the occurrence of hyperoxaemia increased, although this raise was not significant.

    To our knowledge this is the first report of the effect when the TR is significantly narrowed to only the upper part of the original TR when oxygen is manually titrated. Laptook et al 14 reported the effect of changing the SpO2 TR, but the change in range was much smaller (from 90%–95% to 88%–94%) when compared with ours. It is difficult to compare our results with their findings, but they also reported no change in the time SpO2 spent within the TR. They observed also no difference in the mean percentage of time spent within the TRs, but this might be attributed to the small change in TR.14 Mills et al 12 reported a lower compliance when a narrow TR for SpO2 was used, except when preterm infants participated in a trial comparing TRs.

    Changing the TR did not lead to a change in SpO2 distribution when infants were breathing in air and there was no decrease in lower SpO2. This finding, together with the observation that the time SpO2 was 90%–95% did not change when oxygen was given, could indicate that the nurses already had the tendency to keep SpO2 in the higher end of the intended TR when 85%–95% was used. This is in line with previous observation that nurses were less compliant in the upper alarm limits.5 6 11 15 Indeed, the clinical trials comparing lower versus higher SpO2 TR also reported that the median levels of oxygen saturations were higher than intended TR in both treatment groups.1–3 It is likely that caregivers favour SpO2 closer to the higher end of the TR because infants are intrinsically more stable in the higher SpO2 region, resulting in less FiO2 fluctuations.

    We observed a decrease in time SpO2 spent <90% when oxygen was given, which is comparable to the findings of recent trials comparing low (85%–89%) versus high TR (91%–95%). These trials showed that a TR above 90% led to a decrease in mortality.1–3 A low SpO2 TR has been associated with an increased rate of hypoxaemic events.14 16 However, we did not observe a change in hypoxaemia, or hypoxaemic events and how these were handled, after we increased the lower limit of the TR. This lack of effect is probably also a consequence of how nurses titrated oxygen before the TR was changed. Changing the TR towards the higher end led to a non-significant increase in hyperoxaemia and more often hyperoxaemia after an hypoxaemic event. This has also been observed in previous studies, as also in the trials comparing lower and higher TRs,1–3 which could then potentially lead to an increase in ROP.

    Titrating oxygen when using a smaller TR in instable premature infants with fluctuating SpO2 requires constant nursing intervention.8 It has been reported that a narrower TR leads to an inevitable increase of SpO2 alarms.17 These alarms contribute to all other alarms on a NICU where a high number of alarms are false.18 Excessive exposure to alarms can affect response from caregivers and lead to alarm fatigue, which is potentially harmful to patients.19 20 Although we have not measured the number of alarms in our study, this can affect the compliance in TR negatively.

    While maintaining SpO2 within a narrow TR is a difficult task to perform when oxygen needs to be titrated manually, automated oxygen regulation could be more effective and lead to the desired compliance in keeping SpO2 within the narrow range.21–25 However, when Wilinska et al used automated oxygen control and compared the TR 87%–93% with a more narrow TR (90%–93%), similar results as in our study were observed. The narrow range of 90%–93% resulted in less time with lower SpO2 (80%–86%), but more time with higher SpO2 (94%–98%). In addition, there were also no differences in the amount and duration of hypoxaemic events.26

    The non-randomised character of this study is a limitation. Although the compared groups were not different in basic characteristics and there were no further policy changes that occurred during the study period, bias could have been introduced by conditions we did not record or measure. The Masimo oximeter algorithm could not be updated in the Philips monitors that we used in our unit, which is reflected by the well-described dip27 in the frequencies of SpO2 87%–90%. However, the same oximeters and monitors were used in both groups and thus did not influence the observed distributions when comparing the groups. Furthermore, we did not adjust for the contribution of the number of hypoxic events of each patient, but we considered every hypoxaemic event as an independent event because all events are handled similarly for each infant. We could only compare SpO2 values that were routinely sampled every minute and the value is an average of 8 s, which is less frequent than reported in other studies.28–30 It is possible that in both groups, we missed SpO2 fluctuations and hypoxaemic events in between the samples taken. These limitations indicate that the results have to be interpreted with caution; this study was not designed to compare morbidity and mortality.

    In conclusion, narrowing the TR from 85%–95% to 90%–95% in preterm infants was not associated with a change in the time SpO2 spent within 90%–95%. There was however a shift of the SpO2 distribution to the right with a decrease in SpO2 less than 90%, but no change in hypoxaemia. This beneficial effect could be further improved by increasing the compliance to a narrow TR.

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    Footnotes

    • Twitter @heza01

    • Contributors HAvZ was the executive researcher of the study. She performed literature search, data collection, data analysis, data interpretation, writing and submitting of the manuscript. SCP was involved in data analysis, critically reviewed the manuscript and approved the final version. BJS was involved in interpretation of the data, critically reviewed the manuscript and approved the final version. EL critically reviewed the manuscript and approved the final version. FJW critically reviewed the manuscript and approved the final version. ABtP was the project leader and performed literature search, designed the study, and coordinated data analysis, data interpretation, writing, editing and submitting of the manuscript.

    • Competing interests None declared.

    • Ethics approval LUMC Medical Ethics Committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.