You are here

Article Text

Article menu

Download PDFPDF

Original article
The risk for hyperoxaemia after apnoea, bradycardia and hypoxaemia in preterm infants
  1. H A van Zanten1,
  2. R N G B Tan1,
  3. M Thio2,3,
  4. J M de Man-van Ginkel4,
  5. E W van Zwet5,
  6. E Lopriore1,
  7. A B te Pas1
  1. 1Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2University of Melbourne, Melbourne, Victoria, Australia
  3. 3Hospital Sant Joan de Deu, Barcelona, Spain
  4. 4Utrecht University, Utrecht, The Netherlands
  5. 5Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to H A van Zanten, Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, J6-S, PO Box 9600, Leiden 2300 RC, The Netherlands; h.a.van_zanten{at}lumc.nl

Abstract

Objective To investigate the occurrence and duration of oxygen saturation (SpO2) ≥95%, after extra oxygen for apnoea, bradycardia, cyanosis (ABC), and the relation with the duration of bradycardia and/or SpO2 ≤80%.

Methods All preterm infants <32 weeks’ gestation supported with nasal continuous positive airway pressure (nCPAP) admitted to our centre were eligible for the study. We retrospectively identified all episodes of ABCs. In ABCs where oxygen supply was increased, duration and severity of bradycardia (<80 bpm), SpO2 ≤80%, SpO2 ≥95% and their correlation were investigated.

Results In 56 infants, 257 ABCs occurred where oxygen supply was increased. SpO2 ≥95% occurred after 79% (202/257) of the ABCs, duration of extra oxygen supply was longer in ABCs with SpO2 ≥95% than without SpO2 ≥95% (median (IQR) 20 (8–80) vs 2 (2–3) min; p<0.001)). The duration of SpO2 ≥95% was longer than bradycardia and SpO2 ≤80% (median (IQR) 13 (4–30) vs 1 (1–1) vs 2 (1–2) min; p<0.001). SpO2 ≥95% lasted longer when infants were in ambient air than when oxygen was given before the ABC occurred (median (IQR)15 (5–38) min vs 6 (3–24) min; p<0.01).

Conclusions In preterm infants supported with nCPAP in the neonatal intensive care unit (NICU), SpO2 ≥95% frequently occurred when oxygen was increased for ABCs and lasted longer than the bradycardia and SpO2 ≤80%.

  • Neonatology
  • Nursing Care
  • hyperoxemia
  • supplemental oxygen
  • apnea

https://doi.org/10.1136/archdischild-2013-305745

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    What is already known on this topic

    • SpO2 ≥95% during oxygen therapy in preterm infants occurs often, increasing the risk for hyperoxaemia.

    • The long-term consequences of frequent apnoea, bradycardia, cyanosis, are often attributed to bradycardia and hypoxaemia.

    • Hyperoxaemia has been shown to be an important pathogenetic factor for neonatal morbidity as well.

    What this study adds

    • SpO2 ≥95% occurred often after oxygen therapy for apnoea, bradycardia, cyanosis (ABC), and lasted longer than the bradycardia and/or SpO2 ≤80% during ABC.

    • There is a more awareness for alarms of bradycardia and SpO2 ≤80% than for SpO2 ≥95%.

    Introduction

    Apnoea of prematurity, defined as a respiratory pause >20 s or when this pause is combined with hypoxia, pallor, hypotonia and/or bradycardia,1 is one of the most common and recurrent problems in preterm infants.2 The incidence of apnoea is inversely correlated with gestational age (GA) and birth weight. Nearly all infants born at <29 weeks’ gestation exhibit apnoea compared to only 7% at 34–35 weeks’ gestation.2 Treatment of apnoea in preterm infants can sometimes be challenging. If an infant does not respond to tactile stimulation, interventions, such as mask ventilation and an increase in Fraction of Inspired Oxygen (FiO2) are necessary.

    Apnoeas are often combined with bradycardia and cyanosis (ABC) and can result in morbidity, which includes retinopathy of prematurity (ROP), impaired growth, cardiorespiratory instability and impaired neurodevelopmental outcome.3 The risk for hypoxaemic episodes increases when oxygen saturation (SpO2) decreases ≤80% for ≥10 s.3 However, often extra oxygen is given as intervention for ABCs which, alternately, could increase the risk for hyperoxaemia (oxygen saturation ≥95% for ≥10 s).3 In analogy with hypoxaemia, hyperoxaemia has also been shown to be an important pathogenetic factor for neonatal morbidity, such as bronchopulmonary dysplasia (BPD), ROP4 and cerebral palsy.5

    To prevent episodes of SpO2 ≤80% and ≥95%, infants are monitored using pulse oximetry, and oxygen therapy is titrated to maintain the oxygen saturation within a certain range.6 ,7 However, keeping an infant within narrow target oxygen saturation ranges may be challenging for a nurse, and poor compliance has been observed.8–10 Increasing the FiO2 may often be needed, but could also unintendedly lead to a risk for hyperoxaemia.

    Although the long-term consequences of frequent ABCs are attributed to the occurrence of bradycardia and hypoxaemia,3 hyperoxaemia following after an ABC could also contribute to this. Data is scarce on how frequently SpO2 ≥95% occurs after ABCs and the duration of these episodes. We aimed to investigate the occurrence and duration of SpO2 ≥95% in preterm infants treated with extra oxygen after ABCs, and how the duration of SpO2 >95% is related to the duration of bradycardia and SpO2 ≤80%.

    Methods

    A retrospective study was performed in the neonatal intensive care unit (NICU) of Leiden University Medical Center, The Netherlands, which is a tertiary-level perinatal centre with an average of 475 intensive care admissions yearly. Approval was obtained from the medical ethical review board (C12.168).

    All infants with a GA at birth <32 weeks admitted to our NICU between October 2011 and October 2012 and supported with nasal continuous positive airway pressure (nCPAP) were identified and evaluated. In our NICU, nCPAP is given by mechanical ventilators (AVEA, CareFusion, Houten, The Netherlands) which are connected to Patient Data Management System (PDMS) (Metavision; IMDsoft, Tel Aviv, Israel). Infants requiring endotracheal mechanical ventilation were excluded. The more stable infants admitted to the stepdown unit receiving no respiratory support or low flow oxygen therapy via nasal cannula could not be included as the oxygen therapy was not connected to PDMS. Additionally, infants with major congenital heart disease were excluded; different oxygen saturations and separate guidelines for oxygen supply are followed for this group. Clinical parameters of each infant were stored every minute, and collected in PDMS. All infants studied received routinely caffeine (caffeine-base 10 mg/kg loading dose followed by 5 mg/kg/day). Alarm settings in our unit were: saturation alarm settings with oxygen therapy: 85–95%, without oxygen therapy 85–100%. There were no guidelines available for titrating supplemental oxygen.

    In all infants, ABCs (apnoeas ≥20 s, associated with bradycardia (≤80 beats per minute (bpm)) and oxygen desaturation ≤80%, where extra oxygen was given, were identified and analysed in detail. ABCs were retrieved in two ways: (1) apnoea was registered in the respiratory chart in PDMS. As this was not always registered at the exact time point the apnoea occurred, the moment of bradycardia combined with SpO2 ≤80% was retrieved which was the closest to the registered apnoea, (2) apnoea was not registered, but respiratory rate in PDMS was zero and combined with bradycardia and SpO2 ≤80%.

    Data collection was started from the occurrence of an ABC until the extra oxygen was back at the baseline oxygen level before the ABC occurred (figure 1). With every ABC, the following characteristics were recorded: duration and depth of bradycardia, duration and depth of SpO2 ≤80%, baseline oxygen concentration and additional oxygen given, the duration of extra oxygen given (measured from the start of extra oxygen after the ABC until oxygen was titrated to the baseline oxygen), incidence and duration of SpO2 ≥95%. ABC characteristics were analysed comparing exposure to SpO2 >95% versus no SpO2 >95% during apneic episodes. Of those with SpO2 >95%, baseline oxygen characteristics were compared (exposure to ambient air vs supplemental oxygen).

    Figure 1
    Figure 1

    Graphic representation of measuring oxygen saturation (SpO2) ≥95% after an apnoea, bradycardia, cyanosis (ABC).

    Statistical analyses

    Quantitative data are expressed as median and IQR, or number (percentage) when appropriate. ANOVA, independent samples Mann–Whitney U test were used for comparisons between hyperoxaemia or not, and occurrence of hyperoxaemia in baseline oxygen requirements (ambient air or supplemental oxygen). Correlations between the baseline oxygen concentration before ABC and the duration of SpO2 ≥95% after ABC were investigated using Pearson correlation coefficient for normal distributions. p Values less than 0.05 were assumed as statistically significant.

    Statistical analyses were performed by IBM SPSS Statistics V.20 (IBM Software, New York, USA, 2012).

    Results

    From October 2011 until October 2012, 194 infants <32 weeks gestation were admitted to our NICU and received nCPAP during their admission. One infant was diagnosed with a congenital heart disease and was excluded. The medical charts of the 193 eligible infants were reviewed for ABCs where extra oxygen was given. Patients’ characteristics are shown in table 1.

    View this table:
    Table 1

    General characteristics of infants where oxygen was given for ABC

    In 56/193 infants, 257 ABCs occurred where oxygen was increased, which were 11% of all ABCs that occurred. The median (IQR) depth of bradycardia was 70 (63–76) bpm with a duration of 1 (1–1) min. The median (IQR) depth of saturation was 68 (61–73)% with a duration of 2 (1–2) min. The median (IQR) baseline concentration of oxygen before ABC occurred was 23 (21–28)% and increased to 39 (30–67)% after the ABC (absolute increase of 16%). The duration of titrating down the oxygen to the baseline concentration was 14 (4–52) min (table 2).

    View this table:
    Table 2

    ABC characteristics

    ABCs: exposure to SpO2 ≥95% versus no exposure to SpO2 ≥95%

    SpO2 ≥95% occurred in 79% (202/257) of the ABCs where oxygen was increased and lasted a median (IQR) time of 13 (4–30) min. When comparing ABCs where SpO2 ≥95% occurred, with ABCs without the occurrence of SpO2 ≥95%, no differences were observed in the depth of bradycardia, duration of bradycardia, depth of hypoxaemia, duration of hypoxaemia, baseline oxygen concentration and maximum increase of oxygen concentration (table 2). After extra oxygen was given, the time needed to return to baseline level was longer in ABCs with SpO2 ≥95% (20 (8–80) vs 2 (2–3) min; p<0.001) (table 3).

    View this table:
    Table 3

    comparison of ABCs followed by exposure to SpO2 ≥95% versus no exposure to SpO2 ≥95%

    ABCs with exposure to SpO2 ≥95%: ambient air versus supplemental oxygen at baseline

    In 52% (105/202) of ABCs with SpO2 ≥95%, ambient air was given as baseline, and in 48% (97/202), extra oxygen was given as baseline before the ABC occurred. No differences were observed in depth and duration of bradycardia (table 4). The depth was less severe and duration of SpO2 ≤80% lasted shorter in ABCs where ambient air was the baseline concentration than in ABCs where supplemental oxygen was given (median (IQR) SpO2 68 (63–75) vs 67 (58–73)%; p=0.05 and median (IQR) time 2 (1–2) vs 2 (1–3) min; p=0.001). Although there were no differences measured in the median (IQR) time needed to return to baseline level (22 (8–101) vs 19 (8–63) min; ns), the median (IQR) duration of SpO2 ≥95% lasted much longer when ambient air had been given compared to when extra oxygen was given as baseline concentration (14 (5–40) min vs 8 (4–26) min; p=<0.05) (table 4). There was a correlation between the baseline oxygen concentration before ABC, and the duration of SpO2 ≥95% after ABC (r=0.2; p<0.01).

    View this table:
    Table 4

    Comparison of ABCs with exposure to SpO2 ≥95%: ambient air versus supplemental oxygen at baseline

    Discussion

    In this retrospective study in preterm infants on nCPAP, we observed that when extra oxygen was given to treat ABCs, SpO2 ≥95% frequently occurred and lasted significantly longer than the bradycardia or SpO2 ≤80%. SpO2 ≥95% lasted longer when patients were in ambient air before the ABC occurred. Also, titration of oxygen back to the baseline concentration was significantly longer after ABCs where SpO2 ≥95% occurred. Our results suggest that caregivers showed a prompt response to an ABC because of the shorter duration of bradycardia and SpO2 ≤80%, but when extra oxygen is given, it is not carefully titrated down, once the SpO2 ≤80% is over. Caregivers should be more aware of the dangers of the ABCs, and also of the risk for hyperoxaemia that could occur afterwards, when extra oxygen is given.

    The high incidence of SpO2 ≥95% during oxygen therapy and the caregiver's compliance in our unit is comparable to what has been reported in previous studies.11–13 However, this is the first study describing the occurrence and duration of SpO2 ≥95% after oxygen has been increased when ABCs occur. The compliance of nurses could be affected by the nurse to patient ratio, which is in our unit on average 1:2. Sink et al12 showed that duration of SpO2 above the target ranges increased when the nurse to patient ratio increased from 1:1 to 1:3. Also, an incorrect setting of the alarm limits could explain the high incidence and duration of SpO2 ≥95% in this study. Previous studies have reported a low compliance of alarm limits’ settings for pulse oximetry.8–10 The nursing compliance with alarm limits for pulse oximetry in preterm infants was related to the level of supplemental oxygen needed. In infants requiring high levels of supplemental oxygen, the upper alarm limit was set correctly in 35.7%, compared with 23.6% in the moderate group and 6.2% in the low oxygen group.8 Similar to this, we observed that the duration of SpO2 ≥95% was significantly longer when infants were in ambient air before the ABC occurred, and alarm limits were not adjusted when extra oxygen was started (from 85–100% to 85–95%).

    The long-term consequences of ABCs for preterm infants have been well established.3 Most caregivers are aware that frequent bradycardia and hypoxaemic events can result in morbidity, which includes ROP, impaired growth, persistent cardiorespiratory instability and impaired neurodevelopmental outcome.3 However, hyperoxaemia has also been shown to be an important contributing factor for these morbidities.4 ,5 In this study, we observed that the risk for hyperoxaemia occurs often immediately after an ABC, and has lasted even longer than the ABC itself. Although it is not possible to distinguish the effect of SpO2 ≥95% from the effect of bradycardia, hypoxaemia on long-term outcome, the risk for iatrogenic hyperoxaemia, that often follows after an ABC, could also play an important role in the long-term consequences of ABCs. When considering the long duration of hyperoxaia after a short period of hypoxia and bradycardia, it could be possible that preventing duration of hyperoxia could improve the long-term consequences in infants with frequent ABCs.

    It is possible that the lack of proper guidelines for titrating oxygen, oxygen saturations are frequently above target ranges when it is controlled manually by nursing staff.14 Caregivers easily administer large amounts of oxygen in order to prevent hypoxaemia, and adjustments vary widely in frequency and steps.13 Standardisation of FiO2 adjustments could reduce fluctuations of saturations and periods of hypoxaemia and hyperoxaemia.14 Additionally, several studies have shown oxygen saturations were less variable and more often maintained within target ranges when oxygen therapy was automatically adjusted instead of manually.15–18 Also, education and training has shown to be effective in improving the maintenance of the intended range of SpO2,19 By contrast, other studies reported that knowledge about the risk of hyperoxaemia did not reduce the time preterm infants spent in oxygen saturations above the target ranges.20 ,21

    Research in maintaining oxygen levels in premature infants is ongoing. Automated regulation of the fraction of inspired oxygen is a new technology. Controlling oxygen therapy by using an automated loop system for inspired oxygen regulation has the potential to decrease the occurrence and severity of hypoxia and hyperoxia.22 Future studies are needed to test whether this closed-loop system may result in improved neurodevelopmental outcomes in preterm infants.23

    This study had several limitations. In the statistical comparison, we did not adjust for the contribution of amount of ABCs of each patient. However, in this study, we were interested in how ABCs were handled by the nurses and how often hyperoxia was induced after extra oxygen was given. For the purpose of this study, the ABC was the subject, and for this reason we considered every ABC as an independent event.

    Only infants admitted to the NICU could be included in the study. Also, it is possible that the reported occurrence of SpO2 ≥95% due to oxygen therapy for ABCs does not reflect the occurrence in our total cohort of preterm infants. However, we do not expect that this will influence the occurrence considerably as in the stepdown unit, larger and more stable preterm infants are admitted and, therefore, less likely to have significant ABCs.

    Conclusion

    In preterm infants treated with nCPAP, SpO2 ≥95% occurred often after oxygen therapy for ABCs and the duration was longer than the bradycardia and SpO2 ≤80%. The duration of SpO2 ≥95% was much longer in infants breathing ambient air compared to infants who had supplemental oxygen before ABC occurred. This considerably increases the risk for iatrogenic hyperoxaemia after ABC, and it is possible that this also plays a role in the long-term consequences of apnoeas. NICU caregivers should be more aware of the occurrence of the risk for hyperoxaemia after ABCs when extra oxygen is given. More vigilance is needed for alarm settings and oxygen titration to get back to baseline oxygen condition as soon as possible.

    After this study, we now have implemented new guidelines for oxygen titration in our unit and we have created more awareness that alarm limits should be appropriately set. Additionally, after a research period, an automatic loop system for inspired oxygen (CliO2) is currently introduced in our unit for clinical use.

    Acknowledgments

    We thank Rita Kamar, student of medicine, for her help in collecting data, and Erik Olofsen, assistant professor of anaesthesia, for making figure 1.

    References

    1. ↵
      American Academy of Pediatrics. Task Force on Prolonged Apnea. Prolonged apnea. Pediatrics 1978;61:651–2.
      OpenUrlAbstract/FREE Full Text
    2. ↵
      1. Martin RJ,
      2. Abu-Shaweesh JM,
      3. Baird TM
      . Apnoea of prematurity. Paediatr Respir Rev 2004;5(Suppl A):S377–82.
      OpenUrlCrossRefPubMed
    3. ↵
      1. Di Fiore JM,
      2. Bloom JN,
      3. Orge F,
      4. et al
      . A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr 2010;157:69–73.
      OpenUrlCrossRefPubMedWeb of Science
    4. ↵
      1. Saugstad OD,
      2. Aune D
      . In search of the optimal oxygen saturation for extremely low birth weight infants: a systematic review and meta-analysis. Neonatology 2011;100:1–8.
      OpenUrlCrossRefPubMedWeb of Science
    5. ↵
      1. Askie LM,
      2. Brocklehurst P,
      3. Darlow BA,
      4. et al
      . NeOProM: Neonatal oxygenation prospective meta-analysis collaboration study protocol. BMC Pediatr 2011;11:6.
      OpenUrlPubMed
    6. ↵
      1. Martin RJ,
      2. Wang K,
      3. Koroglu O,
      4. et al
      . Intermittent Hypoxic Episodes in Preterm Infants: do they matter? Neonatology 2011;100:303–10.
      OpenUrlCrossRefPubMedWeb of Science
    7. ↵
      1. Finer N,
      2. Leone T
      . Oxygen saturation monitoring for the preterm infant: the evidence basis for current practice. Pediatr Res 2009;65:375–80.
      OpenUrlCrossRefPubMedWeb of Science
    8. ↵
      1. Clucas L,
      2. Doyle LW,
      3. Dawson J,
      4. et al
      . Compliance with alarm limits for pulse oximetry in very preterm infants. Pediatrics 2007;119:1056–60.
      OpenUrlAbstract/FREE Full Text
    9. ↵
      1. Hagadorn JI,
      2. Furey AM,
      3. Nghiem TH,
      4. et al
      . Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks’ gestation: the AVIOx study. Pediatrics 2006;118:1574–82.
      OpenUrlAbstract/FREE Full Text
    10. ↵
      1. Mills BA,
      2. Davis PG,
      3. Donath SM,
      4. et al
      . Improving compliance with pulse oximetry alarm limits for very preterm infants? J Paediatr Child Health 2010;46:255–8.
      OpenUrlCrossRefPubMedWeb of Science
    11. ↵
      1. Laptook AR,
      2. Salhab W,
      3. Allen J,
      4. et al
      . Pulse oximetry in very low birth weight infants: can oxygen saturation be maintained in the desired range? J Perinatol 2006;26:337–41.
      OpenUrlCrossRefPubMedWeb of Science
    12. ↵
      1. Sink DW,
      2. Hope SA,
      3. Hagadorn JI
      . Nurse:patient ratio and achievement of oxygen saturation goals in premature infants. Arch Dis Child Fetal Neonatal Ed 2011;96:F93–8.
      OpenUrlAbstract/FREE Full Text
    13. ↵
      1. van der Eijk AC,
      2. Dankelman J,
      3. Schutte S,
      4. et al
      . An observational study to quantify manual adjustments of the inspired oxygen fraction in extremely low birth weight infants. Acta Paediatr 2012;101:e97–104.
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      1. Lau YY,
      2. Tay YY,
      3. Shah VA,
      4. et al
      . Maintaining optimal oxygen saturation in premature infants. Permanente J 2011;15:e108–13.
      OpenUrl
    15. ↵
      1. Bhutani VK,
      2. Taube JC,
      3. Antunes MJ,
      4. et al
      . Adaptive control of inspired oxygen delivery to the neonate. Pediatr Pulmonol 1992;14:110–17.
      OpenUrlCrossRefPubMedWeb of Science
    16. ↵
      1. Claure N,
      2. Gerhardt T,
      3. Everett R,
      4. et al
      . Closed-loop controlled inspired oxygen concentration for mechanically ventilated very low birth weight infants with frequent episodes of hypoxemia. Pediatrics 2001;107:1120–4.
      OpenUrlAbstract/FREE Full Text
    17. ↵
      1. Morozoff EP,
      2. Smyth JA
      . Evaluation of three automatic oxygen therapy control algorithms on ventilated low birth weight neonates. Conf Proc IEEE Eng Med Biol Soc 2009;2009:3079–82.
      OpenUrlPubMed
    18. ↵
      1. Urschitz MS,
      2. Horn W,
      3. Seyfang A,
      4. et al
      . Automatic control of the inspired oxygen fraction in preterm infants: a randomized crossover trial. Am J Respir Crit Care Med 2004;170:1095–100.
      OpenUrlCrossRefPubMedWeb of Science
    19. ↵
      1. Ford SP,
      2. Leick-Rude MK,
      3. Meinert KA,
      4. et al
      . Overcoming barriers to oxygen saturation targeting. Pediatrics 2006;118(Suppl 2):S177–86.
      OpenUrlAbstract/FREE Full Text
    20. ↵
      1. Sun SC,
      2. Stefen E,
      3. Vangvanichyakorn K
      . Validation of prescribed target SpO(2) range in ELBW infants: A reality check of nurses’ practice. Pediatr Res 2004;55:528A–A.
      OpenUrlCrossRef
    21. ↵
      1. Deuber C,
      2. Abbasi S,
      3. Schwoebel A,
      4. et al
      . The toxigen initiative: targeting oxygen saturation to avoid sequelae in very preterm infants. Adv Neonatal Care 2013;13:139–45.
      OpenUrlCrossRefPubMed
    22. ↵
      1. Claure N,
      2. Bancalari E,
      3. D'Ugard C,
      4. et al
      . Multicenter crossover study of automated control of inspired oxygen in ventilated preterm infants. Pediatrics 2011;127:e76–83.
      OpenUrlAbstract/FREE Full Text
    23. ↵
      1. Claure N,
      2. Bancalari E
      . Automated closed loop control of inspired oxygen concentration. RespirCare 2013;58:151–61.
      OpenUrl

    Footnotes

    • Funding ABtP is recipient of a Veni-grant, The Netherlands Organization for Health Research and Development (ZonMw), part of the Innovational Research Incentives Scheme Veni-Vidi-Vici, project number 91612027.

    • Ethics approval CME Leiden University Medical Centre.

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

    Linked Articles

    • Fantoms
      Highlights from this issue
      Ben Stenson
      Archives of Disease in Childhood - Fetal and Neonatal Edition 2014; 99 F253-F253 Published Online First: 12 Jun 2014. doi: 10.1136/archdischild-2014-306850