Low Oxygen Saturation Target Range is Associated with Increased Incidence of Intermittent Hypoxemia

doi:10.1016/j.jpeds.2012.05.046

The Journal of Pediatrics

Volume 161, Issue 6, December 2012, Pages 1047-1052.e1

https://doi.org/10.1016/j.jpeds.2012.05.046 Get rights and content

Objective

To test the hypothesis that preterm infants randomized to a low vs high O₂ saturation target range have a higher incidence of intermittent hypoxemia.

Study design

A subcohort of 115 preterm infants with high resolution pulse oximetry enrolled in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial were randomized to low (85%-89%) or high (91%-95%) O₂ saturation target ranges. Oxygen saturation was monitored until 36 weeks postmenstrual age or until the infant was breathing room air without respiratory support for ≥72 hours.

Results

The low target O₂ saturation group had a higher rate of intermittent hypoxemia (≤80% for ≥10 seconds and ≤3 minutes) prior to 12 days and beyond 57 days of life (P < .05). The duration shortened (P < .0001) and the severity increased (P < .0001) with increasing postnatal age with no differences between target saturation groups. The higher rate of intermittent hypoxemia events in the low target group was associated with a time interval between events of <1 minute.

Conclusion

A low O₂ saturation target was associated with an increased rate of intermittent hypoxemia events that was dependent on postnatal age. The duration and severity of events was comparable between target groups. Further investigation is needed to assess the role of intermittent hypoxemia and their timing on neonatal morbidity.

Section snippets

Methods

The study population included a new subcohort of 115 preterm infants enrolled in the multi-center SUPPORT study from 2 sites: Rainbow Babies and Children's Hospital, Cleveland, and University of California San Diego. Enrollment criteria for the main trial included infants who were born between 24 weeks 0 days and 27 weeks 6 days of gestation for whom a decision had been made to provide full resuscitation. Infants born in other hospitals and those known to have major anomalies were excluded.

Results

The population of 115 infants had a mean birth weight of 830 ± 181 g and GA of 25.8 ± 1.0 weeks. There were 50 infants in the GA range 24-25 weeks 6 days, and 65 infants in the GA range 26-27 weeks 6 days. Fifty-one percent of the infants were male and 35% were non-Hispanic white. Characteristics of infants randomized to the high (n = 62) and low (n = 53) target group are presented in the Table. There were no differences between groups in birth weight, GA, incidence of bronchopulmonary

Discussion

This study showed an escalation in the incidence of intermittent hypoxemia events at <12 and >57 days of life in the low O₂ saturation target group. In both groups, events became shorter and more severe with increasing postnatal age with no differences between groups. Lastly, the higher incidence of intermittent hypoxemia in the low target group was predominantly associated with a time interval between events of <1 minute.

Intermittent hypoxemia events are ubiquitous in preterm infants.9, 10, 11

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Cited by (105)

Comparison of hyperoxia or normoxia resolution of intermittent hypoxia and intermittent hyperoxia episodes on liver histopathology, IGF-1, IGFBP-3, and GHBP in neonatal rats
2023, Growth Hormone and IGF Research
Extremely low gestational age neonates requiring oxygen therapy for chronic lung disease experience repeated fluctuations in arterial oxygen saturation, or intermittent hypoxia (IH), during the first few weeks of life. These events are associated with a high risk for reduced growth, hypertension, and insulin resistance in later life. This study tested the hypothesis that IH, or intermittent hyperoxia have similar negative effects on the liver; somatic growth; and liver insulin-like growth factor (IGF)-I, IGF binding protein (BP)-3, and growth hormone binding protein (GHBP), regardless of resolution in normoxia or hyperoxia between episodes.
Newborn rats on the first day of life (P0) were exposed to two IH paradigms: 1) hyperoxia (50% O₂) with brief hypoxia (12% O₂); or 2) normoxia (21% O₂) with hypoxia (12% O₂); intermittent hypoxia (50% O₂/21% O₂); hyperoxia only (50% O₂); or room air (RA, 21% O₂). Pups were euthanized on P14 or placed in RA until P21. Controls remained in RA from P0-P21. Growth, liver histopathology, apoptosis, IGFI, IGFBP-3, and GHBP were assessed.
Pathological findings of the liver hepatocytes, including cellular swelling, steatosis, apoptosis, necrosis and focal sinusoid congestion were seen in the IH and intermittent hyperoxia groups, and were particularly severe in the 21–12% O₂ group during exposure (P14) with no significant improvements during recovery/reoxygenation (P21). These effects were associated with induction of HIF_1α, and reductions in liver IGFI, IGFBP-3, and GHBP.
Exposure to IH or intermittent hyperoxia during the first few weeks of life regardless of resolution in RA or hyperoxia is detrimental to the immature liver. These findings may suggest that interventions to prevent frequent fluctuations in oxygen saturation during early neonatal life remain a high priority.
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Citation Excerpt :
There are also important hemodynamic consequences associated with low oxygen levels14–18 and as shown in randomized trials, with increased mortality associated with exposure to lower Spo2 ranges.19,20 The frequency of IH episodes seems to be inversely related to the basal level Spo2.21,22 This relation is likely the reason why there exists considerable tolerance of high Spo2 levels, which may be aimed at reducing the frequency of IH, due to limited staff availability or an excessive response to IH events.1,23,24
Weaning oxygen in infants with bronchopulmonary dysplasia
2021, Paediatric Respiratory Reviews
Bronchopulmonary dysplasia (BPD) is a form of chronic lung disease commonly seen in preterm infants as the sequelae following respiratory distress syndrome. The management of evolving BPD aims to minimise lung injury and prevent the impact of hypoxia and hyperoxia. Proposed morbidities include respiratory instability, pulmonary hypertension, suboptimal growth, altered cerebral oxygenation and long-term neurodevelopmental impairment. The ongoing management and associated morbidity present a significant burden for carers and healthcare systems. Long-term oxygen therapy may be required for variable duration, though there is a lack of consensus and wide variation in practise when weaning supplemental oxygen. Furthermore, a shift in care towards earlier discharge and community care underlines the importance of a structured discharge and weaning process that eliminates the potential risks associated with hypoxia and hyperoxia. This review article describes recent evidence outlining oxygen saturation reference ranges in young infants, on which structured guidance can be based.
Are we over-treating hypoxic spells in preterm infants?
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A frequent challenge in Neonatology is the high frequency of spontaneously occurring hypoxemic events, a majority of which are associated with apnea or hypoventilation. These episodes present a challenge for caregivers and families as they frequently delay discharge of preterm infants. Supplemental oxygen, respiratory support, and caffeine therapy are widely used as therapeutic approaches, but challenges remain regarding their precise indications. Future clinical practice should be directed by an evidence-based approach including automated supplemental oxygen, minimizing the use of medications for gastroesophageal reflux, optimal timing and dosage of caffeine therapy, and standardization of alarm limits and discharge monitoring protocols.

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: Supported by grants from the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of Child Health and Human Development Cooperative Multicenter Neonatal Research Network (HD021364-23). Data collected at participating sites of the NICHD Neonatal Research Network were transmitted to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. The authors declare no conflicts of interest.

^∗: List of members of the SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network is available at www.jpeds.com (Appendix).

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Original ArticleLow Oxygen Saturation Target Range is Associated with Increased Incidence of Intermittent Hypoxemia

Objective

Study design

Results

Conclusion

Section snippets

Methods

Results

Discussion

Neurosci Lett

J Pediatr

J Pediatr

J Pediatr

J Pediatr

J Pediatr

Int J Dev Neurosc

J Pediatr

J Pediatr

Neonatal intermittent hypoxia impairs dopamine signaling and executive functioning

Sleep Breath

The contribution of intermittent hypoxemia to late neurological handicap in mice with hyperoxia-induced lung injury

Neonatology

Original Article
Low Oxygen Saturation Target Range is Associated with Increased Incidence of Intermittent Hypoxemia