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Published on: December 22, 2016
Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm
Sherry L Kausch1, Douglas E Lake2, Juliann M Di Fiore3
1Division of Neonatology, Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA.
Insights
Cardiorespiratory events like apnea and bradycardia can signal late-onset sepsis in extremely preterm infants. These changes often precede a sepsis diagnosis, offering potential early warning signs.
Area of Science:
- Neonatal Medicine
- Pediatric Critical Care
- Respiratory Physiology
Background:
- Late-onset sepsis is a significant concern in extremely preterm infants (<29 weeks gestational age).
- Cardiorespiratory events are common in this population and may be linked to sepsis development.
- Distinguishing sepsis-related cardiorespiratory changes from other causes is clinically challenging.
Purpose of the Study:
- To investigate the association between specific cardiorespiratory events (apnea, periodic breathing, intermittent hypoxemia, bradycardia) and late-onset sepsis in extremely preterm infants.
- To compare these associations in infants on versus off invasive mechanical ventilation.
- To identify potential cardiorespiratory signatures that precede sepsis diagnosis.
Main Methods:
- Retrospective analysis of data from the Pre-Vent observational study (NCT03174301).
- Inclusion of 737 extremely preterm infants (mean GA 26.4 weeks) from 5 level IV NICUs.
- Quantification of daily cardiorespiratory events (apnea, periodic breathing, bradycardia, intermittent hypoxemia) using continuous monitoring data for 719 infants.
Main Results:
- For infants not on mechanical ventilation, increases in apnea, periodic breathing, and bradycardia were observed before sepsis diagnosis.
- For ventilated infants, longer intermittent hypoxemia events (oxygen saturation <80%) and increased bradycardia preceded sepsis.
- Intermittent hypoxemia events were linked to higher sepsis risk but did not show a consistent temporal increase before diagnosis.
- A multivariable model incorporating cardiorespiratory variables and ventilator status predicted sepsis with an AUC of 0.783.
Conclusions:
- Cardiorespiratory patterns can serve as signatures for late-onset sepsis in extremely preterm infants.
- While intermittent hypoxemia increases sepsis risk, its temporal relationship to diagnosis varied by ventilation status.
- Observed increases in bradycardia, apnea, and periodic breathing often precede clinical sepsis diagnosis, suggesting their utility as early warning indicators.
Objective:
The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation.
Study Design:
This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics).
Results:
For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783.
Conclusion:
We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.
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