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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., Competing Interests: Declaration of Competing Interest Some authors have financial conflicts of interest. JRM and DEL own stock in Medical Prediction Sciences Corporation. JRM is a consultant for Nihon Kohden Digital Health Solutions, proceeds donated to the University of Virginia. ZAV is a consultant for Medtronic. All other authors have no financial conflicts to disclose. No authors have any nonfinancial conflicts of interest to disclose. Funding Support: We acknowledge the following NIH grants for funding the work presented in this manuscript. University of Virginia (NCT03174301): U01 HL133708, K23 HD097254, HL133708-05S1. Case Western Reserve University: U01 HL133643. Northwestern University: U01 HL133704. University of Alabama at Birmingham: U01 HL133536, K23 HL157618. University of Miami: U01 HL133689. Washington University: U01 HL133700, F., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Stabilization of respiration and oxygenation continues to be one of the main challenges in clinical care of the neonate. Despite aggressive respiratory support including mechanical ventilation, continuous positive airway pressure, oxygen and caffeine therapy to reduce apnea and accompanying intermittent hypoxemia, the incidence of intermittent hypoxemia events continues to increase during the first few months of life. Even with improvements in clinical care, standards for oxygen saturation targeting and modes of respiratory support have yet to be identified in this vulnerable infant cohort. In addition, we are only beginning to explore the association between the incidence and pattern of cardiorespiratory events during early postnatal life and both short- and long-term morbidity including retinopathy of prematurity, growth, sleep-disordered breathing and neurodevelopmental impairment. Part 1 of this review included a summary of lung development and diagnostic methods of cardiorespiratory monitoring. In Part 2 we focus on clinical interventions and the short- and long-term consequences of cardiorespiratory events in preterm infants.

Hypoxic episodes are troublesome components of bronchopulmonary dysplasia (BPD) in preterm infants. Immature respiratory control seems to be the major contributor, superimposed on abnormal respiratory function. Relatively short respiratory pauses may precipitate desaturation and bradycardia. This population is predisposed to pulmonary hypertension; it is likely that pulmonary vasoconstriction also plays a role. The natural history has been well-characterized in the preterm population at risk for BPD; however, the consequences are less clear. Proposed associations of intermittent hypoxia include retinopathy of prematurity, sleep disordered breathing, and neurodevelopmental delay. Future study should address whether these associations are causal relationships., (Copyright © 2015 Elsevier Inc. All rights reserved.)

With increased survival of preterm infants as young as 23 weeks gestation, maintaining adequate respiration and corresponding oxygenation represents a clinical challenge in this unique patient cohort. Respiratory instability characterized by apnea and periodic breathing occurs in premature infants because of immature development of the respiratory network. While short respiratory pauses and apnea may be of minimal consequence if oxygenation is maintained, they can be problematic if accompanied by chronic intermittent hypoxemia. Underdevelopment of the lung and the resultant lung injury that occurs in this population concurrent with respiratory instability creates the perfect storm leading to frequent episodes of profound and recurrent hypoxemia. Chronic intermittent hypoxemia contributes to the immediate and long term co-morbidities that occur in this population. In this review we discuss the pathophysiology leading to the perfect storm, diagnostic assessment of breathing instability in this unique population and therapeutic interventions that aim to stabilize breathing without contributing to tissue injury., (Copyright © 2013. Published by Elsevier B.V.)

Objective: To examine the temporal relationship between apnea and gastroesophageal reflux (GER) and to assess the effect of GER on apnea duration., Methods: A total of 119 preterm infants underwent 12-hour cardiorespiratory monitoring studies using respiratory inductance plethysmography, heart rate, oxygen saturation (SaO2), and esophageal pH. The studies were scored for GER (pH <4 for > or =5 seconds) and apnea > or =15 seconds or > or =10 seconds that occurred within 30 seconds of GER. Apnea > or =10 seconds was used to assess whether GER would prolong apnea duration., Results: There were 6255 episodes of GER. Only 1% of GER episodes were associated with apnea > or =15 seconds, and there was no difference in apnea rate before, during, or after GER. There was also no difference in rate of apnea > or =10 seconds before versus during GER; however, there was a decrease in apnea rate immediately after GER. The presence of GER during apnea did not prolong apnea duration, and GER had no effect on the lowest SaO2 or heart rate during apnea., Conclusion: There is no evidence of a temporal relationship between acid-based GER and apnea in preterm infants. In addition, GER does not prolong apnea duration and does not exacerbate the resultant decrease in heart rate and SaO2.

Gastroesophageal reflux (GER) and apnea are both common occurrences in premature infants but their relationship is controversial. We present the evidence for and against an association between GER and apnea and discuss the merits and limitations of the various methodologies employed in characterizing such a relationship. Overall, GER and apnea do not appear temporally related in preterm infants, despite strong physiologic evidence that stimulation of laryngeal afferents elicits central apnea and laryngeal adduction. In a subpopulation of infants with neurodevelopmental compromise, there may be an increased incidence of both apnea and GER, although the direct association between GER and apnea in this population is unclear. Therefore, we believe there is no evidence to support widespread use of anti-reflux medications in the treatment of apnea in preterm infants. Further studies are needed to clarify the existence of a small subpopulation of infants who may have GER-induced apnea, to identify potential triggering mechanisms, and to document benefit from newer pharmacological approaches., (Copyright 2005 S. Karger AG, Basel)

Episodes of apnoea, desaturation and bradycardia are a common occurrence in preterm infants and are known to persist after hospital discharge. These events are typically detected by clinical bedside monitoring, but the type and number of events depend on alarm settings, the inclusion of continuous pulse oximetry and the mode of respiratory monitoring used. The long term effects of cardiorespiratory events remain controversial; however, some studies have suggested an association between prolonged apnoea and morbidity such as impaired neurodevelopmental outcome. Common clinical practice requires an event-free period before hospital discharge, although the specific length of time varies between institutions. Therefore, with the current demand to shorten hospital stay, the possible persistence of cardiorespiratory events after hospital discharge and the potential consequences of these events, cardiorespiratory monitoring remains a subject of considerable interest. Since cardiorespiratory event detection is dependent on the mode of monitoring used, this chapter will focus on both the respiratory patterns and types of cardiorespiratory events that occur in the infant population and the modalities of cardiorespiratory monitoring currently available to detect these events.

Background: Episodes of apnea, desaturation, and bradycardia are common in preterm infants. Such infants who have persistent cardiorespiratory events detected by clinical bedside monitoring often are referred for overnight apnea monitoring studies., Objective: To characterize apnea, bradycardia, and desaturation events in infants referred for an overnight apnea monitoring study and compare them with corresponding events in control infants of similar age and weight with no bedside monitor alarms., Methods: Twelve-hour bedside apnea monitoring studies were performed on 68 preterm infants before hospital discharge. This population included 35 infants who were referred by their attending physicians because of persistent bedside monitor alarms (referral group) and 33 infants who had no documented cardiorespiratory events for at least 2 days before the study (control group). Each study monitored respiration via respiratory inductance plethysmography, oxygen saturation (Sao2), and heart rate. Events were defined as meeting 1 of the following criteria: apnea > or =20 seconds, bradycardia < or =80 beats per minute, or Sao2 < or =80%., Results: The incidence of apnea > or =20 seconds was low, with no significant difference between infant groups. Referral infants exhibited a higher occurrence of desaturation episodes (20 +/- 6 vs 6 +/- 3 episodes/12-hour study) and a higher occurrence of bradycardia episodes (4.3 +/- 0.8 vs 1.1 +/- 0.3 episodes/12-hour study) than controls. These episodes of desaturation and bradycardia were always preceded by a respiratory pause, which was shorter in the referral infants (10.0 +/- 0.4 seconds vs 12.0 +/- 1.0 seconds). Baseline Sao2 was lower in referrals than controls (95 +/- 1% vs 98 +/- 1%), and the incidence of periodic breathing was significantly higher., Conclusions: Infants referred for apnea monitoring studies because of persistent bedside monitor alarms have very infrequent prolonged apnea but a higher frequency of desaturation and bradycardia in response to short respiratory pauses than infants without persistent bedside monitor alarms. Referral infants also exhibit a lower baseline Sao2. These abnormalities in oxygenation and cardiorespiratory control may be markers for subtle residual lung disease or functional central nervous system abnormalities.

As part of the Collaborative Home Infant Monitoring Evaluation (CHIME) we compared apnea identified by a customized home monitor using respiratory inductance plethysmography (RIP) with simultaneously recorded polysomnography-acquired nasal end-tidal CO(2) (PET(CO(2))) and nasal/oral thermistor in 422 infants during overnight laboratory recordings to determine concordance between techniques, sources of disagreement, and capacity of RIP to detect obstructed breaths within an apnea. Among 233 episodes of apnea identified by at least one method as >/= 16 s, 120 were observed by the CHIME monitor, 219 by PET(CO(2)), and 163 by thermistor. The positive predictive value of the CHIME-identified apnea was 89.2% (95% CI 83, 95) and 73% (95% CI 65, 81) for PET(CO(2)) and thermistor, respectively. However, the sensitivity of the CHIME monitor in identifying events detected by the other methods was only approximately 50%. Among 87 apnea events identified by all three techniques, no two methods showed high agreement in measurement of apnea duration: RIP and PET(CO(2)) (ICC = 0.54), RIP and thermistor (ICC = 0.13), PET(CO(2)) and nasal thermistor (ICC = 0.41). Among the 179 breaths identified by RIP as obstructed, 79.9% were judged to be obstructed on the PET(CO(2)) and 80.4% were judged to be obstructed on the thermistor channel. Among 238 breaths identified on PET(CO(2)) as obstructed, 54.2% were determined to be obstructed by RIP. Among 204 breaths identified on thermistor as obstructed, 55. 4% were determined to be obstructed by RIP. Reasons for discrepancies in apnea detection among channels included body movement, partial airway obstruction, and obstructed breaths. Despite these limitations the CHIME monitor provides an opportunity to record physiological data previously unavailable in the home.