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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.)

Objective: To evaluate the mechanisms leading to intermittent hypoxemia (IH) episodes in spontaneously breathing extremely premature infants at 32 weeks and 36 weeks postmenstrual age (PMA)., Methods: We studied spontaneously breathing premature infants born at 23-28 weeks of gestational age who presented with IH episodes while on noninvasive respiratory support at 32 or 36 weeks PMA. Daytime recordings of arterial oxygen saturation (SpO 2 ), esophageal pressure, respiratory inductive plethysmography of the abdomen, chest wall, and their sum were obtained during 4 hours at 32 weeks and 36 weeks PMA. IH episodes (SpO 2  <90% for ≥5 seconds) and severe IH episodes (SpO 2  < 80% for ≥5 seconds) were classified as resulting from apnea, active exhalation and breath holding, reduced tidal volume (VT), or reduced respiratory rate (RR) during the preceding 60 seconds., Results: Fifty-one infants with a mean gestational age of 25.9 ± 1.5 weeks and a mean birth weight of 846 ± 185 g were included. Of these, 31 and 41 were included in the analysis at 32 weeks and 36 weeks PMA, respectively. At both 32 weeks and 36 weeks PMA, greater proportions of all IH episodes and severe IH episodes were associated with active exhalation and breath holding than with apnea, reduced RR, or reduced VT. The severity and duration of the IH episodes did not differ between mechanisms., Conclusions: In this group of premature infants, the predominant mechanism associated with daytime IH was active exhalation and breath holding. This etiology is more closely associated with behavioral factors than abnormal respiratory control and can have implications for prevention., Competing Interests: Declaration of Competing Interest Supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health of the Prematurity Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Project (Grants U01 HL133689 and U01 HL133708), the Micah Batchelor Foundation, and the University of Miami Project NewBorn. The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Apnea is a common complication of respiratory syncytial virus (RSV) infection in young infants. The purpose of this study was to determine whether this infection affects apnea triggered by sensorineural stimulation in weanling rats. We also studied which neurotransmitters are involved in this response and whether passive prophylaxis with a specific neutralizing antibody (palivizumab) confers protection against it. Weanling rats were inoculated intranasally with RSV, adenovirus, or virus-free medium. Changes in respiratory rate and apnea in response to nerve stimulation with increasing doses of capsaicin were measured by plethysmography. Capsaicin-induced apnea was significantly longer in RSV-infected rats at postinoculation days 2 (upper airways infection) and 5 (lower airways infection), and apnea-related mortality occurred only in the RSV-infected group. Reduction in the duration of apnea was observed after selective inhibition of central gamma-aminobutyric acid (GABA) type A receptors and neurokinin type 1 receptors for substance P. Prophylactic palivizumab protected against apnea and apnea-related mortality. These results suggest that sensorineural stimulation during RSV infection is associated with the development of apnea and apnea-related death in early life, whose mechanism involves the release of GABA acting on central GABA type A receptors and substance P acting on neurokinin type 1 receptors.

Rationale: Immature control of breathing is associated with apnea, periodic breathing, intermittent hypoxemia, and bradycardia in extremely preterm infants. However, it is not clear if such events independently predict worse respiratory outcome. Objectives: To determine if analysis of cardiorespiratory monitoring data can predict unfavorable respiratory outcomes at 40 weeks postmenstrual age (PMA) and other outcomes, such as bronchopulmonary dysplasia at 36 weeks PMA. Methods: The Prematurity-related Ventilatory Control (PreVent) study was an observational multicenter prospective cohort study including infants born at,29 weeks of gestation with continuous cardiorespiratory monitoring. The primary outcome was either “favorable” (alive and previously discharged or inpatient and off respiratory medications/O2/support at 40 wk PMA) or “unfavorable” (either deceased or inpatient/previously discharged on respiratory medications/O2/support at 40 wk PMA). Measurements and Main Results: A total of 717 infants were evaluated (median birth weight, 850 g; gestation, 26.4 wk), 53.7% of whom had a favorable outcome and 46.3% of whom had an unfavorable outcome. Physiologic data predicted unfavorable outcome, with accuracy improving with advancing age (area under the curve, 0.79 at Day 7, 0.85 at Day 28 and 32 wk PMA). The physiologic variable that contributed most to prediction was intermittent hypoxemia with oxygen saturation as measured by pulse oximetry,90%. Models with clinical data alone or combining physiologic and clinical data also had good accuracy, with areas under the curve of 0.84–0.85 at Days 7 and 14 and 0.86–0.88 at Day 28 and 32 weeks PMA. Intermittent hypoxemia with oxygen saturation as measured by pulse oximetry,80% was the major physiologic predictor of severe bronchopulmonary dysplasia and death or mechanical ventilation at 40 weeks PMA. Conclusions: Physiologic data are independently associated with unfavorable respiratory outcome in extremely preterm infants. [ABSTRACT FROM AUTHOR]

Apnea of prematurity is a developmental disorder affecting most extremely preterm infants. The consequences of apnea of prematurity on neurodevelopment are not well established, but several reports suggest that apnea and hypoxemia episodes may be associated with worse neurological outcome. Caffeine is the only FDA-approved drug for the prevention and treatment of apnea of prematurity. Besides its clear effectiveness to reduce apnea, the use of caffeine appears to have a wide margin of safety and has been associated with possible beneficial effects on later neurodevelopmental outcome. At the same time, there are also many studies in experimental animals and some in preterm infants suggesting potential serious adverse effects from caffeine administration, especially when using higher doses. Because of these uncertainties, there is a wide variation in caffeine use across institutions. This review summarizes some of the available evidence on caffeine use in this population, its indications and best timing of initiation and discontinuation, appropriate dosing, and some of the possible adverse effects of caffeine administration. Because of the many gaps in knowledge, especially as it relates to efficacy and safety, we encourage further basic and clinical studies to provide stronger evidence, not only on its potential beneficial effects but also its side effects. [ABSTRACT FROM AUTHOR]

The article discusses psychological and clinical effects of nasal intermittent positive pressure ventilation (N-IPPV) in pre term infants. It mentions that N-IPPV is better than nasal continuous positive airway pressure (N-CPAP) in reducing the chances of apnoea in pre mature infants. It further states that there are less chances of respiratory distress syndrome (RDS) with the use of N-IPPV as compared to N-CPAP.

Abstract: Non-invasive ventilation (NIV) is increasingly being used in preterm infants with the purpose of reducing the risk of adverse pulmonary outcome associated with invasive mechanical ventilation. This review analyzes the evidence from physiologic and clinical studies on the use of NIV in the preterm infant. Physiologic data indicate advantages of NIV with regard to ventilation, gas exchange, breathing effort and thoraco-abdominal distortion. Data from clinical trials have consistently shown facilitation of weaning from mechanical ventilation and potential benefits in infants with RDS and apnoea. Long term improvements in respiratory outcome have also been reported but need to be confirmed in larger trials. [Copyright &y& Elsevier]

Background: Preterm infants often present with recurrent episodes of hypoxemia after mechanical ventilation. Objective: To evaluate the role of abdominal muscle activity and central apnea on the frequency and severity of hypoxemia episodes (HEs) in preterm infants with a history of mechanical ventilation. Methods: Continuous recordings of arterial oxygen saturation (SpO2), gastric pressure, respiratory inductance plethysmography and abdominal surface electromyography were obtained during 4 h from spontaneously breathing preterm infants who had recently been extubated and presented with frequent HEs. Results: Ten infants (gestational age 26.4 ± 1.1 weeks, body weight 816 ± 128 g, age 44 ± 21 days, FiO2 0.31 ± 0.09, mechanically ventilated for 33 ± 37 days) were studied 12 ± 7 (mean ± SD) days after extubation. These infants presented with 10.2 ± 9.3 HEs/h (SpO2 <88%, ≥10 s). Of these, 8.2 ± 6.2 HEs/h were associated with abdominal muscle contraction while only 2.0 ± 4.5 HEs/h were associated with ≥10 s apnea (p < 0.05). Of the more severe HEs (SpO2 <75%, ≥10 s), 2.7 ± 3.1 HEs/h were associated with abdominal contraction and only 0.7 ± 2.1 HEs/h with apnea (p < 0.05). Resting lung volume decreased by 69 ± 16% of tidal volume in HEs associated with abdominal contraction. Conclusions: In this group of premature infants who presented with frequent HEs after mechanical ventilation, most HEs were associated with abdominal muscles contraction and a loss in lung volume. These findings provide an alternate mechanism to explain these episodes in spontaneously breathing preterm infants with a history of mechanical ventilation. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract, It has been suggested that apnea of prematurity may be caused by "immaturity" of central control of breathing. To test the validity of this hypothesis tidal volume (V[sub T]), alveolar ventilation (V[sub A]), alveolar PCO[sub 2] (P[sub A]CO[sub 2]), esophageal pressure change, and the slope of the CO[sub 2] response curve (change AV[sub E] [minute ventilation]/change P[sub A]CO[sub 2]) were determined in 18 infants with apnea (mean of 32 episodes of more than 20 seconds duration per day) and in 18 healthy newborns used as control subjects. The infants were matched for birth weight (1,068 g v 1,065 g), gestational age (30.2 weeks v 30.2 weeks), and postnatal age (8.6 days v 8.3 days). The results were as follows: V[sub T] (4.4 +/- 1.0 mL/kg v 5.3 +/- 1.6 mL/kg), V[sub A] (96 +/- 21 mL/ kg/min v 129 +/- 33 mL/kg/min), P[sub A]CO[sub 2] (45.4 +/- 8.5 mm Hg v 35.6 +/- 4.7 mm Hg), esophageal pressure change (4.5 +/- 0.9 cm H[sub 2]O v 6.0 +/- 1.8 cm H[sub 2]O), change V[sub E]/change P[sub A]CO[sub 2](20.2 +/10.6 mL/min/kg/mm Hg CO[sub 2] v 40.7 +/-19.9 mL/min/kg/ mm Hg CO[sub 2]). There was a significant difference between infants with and without apnea for all measurements. The results indicate a decreased respiratory center output and a depressed ventilatoty response to CO[sub 2] in infants with apnea. As there was no difference between the two groups in pulmonary mechanics or oxygenation, the findings support the hypothesis that a central disturbance in regulation of breathing is the cause of apnea in these infants. [ABSTRACT FROM AUTHOR]

Abstract. Airway obstruction is a cause of apnea in preterm infants. The activity of protective respiratory reflexes was determined in 18 preterm infants with apnea (mean of 32 episodes of more than 20 seconds duration per day) and in 18 neonates without apnea used as control subjects. This was done in order to elucidate the role of respiratory reflexes in apnea of prematurity. The infants were matched for birth weight (1,068 g v 1,065 g), gestational age (30.2 weeks v 30.2 weeks), and postnatal age (8.6 days v 8.3 days). The airway occlusion technique was used to determine the inspiratory prolongation of the occluded breath and the effective elastance of the respiratory system. Inspiratory prolongation is a measure for the reflex influence on inspiratory duration, and effective elastance reflects load compensating ability. Inspiratory prolongation was 7.3% +/- 33.5% in infants with apnea and 30.6% +/- 22.7% in the control group (P < .025). Effective elastance was 1.1 +/- 0.5 cm H[sub 2]O/mL in the apneic group and 1.5 +/- 0.5 cm H[sub 2]O/mL in the infants without apnea (P < .025). The results indicate that during exposure to respiratory loads, the infants with apnea maintained inspiratory effort poorly and had a decreased ability for load compensation. Their respiratory reflexes were significantly more immature than the reflex activity of the infants without apnea. This functional immaturity of respiratory reflexes may be a contributing factor in the etiology of apnea of prematurity. [ABSTRACT FROM AUTHOR]

ABSTRACT. The effects of aminophylline on the respiratory center output were studied in 14 premature infants with idiopathic apnea. The mean birth weight was 1,052 gm, and the mean gestational age was 30.2 weeks. These infants had a normal expired volume per minute (VE) [291 ml/(min x kg)] and a normal esophageal pressure change per breath (4.5 cm H[sub 2]O); however, their alveolar ventilation per minute (VA) was decreased [89 ml/(min x kg)], resulting in an elevated end-tidal PCO[sub 2] (P[sub A]CO[sub 2]) [47.8 mm Hg]. The reasons for the elevated P[sub A]CO[sub 2] were the relatively large anatomical dead spaces (VD) found in these infants (3.4 ml/kg), and a decreased slope of the CO[sub 2] response curve [22.2 ml/ (min x kg x mm Hg P[sub A]CO[sub 2])], with a shift of the curve to the right. Oxygen consumption was normal [7.0 ml/(min x kg)]. Forty-eight hours after initiating treatment with aminophylline (2 mg/kg of body weight every six hours), the incidence of apneic episodes decreased from 29.7 to 4.4 per 24 hours, VA and P[sub A]CO[sub 2] became normal secondary to a 33% increase in esophageal pressure change per breath, and the position of the CO[sub 2] response curve showed a significant shift to the left without change in slope. Oxygen consumption increased 20% from basal value. These findings support the hypothesis that apnea in premature infants is related to an immature respiratory center characterized by a decreased output. Aminophylline probably increases respiratory center output by lowering the threshold of the central chemorecepter to CO[sub 2]. [ABSTRACT FROM AUTHOR]