Breath-by-Breath Analysis of Cardiorespiratory Interaction for Quantifying Developmental Maturity in Premature Infants

Breath-by-breath analysis of cardiorespiratory interaction for quantifying developmental maturity in premature infants. J Appl Physiol 112: 859-867, 2012. First published December 15, 2011; doi:10.1152/japplphysiol.01152.2011.-In healthy neonates, connections between the heart and lungs through brain stem chemosensory pathways and the autonomic nervous system result in cardiorespiratory synchronization. This interdependence between cardiac and respiratory dynamics can be difficult to measure because of intermittent signal quality in intensive care settings and variability of heart and breathing rates. We employed a phase-based measure suggested by Sch fer and coworkers (Sch fer C, Rosenblum MG, Kurths J, Abel HH. Nature 392: 239-240, 1998) to obtain a breath-by-breath analysis of cardiorespiratory interaction. This measure of cardiorespiratory interaction does not distinguish between cardiac control of respiration associated with cardioventilatory coupling and respiratory influences on the heart rate associated with respiratory sinus arrhythmia. We calculated, in sliding 4-min windows, the probability density of heartbeats as a function of the concurrent phase of the respiratory cycle. Probability density functions whose Shannon entropy had a \u3c 0.1% chance of occurring from random numbers were classified as exhibiting interaction. In this way, we analyzed 18 infant-years of data from 1,202 patients in the Neonatal Intensive Care Unit at University of Virginia. We found evidence of interaction in 3.3 patient-years of data (18%). Cardiorespiratory interaction increased several-fold with postnatal development, but, surprisingly, the rate of increase was not affected by gestational age at birth. We find evidence for moderate correspondence between this measure of cardiorespiratory interaction and cardioventilatory coupling and no evidence for respiratory sinus arrhythmia, leading to the need for further investigation of the underlying mechanism. Such continuous measures of physiological interaction may serve to gauge developmental maturity in neonatal intensive care patients and prove useful in decisions about incipient illness and about hospital discharge

A quantitative comparison of different methods to detect cardiorespiratory coordination during night-time sleep

BACKGROUND: The univariate approaches used to analyze heart rate variability have recently been extended by several bivariate approaches with respect to cardiorespiratory coordination. Some approaches are explicitly based on mathematical models which investigate the synchronization between weakly coupled complex systems. Others use an heuristic approach, i.e. characteristic features of both time series, to develop appropriate bivariate methods. OBJECTIVE: In this study six different methods used to analyze cardiorespiratory coordination have been quantitatively compared with respect to their performance (no. of sequences with cardiorespiratory coordination, no. of heart beats coordinated with respiration). Five of these approaches have been suggested in the recent literature whereas one method originates from older studies. RESULTS: The methods were applied to the simultaneous recordings of an electrocardiogram and a respiratory trace of 20 healthy subjects during night-time sleep from 0:00 to 6:00. The best temporal resolution and the highest number of coordinated heart beats were obtained with the analysis of 'Phase Recurrences'. Apart from the oldest method, all methods showed similar qualitative results although the quantities varied between the different approaches. In contrast, the oldest method detected considerably fewer coordinated heart beats since it only used part of the maximum amount of information available in each recording. CONCLUSIONS: The method of 'Phase Recurrences' should be the method of choice for the detection of cardiorespiratory coordination since it offers the best temporal resolution and the highest number of coordinated sequences and heart beats. Excluding the oldest method, the results of the heuristic approaches may also be interpreted in terms of the mathematical models

Autonomic Regulation during Quiet and Active Sleep States in Very Preterm Neonates

The immature autonomic nervous system (ANS) in premature infants regulates heart rate (HR) and respiration different during quiet sleep (QS) and active sleep (AS). Little information is available about ANS regulation in these subjects. The aim of this study was to investigate changes in autonomic regulation and cardiorespiratory coupling during AS and QS in five very preterm neonates with gestational age (GA) 26–31 weeks, applying univariate and bivariate linear and non-linear dynamics methods to the recorded cardiorespiratory signals. During QS univariate linear indices revealed lower standard deviations and entropies, indicating decreased heart rate (HR) variability. More balanced sympatho-vagal behavior of the ANS was revealed by decreased low frequency (LF), increased high frequency (HF), and a trend toward lower ratio LF/HF in QS. Applied non-linear indices (probabilities, entropies, and fractal measures) quantifying the complexity and scaling behavior of HR regulation processes were significantly altered in QS in comparison to AS. This reflects a lower short-term variability, less complexity, and a loss of fractal-like correlation properties of HR dynamics in QS. One major finding is that cardiorespiratory coupling is not yet completely developed in very preterm neonates with 26–31 weeks GA. Significantly different regulation patterns in bivariate oscillations of HR and respiration during AS and QS could be recognized. These patterns were characterized on the one hand by predominant monotonous regulating sequences originating from respiration independently from HR time series in AS, and to a minor degree in QS, and on the other hand by some prominent HR regulation sequences in QS independent of respiratory regulation. We speculate that these findings might be suitable for monitoring preterm neonates and for detecting disorders in the developing cardiorespiratory system

Cardiorespiratory Phase-Coupling Is Reduced in Patients with Obstructive Sleep Apnea

Cardiac and respiratory rhythms reveal transient phases of phase-locking which were proposed to be an important aspect of cardiorespiratory interaction. The aim of this study was to quantify cardio-respiratory phase-locking in obstructive sleep apnea (OSA). We investigated overnight polysomnography data of 248 subjects with suspected OSA. Cardiorespiratory phase-coupling was computed from the R-R intervals of body surface ECG and respiratory rate, calculated from abdominal and thoracic sensors, using Hilbert transform. A significant reduction in phase-coupling was observed in patients with severe OSA compared to patients with no or mild OSA. Cardiorespiratory phase-coupling was also associated with sleep stages and was significantly reduced during rapid-eye-movement (REM) sleep compared to slow-wave (SW) sleep. There was, however, no effect of age and BMI on phase coupling. Our study suggests that the assessment of cardiorespiratory phase coupling may be used as an ECG based screening tool for determining the severity of OSA

Characterization of cardiorespiratory phase synchronization and directionality in late premature and full term infants

Objective: Though the mutual influence of cardiovascular and respiratory rhythms in healthy newborns has been documented, its full characterization is still pending. In general, the activity of many physiological subsystems has a well-expressed rhythmic character, and often an interdependency between physiological rhythms emerges early in development. Traditional methods of data analysis only address the quantification of the strength of subsystem interactions. In this work, we will investigate system interrelationships in terms of the possible presence of causal or directional interplays. Approach: In this paper, we propose a methodological application that quantifies phase coupling and its directionality in a population of newborn infants born between 35 and 40 weeks of gestational age (GA). The aim is to assess whether GA at birth significantly influences the development of phase synchronization and the directionality of the coupling between the cardiovascular and respiratory system activity. Several studies indicating irregular cardiorespiratory coupling as a leading cause of several pathologies underscore the need to investigate this phenomenon in this at-risk population. Main results: Results from our investigation show a different directionality profile as a function of GA and sleep state. Significance: These findings are a contribution to the understanding of higher risk for the documented negative outcomes in the late preterm population. Moreover, these parameters could provide a tool for the development of early markers of cardiorespiratory dysregulation in infants

Vastasyntyneen ja imeväisikäisen vauvan unenaikaisen hengitys- ja syketaajuuden tarkkailu puettavalla liikeanturilla

Vastasyntyneelle ja imeväisikäiselle nukkuminen on elintärkeä toiminto, ja se on välttämätöntä aivoverkkojen kehitykselle. Tiedetään, että huono unenlaatu aiheuttaa pitkällä tähtäimellä muun muassa kasvun hidastumista ja käyttäytymisongelmia. Imeväisikäisillä melko yleisesti esiintyvät unihäiriöt, kuten yöheräily ja nukahtamisvaikeudet aiheuttavat merkittävää rasitusta ja huolta vanhemmille. Objektiivisen mittausmenetelmän puutteen vuoksi ei ole kuitenkaan voitu selvittää imeväisikäisen unen kehittymistä kotiolosuhteissa. Tässä tutkimuksessa tarkasteltiin puettaviin pöksyihin kiinnitetyn liikeanturin ja EKG-kangaselektrodien soveltuvuutta vastasyntyneiden ja imeväisikäisten vauvojen unenaikaisen hengityksen ja sykkeen tarkkailuun. Tutkimuksen ensimmäisessä vaiheessa päiväaikaisten uni-EEG-tutkimuksien yhteydessä verrattiin liikeanturin mittauskanavien rekisteröimiä mittauskäyriä pietsoanturilla varustettuun hengitysvyöhön. Saatujen tutkimustuloksien perusteella liikeanturin gyroskooppi osoittautui tarkimmaksi hengitystaajuutta mittaavaksi parametriksi, kun taas anturin välittämä EKG-signaali oli tulkintakelpoisin osin luotettavaa. Tutkimuksen toisessa vaiheessa vauvaperheille annettiin unipöksyt ja älypuhelimet kotiin arvioidaksemme yön yli kestävää kotikäyttöä. Tutkimustulokset viittaavat siihen, että eri unitilojen tunnistaminen hengityksen vaihtelusta olisi todennäköisesti mahdollista gyroskooppisignaalista. Vanhemmilta saadun palautteen perusteella unipöksyjä pidettiin käytännöllisinä ja helppokäyttöisinä. Tulevissa tutkimuksissa tulisi keskittyä liikeanturin validointiin kliinisesti hyväksyttyjen mittausparametrien avulla, jotta algoritmeja voisi opettaa tunnistamaan eri uni-valve rytmejä automaattisesti. Näin puettava liikeanturi voisi tarjota tietoa vauvan luonnollisen unirakenteen kehittymisestä pitkällä aikavälillä. Lisäksi anturin kliininen validointi voisi mahdollistaa imeväisikäisten kardiorespiratoristen ongelmien ja liikehäiriöiden diagnostisen lisätyökalun kehittämisen.Sleep is one of the most vital functions of newborns and infants, and it is essential for neuronal network development. Therefore, long-term sleep disturbances have been associated with growth delays and behavioral disorders. Commonly reported infant sleep disturbances, such as night awakenings and difficulties falling asleep, cause distress to parents. Yet, the development of infant sleep in the home environment has not been fully elucidated due to lack of objective measurement parameters. In the current study, we assessed the feasibility of a motion sensor, attached to wearable pants, and ECG textile electrodes to monitor sleep-related respiration and heart rate of newborns and infants. First, we compared signals recorded by the motion sensor’s measurement channels to the standard respiratory piezo effort belt’s signal during daytime EEG recordings. According to our results, the motion sensor’s gyroscope proved to measure respiratory rate most accurately, while the ECG signal transmitted by the sensor was reliable in interpretable sections. We then provided wearable garments and smartphones to families with infants to assess overnight home-use. Our results indicate that different sleep states could likely be identified based on respiration fluctuation visible in the gyroscope’s signals. Moreover, the wearable system was considered practical and easy to use by the parents. Future studies should focus on validating the sensor with clinically approved measures, in order to train the algorithms to automatically identify different sleep-wake states. By doing so, the wearable sensor could provide information on natural infant sleep structure development over long time periods. Additionally, clinical validation of the sensor may result in the development of a companion diagnostic tool for infant cardiorespiratory and movement disorders

Symbolic Dynamic Analysis of Relations Between Cardiac and Breathing Cycles in Patients on Weaning Trials

Traditional time-domain techniques of data analysis are often not sufficient to characterize the complex dynamics of the cardiorespiratory interdependencies during the weaning trials. In this paper, the interactions between the heart rate (HR) and the breathing rate (BR) were studied using joint symbolic dynamic analysis. A total of 133 patients on weaning trials from mechanical ventilation were analyzed: 94 patients with successful weaning (group S) and 39 patients that failed to maintain spontaneous breathing (group F). The word distribution matrix enabled a coarse-grained quantitative assessment of short-term nonlinear analysis of the cardiorespiratory interactions. The histogram of the occurrence probability of the cardiorespiratory words presented a higher homogeneity in group F than in group S, measured with a higher number of forbidden words in group S as well as a higher number of words whose probability of occurrence is higher than a probability threshold in group S. The discriminant analysis revealed the best results when applying symbolic dynamic variables. Therefore, we hypothesize that joint symbolic dynamic analysis provides enhanced information about different interactions between HR and BR, when comparing patients with successful weaning and patients that failed to maintain spontaneous breathing in the weaning procedure

ASSESSMENT OF CARDIORESPIRATORY INTERACTIONS DURING LIFE THREATENING EVENTS IN PRETERM INFANTS USING POINT PROCESS AND BIVARIATE ALGORITHMS

Cardiorespiratory interactions considered as an important indicator of neurodevelopment of preterm infants. The strength of cardiorespiratory interactions are presumed to be weak and rapidly fluctuating. The current signal processing algorithms are insufficient to capture such time varying weak interactions. In addition, detection of these interactions becomes difficult during life threatening events due to lack of information available due to apnea (absence of output from respiratory system) and the transient temporal destabilization of cardiac system due to bradycardia. To detect the cardiorespiratory interactions, a point process algorithm of cardiac system with respiration as covariates is proposed. The bivariate model is embedded on the point process-modeling framework to capture the time varying weak interactions between cardiac and respiratory system. This integrated framework is employed to detect the cardiorespiratory interactions in preterm infants during their life-threatening events

Cardiorespiratory coordination during exercise in adults with Down syndrome

Introduction: Down syndrome (DS) is a chromosomal disorder affecting simultaneously cardiovascular and respiratory systems. There is no research studying the coupling between these systems during cardiorespiratory exercise testing in a population with DS. Cardiorespiratory coordination (CRC), evaluated through principal component analysis (PCA), measures the covariation of cardiorespiratory variables during exercise. Objective: to investigate and compare CRC in adults with and without DS during maximal cardiorespiratory exercise testing. Methods: fifteen adults with DS and 15 adults without disabilities performed a maximal cardiorespiratory exercise test on a treadmill. First, the slope, and afterward the velocity was increased regularly until participants reached exhaustion. The time series of six selected cardiorespiratory variables [ventilation per minute, an expired fraction of O2, the expired fraction of CO2, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP)] were extracted for the analysis. The number of principal components (PCs), the first PC eigenvalues (PC1), and the information entropy were computed for each group (non-DS and DS) and compared using a t-test or a Mann-Whitney U test. Results: two PCs in the non-DS group and three PCs in the DS group captured the variance of the studied cardiorespiratory variables. The formation of an additional PC in the DS group was the result of the shift of SBP and DBP fromthe PC1 cluster of variables. Eigenvalues of PC1 were higher in the non-DS (U = 30; p = 0.02; d = 1.47) than in the DS group, and the entropy measure was higher in the DS compared with the non-DS group (U = 37.5; p = 0.008; d = 0.70). Conclusion: adults with Down syndrome showed higher CRC dimensionality and a higher entropy measure than participants without disabilities. Both findings point toward a lower efficiency of the cardiorespiratory function during exercise in participants with DS. CRC appears as an alternative measure to investigate the cardiorespiratory function and its response to exercise in the DS population

Étude des altérations du contrôle cardiorespiratoire chez des modèles ovins de pathologies néonatales

Introduction : L'implication des RGO dans les événements cardiorespiratoires des prématurés reste controversée. Bien que quelques études réalisées sur des animaux nouveau-nés à terme ou adultes aient montré que la stimulation des récepteurs œsophagiens entraine des réflexes cardiorespiratoires inhibiteurs, l’impact d’une naissance prématurée sur ces derniers demeure inconnu. L’article 1 vise à tester l’hypothèse selon laquelle la naissance prématurée augmente l'inhibition cardiorespiratoire lors d’une stimulation oesophagienne. Le sepsis néonatal est à l’origine d’une mortalité substantielle, en partie en raison de ses conséquences sur le contrôle cardiorespiratoire. Les réponses au sepsis néonatal sont variables et peuvent expliquer un faible diagnostic pendant la phase initiale de l'infection. L'implication du sepsis néonatal sur le contrôle cardiorespiratoire reste mal connue. L’article 2 vise à comprendre davantage le lien entre l’inflammation accompagnant un sepsis néonatal et les altérations cardiaques et respiratoires. Méthodes : Article 1. Huit agneaux nés à terme et dix agneaux nés 14 jours prématurément ont été étudiés. Une polysomnographie a été réalisée pour suivre en continu l’ECG, la respiration, la pression artérielle systémique, les stades de conscience et la saturation en O2. Cinq stimulations de l'œsophage supérieur et/ou inférieur, incluant l'inflation rapide par ballonnet et/ou l'injection d’HCl, ont été effectuées dans un ordre aléatoire. Article 2. Deux polysomnographies de six heures ont été réalisées sur deux jours consécutifs chez huit agneaux. La première a été effectuée suivant une injection IV de solution saline, et la deuxième après une injection IV de 2,5 μg/kg de lipopolysaccharides (LPS). La température, les gaz du sang artériel, les stades de conscience, l'activité locomotrice, les fréquences respiratoire et cardiaque (FR et FC), la variabilité cardiaque et respiratoire (VFC et VFR), la pression artérielle systémique, les apnées et les ralentissements cardiaques ont été évalués. Résultats : Les stimulations œsophagiennes induisent des réflexes cardiorespiratoires inhibiteurs (apnées, bradycardies, désaturations en oxygène) qui sont amplifiés par la naissance prématurée. L'inhibition cardiorespiratoire la plus importante est observée suite à une stimulation simultanée de l'œsophage inférieur et supérieur. L’injection de LPS induit des altérations cliniques (augmentation biphasique de la température et diminution de la mobilité et de l’éveil agité) et cardiorespiratoires (augmentation de la FR et de la FC et diminution de la VFC et de la VFR) en plus d’une inflammation du tronc cérébral. Conclusion : La stimulation œsophagienne entraine une augmentation des événements cardiorespiratoires chez les agneaux prématurés, probablement en raison de l'immaturité globale du système nerveux. L'injection de LPS entraine une inflammation systémique mimant un sepsis bactérien chez les agneaux avec de multiples conséquences, y compris des altérations cardiorespiratoires