Key points
The carotid chemoreceptor mediates the ventilatory and muscle sympathetic nerve activity (MSNA) responses to hypoxia and contributes to tonic sympathetic and respiratory drives. It is ...often presumed that both excitatory and inhibitory tests of chemoreflex function show congruence in the end‐organ responses.
Ventilatory and neurocirculatory (MSNA, blood pressure and heart rate) responses to chemoreflex inhibition elicited by transient hyperoxia and to chemoreflex excitation produced by steady‐state eucapnic hypoxia were measured in a cohort of 82 middle‐aged individuals.
Ventilatory and MSNA responsiveness to hyperoxia and hypoxia were not significantly correlated within individuals.
It was concluded that ventilatory responses to hypoxia and hyperoxia do not predict MSNA responses and it is recommended that tests using the specific outcome of interest, i.e. MSNA or ventilation, are required.
Transient hyperoxia is recommended as a sensitive and reliable means of quantifying tonic chemoreceptor‐driven levels of sympathetic nervous system activity and respiratory drive.
Hypersensitivity of the carotid chemoreceptor leading to sympathetic nervous system activation and ventilatory instability has been implicated in the pathogenesis and consequences of several common clinical conditions. A variety of treatment approaches aimed at lessening chemoreceptor‐driven sympathetic overactivity are now under investigation; thus, the ability to quantify this outcome variable with specificity and precision is crucial. Accordingly, we measured ventilatory and neurocirculatory responses to chemoreflex inhibition elicited by transient hyperoxia and chemoreflex excitation produced by exposure to graded, steady‐state eucapnic hypoxia in middle‐aged men and women (n = 82) with continuous positive airway pressure‐treated obstructive sleep apnoea. Progressive, eucapnic hypoxia produced robust and highly variable increases in ventilation (+83 ± 59%) and muscle sympathetic nerve activity (MSNA) burst frequency (+55 ± 31%), whereas transient hyperoxia caused marked reductions in these variables (−35 ± 14% and −42 ± 16%, respectively). Coefficients of variation for ventilatory and MSNA burst frequency responses, indicating test–retest reproducibility, were respectively 9% and 24% for hyperoxia and 35% and 28% for hypoxia. Based on statistical measures of rank correlation or even comparisons across quartiles of corresponding ventilatory and MSNA responses, we found that the magnitudes of ventilatory inhibition with hyperoxia or excitation with eucapnic hypoxia were not correlated with corresponding MSNA responses within individuals. We conclude that, in conscious, behaving humans, ventilatory sensitivities to progressive, steady‐state, eucapnic hypoxia and transient hyperoxia do not predict MSNA responsiveness. Our findings also support the use of transient hyperoxia as a reliable, sensitive, measure of the carotid chemoreceptor contribution to tonic sympathetic nervous system activity and respiratory drive.
Key points
The carotid chemoreceptor mediates the ventilatory and muscle sympathetic nerve activity (MSNA) responses to hypoxia and contributes to tonic sympathetic and respiratory drives. It is often presumed that both excitatory and inhibitory tests of chemoreflex function show congruence in the end‐organ responses.
Ventilatory and neurocirculatory (MSNA, blood pressure and heart rate) responses to chemoreflex inhibition elicited by transient hyperoxia and to chemoreflex excitation produced by steady‐state eucapnic hypoxia were measured in a cohort of 82 middle‐aged individuals.
Ventilatory and MSNA responsiveness to hyperoxia and hypoxia were not significantly correlated within individuals.
It was concluded that ventilatory responses to hypoxia and hyperoxia do not predict MSNA responses and it is recommended that tests using the specific outcome of interest, i.e. MSNA or ventilation, are required.
Transient hyperoxia is recommended as a sensitive and reliable means of quantifying tonic chemoreceptor‐driven levels of sympathetic nervous system activity and respiratory drive.
Infants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of ...outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants.
Infants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003-2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups.
Fifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups.
Qualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE.
Infants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up. In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value. 72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment. Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants. Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE.
Objective
To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic‐ischemic encephalopathy (HIE).
Methods
Clinical and EEG ...parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure‐prediction models. Clinical parameters included intrapartum complications, fetal distress, gestational age, delivery mode, gender, birth weight, Apgar scores, assisted ventilation, cord pH, and blood gases. The earliest EEG hour provided a qualitative analysis (discontinuity, amplitude, asymmetry/asynchrony, sleep–wake cycle SWC) and a quantitative analysis (power, discontinuity, spectral distribution, inter‐hemispheric connectivity) from full montage and two‐channel amplitude‐integrated EEG (aEEG). Subgroup analysis, only including infants without anti‐seizure medication (ASM) prior to EEG was also performed. Machine‐learning (ML) models (random forest and gradient boosting algorithms) were developed to predict infants who would later develop seizures and assessed using Matthews correlation coefficient (MCC) and area under the receiver‐operating characteristic curve (AUC).
Results
The study included 162 infants with HIE (53 had seizures). Low Apgar, need for ventilation, high lactate, low base excess, absent SWC, low EEG power, and increased EEG discontinuity were associated with seizures. The following predictive models were developed: clinical (MCC 0.368, AUC 0.681), qualitative EEG (MCC 0.467, AUC 0.729), quantitative EEG (MCC 0.473, AUC 0.730), clinical and qualitative EEG (MCC 0.470, AUC 0.721), and clinical and quantitative EEG (MCC 0.513, AUC 0.746). The clinical and qualitative‐EEG model significantly outperformed the clinical model alone (MCC 0.470 vs 0.368, p‐value .037). The clinical and quantitative‐EEG model significantly outperformed the clinical model (MCC 0.513 vs 0.368, p‐value .012). The clinical and quantitative‐EEG model for infants without ASM (n = 131) had MCC 0.588, AUC 0.832. Performance for quantitative aEEG (n = 159) was MCC 0.381, AUC 0.696 and clinical and quantitative aEEG was MCC 0.384, AUC 0.720.
Significance
Early EEG background analysis combined with readily available clinical data helped predict infants who were at highest risk of seizures, hours before they occur. Automated quantitative‐EEG analysis was as good as expert analysis for predicting seizures, supporting the use of automated assessment tools for early evaluation of HIE.
Hypotension or low blood pressure (BP) is a common problem in preterm neonates and has been associated with adverse short and long-term neurological outcomes. Deciding when and whether to treat ...hypotension relies on an understanding of the relationship between BP and brain functioning. This study aims to investigate the interaction (coupling) between BP and continuous multichannel unedited EEG recordings in preterm infants less than 32 weeks of gestational age. The EEG was represented by spectral power in four frequency sub-bands: 0.3-3 Hz, 3-8 Hz, 8-15 Hz and 15-30 Hz. BP was represented as mean arterial pressure (MAP). The level of coupling between the two physiological systems was estimated using linear and nonlinear methods such as correlation, coherence and mutual information. Causality of interaction was measured using transfer entropy. The illness severity was represented by the clinical risk index for babies (CRIB II score) and contrasted to the computed level of interaction. It is shown here that correlation and coherence, which are linear measures of the coupling between EEG and MAP, do not correlate with CRIB values, whereas adjusted mutual information, a nonlinear measure, is associated with CRIB scores (r = -0.57, p = 0.003). Mutual information is independent of the absolute values of MAP and EEG powers and quantifies the level of coupling between the short-term dynamics in both signals. The analysis indicated that the dominant causality is from changes in EEG producing changes in MAP. Transfer entropy (EEG to MAP) is associated with the CRIB score (0.3-3 Hz: r = 0.428, p = 0.033, 3-8 Hz: r = 0.44, p = 0.028, 8-15 Hz: r = 0.416, p = 0.038) and indicates that a higher level of directed coupling from brain activity to blood pressure is associated with increased illness in preterm infants. This is the first study to present the nonlinear measure of interaction between brain activity and blood pressure and to demonstrate its relation to the initial illness severity in the preterm infant. The obtained results allow us to hypothesise that the normal wellbeing of a preterm neonate can be characterised by a nonlinear coupling between brain activity and MAP, whereas the presence of weak coupling with distinctive directionality of information flow is associated with an increased mortality rate in preterms.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heart rate variability (HRV) has previously been assessed as a biomarker for brain injury and prognosis in neonates. The aim of this cohort study was to use HRV to predict the electroencephalography ...(EEG) grade in neonatal hypoxic-ischaemic encephalopathy (HIE) within the first 12 h.
We included 120 infants with HIE recruited as part of two European multi-centre studies, with electrocardiography (ECG) and EEG monitoring performed before 12 h of age. HRV features and EEG background were assessed using the earliest 1 h epoch of ECG-EEG monitoring. HRV was expressed in time, frequency and complexity features. EEG background was graded from 0-normal, 1-mild, 2-moderate, 3-major abnormalities to 4-inactive. Clinical parameters known within 6 h of birth were collected (intrapartum complications, foetal distress, gestational age, mode of delivery, gender, birth weight, Apgar at 1 and 5, assisted ventilation at 10 min). Using logistic regression analysis, prediction models for EEG severity were developed for HRV features and clinical parameters, separately and combined. Multivariable model analysis included 101 infants without missing data.
Of 120 infants included, 54 (45%) had normal-mild and 66 (55%) had moderate-severe EEG grade. The performance of HRV model was AUROC 0.837 (95% CI: 0.759-0.914) and clinical model was AUROC 0.836 (95% CI: 0.759-0.914). The HRV and clinical model combined had an AUROC of 0.895 (95% CI: 0.832-0.958). Therapeutic hypothermia and anti-seizure medication did not affect the model performance.
Early HRV and clinical information accurately predicted EEG grade in HIE within the first 12 h of birth. This might be beneficial when EEG monitoring is not available in the early postnatal period and for referral centres who may want some objective information on HIE severity.
Objective To compare the ability of qualitative versus quantitative methods of end-tidal carbon dioxide (EtCO2 ) detection to maintain normocarbia during face mask ventilation (FMV) of preterm ...infants (<32 weeks) in the delivery room. Study design Preterm infants <32 weeks were randomly assigned to the use of a disposable PediCap EtCO2 detector (Covidien, Dublin, Ireland) (qualitative) or a Microstream side stream capnography device (Covidien) (quantitative) for FMV in the delivery room, via a NeoPuff T-piece resuscitator (Fisher and Paykel, Auckland, New Zealand). The primary outcome was the presence of normocarbia, based on partial pressure of CO2 (PaCO2 ) readings obtained in the neonatal intensive care unit within an hour of birth. Normocarbia was defined as a PaCO2 measure between 37.5 and 60 mm Hg (5-8 kPa). Results Of the 59 infants included, 59% (35/59) were within the PaCO2 target range within an hour of birth. There was no difference in the primary outcome; 64% (21/33) of infants in the quantitative group were within the PaCO2 range compared with 54% (14/26) in the qualitative group ( P = .594); and 93% of participants <28 weeks' gestation were within the PaCO2 normocarbic range (90% 9/10 in quantitative group and 100% 5/5 in the qualitative group P = 1). There was no difference in the intubation rate, days of ventilation, or bronchopulmonary dysplasia rates between the 2 groups. Conclusions Quantitative or qualitative EtCO2 detection methods are both feasible for FMV in the delivery room. Although there was no difference in the incidence of normocarbia, the use of either form of EtCO2 monitoring should be considered during newborn stabilization, especially in infants less than 28 weeks' gestation. Trial registration ISRCTN: ISRCTN10934870.
Eukaryotic algae and cyanobacteria produce hydrogen under anaerobic and limited aerobic conditions. Here we show that novel microalgal strains (Chlorella vulgaris YSL01 and YSL16) upregulate the ...expression of the hydrogenase gene (HYDA) and simultaneously produce hydrogen through photosynthesis, using CO2 as the sole source of carbon under aerobic conditions with continuous illumination. We employ dissolved oxygen regimes that represent natural aquatic conditions for microalgae. The experimental expression of HYDA and the specific activity of hydrogenase demonstrate that C. vulgaris YSL01 and YSL16 enzymatically produce hydrogen, even under atmospheric conditions, which was previously considered infeasible. Photoautotrophic H2 production has important implications for assessing ecological and algae-based photolysis.
To compare cerebral activity and oxygenation in preterm infants (<32 weeks of gestation) randomized to different cord clamping strategies.
Preterm infants born at <32 weeks of gestation were ...randomized to immediate cord clamping, umbilical cord milking (cord stripped 3 times), or delayed cord clamping for 60 seconds with bedside resuscitation. All infants underwent electroencephalogram (EEG) and cerebral near infrared spectroscopy for the first 72 hours after birth. Neonatal primary outcome measures were quantitative measures of the EEG (17 features) and near infrared spectroscopy over 1-hour time frames at 6 and 12 hours of life.
Forty-five infants were recruited during the study period. Twelve infants (27%) were randomized to immediate cord clamping, 19 (42%) to umbilical cord milking, and 14 (31%) to delayed cord clamping with bedside resuscitation. There were no significant differences between groups for measures of EEG activity or cerebral near infrared spectroscopy. Three of the 45 infants (6.7%) were diagnosed with severe IVH (2 in the immediate cord clamping group, 1 in the umbilical cord milking group; P = .35).
There were no differences in cerebral EEG activity and cerebral oxygenation values between cord management strategies at 6 and 12 hours.
ISRCTN92719670.
To test the potential utility of applying machine learning methods to regional cerebral (rcSO
) and peripheral oxygen saturation (SpO
) signals to detect brain injury in extremely preterm infants.
A ...subset of infants enrolled in the Management of Hypotension in Preterm infants (HIP) trial were analysed (
= 46). All eligible infants were <28 weeks' gestational age and had continuous rcSO
measurements performed over the first 72 h and cranial ultrasounds performed during the first week after birth. SpO
data were available for 32 infants. The rcSO
and SpO
signals were preprocessed, and prolonged relative desaturations (PRDs; data-driven desaturation in the 2-to-15-min range) were extracted. Numerous quantitative features were extracted from the biosignals before and after the exclusion of the PRDs within the signals. PRDs were also evaluated as a stand-alone feature. A machine learning model was used to detect brain injury (intraventricular haemorrhage-IVH grade II-IV) using a leave-one-out cross-validation approach.
The area under the receiver operating characteristic curve (AUC) for the PRD rcSO
was 0.846 (95% CI: 0.720-0.948), outperforming the rcSO
threshold approach (AUC 0.593 95% CI 0.399-0.775). Neither the clinical model nor any of the SpO
models were significantly associated with brain injury.
There was a significant association between the data-driven definition of PRDs in rcSO
and brain injury. Automated analysis of PRDs of the cerebral NIRS signal in extremely preterm infants may aid in better prediction of IVH compared with a threshold-based approach. Further investigation of the definition of the extracted PRDs and an understanding of the physiology underlying these events are required.
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