Acute Cardiorespiratory Coupling Impairment in Worsening Sleep Apnea-Related Intermittent Hypoxemia.

OBJECTIVE: Hypoxic load is one of the main characteristics of obstructive sleep apnea (OSA) contributing to sympathetic overdrive and weakened cardiorespiratory coupling (CRC). Whether this association changes with increasing hypoxic load has remained obscure. Therefore, we aimed to study our hypothesis that increasing hypoxic load acutely decreases the CRC. METHODS: We retrospectively analyzed the electrocardiography and nasal pressure signals in 5-min segment pairs (n = 36 926) recorded during clinical polysomnographies of 603 patients with suspected OSA. The segment pairs were pooled into five groups based on the hypoxic load severity described with the the total integrated area under the blood oxygen saturation curve during desaturations. In these severity groups, we determined the frequency-domain heart rate variability (HRV) parameters, the HRV and respiratory high-frequency (HF, 0.15-0.4 Hz) peaks, and the difference between those peaks. We also computed the spectral HF coherence between HRV and respiration in the HF band. RESULTS: The ratio of low-frequency (LF, 0.04-0.15 Hz) to HF power increased from 1.047 to 1.805 (p < 0.001); the difference between the HRV and respiratory HF peaks increased from 0.001 Hz to 0.039 Hz (p < 0.001); and the spectral coherence between HRV and respiration in the HF band decreased from 0.813 to 0.689 (p < 0.001) as the hypoxic load increased. CONCLUSION AND SIGNIFICANCE: The vagal modulation decreases and CRC weakens significantly with increasing hypoxic load. Thus, the hypoxic load could be utilized more thoroughly in contemporary OSA diagnostics to better assess the severity of OSA-related cardiac stress.

Persistent sleep-disordered breathing independently contributes to metabolic syndrome in prepubertal children.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for metabolic syndrome (MetS) in adults, but its association in prepubertal children is still questionable due to the relatively limited cardiometabolic data available and the phenotypic heterogeneity. OBJECTIVE: To identify the role of OSA as a potential mediator of MetS in prepubertal children. METHODS: A total of 255 prepubertal children from the Childhood Adenotonsillectomy Trial were included, with standardized measurements taken before OSA treatment and 7 months later. MetS was defined if three or more of the following criteria were present: adiposity, high blood pressure, elevated glycemia, and dyslipidemia. A causal mediation analysis was conducted to assess the effect of OSA treatment on MetS. RESULTS: OSA treatment significantly impacted MetS, with the apnea-hypopnea index emerging as mediator (p = .02). This mediation role was not detected for any of the individual risk factors that define MetS. We further found that the relationship between MetS and OSA is ascribable to respiratory disturbance caused by the apnea episodes, while systemic inflammation as measured by C-reactive protein, is mediated by desaturation events and fragmented sleep. In terms of evolution, patients with MetS were significantly more likely to recover after OSA treatment (odds ratio = 2.56, 95% confidence interval [CI] 1.20-5.46; risk ratio = 2.06, 95% CI 1.19-3.54) than the opposite, patients without MetS to develop it. CONCLUSION: The findings point to a causal role of OSA in the development of metabolic dysfunction, suggesting that persistent OSA may increase the risk of MetS in prepubertal children. This mediation role implies a need for developing screening for MetS in children presenting OSA symptoms.

Pediatric sleep apnea: Characterization of apneic events and sleep stages using heart rate variability.

Heart rate variability (HRV) is modulated by sleep stages and apneic events. Previous studies in children compared classical HRV parameters during sleep stages between obstructive sleep apnea (OSA) and controls. However, HRV-based characterization incorporating both sleep stages and apneic events has not been conducted. Furthermore, recently proposed novel HRV OSA-specific parameters have not been evaluated. Therefore, the aim of this study was to characterize and compare classic and pediatric OSA-specific HRV parameters while including both sleep stages and apneic events. A total of 1610 electrocardiograms from the Childhood Adenotonsillectomy Trial (CHAT) database were split into 10-min segments to extract HRV parameters. Segments were characterized and grouped by sleep stage (wake, W; non-rapid eye movement, NREMS; and REMS) and presence of apneic events (under 1 apneic event per segment, e/s; 1-5 e/s; 5-10 e/s; and over 10 e/s). NREMS showed significant changes in HRV parameters as apneic event frequency increased, which were less marked in REMS. In both NREMS and REMS, power in BW2, a pediatric OSA-specific frequency domain, allowed for the optimal differentiation among segments. Moreover, in the absence of apneic events, another defined band, BWRes, resulted in best differentiation between sleep stages. The clinical usefulness of segment-based HRV characterization was then confirmed by two ensemble-learning models aimed at estimating apnea-hypopnea index and classifying sleep stages, respectively. We surmise that basal sympathetic activity during REMS may mask apneic events-induced sympathetic excitation, thus highlighting the importance of incorporating sleep stages as well as apneic events when evaluating HRV in pediatric OSA.

Cardiopulmonary coupling indices to assess weaning readiness from mechanical ventilation.

The ideal moment to withdraw respiratory supply of patients under Mechanical Ventilation at Intensive Care Units (ICU), is not easy to be determined for clinicians. Although the Spontaneous Breathing Trial (SBT) provides a measure of the patients' readiness, there is still around 15-20% of predictive failure rate. This work is a proof of concept focused on adding new value to the prediction of the weaning outcome. Heart Rate Variability (HRV) and Cardiopulmonary Coupling (CPC) methods are evaluated as new complementary estimates to assess weaning readiness. The CPC is related to how the mechanisms regulating respiration and cardiac pumping are working simultaneously, and it is defined from HRV in combination with respiratory information. Three different techniques are used to estimate the CPC, including Time-Frequency Coherence, Dynamic Mutual Information and Orthogonal Subspace Projections. The cohort study includes 22 patients in pressure support ventilation, ready to undergo the SBT, analysed in the 24 h previous to the SBT. Of these, 13 had a successful weaning and 9 failed the SBT or needed reintubation -being both considered as failed weaning. Results illustrate that traditional variables such as heart rate, respiratory frequency, and the parameters derived from HRV do not differ in patients with successful or failed weaning. Results revealed that HRV parameters can vary considerably depending on the time at which they are measured. This fact could be attributed to circadian rhythms, having a strong influence on HRV values. On the contrary, significant statistical differences are found in the proposed CPC parameters when comparing the values of the two groups, and throughout the whole recordings. In addition, differences are greater at night, probably because patients with failed weaning might be experiencing more respiratory episodes, e.g. apneas during the night, which is directly related to a reduced respiratory sinus arrhythmia. Therefore, results suggest that the traditional measures could be used in combination with the proposed CPC biomarkers to improve weaning readiness.