A Pilot Study of Heart Rate Variability Synchrony as a Marker of Intraoperative Surgical Teamwork and Its Correlation to the Length of Procedure.

Objective: Quality of intraoperative teamwork may have a direct impact on patient outcomes. Heart rate variability (HRV) synchrony may be useful for objective assessment of team cohesion and good teamwork. The primary aim of this study was to investigate the feasibility of using HRV synchrony in surgical teams. Secondary aims were to investigate the association of HRV synchrony with length of procedure (LOP), complications, number of intraoperative glitches and length of stay (LOS). We also investigated the correlation between HRV synchrony and team familiarity, pre- and intraoperative stress levels (STAI questionnaire), NOTECHS score and experience of team members. Methods: Ear, nose and throat (ENT) and vascular surgeons (consultant and registrar team members) were recruited into the study. Baseline demographics including level of team members' experience were gathered before each procedure. For each procedure, continuous electrocardiogram (ECG) recording was performed and questionnaires regarding pre- and intraoperative stress levels and non-technical skills (NOTECHS) scores were collected for each team member. An independent observer documented the time of each intraoperative glitch. Statistical analysis was conducted using stepwise multiple linear regression. Results: Four HRV synchrony metrics which may be markers of efficient surgical collaboration were identified from the data: 1. number of HRV synchronies per hour of procedure, 2. number of HRV synchrony trends per hour of procedure, 3. length of HRV synchrony trends per hour of procedure, 4. area under the HRV synchrony trend curve per hour of procedure. LOP was inversely correlated with number of HRV synchrony trends per hour of procedure (p < 0.0001), area under HRV synchrony trend curve per hour of procedure (p = 0.001), length of HRV synchrony trends per hour of procedure (p = 0.002) and number of HRV synchronies per hour of procedure (p < 0.0001). LOP was positively correlated with: FS (p = 0.043; R = 0.358) and intraoperative STAI score of the whole team (p = 0.007; R = 0.493). Conclusions: HRV synchrony metrics within operating teams may be used as an objective marker to quantify surgical teamwork. We have shown that LOP is shorter when the intraoperative surgical teams' HRV is more synchronised.

New method to measure interbreath intervals in infants for the assessment of apnoea and respiration.

BACKGROUND: Respiratory disorders, including apnoea, are common in preterm infants due to their immature respiratory control compared with term-born infants. However, our inability to accurately measure respiratory rate in hospitalised infants results in unreported episodes of apnoea and an incomplete picture of respiratory activity. METHODS: We develop, validate and use a novel algorithm to identify interbreath intervals (IBIs) and apnoeas in preterm infants. In 42 preterm infants (1600 hours of recordings), we assess IBIs from the chest electrical impedance pneumograph using an adaptive amplitude threshold for the detection of breaths. The algorithm is refined by comparing its accuracy with clinically observed breaths and pauses in breathing. We develop an automated classifier to differentiate periods of true apnoea from artefactually low amplitude signal. We assess the performance of this algorithm in the detection of morphine-induced respiratory depression. Finally, we use the algorithm to investigate whether retinopathy of prematurity (ROP) screening alters the IBI distribution. RESULTS: Individual breaths were detected with a false-positive rate of 13% and a false-negative rate of 12%. The classifier identified true apnoeas with an accuracy of 93%. As expected, morphine caused a significant shift in the IBI distribution towards longer IBIs. Following ROP screening, there was a significant increase in pauses in breathing that lasted more than 10 s (t-statistic=1.82, p=0.023). This was not reflected by changes in the monitor-derived respiratory rate and no episodes of apnoea were recorded in the medical records. CONCLUSIONS: We show that our algorithm offers an improved method for the identification of IBIs and apnoeas in preterm infants. Following ROP screening, increased respiratory instability can occur even in the absence of clinically significant apnoeas. Accurate assessment of infant respiratory activity is essential to inform clinical practice.

Early Postnatal Heart Rate Variability in Healthy Newborn Infants.

BACKGROUND: Despite the increasing interest in fetal and neonatal heart rate variability (HRV) analysis and its potential use as a tool for early disease stratification, no studies have previously described the normal trends of HRV in healthy babies during the first hours of postnatal life. METHODS: We prospectively recruited 150 healthy babies from the postnatal ward and continuously recorded their electrocardiogram during the first 24 h after birth. Babies were included if born in good condition and stayed with their mother. Babies requiring any medication or treatment were excluded. Five-minute segments of the electrocardiogram (non-overlapping time-windows) with more than 90% consecutive good quality beats were included in the calculation of hourly medians and interquartile ranges to describe HRV trends over the first 24 h. We used multilevel mixed effects regression with auto-regressive covariance structure for all repeated measures analysis and t-tests to compare group differences. Non-normally distributed variables were log-transformed. RESULTS: Nine out of 16 HRV metrics (including heart rate) changed significantly over the 24 h [Heart rate p < 0.01; Standard deviation of the NN intervals p = 0.01; Standard deviation of the Poincaré plot lengthwise p < 0.01; Cardiac sympathetic index (CSI) p < 0.01; Normalized high frequency power p = 0.03; Normalized low frequency power p < 0.01; Total power p < 0.01; HRV index p = 0.01; Parseval index p = 0.03], adjusted for relevant clinical variables. We observed an increase in several HRV metrics during the first 6 h followed by a gradual normalization by approximately 12 h of age. Between 6 and 12 h of age, only heart rate and the normalized low frequency power changed significantly, while between 12 and 18 h no metric, other than heart rate, changed significantly. Analysis with multilevel mixed effects regression analysis (multivariable) revealed that gestational age, reduced fetal movements, cardiotocography and maternal chronic or pregnancy induced illness were significant predictors of several HRV metrics. CONCLUSION: Heart rate variability changes significantly during the first day of life, particularly during the first 6 h. The significant correlations between HRV and clinical risk variables support the hypothesis that HRV is a good indicator of overall wellbeing of a baby and is sensitive to detect birth-related stress and monitor its resolution over time.

The ClassA Framework: HRV Based Assessment of SNS and PNS Dynamics Without LF-HF Controversies.

The powers of the low frequency (LF) and high frequency (HF) components of heart rate variability (HRV) have become the de facto standard metrics in the assessment of the stress response, and the related activities of the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). However, the widely adopted physiological interpretations of the LF and HF components in SNS /PNS balance are now questioned, which puts under serious scrutiny stress assessments which employ the LF and HF components. To avoid these controversies, we here introduce the novel Classification Angle (ClassA) framework, which yields a family of metrics which quantify cardiac dynamics in three-dimensions. This is achieved using a finite-difference plot of HRV, which displays successive rates of change of HRV, and is demonstrated to provide sufficient degrees of freedom to determine cardiac deceleration and/or acceleration. The robustness and accuracy of the novel ClassA framework is verified using HRV signals from ten males, recorded during standardized stress tests, consisting of rest, mental arithmetic, meditation, exercise and further meditation. Comparative statistical testing demonstrates that unlike the existing LF-HF metrics, the ClassA metrics are capable of distinguishing both the physical and mental stress epochs from the epochs of no stress, with statistical significance (Bonferroni corrected p-value ≤ 0.025); HF was able to distinguish physical stress from no stress, but was not able to identify mental stress. The ClassA results also indicated that at moderate levels of stress, the extent of parasympathetic withdrawal was greater than the extent of sympathetic activation. Finally, the analyses and the experimental results provide conclusive evidence that the proposed nonlinear approach to quantify cardiac activity from HRV resolves three critical obstacles to current HRV stress assessments: (i) it is not based on controversial assumptions of balance between the LF and HF powers; (ii) its temporal resolution when estimating parasympathetic dominance is as little as 10 s of HRV data, while only 60 s to estimate sympathetic dominance; (iii) unlike LF and HF analyses, the ClassA framework does not require the prohibitive assumption of signal stationarity. The ClassA framework is unique in offering HRV based stress analysis in three-dimensions.

A pilot study of preoperative heart rate variability predicting pain during local anesthetic varicose vein surgery.

OBJECTIVE: Local anesthetic endovenous procedures were shown to reduce recovery time, to decrease postoperative pain, and to more quickly return the patient to baseline activities. However, a substantial number of patients experience pain during these procedures. The autonomic nervous system modulates pain perception, and its influence on stress response can be noninvasively quantified using heart rate variability (HRV) indices. The aim of our study was to evaluate whether preoperative baseline HRV can predict intraoperative pain during local anesthetic varicose vein surgery. METHODS: Patients scheduled for radiofrequency ablation were included in the study. They had their electrocardiograms recorded from a single channel of a custom-made amplifier. Each patient preoperatively filled in forms Y-1 and Y-2 of Spielberger's State and Trait Anxiety Inventory, completed the Aberdeen Varicose Vein Questionnaire, and rated anxiety level on a numeric scale. Postoperatively, patients filled in the pain they felt during the procedure on the numeric pain intensity scale. MATLAB software (MathWorks, Natick, Mass) was used to extract R waves and to generate HRV signals, and a mathematical model was created to predict the pain score for each patient. RESULTS: In multivariable analysis, we looked into correlation between reported patient's pain score (rPPS) and Aberdeen Varicose Vein Questionnaire score, preoperative forms Y-1 and Y-2, preoperative anxiety level, and predicted patient's pain (pPPS) score. Multivariable analysis found association only between rPPS and pPPS. The pPPS was significantly correlated with rPPS (R = 0.807; P < .001) with accuracy of prediction of 65.2%, which was calculated from R2 on a linear regression model. CONCLUSIONS: This preliminary study shows that preoperative HRV can accurately predict patients' pain, allowing patients with higher predicted score to have the procedure under general anesthesia.

Prognostic Accuracy of Heart Rate Variability Analysis in Neonatal Encephalopathy: A Systematic Review.

BACKGROUND: Heart rate variability analysis offers real-time quantification of autonomic disturbance after perinatal asphyxia, and may therefore aid in disease stratification and prognostication after neonatal encephalopathy (NE). OBJECTIVE: To systematically review the existing literature on the accuracy of early heart rate variability (HRV) to predict brain injury and adverse neurodevelopmental outcomes after NE. DESIGN/METHODS: We systematically searched the literature published between May 1947 and May 2018. We included all prospective and retrospective studies reporting HRV metrics, within the first 7 days of life in babies with NE, and its association with adverse outcomes (defined as evidence of brain injury on magnetic resonance imaging and/or abnormal neurodevelopment at ≥1 year of age). We extracted raw data wherever possible to calculate the prognostic indices with confidence intervals. RESULTS: We retrieved 379 citations, 5 of which met the criteria. One further study was excluded as it analysed an already-included cohort. The 4 studies provided data on 205 babies, 80 (39%) of whom had adverse outcomes. Prognostic accuracy was reported for 12 different HRV metrics and the area under the curve (AUC) varied between 0.79 and 0.94. The best performing metric reported in the included studies was the relative power of high-frequency band, with an AUC of 0.94. CONCLUSIONS: HRV metrics are a promising bedside tool for early prediction of brain injury and neurodevelopmental outcome in babies with NE. Due to the small number of studies available, their heterogeneity and methodological limitations, further research is needed to refine this tool so that it can be used in clinical practice.

The Female Heart: Sex Differences in the Dynamics of ECG in Response to Stress.

Sex differences in the study of the human physiological response to mental stress are often erroneously ignored. To this end, we set out to show that our understanding of the stress response is fundamentally altered once sex differences are taken into account. This is achieved by comparing the heart rate variability (HRV) signals acquired during mental maths tests from ten females and ten males of similar maths ability; all females were in the follicular phase of their menstrual cycle. For rigor, the HRV signals from this pilot study were analyzed using temporal, spectral and nonlinear signal processing techniques, which all revealed significant statistical differences between the sexes, with the stress-induced increases in the heart rates from the males being significantly larger than those from the females (p-value = 4.4 × 10-4). In addition, mental stress produced an overall increase in the power of the low frequency component of HRV in the males, but caused an overall decrease in the females. The stress-induced changes in the power of the high frequency component were even more profound; it greatly decreased in the males, but increased in the females. We also show that mental stress was followed by the expected decrease in sample entropy, a nonlinear measure of signal regularity, computed from the males' HRV signals, while overall, stress manifested in an increase in the sample entropy computed from the females' HRV signals. This finding is significant, since mental stress is commonly understood to be manifested in the decreased entropy of HRV signals. The significant difference (p-value = 2.1 × 10-9) between the changes in the entropies from the males and females highlights the pitfalls in ignoring sex in the formation of a physiological hypothesis. Furthermore, it has been argued that estrogen attenuates the effect of catecholamine stress hormones; the findings from this investigation suggest for the first time that the conventionally cited cardiac changes, attributed to the fight-or-flight stress response, are not universally applicable to females. Instead, this pilot study provides an alternative interpretation of cardiac responses to stress in females, which indicates a closer alignment to the evolutionary tend-and-befriend response.

A Novel Multivariate Sample Entropy Algorithm for Modeling Time Series Synchronization.

Approximate and sample entropy (AE and SE) provide robust measures of the deterministic or stochastic content of a time series (regularity), as well as the degree of structural richness (complexity), through operations at multiple data scales. Despite the success of the univariate algorithms, multivariate sample entropy (mSE) algorithms are still in their infancy and have considerable shortcomings. Not only are existing mSE algorithms unable to analyse within- and cross-channel dynamics, they can counter-intuitively interpret increased correlation between variates as decreased regularity. To this end, we first revisit the embedding of multivariate delay vectors (DVs), critical to ensuring physically meaningful and accurate analysis. We next propose a novel mSE algorithm and demonstrate its improved performance over existing work, for synthetic data and for classifying wake and sleep states from real-world physiological data. It is furthermore revealed that, unlike other tools, such as the correlation of phase synchrony, synchronized regularity dynamics are uniquely identified via mSE analysis. In addition, a model for the operation of this novel algorithm in the presence of white Gaussian noise is presented, which, in contrast to the existing algorithms, reveals for the first time that increasing correlation between different variates reduces entropy.

Pain Prediction From ECG in Vascular Surgery.

Varicose vein surgeries are routine outpatient procedures, which are often performed under local anaesthesia. The use of local anaesthesia both minimises the risk to patients and is cost effective, however, a number of patients still experience pain during surgery. Surgical teams must therefore decide to administer either a general or local anaesthetic based on their subjective qualitative assessment of patient anxiety and sensitivity to pain, without any means to objectively validate their decision. To this end, we develop a 3-D polynomial surface fit, of physiological metrics and numerical pain ratings from patients, in order to model the link between the modulation of cardiovascular responses and pain in varicose vein surgeries. Spectral and structural complexity features found in heart rate variability signals, recorded immediately prior to 17 varicose vein surgeries, are used as pain metrics. The so obtained pain prediction model is validated through a leave-one-out validation, and achieved a Kappa coefficient of 0.72 (substantial agreement) and an area below a receiver operating characteristic curve of 0.97 (almost perfect accuracy). This proof-of-concept study conclusively demonstrates the feasibility of the accurate classification of pain sensitivity, and introduces a mathematical model to aid clinicians in the objective administration of the safest and most cost-effective anaesthetic to individual patients.

Resolving Ambiguities in the LF/HF Ratio: LF-HF Scatter Plots for the Categorization of Mental and Physical Stress from HRV.

It is generally accepted that the activities of the autonomic nervous system (ANS), which consists of the sympathetic (SNS) and parasympathetic nervous systems (PNS), are reflected in the low- (LF) and high-frequency (HF) bands in heart rate variability (HRV)-while, not without some controversy, the ratio of the powers in those frequency bands, the so called LF-HF ratio (LF/HF), has been used to quantify the degree of sympathovagal balance. Indeed, recent studies demonstrate that, in general: (i) sympathovagal balance cannot be accurately measured via the ratio of the LF- and HF- power bands; and (ii) the correspondence between the LF/HF ratio and the psychological and physiological state of a person is not unique. Since the standard LF/HF ratio provides only a single degree of freedom for the analysis of this 2D phenomenon, we propose a joint treatment of the LF and HF powers in HRV within a two-dimensional representation framework, thus providing the required degrees of freedom. By virtue of the proposed 2D representation, the restrictive assumption of the linear dependence between the activity of the autonomic nervous system (ANS) and the LF-HF frequency band powers is demonstrated to become unnecessary. The proposed analysis framework also opens up completely new possibilities for a more comprehensive and rigorous examination of HRV in relation to physical and mental states of an individual, and makes possible the categorization of different stress states based on HRV. In addition, based on instantaneous amplitudes of Hilbert-transformed LF- and HF-bands, a novel approach to estimate the markers of stress in HRV is proposed and is shown to improve the robustness to artifacts and irregularities, critical issues in real-world recordings. The proposed approach for resolving the ambiguities in the standard LF/HF-ratio analyses is verified over a number of real-world stress-invoking scenarios.

Stage call: Cardiovascular reactivity to audition stress in musicians.

Auditioning is at the very center of educational and professional life in music and is associated with significant psychophysical demands. Knowledge of how these demands affect cardiovascular responses to psychosocial pressure is essential for developing strategies to both manage stress and understand optimal performance states. To this end, we recorded the electrocardiograms (ECGs) of 16 musicians (11 violinists and 5 flutists) before and during performances in both low- and high-stress conditions: with no audience and in front of an audition panel, respectively. The analysis consisted of the detection of R-peaks in the ECGs to extract heart rate variability (HRV) from the notoriously noisy real-world ECGs. Our data analysis approach spanned both standard (temporal and spectral) and advanced (structural complexity) techniques. The complexity science approaches-namely, multiscale sample entropy and multiscale fuzzy entropy-indicated a statistically significant decrease in structural complexity in HRV from the low- to the high-stress condition and an increase in structural complexity from the pre-performance to performance period, thus confirming the complexity loss theory and a loss in degrees of freedom due to stress. Results from the spectral analyses also suggest that the stress responses in the female participants were more parasympathetically driven than those of the male participants. In conclusion, our findings suggest that interventions to manage stress are best targeted at the sensitive pre-performance period, before an audition begins.

Characterisation of the complexity of intracranial pressure signals measured from idiopathic and secondary normal pressure hydrocephalus patients.

Hydrocephalus is a condition characterised by enlarged cerebral ventricles, which in turn affects intracranial pressure (ICP); however, the mechanisms regulating ICP are not fully understood. A nonlinear signal processing approach was applied to ICP signals measured during infusion studies from patients with two forms of hydrocephalus, in a bid to compare the differences. This is the first study of its kind. The two forms of hydrocephalus were idiopathic normal pressure hydrocephalus (iNPH) and secondary normal pressure hydrocephalus (SH). Following infusion tests, the Lempel-Ziv (LZ) complexity was calculated from the iNPH and SH ICP signals. The LZ complexity values were averaged for the baseline, infusion, plateau and recovery stages of the tests. It was found that as the ICP increased from basal levels, the LZ complexities decreased, reaching their lowest during the plateau stage. However, the complexities computed from the SH ICP signals decreased to a lesser extent when compared with the iNPH ICP signals. Furthermore, statistically significant differences were found between the plateau and recovery stage complexities when comparing the iNPH and SH results (p = 0.05). This Letter suggests that advanced signal processing of ICP signals with LZ complexity can help characterise different types of hydrocephalus in more detail.

Intracranial pressure for the characterization of different types of hydrocephalus: A Permutation Entropy study.

Hydrocephalus is a condition characterized by altered cerebrospinal fluid (CSF) dynamics and chronic rises in intracranial pressure (ICP). However, the reason why hydrocephalic physiologies fail to inhibit dangerously high ICP levels is not known. Infusion studies are used to raise ICP and evaluate CSF circulation disorders. In this pilot study, ICP signals recorded during infusion tests from 33 patients with normal pressure hydrocephalus and 36 patients having developed a secondary form of normal pressure hydrocephalus were characterized using Permutation Entropy (PE), a symbolic non-linear method to quantify complexity. Each ICP signal was divided into four epochs--baseline (before infusion begins), infusion, plateau, and recovery (after infusion has stopped)--and the mean PE was calculated for each epoch. Statistically significant differences were found between PE for most epochs (p<;0.00833, Bonferroni-corrected Wilcoxon tests), with a significant decrease in the plateau phase. However, differences between PE for normal pressure and secondary hydrocephalus were not significant. Results suggest that the increase in ICP during infusion studies is associated with a significant decrease in PE. PE analysis of ICP signals could be useful for increasing our understanding of CSF dynamics in normal pressure hydrocephalus.