Heart rate markers for prediction of fetal acidosis in an experimental study on fetal sheep.

To overcome the difficulties in interpreting fetal heart rate (FHR), several tools based on the autonomic nervous system and heart rate variability (HRV) have been developed. The objective of this study was to use FHR and HRV parameters for the prediction of fetal hypoxia. It was an experimental study in the instrumented fetal sheep. Repeated umbilical cord occlusions were performed to achieve severe acidosis. Hemodynamic parameters, ECG, and blood gases were analyzed. The variables used were heart rate baseline, HRV analysis (RMSSD, SDNN, LF, HF, HFnu, Fetal Stress Index (FSI), …), and morphological analysis of decelerations. The gold standard used to classify hypoxia was the fetal arterial pH (pH < 7.10). Different multivariable statistical methods (logistic regression and decision trees) were applied for the detection of acidosis. 21 lambs were instrumented. A total of 130 pairs of FHR/fetal pH analysis were obtained of which 29 in the acidosis group and 101 in the non-acidosis group. After logistic regression model with bootstrap resampling and stepwise backward selection, only one variable was selected, FSI. The AUC of FSI alone in this model was 0.81 with a sensitivity of 0.66, specificity of 0.88, PPV of 0.61, and NPV of 0.90 considering a threshold of 68. Decision trees with CHAID and CART algorithms showed a sensitivity of 0.48 and 0.59, respectively, and a specificity of 0.94 for both. All employed methods identified HRV variables as the most predictive of acidosis. The primary variables selected automatically were those from the HRV. Supporting the use of FHRV measures for the screening of fetal acidosis during labour is interesting.

Fetal heart rate variability analysis for neonatal acidosis prediction.

Fetal well-being during labor is usually assessed by visual analysis of a fetal heart rate (FHR) tracing. Our primary objective was to evaluate the ability of automated heart rate variability (HRV) analysis methods, including our new fetal stress index (FSI), to predict neonatal acidosis. 552 intrapartum recordings were analyzed. The analysis occurred in the last 90 min before birth and was conducted during two 5-min intervals: (i) a stable period of FHR and (ii) the period corresponding to the maximum FSI value. For each period, we computed the mean FHR, FSI, short-term variability (STV), and long-term variability (LTV). Visual FHR interpretation was performed using the FIGO classification. The population was separated into two groups: (i) an acidotic group with an arterial pH at birth ≤ 7.10 and a control group. Prediction of a neonatal pH ≤ 7.10 was assessed by computing the receiver-operating characteristic area under the curve (AUC). FHR, FSI, STV, and LTV did not differ significantly between groups during the stable period. During the FSI max peak period, LTV and STV correlated significantly in the acidotic group (- 5.85 ± 2.19, p = 0.010 and - 0.62 ± 0.29, p = 0.037, respectively). The AUC values were 0.569 for FIGO classification, 0.595 for STV, and 0.622 for LTV. The multivariate model (FIGO, FSI, FC, STV, LTV) had the greatest accuracy for predicting acidosis (AUC = 0.719). FSI was not predictive of neonatal acidosis probably because of the low quality of the FHR signal in cardiotocography. When used separately, HRV indexes and visual FHR analysis were poor predictors of neonatal acidosis. Including all indexes in a multivariate model increased the predictive ability.

Comparison of multiple cardiac signal acquisition technologies for heart rate variability analysis.

Heart rate variability analysis is a recognized non-invasive tool that is used to assess autonomic nervous system regulation in various clinical settings and medical conditions. A wide variety of HRV analysis methods have been proposed, but they all require a certain number of cardiac beats intervals. There are many ways to record cardiac activity: electrocardiography, phonocardiography, plethysmocardiography, seismocardiography. However, the feasibility of performing HRV analysis with these technologies and particularly their ability to detect autonomic nervous system changes still has to be studied. In this study, we developed a technology allowing the simultaneous monitoring of electrocardiography, phonocardiography, seismocardiography, photoplethysmocardiography and piezoplethysmocardiography and investigated whether these sensors could be used for HRV analysis. We therefore tested the evolution of several HRV parameters computed from several sensors before, during and after a postural change. The main findings of our study is that even if most sensors were suitable for mean HR computation, some of them demonstrated limited agreement for several HRV analyses methods. We also demonstrated that piezoplethysmocardiography showed better agreement with ECG than other sensors for most HRV indexes.

Closed-loop administration of analgesic drugs based on heart rate variability analysis.

General anesthesia is based on the use of hypnotic, muscle relaxant and analgesic drugs in order to render the patient unresponsive to the surgical procedure. The difficulty for anesthesiologists is then to determinate the minimum efficient dose to avoid any risk of under or over dosing. For several years, monitoring systems were developed in order to measure depth of hypnosis, myorelaxation and analgesia. As soon as all these monitoring systems became available, several teams worked on the closed-loop administration of anesthetic agents. We have developed a closed-loop system allowing the automatic administration of analgesic drugs. This system is based on the analysis of a heart rate variability based index: the ANI (Analgesia Nociception Index). In this paper, we describe this device and demonstrate its efficiency, repeatability and safety in a simulation environment.

Influence of Wilson Ce nter Terminal on fetal electrocardiography acquisition.

The acquisition of a standard 10-leads electrocardiography (ECG) is performed using the Wilson Center Terminal (WCT) reference with a normalized electrode positioning. However, in the case of non-invasive fetal ECG (fECG) acquisition, there is no standardization on the positioning of the electrodes on the abdomen and many authors suggest an acquisition with or without a WCT. The use of the WCT for the acquisition of the fetal heart rate (FHR) is not justified. The objective of this paper is to quantify the influence of this reference compared to a direct measurement. For this purpose, we developed a device allowing the acquisition of the fECG and compared the two configurations on 6 volunteer pregnants. The noise levels and the fetal QRS morphology were compared, showing no superiority of the WCT acquisition compared to a direct differential measurement.

Exploring fetal response to acidosis in ewes: Choosing an adequate experimental model.

INTRODUCTION: Knowledge of fetal physiology during labor has been largely generated from animal models. Our team recently developed a new index to assess parasympathetic activity using different experimental protocols to obtain acidosis. The objective of the present study was to discuss the different protocols and to review other models proposed in the literature. MATERIAL AND METHODS: Pregnant ewes underwent a surgical procedure at the 123±2 days gestational age (term=145 days). Three experimental protocols were used: protocol A consisted of 25%, 50% and 75% umbilical cord occlusion (UCO) for 20min. Protocol B consisted of partial 75% UCO until reaching a pH<7.10. Protocol C consisted of brief, repetitive complete occlusion until severe acidosis occurred. Hemodynamic and blood gas parameters were compared to those of the stability period before UCO. RESULTS: Protocol A led to a progressive response depending on the degree of occlusion (decrease in fetal heart rate, arterial hypertension and pH). Protocol B led to severe acidosis, although the duration of UCO varied per animal. Protocol C also progressively led to acidosis. We observed high inter individual variability in the acidosis response. CONCLUSION: Pregnant ewes are a relevant model for exploring fetal response to acidosis. The frequency of UCO and partial or complete occlusion should be adapted to the expected effects. Knowledge of these protocols is important to respect ethical guidelines and to reduce the required number of animals. Moreover, it is important to consider the high individual variability of the acidosis response in the interpretation of the results.

Correlation of a new index reflecting the fluctuation of parasympathetic tone and fetal acidosis in an experimental study in a sheep model.

The autonomic nervous system plays a leading role in the control of fetal homeostasis. Fetal heart rate variability (HRV) analysis is a reflection of its activity. We developed a new index (the Fetal Stress Index, FSI) reflecting parasympathetic tone. The objective of this study was to evaluate this index as a predictor of fetal acid-base status. This was an experimental study on chronically instrumented fetal lambs (n = 11, surgery at 128 +/- 2 days gestational age, term = 145 days). The model was based on 75% occlusion of the umbilical cord for a maximum of 120 minutes or until an arterial pH ≤ 7.20 was reached. Hemodynamic, gasometric and FSI parameters were recorded throughout the experimentation. We studied the FSI during the 10 minutes prior to pH samplings and compared values for pH>7.20 and pH≤ 7.20. In order to analyze the FSI evolution during the 10 minutes periods, we analyzed the minimum, maximum and mean values of the FSI (respectively FSImin, FSImax and FSImean) over the periods. 11 experimentations were performed. During occlusion, the heart rate dropped with an increase in blood pressure (respectively 160(155-182) vs 106(101-120) bpm and 42(41-45) vs 58(55-62) mmHg after occlusion). The FSImin was 38.6 (35.2-43.3) in the group pH>7.20 and was higher in the group pH less than 7.20 (46.5 (43.3-52.0), p = 0.012). The correlation of FSImin was significant for arterial pH (coefficient of -0.671; p = 0.004) and for base excess (coefficient of -0.632; p = 0.009). The correlations were not significant for the other parameters. In conclusion, our new index seems well correlated with the fetal acid-base status. Other studies must be carried out in a situation close to the physiology of labor by sequential occlusion of the cord.

Influence of ECG sampling rate in fetal heart rate variability analysis.

Fetal hypoxia results in a fetal blood acidosis (pH<;7.10). In such a situation, the fetus develops several adaptation mechanisms regulated by the autonomic nervous system. Many studies demonstrated significant changes in heart rate variability in hypoxic fetuses. So, fetal heart rate variability analysis could be of precious help for fetal hypoxia prediction. Commonly used fetal heart rate variability analysis methods have been shown to be sensitive to the ECG signal sampling rate. Indeed, a low sampling rate could induce variability in the heart beat detection which will alter the heart rate variability estimation. In this paper, we introduce an original fetal heart rate variability analysis method. We hypothesize that this method will be less sensitive to ECG sampling frequency changes than common heart rate variability analysis methods. We then compared the results of this new heart rate variability analysis method with two different sampling frequencies (250-1000 Hz).

Impact of skin-to-skin contact on the autonomic nervous system in the preterm infant and his mother.

Before, during and after mother-newborn skin-to-skin contact (SSC), parasympathetic activity was evaluated by heart rate variability (HRV) analysis. SSC had a favorable impact on maternal and premature infant parasympathetic activities with a more pronounced response for neonates when the basal HRV values were lower, without modifications of EDIN scores, temperatures or oxygen saturation.

A new analysis of heart rate variability in the assessment of fetal parasympathetic activity: An experimental study in a fetal sheep model.

Analysis of heart rate variability (HRV) is a recognized tool in the assessment of autonomic nervous system (ANS) activity. Indeed, both time and spectral analysis techniques enable us to obtain indexes that are related to the way the ANS regulates the heart rate. However, these techniques are limited in terms of the lack of thresholds of the numerical indexes, which is primarily due to high inter-subject variability. We proposed a new fetal HRV analysis method related to the parasympathetic activity of the ANS. The aim of this study was to evaluate the performance of our method compared to commonly used HRV analysis, with regard to i) the ability to detect changes in ANS activity and ii) inter-subject variability. This study was performed in seven sheep fetuses. In order to evaluate the sensitivity and specificity of our index in evaluating parasympathetic activity, we directly administered 2.5 mg intravenous atropine, to inhibit parasympathetic tone, and 5 mg propranolol to block sympathetic activity. Our index, as well as time analysis (root mean square of the successive differences; RMSSD) and spectral analysis (high frequency (HF) and low frequency (LF) spectral components obtained via fast Fourier transform), were measured before and after injection. Inter-subject variability was estimated by the coefficient of variance (%CV). In order to evaluate the ability of HRV parameters to detect fetal parasympathetic decrease, we also estimated the effect size for each HRV parameter before and after injections. As expected, our index, the HF spectral component, and the RMSSD were reduced after the atropine injection. Moreover, our index presented a higher effect size. The %CV was far lower for our index than for RMSSD, HF, and LF. Although LF decreased after propranolol administration, fetal stress index, RMSSD, and HF were not significantly different, confirming the fact that those indexes are specific to the parasympathetic nervous system. In conclusion, our method appeared to be effective in detecting parasympathetic inhibition. Moreover, inter-subject variability was much lower, and effect size higher, with our method compared to other HRV analysis methods.

Understanding fetal physiology and second line monitoring during labor.

Cardiotocography (CTG) is a technique used to monitor intrapartum fetal condition and is one of the most common obstetric procedures. Second line methods of fetal monitoring have been developed in an attempt to reduce unnecessary interventions due to continuous cardiotocography and to better identify fetuses at risk of intrapartum asphyxia. The acid-base balance of the fetus is evaluated by fetal blood scalp samples, the modification of the myocardial oxygenation by the fetal ECG ST-segment analysis (STAN) and the autonomic nervous system by the power spectral analysis of the fetal heart variability. To correctly interpret the features observed on CTG traces or second line methods, it seems important to understand normal physiology during labor and the compensatory mechanisms of the fetus in case of hypoxemia. Therefore, the aim of this review is first to describe fetal physiology during labor and then to explain the modification of the second line monitoring during labor.

Inter-observer reliability of 4 fetal heart rate classifications.

OBJECTIVE: Different classification of fetal heart rate (FHR) pattern have been proposed: FHR classified as either "reassuring" or "non-reassuring", the National Institute of Child Health and Human Development (NICHD) published in 2008 a 3-tier system, the French College of Gynecology and Obstetrics (CNGOF) recommended in 2013 a 5-tier system and recently in 2015, the Federation International of Gynecology and Obstetrics (FIGO) proposed a new classification based on a 3-tier system. Our objective was to assess the inter-observer reliability of these 4 existing classifications. STUDY DESIGN: Four observers reviewed 100 FHR without clinical information. FHR were obtained from term singleton pregnancies. Fetal heart rate patterns were classified by one 2-tier ("reassuring vs. non-reassuring"), two 3-tier (NICHD 2008 and FIGO 2015), and one 5-tier (CNGOF 2013) fetal heart classifications. RESULTS: The global agreement between observers was moderate for each classification: 0.58 (0.40-0.74) for the 2-tier, 0.48 (0.37-0.58) for the NICHD 2008, 0.58 (0.53-0.63) for the CNGOF 2013 and 0.59 (0.49-0.67) for the FIGO 2015 classification. When FHR was classified as reassuring, it was classified as normal in 85.5% for the NICHD 2008 and in 94.5% for the FIGO 2015. For the CNGOF 2013, 65.0% were classified as normal and 32.5% as quasi normal. There was strong concordance between FIGO category I and "reassuring" FHR (kappa=0.95). CONCLUSION: Inter-observer agreement of FHR interpretation is moderate whatever the classification used. To evaluate the superior interest of one classification, it will be interesting to compare their impact on need of second line techniques and on neonatal outcome.

Optimization of extra corporeal enteral prosthesis (ECEP) by selective aspiration of the digestive flow.

Reinfusion is a medical process which collects digestive flow from a proximal stoma to a distal one, in patient who had a post-operative double enteral stoma. This process avoids the risk of under nutrition and frees the patient from a Total Parenteral Nutrition to offset the digestive loss. Most of the previous ways of reinfusion first collect the digestive flow into a bag before instillation. We developed an ambulatory reinfusion pump (ECEP) which had the advantage to collect the digestive flow directly from the proximal stoma and to pump it to the distal one. However, the main risk of such a continuous pumping process is to create mucosae lesions by direct suction. The aim of this study is to up-grade our device by introducing a selective aspiration based on the arrival of digestive flow.

Comparison of pulse rate variability and heart rate variability for high frequency content estimation.

Heart Rate Variability (HRV) analysis can be of precious help in most of clinical situations because it is able to quantify the Autonomic Nervous System (ANS) activity. The HRV high frequency (HF) content, related to the parasympathetic tone, reflects the ANS response to an external stimulus responsible of pain, stress or various emotions. We have previously developed the Analgesia Nociception Index (ANI), based on HRV high frequency content estimation, which quantifies continuously the vagal tone in order to guide analgesic drug administration during general anesthesia. This technology has been largely validated during the peri-operative period. Currently, ANI is obtained from a specific algorithm analyzing a time series representing successive heart periods measured on the electrocardiographic (ECG) signal. In the perspective of widening the application fields of this technology, in particular for homecare monitoring, it has become necessary to simplify signal acquisition by using e.g. a pulse plethysmographic (PPG) sensor. Even if Pulse Rate Variability (PRV) analysis issued from PPG sensors has been shown to be unreliable and a bad predictor of HRV analysis results, we have compared PRV and HRV both estimated by ANI as well as HF and HF/(HF+LF) spectral analysis on both signals.

Physiological Signal Processing for Individualized Anti-nociception Management During General Anesthesia: a Review.

OBJECTIVE: The aim of this paper is to review existing technologies for the nociception / anti-nociception balance evaluation during surgery under general anesthesia. METHODS: General anesthesia combines the use of analgesic, hypnotic and muscle-relaxant drugs in order to obtain a correct level of patient non-responsiveness during surgery. During the last decade, great efforts have been deployed in order to find adequate ways to measure how anesthetic drugs affect a patient's response to surgical nociception. Nowadays, though some monitoring devices allow obtaining information about hypnosis and muscle relaxation, no gold standard exists for the nociception / anti-nociception balance evaluation. Articles from the PubMed literature search engine were reviewed. As this paper focused on surgery under general anesthesia, articles about nociception monitoring on conscious patients, in post-anesthesia care unit or in intensive care unit were not considered. RESULTS: In this article, we present a review of existing technologies for the nociception / anti-nociception balance evaluation, which is based in all cases on the analysis of the autonomous nervous system activity. Presented systems, based on sensors and physiological signals processing algorithms, allow studying the patients' reaction regarding anesthesia and surgery. CONCLUSION: Some technological solutions for nociception / antinociception balance monitoring were described. Though presented devices could constitute efficient solutions for individualized anti-nociception management during general anesthesia, this review of current literature emphasizes the fact that the choice to use one or the other mainly relies on the clinical context and the general purpose of the monitoring.

Performance evaluation of the extra corporeal enteral prosthesis (ECEP) vs a By-Pass.

Intestinal stoma constitutes a symptomatic treatment in a wide range of digestive diseases, such as rectal cancer, digestive traumatic perforation and inflammatory intestinal diseases. It affects a patient's life causing physiologic and social constraints. The stoma can lead to involution of the downstream digestive tissue, impairing his function in case of restored continuity. Some technical solutions have been developed in order to maintain intestinal continuity, reduce inflammatory risk and to increase patient's quality of life. In this paper, we describe a smart intestinal prosthesis equipped with a pump working as an intestinal segment and creating a bypass between the upstream and downstream intestinal sides. We also evaluate the performance the digestive prosthesis ECEP vs a simple digestive By-Pass.

[Impact of the instrumental vaginal delivery on pain perception at two months]. / Impact de l'extraction instrumentale sur les manifestations douloureuses lors d'une vaccination à l'âge de deux mois.

INTRODUCTION: Although instrumental vaginal delivery reduces the risk of neonatal mortality, it increases the risk of specific morbidity including prolonged neonatal discomfort. Previous studies suggest that neonatal exposure to acute pain could have long-term effects on the pain response later in life. The aim of the study was to investigate whether instrumental vaginal delivery may alter the response to a noxious stimulus at the age of two months. METHOD: Newborn infants were enrolled in this prospective observational study after parental consent. A group of children born by instrumental vaginal delivery (group 2) were compared to matched controls born by vaginal delivery (group 1). Pain was assessed in each newborn infant between two and four hours after birth using the scale of pain and discomfort of the newborn baby (EDIN). These children were reassessed for pain response to immunizations (Infanrix(®) and Prevenar(®)) at two months of age using the DAN scale. RESULTS: Thirteen children were enrolled in this study, six in group 1 and seven in group 2. Gestational age, birth weight, Apgar score, and umbilical arterial blood were similar in both groups. The EDIN measured between H2 and H4 was significantly higher in group 2 (median, 4 [IQ, 3] versus 0 [3.25], P<0.05). While the DAN score before and during immunization was similar in the two groups, it was statistically higher in group 2 than in group 1 (4 [3] versus 2 [2.25], P<0.01) within the15 min following the injections. CONCLUSION: These results indicate that birth by instrumental vaginal delivery causes discomfort after birth and increases the pain response to immunization at the age of two months. This study supports the hypothesis that instrumental vaginal delivery may alter pain perception later in life.

A smartphone based cardiac coherence biofeedback system.

Cardiac coherence biofeedback training consist on slowing one's breathing to 0.1 Hz in order to simulate the baroreflex sensitivity and increase the respiratory sinus arrhythmia efficiency. Several studies have shown that these breathing exercises can constitute an efficient therapy in many clinical contexts like cardiovascular diseases, asthma, fibromyalgia or post-traumatic stress. Such a non-intrusive therapeutic solution needs to be performed on an 8 to 10 weeks period. Even if some heart rate variability based solutions exist, they presented some mobility constrain rendering these cardiac / respiratory control technologies more difficult to perform on a daily used. In this paper, we present a new simplified smartphone based solution allowing people to process efficient cardiac coherence biofeedback exercises. Based on photo-plethysmographic imaging through the smartphone camera, this sensor-less technology allows controlling cardiac coherence biofeedback exercises through a simplified heart rate variability algorithm.