Acute Autonomic Nervous System Response to Direct Sacral Nerve Root Stimulation in Lower Urinary Tract Dysfunction: A New Approach to Understand the Mechanism of Action of Sacral Nerve Modulation.

PURPOSE: Our goal was to assess acute autonomic nervous system (ANS) response to direct sacral nerve root (SNR) stimulation in the context of lower urinary tract dysfunction. MATERIAL AND METHODS: In this retrospective monocentric study, patients undergoing 2-stage sacral nerve modulation for overactive bladder, nonobstructive urinary retention, or chronic bladder pain syndrome between March 2022 and June 2023 were analyzed. A standardized stimulation protocol was applied during the lead implantation, each of the 4 contact points being sequentially stimulated at the amplitude required to elicit anal motor response. Stimulations were labeled as StimA, StimB, StimC, and StimD, ordered by ascending order of minimum amplitude required for anal motor response. Heart rate variability parameters were collected using PhysioDoloris Monitor, and computed through the time-domain (standard deviation of normal-to-normal intervals [SDNN], root mean square of successive differences), the frequency-domain (low frequency, high frequency) and the graphical (Analgesia Nociception Index [ANI]) methods. RESULTS: Fifty patients were analyzed, including 35 females. Twelve patients had an underlying neurological disease. Efficacy was deemed achieved in 54% of patients. SDNN variability significantly increased during StimA to StimC, while maximum SDNN significantly increased only during StimA. ANI variability significantly increased during all 4 stimulations, while maximum ANI significantly increased only during StimA. CONCLUSIONS: Direct stimulation of SNR is responsible for a significant increase in ANS and relative parasympathetic nervous system activity, with a greater effect observed when the stimulation was delivered closer to the SNR. These results shed light on potential mechanisms underlying sacral nerve modulation, particularly regarding the treatment of ANS dysregulation in lower urinary tract dysfunction.

Fetal brain response to worsening acidosis: an experimental study in a fetal sheep model of umbilical cord occlusions.

Perinatal anoxia remains an important public health problem as it can lead to hypoxic-ischaemic encephalopathy (HIE) and cause significant neonatal mortality and morbidity. The mechanisms of the fetal brain's response to hypoxia are still unclear and current methods of in utero HIE prediction are not reliable. In this study, we directly analysed the brain response to hypoxia in fetal sheep using in utero EEG. Near-term fetal sheep were subjected to progressive hypoxia induced by repeated umbilical cord occlusions (UCO) at increasing frequency. EEG changes during and between UCO were analysed visually and quantitatively, and related with gasometric and haemodynamic data. EEG signal was suppressed during occlusions and progressively slowed between occlusions with the increasing severity of the occlusions. Per-occlusion EEG suppression correlated with per-occlusion bradycardia and increased blood pressure, whereas EEG slowing and amplitude decreases correlated with arterial hypotension and respiratory acidosis. The suppression of the EEG signal during cord occlusion, in parallel with cardiovascular adaptation could correspond to a rapid cerebral adaptation mechanism that may have a neuroprotective role. The progressive alteration of the signal with the severity of the occlusions would rather reflect the cerebral hypoperfusion due to the failure of the cardiovascular adaptation mechanisms.

Early heart rate variability changes during acute fetal inflammatory response syndrome: An experimental study in a fetal sheep model.

INTRODUCTION: Fetal infection during labor with fetal inflammatory response syndrome (FIRS) is associated with neurodevelopmental disabilities, cerebral palsy, neonatal sepsis, and mortality. Current methods to diagnose FIRS are inadequate. Thus, the study aim was to explore whether fetal heart rate variability (HRV) analysis can be used to detect FIRS. MATERIAL AND METHODS: In chronically instrumented near-term fetal sheep, lipopolysaccharide (LPS) was injected intravenously to model FIRS. A control group received saline solution injection. Hemodynamic, blood gas analysis, interleukin-6 (IL-6), and 14 HRV indices were recorded for 6 h. In both groups, comparisons were made between the stability phase and the 6 h following injection (H1-H6, respectively) and between LPS and control groups. RESULTS: Fifteen lambs were instrumented. In the LPS group (n = 8), IL-6 increased significantly after LPS injection (p < 0.001), confirming the FIRS model. Fetal heart rate increased significantly after H5 (p < 0.01). In our FIRS model without shock or cardiovascular decompensation, five HRV measures changed significantly after H2 until H4 in comparison to baseline. Moreover, significant differences between LPS and control groups were observed in HRV measures between H2 and H4. These changes appear to be mediated by an increase of global variability and a loss of signal complexity. CONCLUSION: As significant HRV changes were detected before FHR increase, these indices may be valuable for early detection of acute FIRS.

RESPIRATION-RELATED VARIATIONS IN CENTRAL VENOUS PRESSURE AS PREDICTORS OF FLUID RESPONSIVENESS IN SPONTANEOUSLY BREATHING PATIENTS.

ABSTRACT: Objective : The hemodynamic parameters used to accurately predict fluid responsiveness (FR) in spontaneously breathing patients (SB) require specific material and expertise. Measurements of the central venous pressure (CVP) are relatively simple and, importantly, are feasible in many critically ill patients. We analyzed the accuracy of respiration-related variations in CVP (vCVP) to predict FR in SB patients and examined the optimization of its measurement using a standardized, deep inspiratory maneuver. Patients and Methods : We performed a monocentric, prospective, diagnostic evaluation. Spontaneously breathing patients in intensive care units with a central venous catheter were prospectively included. The vCVP was measured while the patient was spontaneously breathing, both with (vCVP-st) and without (vCVP-ns) a standardized inspiratory maneuver, and calculated as: Minimum inspiratory v-wave peak pressure - Maximum expiratory v-wave peak pressure. A passive leg raising-induced increase in the left ventricular outflow tract velocity-time integral ≥10% defined FR. Results : Among 63 patients, 38 (60.3%) presented FR. The vCVP-ns was not significantly different between responders and nonresponders (-4.9 mm Hg [-7.5 to -3.1] vs. -4.1 mm Hg [-5.4 to 2.8], respectively; P = 0.15). The vCVP-st was lower in responders than nonresponders (-9.7 mm Hg [-13.9 to -6.2] vs. -3.6 mm Hg [-10.6 to -1.6], respectively; P = 0.004). A vCVP-st < -4.7 mm Hg predicted FR with 89.5% sensitivity, a specificity of 56.0%, and an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.58 to 0.86) ( P = 0.004). Conclusion : When a central venous catheter is present, elevated values for vCVP-st may be useful to identify spontaneously breathing patients unresponsive to volume expansion. Nevertheless, the necessity of performing a standardized, deep-inspiration maneuver may limit its clinical application.

Prospective multicenter study of heart rate variability with ANI monitor as predictor of mortality in critically ill patients with COVID-19.

The purpose of this study is to demonstrate that the most critically ill patients with COVID-19 have greater autonomic nervous system dysregulation and assessing the heart rate variability, allows us to predict severity and 30-day mortality. This was a multicentre, prospective, cohort study. Patients were divided into two groups depending on the 30-day mortality. The heart rate variability and more specifically the relative parasympathetic activity (ANIm), and the SDNN (Energy), were measured. To predict severity and mortality multivariate analyses of ANIm, Energy, SOFA score, and RASS scales were conducted. 112 patients were collected, the survival group (n = 55) and the deceased group (n = 57). The ANIm value was higher (p = 0.013) and the Energy was lower in the deceased group (p = 0.001); Higher Energy was correlated with higher survival days (p = 0.009), and a limit value of 0.31 s predicted mortalities with a sensitivity of 71.9% and a specificity of 74.5%. Autonomic nervous system and heart rate variability monitoring in critically ill patients with COVID-19 allows for predicting survival days and 30-day mortality through the Energy value. Those patients with greater severity and mortality showed higher sympathetic depletion with a predominance of relative parasympathetic activity.

Associations between fetal heart rate variability and umbilical cord occlusions-induced neural injury: An experimental study in a fetal sheep model.

INTRODUCTION: This study evaluated the association between fetal heart rate variability (HRV) and the occurrence of hypoxic-ischemic encephalopathy in a fetal sheep model. MATERIAL AND METHODS: The experimental protocol created a hypoxic condition with repeated cord occlusions in three phases (A, B, C) to achieve acidosis to pH <7.00. Hemodynamic, gasometric and HRV parameters were analyzed during the protocol, and the fetal brain, brainstem and spinal cord were assessed histopathologically 48 h later. Associations between the various parameters and neural injury were compared between phases A, B and C using Spearman's rho test. RESULTS: Acute anoxic-ischemic brain lesions in all regions was present in 7/9 fetuses, and specific neural injury was observed in 3/9 fetuses. The number of brainstem lesions correlated significantly and inversely with the HRV fetal stress index (r = -0.784; p = 0.021) in phase C and with HRV long-term variability (r = -0.677; p = 0.045) and short-term variability (r = -0.837; p = 0.005) in phase B. The number of neurological lesions did not correlate significantly with other markers of HRV. CONCLUSIONS: Neural injury caused by severe hypoxia was associated with HRV changes; in particular, brainstem damage was associated with changes in fetal-specific HRV markers.

Roles of parasympathetic outflow and sympathetic outflow in the cardiovascular response to brief umbilical cord occlusion in fetal sheep.

Fetal heart rate (FHR) deceleration is the most common change seen during labor. The role of the autonomic nervous system in regulating the fetal cardiovascular response during multiple uterine contractions has been well-established. However, the mechanism underlying the hemodynamic response remains unclear and the specific reflex that mediates the cardiovascular modifications is still controversial. This study aimed to determine the role of the sympathetic and parasympathetic systems on fetal hemodynamics in complete cord occlusion. Chronically instrumented fetal sheep were randomized to receive an intravenous injection of atropine 2.5 mg (n = 8), propranolol 5 mg (n = 7), atropine and propranolol (n = 7), or a control protocol (n = 9), followed by three episodes of 1-minute umbilical cord occlusion repeated every 5 minutes. Cord compression induces a rapid decrease in the FHR and a rapid increase in MAP. The decrease in FHR is caused by an increase in parasympathetic activity, (atropine and atropine-propranolol abolish the FHR response to the occlusion). The change in FHR during occlusion was not modified by propranolol injection, showing no effect of sympathetic tone. The increase in MAP during occlusion was similar in the four protocols. After releasing occlusion, the FHR was still lower than that at baseline due to a sustained parasympathetic tone. Suppression of the parasympathetic output to the cardiovascular system unmasks an increase in the FHR above baseline values. The lower FHR with the propranolol protocol further supports an increase in myocardial ß-adrenoceptor stimulation after cord release. The increase in MAP after cord release was similar in the four protocols, except after the early stage of interocclusion period in atropine protocol. Four minutes after cord release, the FHR returned to baseline irrespective of the drugs that were infused, thereby showing recovery of ANS control. Blood gases (pH, PaCO2, PaO2) and plasma lactate concentrations was similar between the four protocols at the end of three applications of UCO. Complete cord compression-induced deceleration is likely due to acute activation of parasympathetic output. ß-adrenoceptor activity is involved in the increase in FHR after cord release. Understanding the reflexes involved in FHR deceleration may help us understand the mechanisms underlying fetal autonomic adaptation during cord occlusion.

Changes in S100B and troponin levels in a fetal sheep model of worsening acidosis.

BACKGROUND: S100B and cardiac troponin T (c-TnT) are relevant biomarkers at birth of hypoxic-ischemic encephalopathy (HIE) and myocardial ischemia secondary to metabolic acidosis during labor, respectively. The purpose was to assess in-utero changes in S100B and c-TnT levels in an experimental model of labor-like acidosis. METHODS: Repeated umbilical cord occlusions (UCOs) in ten experiments were performed in mild (phase A, 1 UCO/5 mn), moderate (phase B, 1 UCO/3 mn), and severe (phase C, 1 UCO/2 mn) period. The experiments were stopped if arterial pH reached 6.90. RESULTS: UCOs resulted in fetal acidosis with pH dropping to 6.99 ±0.13. When compared to the baseline period fetal S100B increased between phases A and B (7% ± 4 vs 17% ± 13, p = 0.030) and between phases A and C (7% ± 4 vs 24% ± 8, p < 0.001). Fetal c-TnT serum levels increased during occlusions: 102 ng/L (58-119) in phase A, vs 119 ng/L (103-198) in phase B vs 169 ng / L (128-268) in phase C (p < 0.05, for all). When compared to the baseline control period, fetal ΔcTnT was significantly modified throughout UCO series: 5.0% (-3; 45) in phase A, 51% (4; 263) in phase B, and 77% (56.5; 269) in phase C (p < 0.05 for all). CONCLUSIONS: S100B and c-TnT increased when fetal acidosis occurred, which reflects the potential neurological damage and fetal cardiovascular adaptation.

Cardiac Autonomic Dysfunction and Risk of Sudden Unexpected Death in Epilepsy.

OBJECTIVE: We aimed to test whether patients who died of sudden unexpected death in epilepsy (SUDEP) had an abnormal cardiac autonomic response to sympathetic stimulation by hyperventilation. METHODS: We conducted a retrospective, observational, case-control study of a group of patients who died of SUDEP and controls who were matched to the patients for epilepsy type, drug resistance, sex, age at EEG recording, age at onset of epilepsy, and duration of epilepsy. We analyzed the heart rate (HR) and HR variability (HRV) at rest and during and after hyperventilation performed during the patient's last EEG recording before SUDEP. In each group, changes over time in HRV indexes were analyzed with linear mixed models. RESULTS: Twenty patients were included in each group. In the control group, the HR increased and the root mean square of successive RR-interval differences (RMSSD) decreased during the hyperventilation and then returned to the baseline values. In the SUDEP group, however, the HR and RMSSD did not change significantly during or after hyperventilation. A difference in HR between the end of the hyperventilation and 4 minutes after its end discriminated well between patients with SUDEP and control patients (area under the receiver operating characteristic curve 0.870, sensitivity 85%, specificity 75%). CONCLUSION: Most of patients with subsequent SUDEP have an abnormal cardiac autonomic response to sympathetic stimulation through hyperventilation. An index reflecting the change in HR on hyperventilation might be predictive of the risk of SUDEP and could be used to select patients at risk of SUDEP for inclusion in trials assessing protective measures.

Changes in Umbilico-Placental Circulation during Prolonged Intact Cord Resuscitation in a Lamb Model.

Some previous studies reported a benefit to cardiopulmonary transition at birth when starting resuscitation maneuvers while the cord was still intact for a short period of time. However, the best timing for umbilical cord clamping in this condition is unknown. The aim of this study was to explore the duration of effective umbilico-placental circulation able to promote cardiorespiratory adaptation at birth during intact cord resuscitation. Umbilico-placental blood flow and vascular resistances were measured in an experimental neonatal lamb model. After a C-section delivery, the lambs were resuscitated ventilated for 1 h while the cord was intact. The maximum and mean umbilico-placental blood flow were respectively 230 ± 75 and 160 ± 12 mL·min-1 during the 1 h course of the experiment. However, umbilico-placental blood flow decreased and vascular resistance increased significantly 40 min after birth (p < 0.05). These results suggest that significant cardiorespiratory support can be provided by sustained placental circulation for at least 1 h during intact cord resuscitation.

The newborn infant parasympathetic evaluation in pediatric and neonatology: a literature review.

PURPOSE: The Newborn Infant Parasympathetic Evaluation (NIPE) is a heart rate variability-based technology for assessing pain and comfort in neonates and infants under 2-years-old. This review aims to investigate the clinical utility of the NIPE. METHODS: Two investigators screened Pubmed/Medline and Google Scholar for relevant studies, independently. One investigator extracted data, which were reviewed by a second investigator. RESULTS: The NIPE was used during/after painful stimuli (6 studies), in the context of general anaesthesia (2 studies), and for comfort assessment (6 studies). A) Evaluation of procedural pain/distress: 2 studies reported that the mean-NIPE could be used for reliable monitoring of prolonged pain, and one study reported the association between instant-NIPE and pain after a stimulus but the instant-NIPE represents the NIPE average over 3 min. Two studies found no correlation between the NIPE and comfort behavior/pain scales, but they mainly differed in patients' gestational age and evaluation methodology. B) There are only 2 studies for the evaluation of nociception during surgery under general anaesthesia with contradictory results. C) Studies assessing neonates' comfort reported increased NIPE scores during skin-to-skin contact and during facilitated tucking associated with a human voice. No effect on NIPE scores of facilitated tucking during echocardiography was reported in preterm infants. One study reported significantly different NIPE scores with 2 surfactant therapy protocols. Overall, study populations were small and heterogeneous. CONCLUSION: The results regarding NIPE's performances differ between studies. Given the limited number of studies and the heterogeneous outcomes, more studies are required to confirm the NIPE usefulness in the different clinical settings.

Opioid effect on the autonomic nervous system in a fetal sheep model.

PURPOSE: Opioid use during labour can interfere with cardiotocography patterns. Heart rate variability indirectly reflects a fluctuation in the autonomic nervous system and can be monitored through time and spectral analyses. This experimental study aimed to evaluate the impact of nalbuphine administration on the gasometric, cardiovascular, and autonomic nervous system responses in fetal sheep. METHODS: This was an experimental study on chronically instrumented sheep fetuses (surgery at 128 ± 2 days of gestational age, term = 145 days). The model was based on a maternal intravenous bolus injection of nalbuphine, a semisynthetic opioid used as an analgesic during delivery. Fetal gasometric parameters (pH, pO2, pCO2, and lactates), hemodynamic parameters (fetal heart rate and mean arterial pressure), and autonomic nervous system tone (short-term and long-term variation, low-frequency domain, high-frequency domain, and fetal stress index) were recorded. Data obtained at 30-60 min after nalbuphine injection were compared to those recorded at baseline. RESULTS: Eleven experiments were performed. Fetal heart rate, mean arterial pressure, and activities at low and high frequencies were stable after injection. Short-term variation decreased at T30 min (P = 0.02), and long-term variation decreased at T60 min (P = 0.02). Fetal stress index gradually increased and reached significance at T60 min (P = 0.02). Fetal gasometric parameters and lactate levels remained stable. CONCLUSION: Maternal nalbuphine use during labour may lead to fetal heart changes that are caused by the effect of opioid on the autonomic nervous system; these fluctuations do not reflect acidosis.

Newborn Infant Parasympathetic Evaluation Index for the Assessment of Procedural Pain in Nonanesthetized Infants: A Multicenter Pilot Study.

OBJECTIVE: The aim of this study is to evaluate the ability of the Newborn Infant Parasympathetic Evaluation (NIPE) index to detect the response to nociceptive stimuli in nonanesthetized infants and to compare these results to simultaneous scoring by behavioral scales. STUDY DESIGN: Thirty-six nonanesthetized infants admitted to neonatal/pediatric intensive care unit (N/PICUs) were enrolled to the study. Due to faulty records of the data, three patients had to be excluded. To detect pain caused by noxious stimuli, the heart-rate-variability-derived NIPE index and behavioral pain scales designed for measuring procedural pain in nonverbal children were used. RESULTS: Forty-one painful events were available for analysis. We observed in the whole group a statistically significant decrease in NIPE values at 1, 2, and 3 minutes after a painful stimulus, in comparison to the NIPE value at rest and the statistically significant differences between the minimum NIPE value within 3 minutes after the stimulus in comparison to NIPE value at rest in the whole group, as well as in the subgroups of moderate and severe pain. Receiver operating characteristic (ROC) analysis has shown the strong sensitivity and specificity of the NIPE in detecting the noxious stimuli (ROC AUC: 0.767). We also found that the stronger the sensation of pain was, the more rapidly NIPE reached its lowest value. DISCUSSION: Our study indicates that the painful procedures are associated with a significant decrease in the NIPE value within 3 minutes after a noxious stimulus. Based on our observation, the minimum value within 3 minutes from the painful procedure seems to be the most distinctive value.

Procedural Pain Assessment in Infants Without Analgosedation: Comparison of Newborn Infant Parasympathetic Evaluation and Skin Conductance Activity - A Pilot Study.

Objective: New technologies to measure pain responses, such as heart rate variability and skin conductance hold promise in the development of tools that can be reliable and quantifiable of detecting pain. The main objective of this study was to assess the capability of two monitors i.e., Newborn Infant Parasympathetic Evaluation (NIPE) and Skin Conductance Algesimeter for detecting procedural pain in non-anesthetized infants. Materials and Methods: Thirty-three non-anesthetized infants were enrolled to the study. To detect pain caused by heel stick, NIPE, and Skin Conductance monitors and behavioral pain scales were used. Three minutes before and just after heel stick, pain was evaluated by behavioral scales, and simultaneously over the whole period by NIPE and SCA. Results: A statistically significant decrease of NIPE Index and an increase of SCA values were found after the HS procedure. There were no statistically significant differences between the decrease in NIPEi values and the increase in PPS values between subgroups based on pain assessment by behavioral-scale scores. Conclusion: Both NIPE and SCA can be useful for detection of procedural pain and may constitue an additional valuable tool for better handling of pain among patients treated in NICUs. More studies on larger groups of patients are needed.

Fetal sheep cerebral electrical activity: A new technique to record EEG.

BACKGROUND: Sheep models are commonly used to study fetal cortical activity, including response to hypoxia. The standard technique consists of recording electrocorticogram (ECOG) in utero using electrodes placed on the dura mater. NEW METHOD: We propose a new method for recording the electroencephalogram (EEG) of fetal sheep, using electrodes placed above the skull bone and fixed to the cranial periosteum. RESULTS: Twelve animals were instrumented with this new technique. The EEG signal recorded in utero was of sufficient quality for visual and quantitative analysis of the fetal cortical activity. COMPARISON WITH EXISTING METHOD: This new method is less invasive than the standard method commonly used to record cerebral activity in fetal sheep, because it avoids drilling the skull by hand. The EEG signal recorded in utero had visual and quantitative characteristics comparable to ECOG. CONCLUSIONS: We present a new method of EEG recording that appears to be an acceptable alternative to the standard ECOG recording method. Fetal sheep EEG can be used to better understand the physiological mechanisms involved in the cerebral response to hypoxia.

Assessment of Procedural Distress in Sedated/Intubated Children Under 3 Years Old Using the Newborn Infant Parasympathetic Evaluation: A Diagnostic Accuracy Pilot Study.

OBJECTIVES: Newborn infant parasympathetic evaluation index is based on heart rate variability and is related to the autonomic response to pain or stress. The Comfort Behavior Scale is used to assess distress intensity in sedated intubated children. The objective of this study was to assess the validity and performance of newborn infant parasympathetic evaluation as a distress indicator during procedural distress. DESIGN: Monocentric, prospective, noninterventional pilot study of diagnostic accuracy between October 1, 2017, and April 30, 2019. SETTING: PICU in a tertiary care university hospital. PATIENTS: Sedated intubated children under 3 years old. INTERVENTIONS: We continuously obtained mean newborn infant parasympathetic evaluation and instantaneous newborn infant parasympathetic evaluation scores and compared them to Comfort Behavior scores obtained before (T1 period), during (T2 period), and after (T3 period) care procedures. MEASUREMENTS AND MAIN RESULTS: We obtained 54 measurements from 32 patients. The median age was 4 months (23 d to 31 mo). Between T1 and T2, there was a significant decrease in the instantaneous newborn infant parasympathetic evaluation and mean newborn infant parasympathetic evaluation scores (64 ± 2 to 42 ± 1 [p 0.0001] and 64 ± 1 to 59 ± 1 [p = 0.007], respectively) and a significant increase in the Comfort Behavior scores (from 12 ± 0 to 16 ± 1; p 0.0001). Comfort Behavior scores and instantaneous newborn infant parasympathetic evaluation and mean newborn infant parasympathetic evaluation scores were significantly inversely correlated (r = -0.44, p 0.0001 and r = -0.19, p = 0.01, respectively). With a instantaneous newborn infant parasympathetic evaluation score threshold of 53, the sensitivity, specificity, positive predictive, and negative predictive values to predict a Comfort Behavior Scale up to 17 were 80.0%, 73.5%, 43.8%, and 93.5%, respectively. CONCLUSIONS: Instantaneous newborn infant parasympathetic evaluation is valid for assessing distress in sedated/intubated children in the PICU. Further studies are needed to confirm these results and for newborn infant parasympathetic evaluation-based comparisons of sedation-analgesia protocols.

Autonomic response to fetal acidosis using an experimental sheep model.

BACKGROUND: The autonomic nervous system has a major role in fetal adaptation to hypoxia. Its activity might be assessed using heart rate variability and heart rate deceleration analyses. OBJECTIVE: To evaluate the ability of different heart rate variability and morphological deceleration analyses to predict fetal acidosis during labor in an experimental fetal sheep model. STUDY DESIGN: Repeated 1-minute total umbilical cord occlusions were performed at mild (1minute every 5 min), moderate (1 min every 3 min), and severe (1 min every 2 min) umbilical cord occlusion periodicities until arterial pH reached 7.10. Hemodynamic,blood gas analysis, morphological analysis of decelerations (magnitude, slope, and area ofdecelerations), and heart rate variability parameters were recorded throughout the experiment.Heart rate variability analysis included temporal analysis (root mean square of successivedifferences between adjacent RR intervals, standard deviation of normal to normal RR intervals, short term variability), spectral analysis (low frequencies, high frequencies,normalized high frequencies), and a new index developed by our team, the Fetal Stress Index.We defined and compared three pH groups: >7.20, 7.10-7.20, and <7.10. RESULTS: Eleven experiments were performed. Repetitive umbilical cord occlusions resulted in progressive fetal acidosis. Fetal Stress Index was correlated with pH and lactate (p < 0.05) and increased with acidosis. There were no significant correlations between pH, lactate, and other indices (spectral analysis, temporal analysis, or morphological analysis of decelerations). CONCLUSION: This protocol allowed us to identify the progressive onset of fetal acidosis in an experimental model close to labor. Fetal Stress Index is a heart rate variability method that varies with acidosis and indicates an increase in parasympathetic nervous system activity in response to fetal acidosis.

High-Frequency Heart Rate Variability Index: A Prospective, Observational Trial Assessing Utility as a Marker for the Balance Between Analgesia and Nociception Under General Anesthesia.

BACKGROUND: Maintaining a balance between nociception and analgesia perioperatively reduces morbidity and improves outcomes. Current intraoperative analgesic strategies are based on subjective and nonspecific parameters. The high-frequency heart rate (HR) variability index is purported to assess the balance between nociception and analgesia in patients under general anesthesia. This prospective observational study investigated whether intraoperative changes in the high-frequency HR variability index correlate with clinically relevant nociceptive stimulation and the addition of analgesics. METHODS: Instantaneous and mean high-frequency HR variability indexes were measured continuously in 79 adult subjects undergoing general anesthesia for laparoscopic cholecystectomy. The indexes were compared just before and 2 minutes after direct laryngoscopy, orogastric tube placement, first skin incision, and abdominal insufflation and just before and 6 minutes after the administration of IV hydromorphone. RESULTS: Data from 65 subjects were included in the final analysis. The instantaneous index decreased after skin incision ([SEM], 58.7 [2.0] vs 47.5 [2.0]; P < .001) and abdominal insufflation (54.0 [2.0] vs 46.3 [2.0]; P = .002). There was no change in the instantaneous index after laryngoscopy (47.2 [2.2] vs 40.3 [2.3]; P = .026) and orogastric tube placement (49.8 [2.3] vs 45.4 [2.0]; P = .109). The instantaneous index increased after hydromorphone administration (58.2 [1.9] vs 64.8 [1.8]; P = .003). CONCLUSIONS: In adult subjects under general anesthesia for laparoscopic cholecystectomy, changes in the high-frequency HR variability index reflect alterations in the balance between nociception and analgesia. This index might be used intraoperatively to titrate analgesia for individual patients. Further testing is necessary to determine whether the intraoperative use of the index affects patient outcomes.

Impact of skin-to-skin contact on maternal comfort in patients with elective caesarean section: A pilot study.

OBJECTIVE: Caesarean section is a well-known cause of difficulties in breastfeeding initiation. Mother-infant skin-to-skin contact allows to improve breastfeeding and maternal comfort but remains few practiced during caesarean section. Our objective was to evaluate maternal comfort before and after immediate skin-to-skin contact in case of elective caesarean section. METHODS: This was a prospective, observational, monocenter study including patients with elective caesarean section. Mother-infant skin-to-skin contact was begun immediately after birth. The Analgesia Nociception Index (ANI) is a well know heart rate variability (HRV) index, currently used in anesthesia, which decreases during painful stimulation and increases with maternal comfort. The Analgesia Nociception Index was compared before and after skin-to-skin contact. RESULTS: 53 patients were included. Skin-to-skin contact was started on average 4min (2-14, IIQ (3-5)) after birth. The median duration was 21min (4-40, IIQ (12.3-29.5)). It was interrupted in 24 patients: 9 from mother's wish, 11 for maternal reasons (drowsiness, stress, pain, maternal hypothermia, lipothymia, vertigo, nausea, cough) and 4 for the newborn (respiratory distress, low pH). The median Analgesia Nociception Index at the end of skin-to-skin contact and at the end of the intervention was statistically higher than that before skin-to-skin contact (p=0.034 and p<10-3 respectively). CONCLUSION: Skin-to-skin contact is possible during caesarean section and allows a better maternal comfort. It should be encouraged and proposed to patients during elective caesarean section. It will be interesting to evaluate it in case of caesarean section during labor.