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.

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.

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.

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.

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.

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.

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.

Parasympathetic nervous system response to acidosis: Evaluation in an experimental fetal sheep model.

INTRODUCTION: Heart rate variability and fetal heart rate decelerations are impacted by parasympathetic function and reflect acid-base status. Our team developed a new heart rate variability index, the fetal stress index (FSI), which has lower interindividual variability and higher sensitivity for detecting fluctuations in parasympathetic nervous system activity. The aim of this study was to explore the ability of the FSI to predict fetal acidosis in a fetal sheep model. MATERIAL AND METHODS: Repeated 1-minute total umbilical cord occlusions (UCOs) were performed every 2.5 minutes over 3 hours to generate fetal acidosis mimicking that which occurs during labor and contractions. Fetal hemodynamic parameters, blood gas, the FSI and the magnitude (from the beginning to the nadir) of the fetal heart rate deceleration were recorded at regular intervals. The data were analyzed over three time intervals because of variation in the duration of the experiments: period A (first 12 UCOs), period B (middle 12 UCOs) and period C (last 12 UCOs). RESULTS: Nine experiments were performed. Acidosis was progressive with a significant difference between the pH, lactate levels and base deficit values for the three periods of occlusion (P < 0.05). Both FSI and the magnitude of fetal heart rate decelerations gradually increased during the UCOs and both differed significantly between periods A and C (P = 0.0008 for FSI and P = 0.003 for deceleration). CONCLUSION: This experimental protocol allowed the development of progressive acidosis in a good model of the physiology of labor. Parasympathetic nervous system activity increased during acidosis and could be measured using our index, the FSI, and the magnitude of fetal heart rate decelerations.

Facilitated tucking during early neonatologist-performed echocardiography in very preterm neonates.

AIM: To assess the effect of facilitated tucking (FT), a nonpharmacologic nursing intervention, on echocardiographic parameters and infant comfort collected prospectively during neonatologist-performed echocardiography. METHODS: Echocardiography was performed twice, in standard conditions and with FT; the order was randomised by computer. Echocardiography provided data on pulmonary artery flow and pressure, right and left ventricular function, and persistent ductus arteriosus. Comfort was assessed by a behavioural scale of pain, variations in heart rate (HR) and SpO2 , and a newborn infant parasympathetic evaluation index based on the high-frequency variability in HR. RESULTS: Fifty newborns, with mean gestational age of 28 [26.6-29.0] weeks and mean birthweight of 950 [780-1190] g, were studied at a postnatal age of 13 [9-27] hours. FT was associated with longer acceleration time/right ventricular ejection time in the main pulmonary artery (p = 0.006), reduced averaged HR variations (p = 0.03) and lower pain scores (p < 0.001). The other haemodynamic parameters and the parasympathetic index were not influenced by FT. CONCLUSION: Echocardiography performed soon after birth in very premature neonates may generate mild discomfort. FT during echocardiography is associated with lower pulmonary artery pressures and improves infant's comfort during this examination.

Fetal Heart-Rate Variability: Validation of a New Continuous, Noninvasive Computerized Analysis.

OBJECTIVE: We developed a computerized heart-rate variability index related to the fetal parasympathetic activity: the Fetal Stress Index (FSI). The objective was to determine whether the FSI is related to the visual analysis of the fetal heart rate (FHR). METHODS: Thirty tracings recorded at a labor ward were classified according to the NICHD categories: (I) normal FHR tracing, (II) intermediate risk of acidosis, and (III) high risk. FSI was calculated as minimum, maximum, and mean, and was evaluated before the onset of the FHR pattern, during the 10 min following, and between 10 and 20 min after that. RESULTS: The FSI for categories II and III was similar to that of category I before the onset of the FHR pattern. FSI min was lower just after the onset of the abnormal FHR in category III, compared with that of category I (33 vs. 43, p < 0.001). Between 10 and 20 min after the onset of the abnormal FHR, we observed a significant reduction in FSI min in categories II and III (44 vs. 39 vs. 29.7, p < 0.0001). CONCLUSION: Although further studies are necessary for the sake of clinical validation, FSI could constitute an interesting method for the evaluation of fetal well-being.

Parasympathetic tone variations according to umbilical cord pH at birth: a computerized fetal heart rate variability analysis.

Non-reassuring fetal heart rate tracings reflect an imbalance between the parasympathetic and sympathetic nervous systems. In this situation, fetal asphyxia can be suspected and may be confirmed by metabolic measurements at birth like low pH or high base deficit values. The objective of this study was to determine whether fetal asphyxia during labor is related to parasympathetic nervous system activity. This is a retrospective study of a database collected in 5 centers. Two hundred and ninety-nine fetal heart rate tracings collected during labor were analyzed. Autonomic nervous system, especially the parasympathetic nervous system, was analyzed using an original index: the FSI (Fetal Stress Index). The FSI is a parasympathetic activity evaluation based on fetal heart rate variability analysis. Infants were grouped based on normal or low pH value at birth. FSI was measured during the last 30 min of labor before birth and compared between groups. The minimum value of the FSI during the last 30 min before delivery was significantly lower in the group with the lower umbilical cord arterial pH value. In this pilot study during labor, FSI was lower in the group of infants with low arterial pH at birth.

[Analysing heart rate variability to improve the monitoring of pain]. / Analyser la variabilité de la fréquence cardiaque pour mieux monitorer la douleur.

An innovative technique based on the analysis of instantaneous heart rate variability helps to improve the prevention and management of pain and discomfort. Simple to implement, this non-invasive technique is based on the continuous recording of the electrocardiograph signal.

A substitution method to improve completeness of events documentation in anesthesia records.

AIMS are optimized to find and display data and curves about one specific intervention but is not retrospective analysis on a huge volume of interventions. Such a system present two main limitation; (1) the transactional database architecture, (2) the completeness of documentation. In order to solve the architectural problem, data warehouses were developed to propose architecture suitable for analysis. However, completeness of documentation stays unsolved. In this paper, we describe a method which allows determining of substitution rules in order to detect missing anesthesia events in an anesthesia record. Our method is based on the principle that missing event could be detected using a substitution one defined as the nearest documented event. As an example, we focused on the automatic detection of the start and the end of anesthesia procedure when these events were not documented by the clinicians. We applied our method on a set of records in order to evaluate; (1) the event detection accuracy, (2) the improvement of valid records. For the year 2010-2012, we obtained event detection with a precision of 0.00 (-2.22; 2.00) min for the start of anesthesia and 0.10 (0.00; 0.35) min for the end of anesthesia. On the other hand, we increased by 21.1% the data completeness (from 80.3 to 97.2% of the total database) for the start and the end of anesthesia events. This method seems to be efficient to replace missing "start and end of anesthesia" events. This method could also be used to replace other missing time events in this particular data warehouse as well as in other kind of data warehouses.

Efficiency of a pneumatic device in controlling cuff pressure of polyurethane-cuffed tracheal tubes: a randomized controlled study.

BACKGROUND: The primary objective of this study was to determine the efficiency of a pneumatic device in controlling cuff pressure (Pcuff) in patients intubated with polyurethane-cuffed tracheal tubes. Secondary objectives were to determine the impact of continuous control of Pcuff, and cuff shape on microaspiration of gastric contents. METHODS: Prospective randomized controlled study. All patients requiring intubation and mechanical ventilation ≥48 h were eligible. The first 32 patients were intubated with tapered polyurethane-cuffed, and the 32 following patients were intubated with cylindrical polyurethane-cuffed tracheal tubes. Patients randomly received 24 h of continuous control of Pcuff using a pneumatic device (Nosten®), and 24 h of routine care of Pcuff using a manometer. Target Pcuff was 25 cmH2O. Pcuff was continuously recorded, and pepsin was quantitatively measured in all tracheal aspirates during these periods. RESULTS: The pneumatic device was efficient in controlling Pcuff (med [IQ] 26 [24, 28] vs 22 [20, 28] cmH2O, during continuous control of Pcuff and routine care, respectively; p = 0.017). In addition, percentage of patients with underinflation (31% vs 68%) or overinflation (53% vs 100%) of tracheal cuff, and percentage of time spent with underinflation (0.9 [0, 17] vs 14% [4, 30]) or overinflation (0 [0, 2] vs 32% [9, 54]) were significantly (p < 0.001) reduced during continuous control of Pcuff compared with routine care.No significant difference was found in microaspiration of gastric content between continuous control of Pcuff compared with routine care, or between patients intubated with tapered compared with cylindrical polyurethane-cuffed tracheal tubes. CONCLUSION: The pneumatic device was efficient in controlling Pcuff in critically ill patients intubated with polyurethane-cuffed tracheal tubes. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (NCT01351259).

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.

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.

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.

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.