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Continuous multivariate electronic fetal monitoring during labor detects early onset of acidemia: Prospective study in fetalsheep model
Abstracts Objectives: The objective of this project is to conduct an analysis of the incidence of neonatal vagal spells at different gestational ages. This study uses Artemis' capability to automatically detect vagal spells. Artemis is a framework for concurrent multipatient, multidiagnosis, and multistream temporal analysis in real time for clinical management and research. Apnea is defined as a pause in breathing for more than 20 seconds or a pause in breathing of any duration associated with cyanosis, pallor, bradycardia, or marked hypotonia [1]. The most common cause of spells in preterm infants is immaturity, although infection, lung collapse, and seizures are other causes. A spell can occur as the result of 1 of 3 types of apnea—central, obstructive, or mixed. In studies of infants who are experiencing spells, mixed apnea is the most common (49.6%), followed by central (39.9%) and obstructive (10.5%) apneic events [2]. Vagal spells are a subtype of central apnea and are the result of stimulation of the vagal nerve. The pattern of events that occurs with a vagal spell is a rapid fall in heart rate accompanied by a simultaneous pause in respiration, followed shortly by a decrease in blood oxygen saturation. Neonatal respiratory physiologists have demonstrated this pattern of vagal spell by stimulating the vagal nerve of preterm lambs with an acid solution sprayed on the larynx. Many neonatologists consider that infants have spells as a result of gastroesophageal acid reflux [3]. This has been difficult to prove in vivo. The polyvagal theory describes an autonomic nervous system that is influenced by the central nervous system. As the central nervous system matures, the output of the autonomic nervous system is modified, and it has been hypothesized that the nature of vagal spells changes with increasing maturity [4]. The modification of vagal tone described in this theory may explain why apnea is rare in term infants with severe gastroesophageal acid reflux. Methods: The Artemis project has high fidelity physiological data stored from more than 300 neonates. We have developed a streams-based algorithm to detect vagal spells and plan to use this analysis to examine the frequency of events at the various gestational ages Conclusions: This analysis will allow us to determine if gestational age affects the incidence of vagal spells. It will also provide the first in-depth analysis of the frequency of vagal spells in neonates.
http://dx.doi.org/10.1016/j.jcrc.2012.10.025
References [1] Committee on Fetus and Newborn. Apnea, sudden infant death syndrome, and home monitoring. Pediatrics 2003;111:914-7. [2] Finer NN, Barrington KJ, Hayes BJ, Hugh A. Obstructive, mixed, and central apnea in the neonate: physiologic correlates. J Pediatr 1992;121(6):943-50. [3] St-hilaire M, Samson N, Duvareille C, Praud J. Laryngeal stimulation by an acid solution in the pre-term lamb. Adv Exp Med Biol 2008;605: 154-8. [4] Belal SY, Emmerson AJ, Beatty PCW. Automatic detection of apnoea of prematurity. Physiol Meas 2011;32:523-42.
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Abstract 10 Continuous multivariate electronic fetal monitoring during labor detects early onset of acidemia: Prospective study in fetalsheep model L. Daniel Durosier a, Mingju Cao a, Izmail Batkin b, Brad J. Matushewski c, Lynn Keenliside d, Christophe Herry b, Geoffrey Green b, Andrew J.E. Seely b, Bryan S. Richardson c, Martin G. Frasch a a CHU Sainte-Justine Research Center, Department of Obstetrics-Gynecology, Université de Montréal, Quebec, Canada b Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada c Departments of Obstetrics and Gynaecology, Physiology and Pharmacology, University of Western Ontario, Ontario, Canada d Lawson Prototyping Facility, Lawson Health Research Institute, London, ON
Objectives: There is an urgent need to identify early signs of fetal acidemia because it confers a risk of lasting neurologic deficits. Changes in root mean square of successive differences in R-R intervals of electrocardiogram (RMSSD) reflect modulation of fetal heart rate (FHR) variability (fHRV) by vagal activity on a beat-to-beat time scale and are more precise than the current clinical short-term FHR variation measures used in electronic fetal monitoring (EFM). Electronic fetal monitoring samples FHR at ~ 4 Hz. An augmented bedside fetal monitoring would have to perform reliably even at this low sampling rate. We have shown that with fHRV sampled at 1000 Hz, RMSSD increases ~ 70 minutes (range, 17 minutes–1 hour and 39 minutes) before the onset of severe acidemia (pH b 7.00). When measured at an fHRV sampling rate of 4 Hz, RMSSD increase was delayed by 40 minutes and so missed the onset of severe acidemia in 2 of 7 fetuses. In the remaining 5 fetuses, RMSSD increased at ~ 50 minutes (range, 40-60 minutes) before the pH falling b 7.00. Sample entropy (SampEn), a measure of fHRV complexity, has shown promise in early detection of neonatal sepsis and may also reflect alterations in the autonomic nervous system during acidemia, complementary to the linear time domain fHRV measure RMSSD. Amplitude of the fetal sheep electroencephalogram (EEG) is predictably altered with worsening acidemia because it shows temporal correlation with the accompanying FHR decelerations. It might hence prove useful for EFM during labor. We found that such EEG-FHR pattern alerts to the pH drop less than 7.00 emerging ~ 58 minutes in advance (range, 19 minutes–1 hour and 52 minutes). Thus, there is a considerable interindividual variability of changes in RMSSD and EEG-FHR pattern in advance of severe acidemia. We hypothesized that a continuous multivariate fHRV-EEG-FHR EFM during labor will better detect incipient severe fetal acidemia than each of these modalities alone. Methods: Seven near-term fetal sheep were prepared with arterial catheters, electrocardiogram, EEG electrodes, and an umbilical cord occluder. For 1 minute every 2.5 minutes, animals underwent mild then moderate partial umbilical cord occlusions (UCO) over a 1hour period, and then severe complete UCO over a 1- to 2-hour period, until arterial pH reached less than 7.00. This timing was chosen to model human labor. Arterial blood samples were drawn at baseline and every 20 minutes during the UCO period. We tested the performance of RMSSD and SampEn when determined with 1000- and 4-Hz sampling rates using the automated and
e6 standardized Continuous Individualized Multiorgan Variability Analysis system. Results: Repetitive fetal UCO resulted in marked acidemia (pH 7.36 ± 0.01 decreasing to 6.99 ± 0.01, mean ± SEM). We found individual differences in the timing of increase in RMSSD and SampEn compared with EEG-FHR pattern onset. At the 1000-Hz fHRV sampling rate, in 2 animals RMSSD increased ~ 1 hour and 6 minutes before the onset of the EEG-FHR pattern at ~ 23 minutes before pH b 7.00 drop. With SampEn, this time was increased by another hour for all 7 fetuses at ~ 2 hour and 11 minutes (range, 1 hour and 17 minutes–2 hours and 40 minutes) before pH b 7.00. At the 4-Hz fHRV sampling rate, the same 2 of 7 fetuses were missed with SampEn as with RMSSD. Sample entropy decreased at ~ 44 minutes (range, 22 minutes–1 hour and 39 minutes) before pH b 7.00. In 6 of 7 fetuses, EEG-FHR pattern emerged ~ 34 minutes earlier than SampEn increase (range, 6 minutes–1 hour). In contrast, in 1 fetus, the increase of SampEn was found 20 minutes and that of RMSSD was 40 minutes earlier than EEG-FHR pattern onset. Moreover, RMSSD increased ~ 26 minutes earlier than EEGFHR pattern onset in 2 of 7 fetuses. Conclusions: At 1000 Hz, SampEn extends our ability to detect fetal acidemia. At 4 Hz, EEG-FHR monitoring is augmented by the addition of fHRV RMSSD monitoring, but not by SampEn. Our findings support the hypothesis that multivariate EEG-FHRfHRV EFM is more likely to detect fetal acidemia early than any of these modalities alone, even at the low fHRV sampling rate of 4 Hz used clinically. http://dx.doi.org/10.1016/j.jcrc.2012.10.026
Abstract 11 How can blood pressure and depth of narcosis prediction benefit from a networked operating room? Marcus Koeny a, Anna Kerekes a, Michael Czaplik b, Rolf Rossaint b, Steffen Leonhardt a a Chair for Medical Information Technology, RWTH Aachen, Aachen, Germany b Department of Anaesthesiology, University Hospital Aachen, Aachen, Germany
Objectives: During standard surgical interventions, the anesthesiologist controls the depth of anesthesia (DoA) using several drugs. Currently, decisions are made based on vital signs such as heart rate and blood pressure from monitors, anesthesia machines, and by observing visual events such as sweating or patient movement. The anesthesiologist must regard information displayed on each of these devices in the context of the simultaneous surgical intervention, to react to events such as pain stimuli or CO2 insufflation. For optimal anesthesia, not only the current situation and context are relevant but also anticipated procedures. Moreover, in some cases, heart rate and blood pressure follow a certain trend due to the pharmacokinetic (PK) and pharmacodynamic (PD) properties of applied drugs and therefore are potentially predictable. This fact is already in use for some commercially available projects like SmartPilot View (Draeger, Luebeck, Germany). The smart operating room research project aims to build a manufacturer independent standard that networks all medical devices used in the operating room. Consolidated information about the patient condition and relevant parameters from
Abstracts networked devices are collected and shown on central displays optimized for the surgical and anesthesiology workplaces, respectively. As an application example, we present an approach to estimate and predict blood pressure and DoA based on a PK/PD model together with information gathered from the networked operating room. In particular, we focus on intravenous anesthesia using propofol and remifentanil. Methods: The PK modeling uses standard models and parameters that are already in use in target-controlled infusion pumps. Blood pressure is estimated using a linear combination of the concentrations of propofol and remifentanil. In addition, the Bateman function models the influence of manually applied drugs. Finally, the influence of pain stimuli is modeled using a simple proportional time delay in combination with information about the event. Vital signs and information about applied drugs are automatically obtained from devices within the smart operating room network in real time. Information about further events such as pain stimuli are currently obtained post hoc. In future, these events will be provided by a combination of an expert system and a workflow engine. Results: Using the described PK/PD model, blood pressure can be estimated and predicted during neutral conditions, depending on parameters such as patient weight, age, size, and sex. The influence of pain stimuli can currently only be simulated post hoc because of high interpatient variation. Once the parameters have been estimated for a specific patient, the influence of pain stimuli can be considered during the prediction of blood pressure. Unfortunately, because such a calibration would require forced pain stimuli, it is not feasible due to practical and ethical reasons. Conclusions: Blood pressure can be predicted during normal conditions. As a matter of fact, DoA cannot be assessed and predicted reasonably using only the blood pressure. Therefore, further vital signs and other clinical observations must be considered. Nevertheless, the aim of the prediction is to assist and not to replace the anesthesiologist by means of a combination of a PK/PD model and a workflow-supported expert system, especially in critical situations. http://dx.doi.org/10.1016/j.jcrc.2012.10.027
Abstract 12 Thermoregulatory responses of coronary bypass patients to a removal of the heating blanket Tim Tambuyzer a, Jasmine Craps a, Geert Meyfroidt b, Greet Van Den Berghe b, Daniel Berckmans a, Jean-Marie Aerts a a Measure, Model & Manage Bioresponses (M3-BIORES), Department of Biosystems, KU Leuven, Leuven, Belgium b Surgical Intensive Care Unit, Department of Intensive Care Medicine , KU Leuven, Leuven, Belgium
Objectives: The control and regulation of body temperature is one of the key homeostatic functions of the body. In response to internal or external stimuli (such as thermal disturbances of the environment, invading pathogens, medications, surgical trauma, psychological stress, etc), these complex control mechanisms are continuously adjusted to maintain an optimal internal microenvironment. After a cardiac surgery, the thermoregulation is often highly disturbed. In this study, we hypothesized that insight in the dynamics of the thermoregulatory responses of coronary bypass patients can provide critical information about the health status of
http://dx.doi.org/10.1016/j.jcrc.2012.10.025
References [1] Committee on Fetus and Newborn. Apnea, sudden infant death syndrome, and home monitoring. Pediatrics 2003;111:914-7. [2] Finer NN, Barrington KJ, Hayes BJ, Hugh A. Obstructive, mixed, and central apnea in the neonate: physiologic correlates. J Pediatr 1992;121(6):943-50. [3] St-hilaire M, Samson N, Duvareille C, Praud J. Laryngeal stimulation by an acid solution in the pre-term lamb. Adv Exp Med Biol 2008;605: 154-8. [4] Belal SY, Emmerson AJ, Beatty PCW. Automatic detection of apnoea of prematurity. Physiol Meas 2011;32:523-42.
e5
Abstract 10 Continuous multivariate electronic fetal monitoring during labor detects early onset of acidemia: Prospective study in fetalsheep model L. Daniel Durosier a, Mingju Cao a, Izmail Batkin b, Brad J. Matushewski c, Lynn Keenliside d, Christophe Herry b, Geoffrey Green b, Andrew J.E. Seely b, Bryan S. Richardson c, Martin G. Frasch a a CHU Sainte-Justine Research Center, Department of Obstetrics-Gynecology, Université de Montréal, Quebec, Canada b Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada c Departments of Obstetrics and Gynaecology, Physiology and Pharmacology, University of Western Ontario, Ontario, Canada d Lawson Prototyping Facility, Lawson Health Research Institute, London, ON
Objectives: There is an urgent need to identify early signs of fetal acidemia because it confers a risk of lasting neurologic deficits. Changes in root mean square of successive differences in R-R intervals of electrocardiogram (RMSSD) reflect modulation of fetal heart rate (FHR) variability (fHRV) by vagal activity on a beat-to-beat time scale and are more precise than the current clinical short-term FHR variation measures used in electronic fetal monitoring (EFM). Electronic fetal monitoring samples FHR at ~ 4 Hz. An augmented bedside fetal monitoring would have to perform reliably even at this low sampling rate. We have shown that with fHRV sampled at 1000 Hz, RMSSD increases ~ 70 minutes (range, 17 minutes–1 hour and 39 minutes) before the onset of severe acidemia (pH b 7.00). When measured at an fHRV sampling rate of 4 Hz, RMSSD increase was delayed by 40 minutes and so missed the onset of severe acidemia in 2 of 7 fetuses. In the remaining 5 fetuses, RMSSD increased at ~ 50 minutes (range, 40-60 minutes) before the pH falling b 7.00. Sample entropy (SampEn), a measure of fHRV complexity, has shown promise in early detection of neonatal sepsis and may also reflect alterations in the autonomic nervous system during acidemia, complementary to the linear time domain fHRV measure RMSSD. Amplitude of the fetal sheep electroencephalogram (EEG) is predictably altered with worsening acidemia because it shows temporal correlation with the accompanying FHR decelerations. It might hence prove useful for EFM during labor. We found that such EEG-FHR pattern alerts to the pH drop less than 7.00 emerging ~ 58 minutes in advance (range, 19 minutes–1 hour and 52 minutes). Thus, there is a considerable interindividual variability of changes in RMSSD and EEG-FHR pattern in advance of severe acidemia. We hypothesized that a continuous multivariate fHRV-EEG-FHR EFM during labor will better detect incipient severe fetal acidemia than each of these modalities alone. Methods: Seven near-term fetal sheep were prepared with arterial catheters, electrocardiogram, EEG electrodes, and an umbilical cord occluder. For 1 minute every 2.5 minutes, animals underwent mild then moderate partial umbilical cord occlusions (UCO) over a 1hour period, and then severe complete UCO over a 1- to 2-hour period, until arterial pH reached less than 7.00. This timing was chosen to model human labor. Arterial blood samples were drawn at baseline and every 20 minutes during the UCO period. We tested the performance of RMSSD and SampEn when determined with 1000- and 4-Hz sampling rates using the automated and
e6 standardized Continuous Individualized Multiorgan Variability Analysis system. Results: Repetitive fetal UCO resulted in marked acidemia (pH 7.36 ± 0.01 decreasing to 6.99 ± 0.01, mean ± SEM). We found individual differences in the timing of increase in RMSSD and SampEn compared with EEG-FHR pattern onset. At the 1000-Hz fHRV sampling rate, in 2 animals RMSSD increased ~ 1 hour and 6 minutes before the onset of the EEG-FHR pattern at ~ 23 minutes before pH b 7.00 drop. With SampEn, this time was increased by another hour for all 7 fetuses at ~ 2 hour and 11 minutes (range, 1 hour and 17 minutes–2 hours and 40 minutes) before pH b 7.00. At the 4-Hz fHRV sampling rate, the same 2 of 7 fetuses were missed with SampEn as with RMSSD. Sample entropy decreased at ~ 44 minutes (range, 22 minutes–1 hour and 39 minutes) before pH b 7.00. In 6 of 7 fetuses, EEG-FHR pattern emerged ~ 34 minutes earlier than SampEn increase (range, 6 minutes–1 hour). In contrast, in 1 fetus, the increase of SampEn was found 20 minutes and that of RMSSD was 40 minutes earlier than EEG-FHR pattern onset. Moreover, RMSSD increased ~ 26 minutes earlier than EEGFHR pattern onset in 2 of 7 fetuses. Conclusions: At 1000 Hz, SampEn extends our ability to detect fetal acidemia. At 4 Hz, EEG-FHR monitoring is augmented by the addition of fHRV RMSSD monitoring, but not by SampEn. Our findings support the hypothesis that multivariate EEG-FHRfHRV EFM is more likely to detect fetal acidemia early than any of these modalities alone, even at the low fHRV sampling rate of 4 Hz used clinically. http://dx.doi.org/10.1016/j.jcrc.2012.10.026
Abstract 11 How can blood pressure and depth of narcosis prediction benefit from a networked operating room? Marcus Koeny a, Anna Kerekes a, Michael Czaplik b, Rolf Rossaint b, Steffen Leonhardt a a Chair for Medical Information Technology, RWTH Aachen, Aachen, Germany b Department of Anaesthesiology, University Hospital Aachen, Aachen, Germany
Objectives: During standard surgical interventions, the anesthesiologist controls the depth of anesthesia (DoA) using several drugs. Currently, decisions are made based on vital signs such as heart rate and blood pressure from monitors, anesthesia machines, and by observing visual events such as sweating or patient movement. The anesthesiologist must regard information displayed on each of these devices in the context of the simultaneous surgical intervention, to react to events such as pain stimuli or CO2 insufflation. For optimal anesthesia, not only the current situation and context are relevant but also anticipated procedures. Moreover, in some cases, heart rate and blood pressure follow a certain trend due to the pharmacokinetic (PK) and pharmacodynamic (PD) properties of applied drugs and therefore are potentially predictable. This fact is already in use for some commercially available projects like SmartPilot View (Draeger, Luebeck, Germany). The smart operating room research project aims to build a manufacturer independent standard that networks all medical devices used in the operating room. Consolidated information about the patient condition and relevant parameters from
Abstracts networked devices are collected and shown on central displays optimized for the surgical and anesthesiology workplaces, respectively. As an application example, we present an approach to estimate and predict blood pressure and DoA based on a PK/PD model together with information gathered from the networked operating room. In particular, we focus on intravenous anesthesia using propofol and remifentanil. Methods: The PK modeling uses standard models and parameters that are already in use in target-controlled infusion pumps. Blood pressure is estimated using a linear combination of the concentrations of propofol and remifentanil. In addition, the Bateman function models the influence of manually applied drugs. Finally, the influence of pain stimuli is modeled using a simple proportional time delay in combination with information about the event. Vital signs and information about applied drugs are automatically obtained from devices within the smart operating room network in real time. Information about further events such as pain stimuli are currently obtained post hoc. In future, these events will be provided by a combination of an expert system and a workflow engine. Results: Using the described PK/PD model, blood pressure can be estimated and predicted during neutral conditions, depending on parameters such as patient weight, age, size, and sex. The influence of pain stimuli can currently only be simulated post hoc because of high interpatient variation. Once the parameters have been estimated for a specific patient, the influence of pain stimuli can be considered during the prediction of blood pressure. Unfortunately, because such a calibration would require forced pain stimuli, it is not feasible due to practical and ethical reasons. Conclusions: Blood pressure can be predicted during normal conditions. As a matter of fact, DoA cannot be assessed and predicted reasonably using only the blood pressure. Therefore, further vital signs and other clinical observations must be considered. Nevertheless, the aim of the prediction is to assist and not to replace the anesthesiologist by means of a combination of a PK/PD model and a workflow-supported expert system, especially in critical situations. http://dx.doi.org/10.1016/j.jcrc.2012.10.027
Abstract 12 Thermoregulatory responses of coronary bypass patients to a removal of the heating blanket Tim Tambuyzer a, Jasmine Craps a, Geert Meyfroidt b, Greet Van Den Berghe b, Daniel Berckmans a, Jean-Marie Aerts a a Measure, Model & Manage Bioresponses (M3-BIORES), Department of Biosystems, KU Leuven, Leuven, Belgium b Surgical Intensive Care Unit, Department of Intensive Care Medicine , KU Leuven, Leuven, Belgium
Objectives: The control and regulation of body temperature is one of the key homeostatic functions of the body. In response to internal or external stimuli (such as thermal disturbances of the environment, invading pathogens, medications, surgical trauma, psychological stress, etc), these complex control mechanisms are continuously adjusted to maintain an optimal internal microenvironment. After a cardiac surgery, the thermoregulation is often highly disturbed. In this study, we hypothesized that insight in the dynamics of the thermoregulatory responses of coronary bypass patients can provide critical information about the health status of