The effect of ketamine on depth of hypnosis indices during total intravenous anesthesia-a comparative study using a novel electroencephalography case replay system.

Ketamine may affect the reliability of electroencephalographic (EEG) depth-of-hypnosis indices as it affects power in high-frequency EEG components. The purpose of this study was to compare the effects of ketamine on three commonly-used depth-of-hypnosis indices by extending our EEG simulator to allow replay of previously-recorded EEG. Secondary analysis of previously-collected data from a randomized controlled trial of intravenous anesthesia with ketamine: Group 0.5 [ketamine, 0.5 mg kg-1 bolus followed by a 10 mcg kg-1 min-1 infusion], Group 0.25 [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion], and Control [no ketamine]. EEG data were replayed to three monitors: NeuroSENSE (WAV), Bispectral Index (BIS), and Entropy (SE). Differences in depth-of-hypnosis indices during the initial 15 min after induction of anesthesia were compared between monitors, and between groups. Monitor agreement was evaluated using Bland-Altman analysis. Available data included 45.6 h of EEG recordings from 27 cases. Ketamine was associated with higher depth-of-hypnosis index values measured at 10 min (BIS, χ2 = 8.01, p = 0.018; SE, χ2 = 11.44, p = 0.003; WAV, χ2 = 9.19, p = 0.010), and a higher proportion of index values > 60 for both ketamine groups compared to the control group. Significant differences between monitors were not observed, except between BIS and SE in the control group. Ketamine did not change agreement between monitors. The ketamine-induced increase in depth-of-hypnosis indices was observed consistently across the three EEG monitoring algorithms evaluated. The observed increase was likely caused by a power increase in the beta and gamma bands. However, there were no lasting differences in depth-of-hypnosis reported between the three compared indices.

Feasibility of Using a Single Heart Rate-Based Measure for Real-time Feedback in a Voluntary Deep Breathing App for Children: Data Collection and Algorithm Development.

BACKGROUND: Deep diaphragmatic breathing, also called belly breathing, is a popular behavioral intervention that helps children cope with anxiety, stress, and their experience of pain. Combining physiological monitoring with accessible mobile technology can motivate children to comply with this intervention through biofeedback and gaming. These innovative technologies have the potential to improve patient experience and compliance with strategies that reduce anxiety, change the experience of pain, and enhance self-regulation during distressing medical procedures. OBJECTIVE: The aim of this paper was to describe a simple biofeedback method for quantifying breathing compliance in a mobile smartphone app. METHODS: A smartphone app was developed that combined pulse oximetry with an animated protocol for paced deep breathing. We collected photoplethysmogram data during spontaneous and subsequently paced deep breathing in children. Two measures, synchronized respiratory sinus arrhythmia (RSAsync) and the corresponding relative synchronized inspiration/expiration heart rate ratio (HR-I:Esync), were extracted from the photoplethysmogram. RESULTS: Data collected from 80 children aged 5-17 years showed a positive RSAsync effect in all participants during paced deep breathing, with a median (IQR; range) HR-I:Esync ratio of 1.26 (1.16-1.35; 1.01-1.60) during paced deep breathing compared to 0.98 (0.96-1.02; 0.82-1.18) during spontaneous breathing (median difference 0.25, 95% CI 0.23-0.30; P<.001). The measured HR-I:Esync values appeared to be independent of age. CONCLUSIONS: An HR-I:Esync level of 1.1 was identified as an age-independent threshold for programming the breathing pattern for optimal compliance in biofeedback.

Development and Implementation of the Portable Operating Room Tracker App With Vital Signs Streaming Infrastructure: Operational Feasibility Study.

BACKGROUND: In the perioperative environment, a multidisciplinary clinical team continually observes and evaluates patient information. However, data availability may be restricted to certain locations, cognitive workload may be high, and team communication may be constrained by availability and priorities. We developed the remote Portable Operating Room Tracker app (the telePORT app) to improve information exchange and communication between anesthesia team members. The telePORT app combines a real-time feed of waveforms and vital signs from the operating rooms with messaging, help request, and reminder features. OBJECTIVE: The aim of this paper is to describe the development of the app and the back-end infrastructure required to extract monitoring data, facilitate data exchange and ensure privacy and safety, which includes results from clinical feasibility testing. METHODS: telePORT's client user interface was developed using user-centered design principles and workflow observations. The server architecture involves network-based data extraction and data processing. Baseline user workload was assessed using step counters and communication logs. Clinical feasibility testing analyzed device usage over 11 months. RESULTS: telePORT was more commonly used for help requests (approximately 4.5/day) than messaging between team members (approximately 1/day). Passive operating room monitoring was frequently utilized (34% of screen visits). Intermittent loss of wireless connectivity was a major barrier to adoption (decline of 0.3%/day). CONCLUSIONS: The underlying server infrastructure was repurposed for real-time streaming of vital signs and their collection for research and quality improvement. Day-to-day activities of the anesthesia team can be supported by a mobile app that integrates real-time data from all operating rooms.

Design and Evaluation of a Closed-Loop Anesthesia System With Robust Control and Safety System.

BACKGROUND: Closed-loop control of anesthesia involves continual adjustment of drug infusion rates according to measured clinical effect. The NeuroSENSE monitor provides an electroencephalographic measure of depth of hypnosis (wavelet-based anesthetic value for central nervous system monitoring [WAVCNS]). It has previously been used as feedback for closed-loop control of propofol, in a system designed using robust control engineering principles, which implements features specifically designed to ensure patient safety. Closed-loop control of a second drug, remifentanil, may be added to improve WAVCNS stability in the presence of variable surgical stimulation. The objective of this study was to design and evaluate the feasibility of a closed-loop system for robust control of propofol and remifentanil infusions using WAVCNS feedback, with an infusion safety system based on the known pharmacological characteristics of these 2 drugs. METHODS: With Health Canada authorization, research ethics board approval, and informed consent, American Society of Anesthesiologists I-III adults, requiring general anesthesia for elective surgery, were enrolled in a 2-phase study. In both phases, infusion of propofol was controlled in closed loop during induction and maintenance of anesthesia, using WAVCNS feedback, but bounded by upper- and lower-estimated effect-site concentration limits. In phase I, remifentanil was administered using an adjustable target-controlled infusion and a controller was designed based on the collected data. In phase II, remifentanil was automatically titrated to counteract rapid increases in WAVCNS. RESULTS: Data were analyzed for 127 patients, of median (range) age 64 (22-86) years, undergoing surgical procedures lasting 105 (9-348) minutes, with 52 participating in phase I and 75 in phase II. The overall control performance indicator, global score, was a median (interquartile range) 18.3 (14.2-27.7) in phase I and 14.6 (11.6-20.7) in phase II (median difference, -3.25; 95% confidence interval, -6.35 to -0.52). The WAVCNS was within ±10 of the setpoint for 84.3% (76.6-90.6) of the maintenance of anesthesia in phase I and 88.2% (83.1-93.4) in phase II (median difference, 3.7; 95% confidence interval, 0.1-6.9). The lower propofol safety bound was activated during 30 of 52 (58%) cases in phase I and 51 of 75 (68%) cases in phase II. CONCLUSIONS: Adding closed-loop control of remifentanil improved overall controller performance. This controller design offers a robust method to optimize the control of 2 drugs using a single sensor. The infusion safety system is an important component of a robust automated anesthesia system, but further research is required to determine the optimal constraints for these safe conditions.

Detecting obstructive sleep apnea in children by self-affine visualization of oximetry.

Obstructive sleep apnea (OSA), characterized by cessations of breathing during sleep due to upper airway collapse, can affect the healthy growth and development of children. The gold standard for OSA diagnosis, polysomnography(PSG), is expensive and resource intensive, resulting in long waiting lists to perform a PSG. Previously, we investigated the time-frequency analysis of blood oxygen saturation (SpO2) to screen for OSA. We used overnight pulse oximetry from 146 children, collected using a smartphone-based pulse oximeter (Phone Oximeter), simultaneously with standard PSG. Sleep technicians manually scored PSG and provided the average of apnea/hypoapnea events per hour (AHI). In this study, we proposed an alternative method for analyzing SpO2, in which a set of contracting transformations form a self-affine set with a 2D attractor, previously developed for qualitative visualization of the photoplethysmogram and electroencephalogram. We applied this technique to the overnight SpO2 signal from individual patients and extracted features based on the distribution of points (radius and angle) in the visualization. The cloud of points in children without OSA (NonOSA) was more confined than in children with OSA, which was reflected by more empty pixels (radius and angles). The maximum value, skewness and standard deviation of the distribution of points located at different radius and angles were significantly (Bonferroni corrected) higher in NonOSA compared to OSA children. To detect OSA defined at different levels (AHI≥5, AHI≥10 and AHI≥15), three multivariate logistic regression models were implemented using a stepwise feature selection and internally validated through bootstrapping. The models (AHI≥5, AHI≥10, AHI≥15), consisting of 3, 4 and 1 features respectively, provided a bootstrap-corrected AUC of 73%, 81%, 73%. Thus, applying this visualization to nocturnal SpO2 could yield both visual and quantitative information that might be useful for screening children for OSA.

Thresholds for the Oxford Hip Score after total hip replacement surgery: a novel approach to postoperative evaluation.

BACKGROUND: This is a prospective cohort study to define the thresholds to distinguish patients with a satisfactory or unsatisfactory outcome after total hip replacement (THR) based on patient-reported outcome measures (PROMs) including the Oxford Hip Score (OHS), and using patient satisfaction and patient-perceived function as global transition items. The thresholds are intended to be used as a tool in the process of determining which patients are in need of postoperative outpatient evaluation. METHODS: One hundred and three THR patients who had completed a preoperative questionnaire containing the OHS questionnaire were invited to complete the same questionnaire and supplementary questions at a mean of 6 (4-9) months after surgery. Correlations between outcome measures and anchors were calculated using Pearson's correlation coefficient. Thresholds were established by receiver operating characteristic (ROC) analysis, using multiple anchors. RESULTS: Significant correlations were found between outcome measures and anchors. Thresholds were determined for outcome measures coupled with satisfaction, patient-perceived function and a combination thereof using a cut-off of 50 and 70. CONCLUSIONS: We have established a set of thresholds for Oxford scores that may help determine which THR patients are in need of postoperative evaluation. These thresholds can be implemented in clinical practice. LEVEL OF EVIDENCE: Level 3.

Evaluation of cardiac modulation in children in response to apnea/hypopnea using the Phone Oximeter(™).

Individuals with sleep disordered breathing (SDB) can experience changes in automatic cardiac regulation as a result of frequent sleep fragmentation and disturbance in normal respiration and oxygenation that accompany most apnea/hypopnea events. In adults, these changes are reflected in enhanced sympathetic and reduced parasympathetic activity. In this study, we examined the autonomic cardiac regulation in children with and without SDB, through spectral and detrended fluctuation analysis (DFA) of pulse rate variability (PRV). PRV was measured from pulse-to-pulse intervals (PPIs) of the photoplethysmogram (PPG) recorded from 160 children using the Phone Oximeter(™) in the standard setting of overnight polysomnography. Spectral analysis of PRV showed the cardiac parasympathetic index (high frequency, HF) was lower (p < 0.01) and cardiac sympathetic indices (low frequency, LF and LF/HF ratio) were higher (p < 0.01) during apnea/hypopnea events for more than 95% of children with SDB. DFA showed the short- and long-range fluctuations of heart rate were more strongly correlated in children with SDB compared to children without SDB. These findings confirm that the analysis of the PPG recorded using the Phone Oximeter(™) could be the basis for a new screening tool for assessing PRV in non-clinical environment.

Variability in estimating shunt from single pulse oximetry measurements.

Virtual shunt describes the overall loss of O2 content between the alveolar gas and arterial blood. Clinicians indirectly estimate the magnitude of the virtual shunt by monitoring peripheral blood oxygen saturation (SpO2) using non-invasive pulse oximetry. An inherent limitation of this method is the variable precision of pulse oximeters and the non-linear relationship between virtual shunt and SpO2 which is rarely depicted.We propose a model using a combination of basic physiological equations to analyze the estimation of virtual shunt from inspired oxygen (FiO2) and SpO2. The model emphasizes the effect of the non-linearity of the Hb-O2 dissociation curve. Furthermore, it accounts for the variability in SpO2 measurements due to the precision of pulse oximeters.The model was validated with experiments conducted on healthy subjects in a normobaric hypoxia chamber comparing the simultaneous readings from two different commercial pulse oximeters at FiO2 = 21% and 17%. SpO2 probability distributions calculated from the model were estimated. Although a variable bias (1.2-2.1%) in SpO2 between the pulse oximeter brands was observed, the tested pulse oximeters were both within tolerance specified by the manufacturers and matched the probability distributions from the model.The theoretical and experimental findings show that the estimation of virtual shunt is challenging with a single SpO2 measurement using pulse oximeters with tolerances of 2%. Clinical decisions must be based on an appreciation of these limitations.

Estimating instantaneous respiratory rate from the photoplethysmogram.

The photoplethysmogram (PPG) obtained from pulse oximetry shows the local changes of blood volume in tissues. Respiration induces variation in the PPG baseline due to the variation in venous blood return during each breathing cycle. We have proposed an algorithm based on the synchrosqueezing transform (SST) to estimate instantaneous respiratory rate (IRR) from the PPG. The SST is a combination of wavelet analysis and a reallocation method which aims to sharpen the time-frequency representation of the signal and can provide an accurate estimation of instantaneous frequency. In this application, the SST was applied to the PPG and IRR was detected as the predominant ridge in the respiratory band (0.1 Hz - 1 Hz) in the SST plane. The algorithm was tested against the Capnobase benchmark dataset that contains PPG, capnography, and expert labelled reference respiratory rate from 42 subjects. The IRR estimation accuracy was assessed using the root mean square (RMS) error and Bland-Altman plot. The median RMS error was 0.39 breaths/min for all subjects which ranged from the lowest error of 0.18 breaths/min to the highest error of 13.86 breaths/min. A Bland-Altman plot showed an agreement between the IRR obtained from PPG and reference respiratory rate with a bias of -0.32 and limits agreement of -7.72 to 7.07. Extracting IRR from PPG expands the functionality of pulse oximeters and provides additional diagnostic power to this non-invasive monitoring tool.

Design and evaluation of a low-cost smartphone pulse oximeter.

Infectious diseases such as pneumonia take the lives of millions of children in low- and middle-income countries every year. Many of these deaths could be prevented with the availability of robust and low-cost diagnostic tools using integrated sensor technology. Pulse oximetry in particular, offers a unique non-invasive and specific test for an increase in the severity of many infectious diseases such as pneumonia. If pulse oximetry could be delivered on widely available mobile phones, it could become a compelling solution to global health challenges. Many lives could be saved if this technology was disseminated effectively in the affected regions of the world to rescue patients from the fatal consequences of these infectious diseases. We describe the implementation of such an oximeter that interfaces a conventional clinical oximeter finger sensor with a smartphone through the headset jack audio interface, and present a simulator-based systematic verification system to be used for automated validation of the sensor interface on different smartphones and media players. An excellent agreement was found between the simulator and the audio oximeter for both oxygen saturation and heart rate over a wide range of optical transmission levels on 4th and 5th generations of the iPod TouchTM and iPhoneTM devices.

Ultra-low-cost clinical pulse oximetry.

An ultra-low-cost pulse oximeter is presented that interfaces a conventional clinical finger sensor with a mobile phone through the headset jack audio interface. All signal processing is performed using the audio subsystem of the phone. In a preliminary volunteer study in a hypoxia chamber, we compared the oxygen saturation obtained with the audio pulse oximeter against a commercially available (and FDA approved) reference pulse oximeter (Nonin Xpod). Good agreement was found between the outputs of the two devices.

Robust closed-loop control of induction and maintenance of propofol anesthesia in children.

BACKGROUND: During closed-loop control, a drug infusion is continually adjusted according to a measure of clinical effect (e.g., an electroencephalographic depth of hypnosis (DoH) index). Inconsistency in population-derived pediatric pharmacokinetic/pharmacodynamic models and the large interpatient variability observed in children suggest a role for closed-loop control in optimizing the administration of intravenous anesthesia. OBJECTIVE: To clinically evaluate a robustly tuned system for closed-loop control of the induction and maintenance of propofol anesthesia in children undergoing gastrointestinal endoscopy. METHODS: One hundred and eight children, aged 6-17, ASA I-II, were enrolled. Prior to induction of anesthesia, NeuroSENSE™ sensors were applied to obtain the WAVCNS DoH index. An intravenous cannula was inserted and lidocaine (0.5 mg·kg(-1) ) administered. Remifentanil was administered as a bolus (0.5 µg·kg(-1) ), followed by continuous infusion (0.03 µg·kg(-1) ·min(-1) ). The propofol infusion was closed-loop controlled throughout induction and maintenance of anesthesia, using WAVCNS as feedback. RESULTS: Anesthesia was closed-loop controlled in 102 cases. The system achieved and maintained an adequate DoH without manual adjustment in 87/102 (85%) cases. Induction of anesthesia (to WAVCNS  ≤ 60) was completed in median 3.8 min (interquartile range (IQR) 3.1-5.0), culminating in a propofol effect-site concentration (Ce ) of median 3.5 µg·ml(-1) (IQR 2.7-4.5). During maintenance of anesthesia, WAVCNS was measured within 10 units of the target for median 89% (IQR 79-96) of the time. Spontaneous breathing required no manual intervention in 91/102 (89%) cases. CONCLUSIONS: A robust closed-loop system can provide effective propofol administration during induction and maintenance of anesthesia in children. Wide variation in the calculated Ce highlights the limitation of open-loop regimes based on pharmacokinetic/pharmacodynamic models.