Christian L. Petersen

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

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.

Design and Clinical Evaluation of Robust PID Control of Propofol Anesthesia in Children

This paper describes the design of a robust proportional-integral derivative (PID) controller for propofol infusion in children and presents the results of clinical evaluation of this closed-loop system during endoscopic investigations in children age 6-17. The controller design is based on a set of models that describes the interpatient variability in the response to propofol infusion in the study population. The PID controller is tuned to achieve sufficient robustness margins for the identified uncertainty. 108 children were enrolled in this study, and anesthesia was closed-loop controlled in 102 of these cases. Clinical evaluation of the system shows that closed-loop control of both induction and maintenance of anesthesia in children based on the WAVCNS index as a measure of clinical effect is feasible. A robustly tuned PID controller can accommodate the interpatient variability in children and spontaneous breathing can be maintained in most subjects.

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 Touch™ and iPhone™ devices.

Development of mHealth applications for pre-eclampsia triage.

The development of mobile applications for the diagnosis and management of pregnant women with pre-eclampsia is described. These applications are designed for use by community-based health care providers (c-HCPs) in health facilities and during home visits to collect symptoms and perform clinical measurements (including pulse oximeter readings). The clinical data collected in women with pre-eclampsia are used as the inputs to a predictive model providing a risk score for the development of adverse outcomes. Based on this risk, the applications provide recommendations on treatment, referral, and reassessment. c-HCPs can access patient records across multiple visits, using multiple devices that are synchronized using a secure Research Electronic Data Capture server. A unique feature of these applications is the ability to measure oxygen saturation with a pulse oximeter connected to a smartphone (Phone Oximeter). The mobile health application development process, including challenges encountered and solutions are described.

Closed-Loop Anesthesia in Children using a PID Controller: A Pilot Study

8 Measuring adeQuacy of analgesia with cardiorespiratory coherence Chris Brouse, Walter Karlen, Guy Dumont, Dorothy Myers, Erin Cooke, Jonathan Stinson, Joanne Lim, J. Mark Ansermino The University of British Columbia, Vancouver, Canada Introduction: An automated nociception monitor would be very useful in general anesthesia, providing anesthesiologists with real-time feedback about the adequacy of analgesia. We have developed an algorithm to measure nociception using respiratory sinus arrhythmia (RSA) in heart rate variability (HRV). We have previously shown that this algorithm can detect patient movement (strongly nociceptive events) during general anesthesia 1. We will now attempt to determine if the algorithm responds to boluses of anesthetic drugs (strongly anti-nociceptive events). Method: Algorithm: The algorithm estimates cardiorespiratory coherence, which is the strength of linear coupling between HR and respiration (one measure of RSA). It measures and combines the spectral power in both signals using wavelet analysis. Coherence is dimensionless, and ranges from 0 (no coherence, strong nociception) to 1 (perfect coherence, no nociception). Data Analysis: Following ethics approval and informed consent, 60 drug bolus events (excluding induction of anesthesia) were recorded in 47 pediatric patients receiving general anesthesia during dental surgery. In post hoc analysis, coherence was averaged over the 60s immediately preceding the bolus dose of drug (nociceptive period). The bolus was given 30s to take effect, after which the coherence was averaged over the following 60s (anti-nociceptive period). The change in average coherence between the two periods was calculated. The change in average HR was also calculated, for comparison. Results: Coherence increased by an average of 0.14 (32%) in response to the bolus dose of anesthetic drug. HR decreased by an average of 4.1 beats/min (3.9%). Discussion: Cardiorespiratory coherence responded much more strongly to the anesthetic boluses than did HR alone. This result, combined with previous work showing that coherence is low during periods of nociception [1], demonstrates that cardiorespiratory coherence can be used to measure the adequacy of analgesia during general anesthesia. We are currently adapting the algorithm so that it can be used in real-time.

Experience report: functional programming of mHealth applications

A modular framework for the development of medical applications that promotes deterministic, robust and correct code is presented. The system is based on the portable Gambit Scheme programming language and provides a flexible cross-platform environment for developing graphical applications on mobile devices as well as medical instrumentation interfaces running on embedded platforms. Real world applications of this framework for mobile diagnostics, telemonitoring and automated drug infusions are reported. The source code for the core framework is open source and available at: https://github.com/part-cw/lambdanative.

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.

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.

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.

A Procedural Electroencephalogram Simulator for Evaluation of Anesthesia Monitors

BACKGROUND:Recent research and advances in the automation of anesthesia are driving the need to better understand electroencephalogram (EEG)–based anesthesia end points and to test the performance of anesthesia monitors. This effort is currently limited by the need to collect raw EEG data directly from patients. METHODS:A procedural method to synthesize EEG signals was implemented in a mobile software application. The application is capable of sending the simulated signal to an anesthesia depth of hypnosis monitor. Systematic sweeps of the simulator generate functional monitor response profiles reminiscent of how network analyzers are used to test electronic components. RESULTS:Three commercial anesthesia monitors (Entropy, NeuroSENSE, and BIS) were compared with this new technology, and significant response and feature variations between the monitor models were observed; this includes reproducible, nonmonotonic apparent multistate behavior and significant hysteresis at light levels of anesthesia. CONCLUSIONS:Anesthesia monitor response to a procedural simulator can reveal significant differences in internal signal processing algorithms. The ability to synthesize EEG signals at different anesthetic depths potentially provides a new method for systematically testing EEG-based monitors and automated anesthesia systems with all sensor hardware fully operational before human trials.