Nociception level during anaesthesia : analysis and control

Tese de Programa Doutoral. Engenharia Biomédica. Universidade do Porto. Faculdade de Engenharia. 201

Towards automation in anaesthesia: a review

Simpósio Internacional MeMeA, realizado em 2014.Surgeries represent a risk for patients and a big cost for the hospital. Anaesthesia represents a complex part of surgery also carries risks for patients. The most known are awareness (with deep psychological consequences); increased risk of morbidity and mortality; adverse reactions and long post-op recovery. The complexity of anaesthesia management can be reduced by studying the patients' responses and developing indicators of the patient state. To assess the level of depth of anaesthesia, the anaesthetist needs to be aware of the patient physiological responses to the drugs and to surgical stimuli. A system that could advise on the patient state considering all clinical signs being measured, the patient individual response and the amount of drugs, will have a big impact on patient overall safety and future health, post-op recovery and hospital resources. This paper does a review of different systems and methods applied to several aspects of the anaesthesia field. All with the goal of working towards automation in this very complex area, that involves high risks for patients. This paper covers advisor systems; signal processing; new monitors and devices; mathematical modelling; and control algorithms; all focused on practical clinical implementation. The objective is to have an overview of the work done so far and the steps taken towards automation in anaesthesia.ISPA - System Integration and Process Automation Unit - Part of the LAETA (Associated Laboratory of Energy, Transports and Aeronautics) a I&D Unit of the Foundation for Science and Technology (FCT), Portugal. FCT support under project PEst-OE/EME/LA0022/2013.info:eu-repo/semantics/publishedVersio

Impact of hypnosis on psychophysiological measures: A scoping literature review.

Exploring psychophysiological changes during hypnosis can help to better understand the nature and extent of the hypnotic phenomenon by characterizing its influence on the autonomic nervous system (ANS), in addition to its central brain effects. Hypnosis is thought to induce a relaxation response, yet studies using objective psychophysiological measures alongside hypnosis protocols show various results. We review this literature and clarify the effects of hypnosis on psychophysiological indices of ANS activity and more specifically of the stress/relaxation response, such as heart rate variability and electrodermal activity. Studies reporting psychophysical measures during hypnosis were identified by a series of Pubmed searches. Data was extracted with an interest for the influence of hypnotizability and effects of specific suggestions or tasks on the findings. We found 49 studies comprising 1315 participants, 45 concerning healthy volunteers and only 4 on patients. Sixteen compared high vs. low hypnotizable people; 30 measured heart rate, 18 measured heart rate variability, 25 electrodermal activity, and 23 respiratory signals as well as other physiological parameters. Globally, results converge to show reductions in sympathetic responses and/or increases in parasympathetic tone under hypnosis. Several methodological limitations are underscored, such as older studies (N = 16) using manual analyses, small sample sizes (<30, N = 31), as well as uncontrolled multiple comparisons. Nevertheless, we confirm that hypnosis leads to a physiological relaxation response and highlight promising avenues for this research. Suggestions are made for guiding future work in this field

Advanced Signal Processing and Control in Anaesthesia

This thesis comprises three major stages: classification of depth of anaesthesia (DOA); modelling a typical patient’s behaviour during a surgical procedure; and control of DOAwith simultaneous administration of propofol and remifentanil. Clinical data gathered in theoperating theatre was used in this project. Multiresolution wavelet analysis was used to extract meaningful features from the auditory evoked potentials (AEP). These features were classified into different DOA levels using a fuzzy relational classifier (FRC). The FRC uses fuzzy clustering and fuzzy relational composition. The FRC had a good performance and was able to distinguish between the DOA levels. A hybrid patient model was developed for the induction and maintenance phase of anaesthesia. An adaptive network-based fuzzy inference system was used to adapt Takagi-Sugeno-Kang (TSK) fuzzy models relating systolic arterial pressure (SAP), heart rate (HR), and the wavelet extracted AEP features with the effect concentrations of propofol and remifentanil. The effect of surgical stimuli on SAP and HR, and the analgesic properties of remifentanil were described by Mamdani fuzzy models, constructed with anaesthetist cooperation. The model proved to be adequate, reflecting the effect of drugs and surgical stimuli. A multivariable fuzzy controller was developed for the simultaneous administration of propofol and remifentanil. The controller is based on linguistic rules that interact with three decision tables, one of which represents a fuzzy PI controller. The infusion rates of the two drugs are determined according to the DOA level and surgical stimulus. Remifentanil is titrated according to the required analgesia level and its synergistic interaction with propofol. The controller was able to adequately achieve and maintain the target DOA level, under different conditions. Overall, it was possible to model the interaction between propofol and remifentanil, and to successfully use this model to develop a closed-loop system in anaesthesia

Decision tree method to classify the electroencephalography-based emotion data

Electroencephalography (EEG) data contains recordings of brain signal activity divided into several channels with different impulse responses that can be used to detect human emotions. In classifying emotions, EEG data needs to be parsed or signal processed into values ​​that can help recognize emotions. Research related to electroencephalography has been carried out previously and has experienced success using the Fuzzy C-Means, Multiple Discriminant Analysis, and Deep Neural Network methods. This study was conducted to classify human emotions from electroencephalography data on 10 participants. Each participant carried out 40 trials of testing using the Power Spectral Density (PSD) and Discrete Wavelet Transform (DWT) methods at the initial stage of classification and the Decision Tree method as the final method that can improve the accuracy of the two methods at the initial stage of classification. The results of this study were the finding of 2 participants (3 trials) who were unmatched from a total of 10 participants (400 trials), which were analyzed using the decision tree method. The decision tree method can correct this error and increase the classification result to 100%. The DWT method is used as a reference in the classification of emotions, considering that the DWT method has an output of arousal and valance values ​​. In contrast, the PSD method only has a combined output.Electroencephalography (EEG) data contains recordings of brain signal activity divided into several channels with different impulse responses that can be used to detect human emotions. In classifying emotions, EEG data needs to be parsed or signal processed into values ​​that can help recognize emotions. Research related to electroencephalography has been carried out previously and has experienced success using the Fuzzy C-Means, Multiple Discriminant Analysis, and Deep Neural Network methods. This study was conducted to classify human emotions from electroencephalography data on 10 participants. Each participant carried out 40 trials of testing using the Power Spectral Density (PSD) and Discrete Wavelet Transform (DWT) methods at the initial stage of classification and the Decision Tree method as the final method that can improve the accuracy of the two methods at the initial stage of classification. The results of this study were the finding of 2 participants (3 trials) who were unmatched from a total of 10 participants (400 trials), which were analyzed using the decision tree method. The decision tree method can correct this error and increase the classification result to 100%. The DWT method is used as a reference in the classification of emotions, considering that the DWT method has an output of arousal and valance values ​​. In contrast, the PSD method only has a combined output

Measurements of adequacy of anesthesia and level of consciousness during surgery and intensive care

The adequacy of anesthesia has been studied since the introduction of balanced general anesthesia. Commercial monitors based on electroencephalographic (EEG) signal analysis have been available for monitoring the hypnotic component of anesthesia from the beginning of the 1990s. Monitors measuring the depth of anesthesia assess the cortical function of the brain, and have gained acceptance during surgical anesthesia with most of the anesthetic agents used. However, due to frequent artifacts, they are considered unsuitable for monitoring consciousness in intensive care patients. The assessment of analgesia is one of the cornerstones of general anesthesia. Prolonged surgical stress may lead to increased morbidity and delayed postoperative recovery. However, no validated monitoring method is currently available for evaluating analgesia during general anesthesia. Awareness during anesthesia is caused by an inadequate level of hypnosis. This rare but severe complication of general anesthesia may lead to marked emotional stress and possibly posttraumatic stress disorder. In the present series of studies, the incidence of awareness and recall during outpatient anesthesia was evaluated and compared with that of in inpatient anesthesia. A total of 1500 outpatients and 2343 inpatients underwent a structured interview. Clear intraoperative recollections were rare the incidence being 0.07% in outpatients and 0.13% in inpatients. No significant differences emerged between outpatients and inpatients. However, significantly smaller doses of sevoflurane were administered to outpatients with awareness than those without recollections (p<0.05). EEG artifacts in 16 brain-dead organ donors were evaluated during organ harvest surgery in a prospective, open, nonselective study. The source of the frontotemporal biosignals in brain-dead subjects was studied, and the resistance of bispectral index (BIS) and Entropy to the signal artifacts was compared. The hypothesis was that in brain-dead subjects, most of the biosignals recorded from the forehead would consist of artifacts. The original EEG was recorded and State Entropy (SE), Response Entropy (RE), and BIS were calculated and monitored during solid organ harvest. SE differed from zero (inactive EEG) in 28%, RE in 29%, and BIS in 68% of the total recording time (p<0.0001 for all). The median values during the operation were SE 0.0, RE 0.0, and BIS 3.0. In four of the 16 organ donors, EEG was not inactive, and unphysiologically distributed, nonreactive rhythmic theta activity was present in the original EEG signal. After the results from subjects with persistent residual EEG activity were excluded, SE, RE, and BIS differed from zero in 17%, 18%, and 62% of the recorded time, respectively (p<0.0001 for all). Due to various artifacts, the highest readings in all indices were recorded without neuromuscular blockade. The main sources of artifacts were electrocauterization, electromyography (EMG), 50-Hz artifact, handling of the donor, ballistocardiography, and electrocardiography. In a prospective, randomized study of 26 patients, the ability of Surgical Stress Index (SSI) to differentiate patients with two clinically different analgesic levels during shoulder surgery was evaluated. SSI values were lower in patients with an interscalene brachial plexus block than in patients without an additional plexus block. In all patients, anesthesia was maintained with desflurane, the concentration of which was targeted to maintain SE at 50. Increased blood pressure or heart rate (HR), movement, and coughing were considered signs of intraoperative nociception and treated with alfentanil. Photoplethysmographic waveforms were collected from the contralateral arm to the operated side, and SSI was calculated offline. Two minutes after skin incision, SSI was not increased in the brachial plexus block group and was lower (38 ± 13) than in the control group (58 ± 13, p<0.005). Among the controls, one minute prior to alfentanil administration, SSI value was higher than during periods of adequate antinociception, 59 ± 11 vs. 39 ± 12 (p<0.01). The total cumulative need for alfentanil was higher in controls (2.7 ± 1.2 mg) than in the brachial plexus block group (1.6 ± 0.5 mg, p=0.008). Tetanic stimulation to the ulnar region of the hand increased SSI significantly only among patients with a brachial plexus block not covering the site of stimulation. Prognostic value of EEG-derived indices was evaluated and compared with Transcranial Doppler Ultrasonography (TCD), serum neuron-specific enolase (NSE) and S-100B after cardiac arrest. Thirty patients resuscitated from out-of-hospital arrest and treated with induced mild hypothermia for 24 h were included. Original EEG signal was recorded, and burst suppression ratio (BSR), RE, SE, and wavelet subband entropy (WSE) were calculated. Neurological outcome during the six-month period after arrest was assessed with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Twenty patients had a CPC of 1-2, one patient had a CPC of 3, and nine patients died (CPC 5). BSR, RE, and SE differed between good (CPC 1-2) and poor (CPC 3-5) outcome groups (p=0.011, p=0.011, p=0.008, respectively) during the first 24 h after arrest. WSE was borderline higher in the good outcome group between 24 and 48 h after arrest (p=0.050). All patients with status epilepticus died, and their WSE values were lower (p=0.022). S-100B was lower in the good outcome group upon arrival at the intensive care unit (p=0.010). After hypothermia treatment, NSE and S-100B values were lower (p=0.002 for both) in the good outcome group. The pulsatile index was also lower in the good outcome group (p=0.004). In conclusion, the incidence of awareness in outpatient anesthesia did not differ from that in inpatient anesthesia. Outpatients are not at increased risk for intraoperative awareness relative to inpatients undergoing general anesthesia. SE, RE, and BIS showed non-zero values that normally indicate cortical neuronal function, but were in these subjects mostly due to artifacts after clinical brain death diagnosis. Entropy was more resistant to artifacts than BIS. During general anesthesia and surgery, SSI values were lower in patients with interscalene brachial plexus block covering the sites of nociceptive stimuli. In detecting nociceptive stimuli, SSI performed better than HR, blood pressure, or RE. BSR, RE, and SE differed between the good and poor neurological outcome groups during the first 24 h after cardiac arrest, and they may be an aid in differentiating patients with good neurological outcomes from those with poor outcomes after out-of-hospital cardiac arrest.Anestesian syvyyden riittävyyttä on tutkittu yhtä kauan kuin yleisanestesioita on annettu. Rutiinikäyttöön soveltuvia aivosähkökäyrään (EEG) perustuvia anestesian syvyyttä mittaavia laitteita on ollut markkinoilla 1990-luvulta alkaen. Nämä aivojen kortikaalista toimintaa mittaavat laitteet kuvaavat unen syvyyttä ja toimivat luotettavasti yleisimmin käytössä olevien nukutusaineiden kanssa. Lukuisat ulkoiset tekijät aiheuttavat kuitenkin häiriöitä indekseihin, mikä on toistaiseksi estänyt mittarien luotettavan käytön tehohoidossa. Vaikka kivunhoito on yksi merkittävimmistä yleisanestesian komponenteista, luotettavaa kipumittaria ei toistaiseksi ole ollut markkinoilla. Anestesian aikainen hereilläolo on harvinainen mutta vakava komplikaatio, joka voi johtaa huomattavalla osalla potilaista posttraumaattisen stressireaktion syntyyn. Tutkimuksessa verrattiin 1500 päiväkirurgista potilasta 2343 vuodeosastolta käsin leikattuun potilaaseen. Haastattelututkimukseen perustuen selkeitä anestesian aikaisia muistikuvia esiintyi 0.07 % päiväkirurgisista ja 0.13 % osastopotilaista. Ryhmien välillä ei todettu tilastollisesti merkitsevää eroa. Ne päiväkirurgiset potilaat, joilla todettiin anestesian aikainen hereillä olo, saivat merkittävästi vähemmän hypnoottista ainetta (sevofluraania) kuin ne potilaat, joilla tätä komplikaatiota ei esiintynyt. Aivosähkökäyrään vaikuttavia häiriötekijöitä tutkittiin 16 kliinisesti aivokuolleelta elinluovuttajalta. Anestesian aikana käytettäviä unen syvyyttä kuvaavia mittareita, BIS (bispektraali-indeksi)- ja Entropia-monitoria (SE= State Entropy, RE= Response Entropy), käytettiin otsalta kerätyn biosignaalin rekisteröimiseen. Tutkimuksen hypoteesina oli, että valtaosa rekisteröidystä biosignaalista koostuisi aivokuolleilla elinluovuttajilla EEG-rekisteröintiä häiritsevistä artefakteista. Elinluovutusleikkauksen aikana BIS oli herkempi häiriötekijöille ja erosi indeksi-luvusta nolla (inaktiivinen EEG) 68 % rekisteröintiajasta. SE poikkesi nollasta 28 ja RE 29 % rekisteröintiajasta. Leikkauksen yhteydessä käytettävien sähköisten laitteiden, elinluovuttajan liikuttelun sekä jäljellä olevan lihas- ja sydämen sähköisen toiminnan aiheuttamat muutokset olivat pääasialliset BIS- ja Entropia-monitorointia häiritsevät tekijät elinluovutusleikkauksen aikana. Anestesian aikaista reagoimattomuutta kipuun tutkittiin uuden, kajoamattoman mittarin, SSI:n (Surgical Stress Index, myöhemmin SPI, Surgical Pleth Index) avulla 26 olkapääleikkaukseen tulleella potilaalla. SSI lasketaan sormesta mitattavan sykeaallon amplitudiin ja sydämen syketaajuuteen perustuen, joten sen lukuarvo suurenee sympaattisen stimulaation lisääntyessä. SSI-lukema oli alhaisempi potilailla, jotka saivat leikkausta edeltävästi olkapunoksen sentraalisen puudutuksen kuin potilailla, jotka leikattiin ilman puudutusta. Kaikki potilaat nukutettiin toimenpiteen ajaksi ja anestesian syvyyttä kontrolloitiin pitämällä SE tasolla 50 desfluraani-annosta nostamalla tai laskemalla. Kohonnut pulssi- tai verenpainetaso, potilaan liikkuminen, kyynelehtiminen tai yskiminen tulkittiin merkiksi riittämättömästä kipulääketasosta, mikä hoidettiin alfentaniili-lääkityksellä. Kahden minuutin kuluttua ihoviillosta mitattuna SSI ei noussut alkutasoon verrattuna olkapunospuudutuksen saaneilla potilailla ja oli merkitsevästi matalampi kuin puuduttamattomilla verrokkipotilailla. Verrokkipotilailla minuutti ennen kipulääketarvetta mitattu SSI oli huomattavasti korkeampi kuin SSI samoilla potilailla ajanjaksoina, jolloin kipulääkitystä ei tarvittu. Leikkauksenaikainen kumulatiivinen kipulääkityksen määrä oli suurempi potilailla, jotka eivät saaneet puudutusta leikkausta edeltävästi. Olkapunoksen puudutuksen saaneiden potilaiden joukossa standardisoituna kipuärsytyksenä käytetty tetaaninen ärsytys nosti SSI-lukemaa ainoastaan niillä potilailla, joilla puutunut alue ei kattanut kipuärsytysaluetta. Onnistuneestikin elvytetyille sydämenpysähdyspotilaille jää usein eriasteisia neurologisia vaurioita. Aikaisemmissa tutkimuksissa on saatu viitteitä siitä, että aivosähkökäyrä (EEG) kertoo neurologisesta toipumisesta, mutta tulkinnan vaikeus on rajoittanut sen käyttöä teho-osastoilla. EEG:stä johdettujen indeksien toimivuutta neurologisen ennustearvion tekemisessä tutkittiin kolmellakymmenellä sairaalan ulkopuolella kammiovärinästä elvytetyllä potilaalla, jotka saivat teho-osastolla aivoja suojaavan viilennyshoidon. EEG:stä johdettiin seuraavat kvantitatiiviset suureet: purskevaimentumasuhde (burst suppression ratio, BSR), tilaentropia (state entropy, SE), vaste-entropia (response entropy, RE) ja aallokemuunnoksen osakaistan entropia (wavelet subband entropy, WSE). Iskeemisen aivovaurion merkkiaineista määritettiin seerumin neuronispesifinen enolaasi ja S-100B. Aivojen verenkiertoa mitattiin transkraniaalisella kaikututkimuksella. Tutkimukseen otetuista potilaista 20 toipui neurologisesti hyväkuntoisiksi, yhden potilaan toipuminen oli heikkoa ja yhdeksän potilasta kuoli. Tutkimus osoitti, että neurologisesti hyvin ja heikosti toipuneet erottuivat EEG:n kvantitatiivisten suureiden perusteella jo ensimmäisen tehohoitovuorokauden aikana. Lisäksi kaikki potilaat, joiden EEG:n jälkianalyysissä todettiin kouristukseton epileptinen sarjakohtaus, menehtyivät ja heidän aallokemuunnoksen osakaistan entropiansa oli pienempi kuin neurologisesti hyväkuntoisiksi toipuneilla. Tuloksen perusteella näyttäisi siltä, että aallokemuunnoksen osakaistan vähenevä entropia auttaa havaitsemaan kouristuksettoman epileptisen sarjakohtauksen, jonka ilmaantuminen viittaa erittäin huonoon toipumisennusteeseen. Huonoon ennusteeseen liittyivät myös transkraniaalisen kaikututkimuksen pulssisuusindeksin, S100B:n ja neuronispesifisen enolaasin suuret arvot. Tutkimuksen yhteenvetona voidaan todeta, että päiväkirurgiseen yleisanestesiaan ei liity lisääntynyttä anestesian aikaisen hereillä olon riskiä. Anestesian syvyysmittareiden herkkyys lukuisille häiriötekijöille osoitettiin myös tässä väitöskirjatyössä. Entropia-monitori tunnisti häiriötekijät BIS-monitoria paremmin. Yleisanestesian aikana SSI (SPI)-monitori kuvasi luotettavasti kipulääkityksen (tai kivunhoitotekniikan) ja kirurgisen ärsytyksen välistä tasapainotilaa. EEG:stä johdetut indeksit ennustivat neurologista toipumista luotettavasti jo ensimmäisen elvytyksen jälkeisen vuorokauden aikana. Käytetyt parametrit yksinkertaistavat aivosähkökäyrän tulkintaa ja pitkän aikavälin tavoitteena on kehittää keskushermoston monitorointia siten, että aivojen tilan jatkuva seuranta teho-osastoilla olisi mahdollista ja että hoitohenkilökunta voisi reagoida heti potilaan aivotoiminnan muutoksiin

CLOSED-LOOP CONTROLLED TOTAL INTRA VENOUS ANAESTHESIA

Anaesthesia is important for both surgery and intensive care and intravenous anaesthetics are widely used to provide rapid onset, stable maintenance, and rapid recovery compared with inhaled anaesthetics. The aim of the project on which this thesis is based was to investigate a reliable and safe methodology for delivering total intravenous anaesthesia using closed-loop control technology and bispectral analysis of human electroencephalogram (EEG) waveform. In comparison with Target Controlled Infusion (TCI), drug effect is measured during drug infusion in closed loop anaesthesia (CLAN). This may provide superior safety, better patient care, and better quality of anaesthesia whilst relieving the clinician of the need to make recurrent and minor alterations to drug administration. However, the development of a CLAN system has been hindered by the Jack of a 'gold standard' for anaesthetic states and difficulties with patient variability in pharmacokinetic and pharmacodynamic modelling, and a new and generic mathematical model of a closed-loop anaesthesia system was developed for this investigation. By using this CLAN model, investigations on pharmacokinetic and pharmacodynamic variability existing in patients were carried out. A new control strategy that combines a Proportional, Integral, Derivative (PID) controller, bispectral analysis of EEG waveform and pharmacokinetic/ pharmacodynamic models was investigated. Based on the mathematical model, a prototype CLAN system, the first CLAN system capable of delivering both hypnotics and analgesics simultaneously for total intravenous anaesthesia, was developed. A Bispectral Index (BIS), derived from power spectral and bispectral analysis on EEG waveform, is used to measure depth of anaesthesia. A supervision system with built-in digital signal processing techniques was developed to compensate the non-linear characteristics inherent in the system while providing a comprehensive protection mechanism for patient safety. The CLAN system was tested in 78125 virtual patients modelled using published data. Investigations on intravenous anaesthesia induction and maintenance with the CLAN system were carried out in various clinical settings on 21 healthy volunteers and 15 patients undergoing surgery. Anaesthesia targets were achieved quickly and well maintained in all volunteers/patients except for 2 patients with clinically satisfactory anaesthesia quality.Derriford Hospita