Technical and clinical evaluation of a closed loop TIVA system with SEDLineTM spectral density monitoring: Multicentric prospective cohort study

Introduction: Closed loop total intravenous anesthesia is a technique in which the patient’s hemodynamic and anesthetic depth variables are monitored, and based on this information, a computer controls the infusion rate of drugs to keep them within pre-established clinical parameters. Objective: To describe the technical and clinical performance of a closed loop system for total intravenous anesthesia with propofol and remifentanil, using the SEDLineTM monitor Design: Multicentric prospective cohort study Setting: Surgery room Patients: ASA I-II undergoing elective surgery Measurements: The authors designed a closed loop system that implements a control algorithm based on anesthetic depth monitoring and the Patient State Index (PSITM) of the SEDLine monitor for propofol, and on hemodynamic variables for remifentanil. The measurement of clinical performance was made based on the percentage of PSITM maintenance time in the range 20–50. Precision analysis was evaluated by measuring median performance error (MDPE) can be defined as the median difference between actual and desired values, which refers to the degree of precision in which the controller is able to maintain the control variable within the objective set by the anesthesiologist; it represents the direction (over-prediction or underprediction) of performance error (PE) rather than size of errors, which is represented by MDAPE, median absolute percentage error, Wobble index, which is used for measuring the intrasubject variability in performance error. Results: Data were obtained from 93 patients in three healthcare centers. The percentage of PSITM maintenance time in the 20–50 range was 92% (80.7–97.0). MDPE was 10.7 (− 11.0–18.0), MDAPE 21.0 (14.2– 26.8) and wobble 10.7 (7.0–16.9). No adverse surgical or anesthetic events were found

Total Mass TCI driven by Parametric Estimation

This paper presents the Total Mass Target Controlled Infusion algorithm. The system comprises an On Line tuned Algorithm for Recovery Detection (OLARD) after an initial bolus administration and a Bayesian identification method for parametric estimation based on sparse measurements of the accessible signal. To design the drug dosage profile, two algorithms are here proposed. During the transient phase, an Input Variance Control (IVC) algorithm is used. It is based on the concept of TCI and aims to steer the drug effect to a predefined target value within an a priori fixed interval of time. After the steady state phase is reached the drug dose regimen is controlled by a Total Mass Control (TMC) algorithm. The mass control law for compartmental systems is robust even in the presence of parameter uncertainties. The whole system feasibility has been evaluated for the case of Neuromuscular Blockade (NMB) level and was tested both in simulation and in real cases

On Automation in Anesthesia

The thesis discusses closed-loop control of the hypnotic and the analgesic components of anesthesia. The objective of the work has been to develop a system which independently controls the intravenous infusion rates of the hypnotic drug propofol and analgesic drug remifentanil. The system is designed to track a reference hypnotic depth level, while maintaining adequate analgesia. This is complicated by inter-patient variability in drug sensitivity, disturbances caused foremost by surgical stimulation, and measurement noise. A commercially available monitor is used to measure the hypnotic depth of the patient, while a simple soft sensor estimates the analgesic depth. Both induction and maintenance of anesthesia are closed-loop controlled, using a PID controller for propofol and a P controller for remifentanil. In order to tune the controllers, patient models have been identified from clinical data, with body mass as only biometric parameter. Care has been taken to characterize identifiability and produce models which are safe for the intended application. A scheme for individualizing the controller tuning upon completion of the induction phase of anesthesia is proposed. Practical aspects such as integrator anti-windup and loss of the measurement signal are explicitly addressed. The validity of the performance measures, most commonly reported in closed-loop anesthesia studies, is debated and a new set of measures is proposed. It is shown, both in simulation and clinically, that PID control provides a viable approach. Both results from simulations and clinical trials are presented. These results suggest that closed-loop controlled anesthesia can be provided in a safe and efficient manner, relieving the regulatory and server controller role of the anesthesiologist. However, outlier patient dynamics, unmeasurable disturbances and scenarios which are not considered in the controller synthesis, urge the presence of an anesthesiologist. Closed-loop controlled anesthesia should therefore not be viewed as a replacement of human expertise, but rather as a tool, similar to the cruise controller of a car

An Optimized Type-2 Self-Organizing Fuzzy Logic Controller Applied in Anesthesia for Propofol Dosing to Regulate BIS

During general anesthesia, anesthesiologists who provide anesthetic dosage traditionally play a fundamental role to regulate Bispectral Index (BIS). However, in this paper, an optimized type-2 Self-Organizing Fuzzy Logic Controller (SOFLC) is designed for Target Controlled Infusion (TCI) pump related to propofol dosing guided by BIS, to realize automatic control of general anesthesia. The type-2 SOFLC combines a type-2 fuzzy logic controller with a self-organizing (SO) mechanism to facilitate online training while able to contend with operational uncertainties. A novel data driven Surrogate Model (SM) and Genetic Programming (GP) based strategy is introduced for optimizing the type-2 SOFLC parameters offline to handle inter-patient variability. A pharmacological model is built for simulation in which different optimization strategies are tested and compared. Simulation results are presented to demonstrate the applicability of our approach and show that the proposed optimization strategy can achieve better control performance in terms of steady state error and robustness

Integrated anaesthesia software : data acquisition, controlled infusion schemes and intelligent alarms

Tese de doutoramento. Engenharia Biomédica. Universidade do Porto. Faculdade de Engenharia. 201

Développement d’un système d’administration de l’anesthésie en boucle fermée

En salle d’opération, les tâches de l’anesthésiste sont nombreuses. Alors que l’utilisation de nouveaux outils technologiques l’informe plus fidèlement sur ce qui se passe pour son patient, ces outils font que ses tâches deviennent plus exigeantes. En vue de diminuer cette charge de travail, nous avons considérer l’administration automatique d’agents anesthésiques en se servant de contrôle en boucle fermée. À cette fin, nous avons développé un système d’administration d’un agent anesthésique (le propofol) visant à maintenir à un niveau optimal la perte de conscience du patient pendant toute la durée d’une chirurgie. Le système comprend un ordinateur, un moniteur d’anesthésie et une pompe de perfusion. L’ordinateur est doté d’un algorithme de contrôle qui, à partir d’un indice (Bispectral IndexTM ou BIS) fournit par le moniteur d’anesthésie détermine le taux d’infusion de l’agent anesthésiant. Au départ, l’anesthésiste choisit une valeur cible pour la variable de contrôle BIS et l’algorithme, basé sur système expert, calcule les doses de perfusion de propofol de sorte que la valeur mesurée de BIS se rapproche le plus possible de la valeur cible établie. Comme interface-utilisateur pour un nouveau moniteur d’anesthésie, quatre sortes d’affichage ont été considérés: purement numérique, purement graphique, un mélange entre graphique et numérique et un affichage graphique intégré (soit bidimensionnel). À partir de 20 scenarios différents où des paramètres normaux et anormaux en anesthésie étaient présentés à des anesthésistes et des résidents, l’étude des temps de réaction, de l’exactitude des réponses et de la convivialité (évaluée par le NASA-TLX) a montré qu’un affichage qui combine des éléments graphiques et numériques était le meilleur choix comme interface du système. Une étude clinique a été réalisée pour comparer le comportement du système d’administration de propofol en boucle fermée comparativement à une anesthésie contrôlée de façon manuelle et conventionnelle où le BIS était aussi utilisé. Suite à l’approbation du comité d’éthique et le consentement de personnes ayant à subir des chirurgies générales et orthopédiques, 40 patients ont été distribués également et aléatoirement soit dans le Groupe contrôle, soit dans le Groupe boucle fermée. Après l’induction manuelle de propofol (1.5 mg/kg), le contrôle en boucle fermée a été déclenché pour maintenir l’anesthésie à une cible de BIS fixée à 45. Dans l’autre groupe, le propofol a été administré à l’aide d’une pompe de perfusion et l’anesthésiste avait aussi à garder manuellement l’indice BIS le plus proche possible de 45. En fonction du BIS mesuré, la performance du contrôle exercé a été définie comme excellente pendant les moments où la valeur du BIS mesurée se situait à ±10% de la valeur cible, bonne si comprise de ±10% à ±20%, faible si comprise de ±20% à ±30% ou inadéquate lorsque >±30%. Dans le Groupe boucle fermée, le système a montré un contrôle excellent durant 55% du temps total de l’intervention, un bon contrôle durant 29% du temps et faible que pendant 9% du temps. Le temps depuis l’arrêt de la perfusion jusqu’à l’extubation est de 9 ± 3.7 min. Dans le Groupe contrôle, un contrôle excellent, bon, et faible a été enregistré durant 33%, 33% et 15% du temps respectivement et les doses ont été changées manuellement par l’anesthésiste en moyenne 9.5±4 fois par h. L’extubation a été accomplie après 11.9 ± 3.3 min de l’arrêt de la perfusion. Dans le Groupe boucle fermée, un contrôle excellent a été obtenu plus longtemps au cours des interventions (P<0.0001) et un contrôle inadéquat moins longtemps (P=0.001) que dans le Groupe contrôle. Le système en boucle fermée d’administration de propofol permet donc de maintenir plus facilement l’anesthésie au voisinage d’une cible choisie que l’administration manuelle.In the operating room, the anaesthetist performs numerous tasks. New technological tools better inform him about the state of the patient but render his task more demanding. To alleviate the anaesthetist workload, we have considered the automatic administration of anesthetic drugs using closed-loop control. In this respect, we have developed a system for the administration of an anesthetic agent (propofol) in order to maintain loss of consciousness at an optimal level throughout a surgery. The system comprises a computer, an anaesthesia monitor and an infusion pump. A control algorithm installed on the computer determines the infusion rate of the hypnotic drug based on the Bispectral IndexTM (BIS) provided by the monitor. At first, the anaesthetist chooses a target value for the control variable BIS and the algorithm, which consists of an expert system, calculates the infusion doses of propofol in order to steer the measured BIS value closer to the target value. For the user-interface of a novel anaesthesia monitor, four display types were considered: purely numeric, purely graphical, a mixed graphical and numerical and a bi-dimensional integrated graphical display. Based on 20 different scenarios where normal and abnormal anaesthesia parameters were presented to anaesthetists and residents, the study of the reaction time, response accuracy and user-friendliness (assessed by the NASA-TLX) showed that a mixed graphical and numerical display is the best preferred for the interface of the system. A clinical study was conducted in order to compare the behaviour of the system of administering propofol in closed-loop to manually controlled anaesthesia guided by BIS. After Institutional Review Board approval and written consent, 40 patients undergoing orthopaedic or general surgery were randomly assigned to 2 groups of equal size. After manual propofol induction (1.5 mg/kg), closed loop control was used to maintain anesthesia at a target BIS of 45 (Closed-loop group); in the other group, propofol was administered manually using a syringe pump by an experienced anaesthesiologist in order to maintain a target BIS of 45 as closely as possible (Control group). The performance of the system was defined as excellent, good, poor or inadequate, when the BIS was within 10%, between 10 and 20%, between 20 and 30% or outside 30% of the target BIS, respectively. In the Closed-loop group, the system showed excellent control during 55% of the total anaesthesia time, good control during 29% of the time and poor control during 9% of the time. The time from the end of infusion to extubation was 9 ± 3.7 min. In the Control group, excellent, good and poor control were noted during 33%, 33% and 15% of the time, respectively and doses were changed 9.5 ± 4 times per h. Extubation was achieved after 11.9 ± 3.3 min from the end of infusion. In the Closed-loop group, excellent control of anesthesia occurred significantly more often (P<0.0001) and inadequate control less often than in the Control group (P=0.001). The present system of administering propofol in closed-loop maintains the anesthesia level closer to a given target than manual administration

Controlo de sistemas compartimentais com incertezas

Doutoramento em MatemáticaOs sistemas compartimentais são frequentemente usados na modelação de diversos processos em várias áreas, tais como a biomedicina, ecologia, farmacocinética, entre outras. Na maioria das aplicações práticas, nomeadamente, aquelas que dizem respeito à administração de drogas a pacientes sujeitos a cirurgia, por exemplo, a presença de incertezas nos parâmetros do sistema ou no estado do sistema é muito comum. Ao longo dos últimos anos, a análise de sistemas compartimentais tem sido bastante desenvolvida na literatura. No entanto, a análise da sensibilidade da estabilidade destes sistemas na presença de incertezas tem recebido muito menos atenção. Nesta tese, consideramos uma lei de controlo por realimentação do estado com restrições de positividade e analisamos a sua robustez quando aplicada a sistemas compartimentais lineares e invariantes no tempo com incertezas nos parâmetros. Além disso, para sistemas lineares e invariantes no tempo com estado inicial desconhecido, combinamos esta lei de controlo com um observador do estado e a robustez da lei de controlo resultante também é analisada. O controlo do bloqueio neuromuscular por meio da infusão contínua de um relaxante muscular pode ser modelado como um sistema compartimental de três compartimentos e tem sido objecto de estudo por diversos grupos de investigação. Nesta tese, os nossos resultados são aplicados a este problema de controlo e são fornecidas estratégias para melhorar os resultados obtidos.Compartmental systems are widely used for modeling several processes in many fields such as biomedicine, ecology, pharmacokinetics, among others. In most practical applications, as for instance those concerning drug administration to patients undergoing surgery, the presence of uncertainties in the system parameters or in the system state is very common. Over the last several years the analysis of compartmental systems has been widely developed in the literature. However, the analysis of the sensitivity of the stability of these systems under the presence of uncertainties has received far less attention. In this thesis, we consider a state feedback control law with positivity constraints and analyze its robustness when applied to linear time-invariant compartmental systems with parameter uncertainties. Moreover, for linear timeinvariant compartmental systems with unknown initial state, we combine this control law with a state-observer and the robustness of the resulting control law is also analyzed. The control of the neuromuscular blockade by the continuous infusion of a muscle relaxant may be modelled as a three-compartment system and has been a subject of study by several research groups. In this thesis, our results are applied to this control problem and strategies for improving the obtained results are provided.FCT; POPH/FS