Nadja Bressan

A step towards effect‐site target‐controlled infusion with propofol in dogs: a ke0 for propofol

Target-controlled infusion (TCI) anesthesia using target effect-site concentration rather than plasma concentration provides less drug consumption, safer anesthesia, less undesired side effects and improved animal welfare. The aim of this study was to calculate the constant that converts propofol plasma into effect-site concentration (k(e0)) in dogs, and to implement it in a TCI system and compare it with the effect on the central nervous system (CNS). All dogs were subjected to general anesthesia using propofol. Fourteen dogs were used as the pilot group to calculate k(e0), using the t(peak) method. Fourteen dogs were used as the test group to test and validate the model. RUGLOOP II software was used to drive the propofol syringe pump and to collect data from S/5 Datex monitor and cerebral state monitor. The calculated k(e0) was incorporated in an existing pharmacokinetic model (Beths Model). The relationship between propofol effect site concentrations and anesthetic planes, and propofol plasma and effect-site concentrations was compared using Pearsons correlation analysis. Average t(peak) was 3.1 min resulting in a k(e0) of 0.7230 min(-1). The test group showed a positive correlation between anesthetic planes and propofol effect-site concentration (R = 0.69; P < 0.0001). This study proposes a k(e0) for propofol with results that demonstrated a good adequacy for the pharmacokinetic model and the measured effect. The use of this k(e0) will allow an easier propofol titration according to the anesthetic depth, which may lead to a reduction in propofol consumption and less undesired side effects usually associated to high propofol concentrations in dogs.

Modelling the dynamics of depth of anaesthesia: Cerebral state index in dogs

The goal of this study was to obtain models that described the relation between the anaesthetic drug infusions (propofol) and an electroencephalogram (EEG) derived index (Cerebral State Index -CSI) during general anaesthesia in dogs. The first phase integrated the adaptation of hardware for EEG acquisition and exploration for the best electrodes position in dogs skull. The clinical protocol implementation and data collection were the next steps followed by CSI modeling. CSI showed adequate response to changes in drug infusion, reflecting the changes of depth of anaesthesia in dogs. The models obtained adjusted well to the original CSI data and also predicted the CSI trend during surgery. Using this monitor in current practice might improve quality in the anaesthesia procedure providing a useful tool to administer a correct sedation.

Synchronization Software for Automation in Anesthesia

This work presents the development of a software for data acquisition and control (ASYS) on a clinical setup. Similar to the industrial Supervisory Control And Data Acquisition (SCADA) the software assembles a target controlled infusion (TCI) monitoring and supervisory control data in real time from devices in a surgical room. The software is not a full controller since the TCI systems comprehend permanent interaction from the anesthesiologist. Based on pharmacokinetic models, the effect-site and plasma concentrations can be related with the drug dose infused and vice versa. The software determines the infusion rates of the drug which are given as commands to the infusion pumps. This software provides the anesthesiologist with a trustworthy tool for managing a safe and balanced anesthesia. Since it also incorporates the acquisition and display of patients brain signals.

Dogs mean arterial pressure and heart rate responses during high propofol plasma concentrations estimated by a pharmacokinetic model

Propofol total intravenous anesthesia should provide stability of the cardiovascular system. In this study, mean arterial pressure and heart rate were evaluated in eight healthy dogs anesthetized with increasing rates of propofol. The cerebral state index (CSI) was studied as an additional parameter. Although the estimated propofol plasma concentration reached a maximal value of 15.3 μg ml(-1), no hypotension or bradycardia were observed. Exploration of each animals data revealed high inter-individual variability regarding mean arterial pressure and heart rate. Considering the logarithmic of the concentration, a moderate depressant effect of propofol on mean arterial pressure was revealed in five dogs but the effect was not followed on heart rate.

Target controlled infusion algorithms for anesthesia: Theory vs practical implementation

Target Controlled Infusion (TCI) systems are based in drug pharmacokinetic and pharmacodynamic models implemented in an algorithm to drive an infusion pump. Infusion control algorithms have been designed, implemented and validated for several anesthetic drugs, devices and controllers. The maintenance phase in these algorithms is represented by an equation that compensates the loss of drug from the central compartment and maintains the set target concentration. The goal of the current study was to improve existing TCI software with a new method for the maintenance phase. We compared and analyzed two different methods to find the more efficient method for the maintenance phase in an open-loop control TCI system.

Automation in Anesthesia: Computer controlled propofol infusion and data acquisition

This work presents the improvement of a software for a clinical setup, the Anesthesia Synchronization Software (ASYS). The first version presented the data acquisition from cerebral monitors and a partial control with Target Controlled Infusion (TCI) system. Based on pharmacokinetic models, the effect-site and plasma concentrations can be related with the drug dose infused and vice versa. This later version comes with the implementation of the hemodynamic monitor always present in operating rooms and with the full TCI system developed to determine the infusion rates of the drug which are given as commands to the infusion pumps.

Anaesthesia Synchronization Software: Target Controlled Infusion system evaluation

Target Controlled Infusion (TCI) systems are based in drug Pharmacokinetic (Pk) and Pharmacodynamic (Pd) models implemented in an algorithm to drive an infusion device. Several studies had compare manual titration of anesthesia and TCI system use; some studies evaluate the performance of the control algorithms for TCI systems, and a considerable number of studies assess the performance of Pk/Pd models implemented into TCI systems. This study presents a set of tests to validate the performance of a TCI system as a computer-aided. The goal of the current study was to assess the performance of the TCI system, Anaesthesia Synchronization Software (ASYS), on clinical set up to evaluate communication consistence (computer - infusion device) and controller performance in real time. These measures provided quantitative and qualitative evidences of software robustness and accuracy to be used at clinical environment.

Nonlinear Modeling of Cerebral State Index in Dogs

The Cerebral State Index (CSI) is an electroencephalogram derived signal representing the depression of central nervous activity produced by anesthetic drugs. In this study, a nonlinear model was developed to describe the CSI tendency during general anesthesia in dogs, by evaluating the effect of the anesthetic drug propofol. The model was based on a compartmental and Hill Equation structure with individually identified parameters. The clinical data of 14 dog surgeries were collected and used for modeling and testing. The model presented good results, following the CSI trend. A model for drug-effect for veterinarian anesthesia is an important step when developing advisory, educational and control systems. The overall aim is to improve animal safety and comfort.