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Abstract Background The wide range of fresh gas flow - vaporizer setting (FGF - FD) combinations used by different anesthesiologists during the wash-in period of inhaled anesthetics indicates that the selection of FGF and FD is based on habit and personal experience. An empirical model could rationalize FGF - FD selection during wash-in. Methods During model derivation, 50 ASA PS I-II patients received desflurane in O2 with an ADU® anesthesia machine with a random combination of a fixed FGF - FD setting. The resulting course of the end-expired desflurane concentration (FA) was modeled with Excel Solver, with patient age, height, and weight as covariates; NONMEM was used to check for parsimony. The resulting equation was solved for FD, and prospectively tested by having the formula calculate FD to be used by the anesthesiologist after randomly selecting a FGF, a target FA (FAt), and a specified time interval (1 - 5 min) after turning on the vaporizer after which FAt had to be reached. The following targets were tested: desflurane FAt 3.5% after 3.5 min (n = 40), 5% after 5 min (n = 37), and 6% after 4.5 min (n = 37). Results Solving the equation derived during model development for FD yields FD=-(e(-FGF*-0.23+FGF*0.24)*(e(FGF*-0.23)*FAt*Ht*0.1-e(FGF*-0.23)*FGF*2.55+40.46-e(FGF*-0.23)*40.46+e(FGF*-0.23+Time/-4.08)*40.46-e(Time/-4.08)*40.46))/((-1+e(FGF*0.24))*(-1+e(Time/-4.08))*39.29). Only height (Ht) could be withheld as a significant covariate. Median performance error and median absolute performance error were -2.9 and 7.0% in the 3.5% after 3.5 min group, -3.4 and 11.4% in the 5% after 5 min group, and -16.2 and 16.2% in the 6% after 4.5 min groups, respectively. Conclusions An empirical model can be used to predict the FGF - FD combinations that attain a target end-expired anesthetic agent concentration with clinically acceptable accuracy within the first 5 min of the start of administration. The sequences are easily calculated in an Excel file and simple to use (one fixed FGF - FD setting), and will minimize agent consumption and reduce pollution by allowing to determine the lowest possible FGF that can be used. Different anesthesia machines will likely have different equations for different agents.

Continuous sedation at the end of life is a practice that has attracted a great deal of attention. An increasing number of guidelines on the proposed correct performance of the practice have been drafted. All of the guidelines stress the importance of using sedation in proportion to the severity of the patient's symptoms, thus to reduce the patient's consciousness no more than is absolutely necessary. As different patients can have different experiences of suffering, the amount of suffering should, ideally, be assessed subjectively; that is, via communication with the patient. Continuously sedated patients are often unable to communicate, however, making subjective methods of pain assessment unusable. For these patients, the degree of consciousness is the sole available measure. It therefore seems important to adequately measure how deeply the patient is sedated, thereby allowing sedation to be increased when it is too light and decreased when it is too heavy. This is in accordance with the idea that reducing consciousness is not an ethically neutral act. Although consciousness measuring techniques are a hot topic in anesthesiology, almost no research exists on the use of such techniques in the context of continuous sedation at the end of life. This article aims to review existing techniques to measure consciousness and to evaluate their applicability, efficiency, and invasiveness for patients who are continuously sedated until death. Techniques commonly used to assess the depth of sedation in continuously sedated patients are basic clinical assessment and sedation scales, as they are often considered reliable and non-invasive. These techniques might not be very reliable, however, since it is known that some patients are nonresponsive and yet aware. Moreover, sedation scales require stimulation of the patient (for example prodding, shaking, or providing painful stimuli), and can thus be considered invasive of one's bodily integrity or dignity. Other techniques, such as EEG (electroencephalography) derivatives, may score better on reliability and invasiveness. Yet these have so far never been compared to sedation scale scores for patients receiving continuous sedation at the end of life. Therefore, we conclude that, for both clinical and ethical reasons, research into the efficiency and applicability of other techniques, such as derivatives of EEG, are urgently needed. [ABSTRACT FROM AUTHOR]

Closed-loop systems are able to make their own decisions and to try to reach and maintain a preset target. As a result, they might help the anaesthetist to optimise the titration of drug administration without any overshoot, controlling physiological functions and guiding monitoring variables. Thanks to the development of fast computer technology and more reliable pharmacological effect measures, the study of automation in anaesthesia has regained popularity. This short review focuses on the most recently developed and tested feedback systems in anaesthesia. Various new approaches for controlling the administration of intravenous and inhaled hypnotic–anaesthetic drugs have recently been published. For analgesics, a framework for further research has been presented in the literature. For other drugs, such as muscle relaxants and haemodynamic agents, only short reviews can be found. Until now, most of these systems have had to be under development. The challenge is now fully to establish the safety, efficacy, reliability and utility of closed-loop anaesthesia so that it can be adopted in the clinical setting. Besides, their role in optimising the controlled variables and control models, these systems have to be tested in extreme circumstances in order to test their robustness. [Copyright &y& Elsevier]

The article focuses on a study which examines the interaction between propofol and sevoflurane with the use of a response surface methodology. In this study, 60 patients preoperatively receive different combined concentrations of propofol and sevoflurane. It discovers that the interaction of propofol and sevoflurane is determined as additive for both electroencephalographic suppression and tolerance to stimulation. It suggests that response surface data can be applied for rational dose finding when it comes to propofol and sevoflurane administration.

The article focuses on a randomized study which examines the impact of administration rate on early phase kinetics and dynamics of propofol with the use of structural pharmacokinetic model. In this study, 50 patients are randomized to receive propofol and arterial blood samples are taken. Four basic pharmacokinetic models are compared and a sigmoidal maximum possible drug effect pharmacodynamic model is examined. It concludes that a combined pharmacokinetic-dynamic model describes the early phase pharmacology of propofol.