Horst Stoeckel

Closed-loop feedback control of methohexital anesthesia by quantitative EEG analysis in humans.

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital anesthesia in 13 volunteers. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Median frequency values from 2–3 Hz were chosen as the desired EEG level (set-point). In 11 volunteers, the feedback system succeeded in maintaining a satisfactory depth of anesthesia (i.e., unresponsiveness to verbal commands and tactile stimuli). During feedback control, 75% of all measured median frequency values were in the preset range of 2–3 Hz. This distribution of median frequency was obtained by applying random stimulation (six different acoustic and tactile stimuli) to the volunteers approximately every 1.5 min. The decrease of median frequency from baseline to anesthetic values was primarily induced by increasing the fractional power in the frequency band of 0.5–2 Hz from 12.6 ± 4.5% (mean ± SD) to 46.0 ± 2.5%. The median time to recovery (as defined by opening eyes on command) after cessation of the feedback control period was 20.6 min (10.7–44.5 min) when median EEG frequency was 5.2 Hz (4.7–8.4 Hz). The average requirement of methohexital (mean ± SD) during the 2 h was 1.02 ± 0.16 g. It is concluded that pharmacokinetic-pharmacodynamic models of intravenous anesthetics established previously may be used to form a suitable background for model-based feedback control of anesthesia by quantitative EEG analysis. This approach gives a possible solution to the problem of adapting pharmacokinetic and pharmacodynamic data to individuals when using population mean data as starting values for drug therapy.

The effects of a benzodiazepine antagonist Ro 15-1788 in the presence of stable concentrations of midazolam.

The benzodiazepine antagonist Ro 15–1788 was administered in a 10-mg intravenous bolus dose to seven healthy young adult volunteers to evaluate the drugs efficacy and duration of action against midazolam. A steady state serum concentration of midazolam was obtained by an initial fast infusion rate of 6.0 mg/min (duration: 10 min) and a maintenance infusion rate of 0.275 mg/min. After administering the antagonist, all subjects opened their eyes without any command in a median time of 36 s (range: 28–48 s). Their personal, temporal and local orientation was reestablished within 54–120 s (median time: 65 s). The subjects fell deeply asleep, again in a median time of 145 min (range: 115–150 min), which was interpreted as an indication of the returning action of midazolam, which was infused for a total period of 210 min. Ro 15–1788 deserves further study as an antagonist, since it could prove useful in the management of benzodiazepine overdosage and in the reversal of benzodizepine action following surgical anesthesia and in the intensive care.

Endobronchial instillation of epinephrine during cardiopulmonary resuscitation

We used a standard animal CPR model to study the effectiveness and hemodynamic response of 100 micrograms/kg epinephrine administered endobronchially and to compare the findings after conventional iv administration. Results showed that the endobronchial and iv epinephrine medication improved the survival rate by 100% compared to that of a control group receiving no medication. Although the hemodynamic conditions during cardiac compression were not significantly different after both routes of drug administration, endobronchial instillation produced a prolonged drug action during the first hour of restored spontaneous circulation. A more extensive use of this type of drug administration, especially in out-of-hospital resuscitation, is suggested.

Effective therapeutic infusions produced by closed-loop feedback control of methohexital administration during total intravenous anesthesia with fentanyl.

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital delivery during total intravenous anesthesia with fentanyl in 11 surgical patients. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Based on previous investigations a median frequency from 2-3 Hz was chosen as the desired EEG set point. In addition to methohexital, patients were given a 10-min loading infusion of 0.5 mg of fentanyl followed by a constant-rate infusion of 0.22 mg/h. In agreement with an earlier similar study in volunteers given only methohexital and aiming at the same set point, identical distribution of EEG power was achieved in the current study. The decrease of median EEG frequency to 2-3 Hz was primarily induced by an increase in fractional power in the 0.5-2- Hz frequency band to 46 +/- 4%. The average requirement of methohexital during the first 2 h was 675 +/- 250 mg. The authors conclude that model-based feedback control of intravenous methohexital delivery can help establish and quantitate methohexital requirements during total intravenous anesthesia with fentanyl.

Control and automation in anaesthesia

I General Methods of Control and Automation.- Decision Support via Fuzzy Technology.- Principles of Adaptive Neural Networks for Control.- Artificial Intelligence and Expert Systems.- II Assessment and Evaluation of Signals and Measurements.- a) Anaesthesia Machine Monitoring.- Which Monitoring Qualities Ensure Proper Machine Function?.- Reliability, Testability, Alarms, and the Fail-Safe Concept.- The Differences Between Closed-circuit, Low-flow, and High-flow Breathing Systems: Controllability, Monitoring, and Engineering Aspects.- b) Therapeutic Monitoring of Patients.- Does the EEG Measure Therapeutic Opioid Drug Effect?.- Somatosensory Evoked Potentials: Objective Measures of Antinociception in the Anaesthetized Patient?.- Do Auditory Evoked Potentials Assess Awareness?.- Should Neuromuscular Transmission Be Monitored Routinely During Anaesthesia?.- III Control and Automation of Artificial Ventilation.- Pulmonary Function and Ventilatory Patterns During Anaesthesia.- What Can and What Should Be Controlled During Artificial Ventilation?.- Closed-Loop Control of Artificial Ventilation.- IV Control and Automation of Drug Delivery.- a) Volatile Anaesthetics.- Adaptive Closed-Loop Control of End-Tidal Concentrations of Volatile Agents.- Fuzzy Control of Arterial Blood Pressure by Volatile Anaesthetics.- Model-based Adaptive Control of Volatile Anaesthetics by Quantitative EEG.- b) Intravenous Anaesthetics.- The Target of Control: Plasma Concentrations or Drug Effect.- Open-Loop Control Systems and Their Performance for Intravenous Anaesthetics.- Feedback Control of Intravenous Anaesthetics by Quantitative EEG.- Adaptive Control of Intravenous Anaesthesia by Evoked Potentials.- c) Neuromuscular Blocking Agents and Vasoactive Drugs New Drug-Delivery Devices.- Model-based Adaptive Control of Neuromuscular Blocking Agents.- Supervisory Adaptive Control of Arterial Blood Pressure by Vasoactive Agents.- New Drug-Delivery Devices for Volatile Anaesthetics.- New Drug-Delivery Systems for Intravenous Anaesthetics.- V Nonmedical Aspects of Automated Control: Requirements and Liability for Automated Systems.- The Technical Point of View.- Regulatory Aspects.- The Manufacturers Point of View.