Anesthesia and its effect on the EEG
Anesthesia is one of the most valued discoveries in all of history. Almost immediately after the first public demonstration of ether anesthesia, a search for a better drug began. Ether, despite its flammability, persisted as the primary inhalation agent for over a hundred years. The breakthrough came with the introduction of a non-flammable volatile anesthetic called halothane in 1955. The FDA approved the drug in 1958, and it quickly became the most commonly used agent in the United States. It was a quantum leap forward in the safety of anesthetic drugs. It became obsolete in 1988 because of hepatotoxicity.(1) In 1950, researchers sought to study the effect of anesthetic gases and anesthesia on consciousness via the EEG (electroencephalogram) analysis, which measures and analyses cortical activity and has been studied since the first human EEG recordings were made in 1924 (2). The effect of anesthetic drugs on cortical potentials is complex, and it changes with the drug employed. They noted that EEG change in frequency accompanied deepening anesthesia. They felt that the constancy of the relationship between the electrical energy output of the cortex and the depth of anesthesia suggested the possibility of employing brain potentials to regulate the dose of the anesthetic agent so that an entirely automatic administration might be achieved. They proposed that the constancy of the relationship between the electrical energy output of the cortex and the depth of anesthesia suggested the possibility of employing brain potentials to regulate the dose of the anesthetic. (3) The circuit diagram for this apparatus shows how the brain potentials derived from the frontal and occipital areas of the scalp are amplified and activate the stepping relay, which causes the rotations of the threaded shaft, which engages a threaded block that presses on the plunger of the syringe injecting the anesthetic agent.(3)
Early EEG driven anesthesia system
They proceeded to build the apparatus and test it on a cat. The researchers proposed that because of its feedback cycle, the apparatus has some of the properties of a homeostatic system, and it would compensate for factors that disturb the equilibrium. In the example they gave, if the anesthetic mixture is diluted or a leak develops in the intravenous tube, the machine automatically increases its rate of administration in an attempt to compensate for these changes. In 1950 they postulated that it would be possible to keep animals and humans automatically anesthetized without any readjustment of the circuit controls and thought that the system could compensate effectively for the changes occurring under these conditions. (3)
The use of BIS for anesthesia management
In 1987 the report on a controller of an ON/OFF type for halothane anesthesia was published. They noted that a proportional-plus-integral controller with time-delay compensation proved not to be robust enough for the known clinical situation, as shown both in computer simulations and in animal trials. Thus, the ON/OFF controller proved to be less sensitive to parameter mismatches, and repeated animal trials showed a short response time and acceptable steady-state tracking. A method for switching the controlled effect of the drug was also developed since anesthetic agents have multiple effects. Mean arterial blood pressure and a measure of EEG frequency were chosen as controlled variables, both being depressed by halothane. They described a coordinator, which forces the system state as near the desired values of these variables as possible, given that only one drug was used. (4) The Bispectral Index (BIS) is an electroencephalogram-derived measure of anesthetic depth. (5) In 2002, a closed-loop anesthesia system was built using BIS as the control variable, a proportional-integral-differential control algorithm, and a propofol target-controlled infusion system as the control actuator. Closed-loop performance was assessed in 10 adult patients. The system was able to provide clinically adequate anesthesia in 9 of 10 patients. (6) The same researchers revised the closed-loop infusion system in patients undergoing minor surgery under propofol and remifentanil anesthesia. They improve the control algorithm by taking into account the effect-site steering. They found that the system could provide clinically adequate anesthesia in all patients, with better accuracy of control than in the previous study. There was a tendency for more accurate control in those patients in whom the control algorithm incorporated effect-site steering. (6)
Closed loop anesthesia system
The development of electroencephalographic indices of anesthetic depth has generated interest in automated anesthesia delivery systems using these as the input variable. A patented closed loop anesthesia delivery system (CLADS) (502/DEL/2003) was is compared in a study manual control of propofol delivery titrated to the bispectral index (BIS). Forty ASA I-II patients undergoing elective surgery under general anesthesia were enrolled in the study. The study participants were randomized using computer generated random numbers to two equal groups. One group received propofol titrated by the CLADS while in the other group (control), anesthetic delivery was manually titrated to BIS. In the study closed loop anesthetic delivery of that system led to lower induction doses of propofol and less overshoot of the target BIS. Smaller amounts of anesthetic agent were required and there was faster postoperative recovery. They concluded that automated delivery of propofol adjusted to the bispectral index using our CLADS was both effective and efficient as compared to manual control. (7)
McSleepy and ruled-baed closed-loop systems
A group in Canada proposed and evaluated the performance of a rule-based adaptive closed-loop system for propofol administration using the bispectral index (BIS(R)) and to compare the system's performance with manual administration. They determined the effectiveness of the closed-loop system in maintaining BIS close to a target of 45 vs. manual administration. They proposed that in their study, the closed-loop system for propofol administration showed better clinical and control system performance than manual administration of propofol. This paper references McSleepy®, an automated system created by the same author that integrates all three components of anesthesia - hypnosis, analgesia, and muscle relaxation. It had a user interface that showed combined graphical-numerical elements(8)
Commercial Anesthesia system for sedation
In 2011, a review about the SEDASYS CAPS system (Ethicon Endo-Surgery Inc, Cincinnati, Ohio), came out. This system was designed to facilitate the safe administration of 1% propofol-based minimal to moderate sedation to relatively healthy adults (ASA physical status I and II) undergoing elective colonoscopy or EGD, by an endoscopist-nurse team whose members are not trained in general anesthesia. It is not intended for administration of deep sedation or general anesthesia, or administration of any level of sedation to high-risk patients. The system was designed to comply with the practice guidelines for sedation and analgesia by non-anesthesiologists developed by the ASA,10 as well as the dosing guidelines in the U.S. Food and Drug Administration (FDA)–approved propofol labeling. The Anesthesiology and Respiratory Therapy Devices Advisory Panel of the FDA voted in favor of approval of the SEDASYS system in May 2009. However, in April 2010, the manufacturer received a not-approvable letter from the FDA. The manufacturer appealed this decision, and the FDA has granted the appeal.11 A new independent advisory panel will be appointed to reconsider the clinical trial data. The device has been approved in Canada for sedation of patients undergoing colonoscopy, in Australia for sedation of patients undergoing colonoscopy and EGD, and in May 2010 was granted the Conformité Européene (CE) mark of approval in the European Union for use during routine colonoscopy and EGD. With this sytem physiological patient data (oxygen saturation, capnometry, respiratory rate, heart rate, blood pressure, electrocardiography, and patient responsiveness) are monitored continuously by the device. The device then processes these physiological data and, using a computerized drug delivery algorithm, is able to titrate sedation by varying the propofol infusion and administering boluses of propofol. It is also able to increase oxygen delivery in response to hypoxemia and apnea.(9) The idea of robotic anesthesia was outlined by the creator of McSleepy™ in 2011. He wrote that in order to create a true Anesthesia robot, all three components of anesthesia, hypnosis, analgesia, and muscle relaxation, need to be controlled automatically, from induction to emergence. 'McSleepy' integrates closed-loop control of all three components of general anesthesia with a user interface where the anesthesiologist can choose between fully automated or semi-automated control (manual control of one or more components). Its setup on a touch screen starts with communication with the user: the user needs to put in relevant patient data, such as weight, age, height, ASA classification, but also information such as the type of surgery, whether the patient takes specific drugs which might interact with the system control, e.g., beta-blocking agents, or any additional information concerning the pain control, e.g., concomitant neuraxial anesthesia. In fully automated mode, the system will then induce anesthesia using remifentanil, propofol, and rocuronium or cisatracurium. (10)
1. Giesecke AH. First use of halothane in the United States, C. Ronald Stephen, M.D. (1916-2006). Bull Anesth Hist. 2008 Aug;26(2):1, 4; discussion 5.
2. Nunez PL, Srinivasan R. Electroencephalogram. Scholarpedia. 2007 Feb 4;2(2):1348.
3. Bickford RG. Automatic electroencephalographic control of general anesthesia. Electroencephalography and Clinical Neurophysiology. 1950 Jan 1;2(1):93–6.
4. Kraft HH, Lees DE. Closing the loop: how near is automated anesthesia? South Med J. 1984 Jan;77(1):7–12.
5. Mathur S, Patel J, Goldstein S, Jain A. Bispectral Index. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Apr 23]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK539809/
6. Absalom AR, Sutcliffe N, Kenny GN. Closed-loop control of anesthesia using Bispectral index: performance assessment in patients undergoing major orthopedic surgery under combined general and regional anesthesia. Anesthesiology. 2002 Jan;96(1):67–73.
7. Puri GD, Kumar B, Aveek J. Closed-loop anaesthesia delivery system (CLADS) using bispectral index: a performance assessment study. Anaesth Intensive Care. 2007 Jun;35(3):357–62.
8. Hemmerling TM, Charabati S, Zaouter C, Minardi C, Mathieu PA. A randomized controlled trial demonstrates that a novel closed-loop propofol system performs better hypnosis control than manual administration. Can J Anaesth. 2010 Aug;57(8):725–35.
9. ASGE Technology Committee, Banerjee S, Desilets D, Diehl DL, Farraye FA, Kaul V, et al. Computer-assisted personalized sedation. Gastrointest Endosc. 2011 Mar;73(3):423–7.
10. Hemmerling TM, Taddei R, Wehbe M, Morse J, Cyr S, Zaouter C. Robotic Anesthesia – A Vision for the Future of Anesthesia. Transl Med UniSa. 2011 Oct 17;1:1–20.