With multifaceted effects from analgesia, amnesia, paralysis and loss of consciousness the mechanisms of anesthesia are still a mystery. Can tracking with EEG provide deeper insight into the experience of anesthesia and its effects?
Unimaginable today, but less than 200 years ago having surgery meant simply downing as much alcohol as possible, submitting to restraints, and then biting down on a piece of cloth to endure the immense pain of a knife ripping through your skin, muscle and bone. Limbs were sawn off, tumors removed and eyeballs were cut out this way. Many simply died from the shock, others screamed blood curdling cries throughout the procedure.
To be a surgeon back then required a different kind of skill and courage – not just speed and precision but the ability to dissociate from the patient’s pain and struggle. Some surgeons reported that going into surgery had the feeling of going to a hanging, and they entered with dry mouth and the sensation of nausea.
It was not until 1846 that the anesthetic effect of ether was discovered by dentist William Morton. On Oct 16 of that year, in a dramatic demonstration at the Massachusetts General Hospital in Boston, Morton administered ether to an apprehensive patient called Glenn Abbott about to undergo the removal of a vascular tumor in his neck. The surgeon, John Warren, performed a successful operation. Abbott never flinched or cried out. Anesthesia is not just a blessing for the patient. It is an enormous relief for the surgeon.
The Mechanism of Anesthesia
Since then numerous anesthetics have been discovered. Anesthesia has multifaceted effects that go much beyond analgesia or the blocking of pain to include various other facets such as blocking the formation of memory (amnesia), blocking muscle movement (paralysis) and even unconsciousness. Yet how they work is still unclear. Anesthetics have a wide variety of molecular structures and have been shown to have effects on a host of different kinds of receptors from GABA and NMDA receptors to more exotic targets such as nicotinic and achetylcholine receptors, as well as a host of ion channels including the ubiquitous sodium and potassium channels . More exotic theories suggest that they act by being absorbed into neuronal membranes. The question that remains is perhaps how these various mechanisms ultimately affect the overall functioning of the brain and how the different elements of functioning are related to the different facets of anesthetic effect.
In the aggregate, most anesthetics strongly inhibit neuronal activity in the thalamocortical system at concentrations that result in loss of consciousness. On the other hand, ketamine produces loss of consciousness without blocking thalamocortical information flow. At lower concentrations of anesthetics such as Propofol, there is no loss of consciousness but there is an impairment in the ability to form memories and other higher order functions. Essentially higher cognitive function in the frontal cortex is more sensitive to lower doses of Propofol than event related potentials (ERPs) generated in the auditory cortex [2, 3].
At one level the evidence suggests a hierarchical ordering of effects where higher order, more integrated functions are lost before sensory functions, after which loss of thalamocortical signaling finally renders you immobile and unconscious. It sounds good until you consider the exceptions – not just example like Ketamine, but also the rare, but very real phenomenon of awareness under general anesthesia with more standard anesthetics. A small number of people under general anesthesia experience an excruciating awareness during the surgery. Some people find themselves immobilized and free of pain and yet aware of the proceedings of the surgery. Others experience profound pain and are yet immobilized and not able to vocalize it. The experience is common enough that there is a registry and support group for patients who have had this experience. More importantly, it points to multiple levels of intra-person variability.
see related post Intra-person Variability in the EEG
EEG and Anesthesia
EEG is probably one of the most promising tools for brain monitoring during general anesthesia since it can be easily measured continuously without obstructing the surgical process. Can it eventually be used to determine the different aspects of the patient experience from amnesia to loss of sensation to loss of consciousness? Presently various metrics have been shown to roughly track subjective and metabolic assessments of consciousness such as the transition between when the patient is responsive to when they cease to be. These include changes in the power spectrum [for example 4], connectivity measures [for example 5]and entropy measures [for example 6].
see related posts Measuring Entropy in the EEG Signal
The figure below from  shows the tracking of entropy in a patient undergoing anesthesia. C-E uses a coarse graining method and didn’t work well while F-I used a moving average method and worked better
However, this is an extremely general metric and exceptions where it did not work have been reported . Quite possibly, more sophisticated analytical constructs applied across different experiences of anesthesia could eventually help better track the experience of anesthesia during surgery, and even contribute to parsing out the global signatures of the different facets from analgesia and memory loss to paralysis and loss of consciousness.
see related post Getting at Consciousness
 Shu Diao, Jing Ni, Xiaowei Shi, Peirong Liu, Wei Xia Mechanisms of action of general anesthetics, Frontiers in Bioscience 19, 747-757, January 1, 2014
 A. Veselis, R. A. Reinsel, V. A. Feshchenko and A. M. Dnistrian: A neuroanatomical construct for the amnesic effects of propofol. Anesthesiology, 97(2), 329-37 (2002)
 W. Heinke, C. J. Fiebach, C. Schwarzbauer, M. Meyer, D. Olthoff and K. Alter: Sequential effects of propofol on functional brain activation induced by auditory language processing: an event-related functional magnetic resonance imaging study. Br J Anaesth, 92(5), 641-50 (2004)
 Blain-Moraes S et al. Network Efficiency and Posterior Alpha Patterns Are Markers of Recovery from General Anesthesia: A High-Density Electroencephalography Study in Healthy Volunteers.
 Kim PJ et al Disruption of frontal-parietal connectivity during conscious sedation by propofol administration. Neuroreport. 2017 Sep 27;28(14):896-902
 Su C et al. A Comparison of Multiscale Permutation Entropy Measures in On-Line Depth of Anesthesia Monitoring. PLoS One. (2016)
 Kim YS et al Unusual elevation in Entropy but not in PSI during general anesthesia: a case report Neuroreport. 2017 Sep 27;28(14):896-902.