General Anesthesia Causes Patterns of Brain Activity.

Drugs lead to predictable large-scale changes in brain waves that can help anesthetists assign anesthesia and develop narcotic therapies.

Before the advent of general anesthesia in the mid-nineteenth century, surgery was a painful experience for everyone involved: the patient, of course, but also the medical staff and anyone who walked by the surgery room and could hear the Scream. The practice of putting patients in a coma-like state has changed surgery to humane treatment and often saves lives. Because general anesthesia was a change in the game, these medications were implemented in the operating room several decades before the researchers understood how they worked.

Currently, researchers and anesthetists know a lot about the underlying mechanisms behind the effects of narcotics and how they produce a profound change in the state of behavior, which means a complete lack of perception. Anesthetics work mainly in receptors in the brain and produce oscillations in the circuits of the brain, leading to a state of consciousness very similar to coma on sleep. Anesthesiologists often use vital signs, such as heart rate and blood pressure, to assess the suitability of the narcotic and the treatment of pain signals. However, the effects of anesthesia on brain circuits lead to clear oscillations in brain electrical activity, leading to the addition of an electroencephalogram (EEG) to monitor the brain state of an anesthetized patient.

Beginning in the 1990s, researchers developed algorithms to standardize the signals of multiple EEG electrodes into a single number that provides a simplified measure of the level of excitation. Recently, direct observation of EEG signals and their timely disintegration by frequency, spectroscopy, traction acquisition to control patients during general anesthesia. Learning to interpret raw brain activity and its spectral program, rather than relying on a one-digit summary, has allowed anesthesiologists to evaluate the effect of different anesthesia on brain activity and anesthesia production.

By tracking brain activity during general anesthesia, researchers also discover a wealth of new information that helps them understand the basic biological concepts of how to change brain functions in the case of anesthesia. In addition, general anesthesia offers new options to treat a variety of diseases, from sleep problems to depression.

Ether follies

People have had surgery for thousands of years and may have been looking for ways to reduce pain and discomfort during invasive procedures. Wine and opium are among the first to be tested. Opium is a strong and mild analgesic, and ethyl alcohol in wine is analgesic, but none of these medications makes patients not aware of the trauma in their bodies during surgery.

In the first half of the nineteenth century, dentists found two promising formulas: nitrous oxide, which was widely used in the United States and Europe for tooth extraction, and chloroform, which was used in veterinary and human operations a few decades ago. Due to security concerns. In the 1840s, the Boston dentist, William Morton, was looking for ways to perform painless dental procedures and was thinking about using nitrous oxide. But nevertheless

Charles Jackson, a chemist at Harvard Medical School, advised him to try another option: ether.

At that time, it was common in the academic world and in other social circles to hold parties, called “ether follies”, where people inhale the ether due to its charming properties. Jackson had seen a man with a large leg injury during one of the allegations. The man, who was high in the ether, showed no signs of pain. Morton followed Jackson’s advice and proceeded to test the ether with him and his dog, and then performed many dental procedures on his patients after administering medications.

Morton contacted Harvard Medical School, Henry Bigelow, and organized what became known as the first public demonstration of surgery performed under general anesthesia. On October 16, 1846, in the operating room now known as the Atheroscope at the Massachusetts General Hospital, John Collins Warren, the founding dean of Harvard Medical School and the hospital’s chief surgeon, extracted a tumor from the neck of the patient Edward. Gilbert Abbott, while Morton was carrying a glass bottle containing ether vapor was emitted through a glass tube installed in Abbott’s nose. He saw many surgeons and prominent doctors from the observation area in the theater.

Warren performed a surgical operation with the patient who showed minimal signs of pain; 2 at the end of the operation, Warren declared famous: “Gentlemen, this is not nonsense”. After that, Abbott stated that he suffered feelings, though not pain, during the surgery. The next day, defects in the intake of ether were corrected, and a second patient announced the removal of the tumor he felt and knew nothing. The surgery was performed under anesthesia with ether in nearby hospitals, and in a few months began to change the medical practice around the world.

The modern definition of general anesthesia requires five endpoints. (See box above). The ether provides all these endpoints fairly. Most modern anesthetic anesthetics, such as isoflurin, disfluoran and cefoflurin, are chemical derivatives of ether, but are more effective and less flammable and are administered with evaporators and modern technologies. Improvements in the subcutaneous needle achieved in the second half of the nineteenth century allowed the development of intravenous anesthesia, and doctors began to combine anesthetics with opiates to achieve more effective analgesia. Later, muscle relaxants were added to ensure inertia.

The modern practice of general anesthesia, known as balanced anesthesia, uses groups of medications to keep the patient away from the trauma of the body and minimize side effects. More recently, researchers have detailed the mechanism behind modern anesthesia, identifying the links between neural receptors in which drugs work and patterns of brain activity associated with changes in neural activation. These links allow anesthesiologists to track brain activity patterns during general anesthesia to improve patient experiences and outcomes, as well as to learn more about how anesthesia works.

How Is General Anesthesia Achieved?

One of the most obvious characteristics of general anesthesia is the profound state of unconsciousness. Until the 1980s, the predominant hypothesis on how to achieve loss of consciousness was affected by the observation that the strength of anesthesia is directly related to the fusion in olive oil, suggesting a hydrophobic site of water, as the lipid membranes of two layers of neurons. The researchers speculated that drugs interrupt the function of natural membranes and prevent the delivery of work potential. This idea was known as the fat hypothesis. Nicholas Franks and William Leap, from Imperial College London, showed that the real targets of anesthetics are the receptors of the neurons in the membrane.

Neural receptors regulate the possibility that neurons can release movement, often controlling the channels of certain ions to enter and exit neurons. The activation of excitatory receptors increases the likelihood of nerve cell release, while the activation of inhibitory receptors decreases. Therefore, anesthetics can, in principle, be divided into two main categories: those that activate the inhibitory receptors and those that inhibit the excitation receptors. (See illustration)

Inflammatory ether derivatives and intravenous propofol, the most commonly used anesthetic drugs, are associated with GABAA inhibitory receptors. Under natural and physiological conditions, the receptor is activated by gamma-aminopic acid (GABA) released by inhibitory neurons, allows chloride ions to flow into the cell and decreases the relative voltage within the plants of the neurons, which reduces the probability of triggering the probability of operation. Narcotics directed to this future act as stimulants to improve the flow of chloride ions, which further suppresses the ability of the cell to shoot.

Other anesthetics, such as ketamine, which was manufactured in 1962, and nitrous oxide (N2O) act on blocking the N-methyl D-aspartate (NMDA) receptor channel. NMDA receptors are naturally activated by the neurotransmitter glutamate emitted by excited neurons, allowing the flow of extracellular potassium ions and calcium and sodium ions, which increases the relative voltage within the plants of neurons and, therefore, therefore, the probability of releasing the movement potential increases. Narcotic drugs aimed at this future act as opponents to prevent the flow of these ions, which reduces the ability of the cell to shoot.

However, knowing the behavior of narcotics in the receptors does not fully explain how unconsciousness occurs. Both GABA and NMDA receptors were found in inhibitory and inhibitory neurons that form neural circuits. The function of these circuits and their relation to behavior within systems neuroscience can be understood: the changes in the ion fluxes that result from receptor binding to receptors greatly alter the activity of neurons throughout the brain, which produces highly regulated oscillations. In humans, these oscillations are easily visible in EEG readings. They are of great amplitude and fall within well defined frequency bands that are smaller than the oscillations of low amplitude that are seen in the brain of the conscious person.

The observed waves depend critically on the associated receptors and on how the target regions are related to other areas of the brain. The frequencies fluctuate regularly with the class of drugs, the dose of medication and the age of the patient. For example, the alpha oscillations (8 to 12 Hz) produced by GABAergic lethal anesthetics depend fundamentally on the connections between the thalamus and the cortex.4 The beta / gamma fluctuations (15-50 Hz) produced by ketamine 5 can oscillate. NMDA receptors inhibit the excitatory neurons in the cortex, while the slow oscillations produced by the antagonists of GABA 6.7 and NMDA may depend on the inhibition of the brainstem and its projections to the thalamus and cortex. Older patients have lower amplitude oscillations in all frequency bands. These oscillations also change dramatically when neurons can increase, preventing communication between regions of the brain that play a role in consciousness.

The properties of the oscillations resulting from anesthesia indicate that they are an important part of the mechanism of anesthesia and explain how the brain state of the patient can be controlled reliably under the EEG. However, the monitoring of brain activity was not standard in the practice of anesthesia. Early attempts to use the EEG as an additional piece of information to monitor patients and report the dose and rate of narcotic administration focused on the development of an index would provide a single reading for anesthesia. However, the EEG activity observed during general anesthesia varies between people of different ages, and these indicators can be deceptive when used in children or the elderly. In addition, EEGs under general anesthesia vary according to the drug, and the indicators collected can not take these differences into account.

For these reasons, anesthesiologists have begun in recent years to monitor EEG readings of brain signals during procedures that include general anesthesia. Oscillation patterns can be identified for the trained eye’s articular anesthesia, and its real-time frequency evaluation can be performed with computer assistance, which provides a more accurate picture of the patient’s brain state. This allowed physicians to administer doses of drugs more accurately and reduce the amount of anesthesia needed to achieve the same medication condition. 8 As we understand more about how anesthesia works and gain more experience in monitoring EEGs generated directly during anesthesia, the practice will continue to improve.

General Anesthesia As A Treatment.

In recent decades, research on patterns of brain activity and general anesthesia has produced ideas not only about the effects of anesthesia itself, but also on neurotransmissions related to conditions in which brain oscillations such as aging are altered and the disease, including autism. 10 In addition, it has been shown that methylhexetal and fentanyl anesthetics are useful for stimulating seizure activity in the brains of patients with epilepsy, which helps neurosurgeons determine the exact tissue. Developments in this area also suggest that anesthesia can be used as a treatment for a handful of brain-related conditions.

This concept is not entirely new. For example, during general anesthesia and coma, an EEG pattern known as explosion suppression is observed. This pattern consists of bursts of electrical activity alternating with flat periods of inactivity. Neurosurgery often uses anesthesia to induce a medical coma in patients with difficult-to-treat seizures or intracranial pressure to stop seizure activity or reduce inflammation of the brain. The coma is maintained by observing the EEG and by calibrating the speed of the anesthesia pump to maintain a certain number of bursts per minute. This procedure usually requires a human being to evaluate the rate of explosion suppression and manually adjust the anesthetic dose, but our research indicates that complete automation of this process is possible.

Other areas where ideas about the neural mechanisms of anesthesia can help improve treatment options include sleep. The dream consists of two main stages: rapid eye movement (REM) and a different dream of rapid eye movement (REM). Sleeping without rapid movements of the eyes is a state of profound unconsciousness that scientists consider the most important to achieve a comfortable sleep properly.

Sleeping without rapid eye movements is characterized by two main types of oscillations of brain activity: sleep spindles (10-15 Hz) and slow oscillations. Most medicines that help to sleep do not produce fluctuating brain activity as the activity observed during normal sleep. However, the anesthetic dixemidomidine, which affects the circuits in the brainstem and is involved in surveillance control, electrocardiogram patterns similar to those that occur during sleep other than rapid eye movements. Clinical trials are being conducted to test its effectiveness as an auxiliary sleep.

It has already been shown that anesthetics such as ketamine, zinone and nitrous oxide have serious antidepressant effects. There is evidence that other anesthetics, such as isoflurine and propofol, when ingested at the level of impulse suppression production that refers to a medical coma, have long-lasting antidepressant effects without short-term cognitive impairment and associated memory loss. with electro-shock therapy. Ketamine can exert its antidepressant effect by increasing the number of interlaced receptors and other interlaced signaling proteins, and even increasing the number of neuronal connections in the brain.

More than 170 years after the first public demonstration, general anesthesia allows millions of non-painful surgeries to be performed every day throughout the world and the basic basis for most surgeries remains. At the same time, the study of the effects of anesthesia on brain function opens up many interesting opportunities to develop new models of narcotics and explore other issues in clinical neuroscience.

Emery Brown is professor of anesthesia Warren M. Zabol at the Harvard Medical School, an anesthesiologist at the Massachusetts General Hospital and professor of medical engineering and neuroscience at Edward Hood at the Massachusetts Institute of Technology. Francisco j. Flores is an anesthesiologist at Massachusetts General Hospital and Harvard Medical School.


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