General Anesthesia Effects Can Now Be Rapidly Reversed

Researchers from MIT and Massachusetts General Hospital are a step closer to helping patients wake up rapidly after undergoing a surgery under general anesthesia.

The paper, published on 24th October in the Proceeding of the National Academy of Sciences of the United States of America (PNAS), showed that the activation of dopamine containing neurons in the ventral tegmental area of the midbrain has a pivotal role to play under the scenario.

The research is led by Ken Solt who works as an anesthesiologist at the Massachusetts General Hospital and is also a researcher affiliated with the Department of Brain and Cognitive Sciences at MIT.

In this groundbreaking study exploring the fundamental principle of using general anesthesia for surgery, the experts studied the mechanisms which facilitated people to regain consciousness.

Which Part Of The Brain Is At Play?

Ventral tegmental area (VTA) is a major dopaminergic area (area responsible for dopamine secretion) which makes it an essential region to control various cognitive and emotional processes in the brain. It houses a network of neurons which receive information from various regions of the body and other parts of the brain.

Once VTA receives information, it directs it to the nucleus accumbens for further signal processing. Being a transit point for several signals, VTA is enriched with dopamine, which is an essential neurotransmitter.

While the functions of ventral tegmental area are diversified in nature, it is popularly known for regulating an individual’s motivation, substance addiction and motivation.

Talking about dopamine, it is known to have a strong association with cognition, thereby disrupted dopamine levels lead to psychological disorders which include schizophrenia, depression, Parkinson’s disease and attention deficit hyperactivity disorder (ADHD).

A novel association with anesthesia-triggered unconsciousness is also found to VTA after this study. By far, the events at the cellular levels following anesthesia administration are not well understood, which is why doctors know little about the exact time a patient regains post-operation consciousness. For some people the time is short, while for others regaining consciousness with normal alertness and cognitive awareness lingers on a few more hours.

This very mystery behind the working of anesthesia led the researchers to delve into understanding the entire process. In this regard, Solt said, “The process of how the neural circuits come back online following anesthesia has not really been studied in depth, and this is something that interested us from a clinical standpoint because we are investigating ways to rapidly reverse anesthesia.”

Previously, it was found that a drug for the treatment of ADHD known as Ritalin showed to help rats regain consciousness immediately after administering the drug, which were put to unconsciousness by the effect of anesthesia.

Interestingly, by now, we know that ADHD has a well-knit connection with dopamine levels and this very drug helped in symptom detection of ADHD by increasing the levels of dopamine in the brain.

An accidental finding gave the scientists their first hint pointing at the role of dopamine in stimulating alertness following anesthesia-triggered unconsciousness.

Now that the role of dopamine became central in the quest of understanding the working of anesthesia, the scientists went on to learn how precisely dopamine was involved.

For this, the scientists made use of ontogenetics which is a technique to genetically modify cells in a living system to give out light when activated. Typically used for observing the neuron functions and expressing light-sensitive ion channels in the neural cells, the technique proved to be a helpful tool for the researchers of this study, as well.

Through this technique, the scientists selectively activated dopamine neurons in VTA of mice which were under the effects of anesthesia. These modified light-sensitive neurons were activated by shining blue laser light at them.

Then dopamine releasing neurons were activated in the mice that were laying on their back under a standard dose of anesthesia. As a result, the mice regained consciousness instantly and many began to walk around soon after.

Fascinated by their findings, the researchers said that dopamine in a particular part of brain, VTA in this case, had never been associated with reversing the effects of anesthesia. This new discovery in animal model will lead them to further investigate the process in humans.

How Does General Anesthesia Work?

In layman’s terms, this type of anesthesia knocks out the whole body. On the contrary, the local anesthesia works by numbing a localized area wherein invasive procedure is to be carried out.

For carrying out serious surgeries, general anesthesia is the doctor’s choice. It keeps one to sleep so that the physiological responses to the surgical are limited during the procedure and so that the individual’s sensitivity to the aggressive pain is diminished. As the physiological responses are toned down during the surgery, the patient who is undergoing the surgery is able to maintain optimal heart rate, blood pressure and stress hormone release levels.

General anesthesia use is carefully managed by anesthesiologists. It is a mixture of inhalable gases including the derivatives of ether and nitrous oxide. While the working principle largely remains a mystery to scientists, it is believed that the anesthetics work by dissolving some fats in brain cells, which disrupts the signal pathways along the nerves and result in insensitivity to pain by stimulating neural unconsciousness.

According to the American Society of Anesthesiologists, generally the short lived side effects of general anesthesia include nausea, vomiting, confusion, sore throat, muscular pain, chills, shivering or itching. Although rarely but it can also lead to serious side effects like post-operative delirium (mental disorientation and confusion) for a few days, permanent cognitive dysfunction like reduced ability to learn, recall or concentration, Alzheimer’s disease or Parkinson’s disease or malignant hyperthermia.

Emphasizing the importance of the finding, the researchers hope that this study will help in freeing up operating room time, making facilities available for more patients and helping in reducing the side effects. Co-author Emery Brown concluded by saying, “We are trying to create a new phase for anesthesia practice in which you actively turn someone’s brain back on after having general anesthesia.”

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