Sixty thousand people receive general anesthesia every day. Mass General's Emery N. Brown, MD, PhD, describes how neuroscience research will make it better.

World renowned Mass General anesthesiologist and computational neuroscientist Emery N. Brown, MD, PhD, speaks candidly about the need to improve anesthesia and how neuroscience can play a key role.

What is general anesthesia?

General anesthesia is a drug-induced, reversible state that includes unconsciousness, memory loss, immobility and elimination of pain with maintenance of stable vital functions. It is pretty wild when you think of what anesthesia allows us to do – open up a chest to repair a heart or to remove a tumor from inside someone’s brain.

Why is it important to improve anesthesia?

The ability to do surgery or invasive diagnostic procedures safely and humanely is predicated on being able to give anesthesia care. The better anesthesia is, the better surgeons and other physicians can carry out these procedures. In the U.S, more than 100,000 patients receive general anesthesia every day for surgery alone. Now, after 170 years of giving anesthesia, how anesthesia works is no longer a mystery.

“If you’re throwing up and/or your brain doesn’t work well for days or even months (after anesthesia), that’s not okay.”

What we have learned is that the anesthesia drugs create oscillations [a rapid onset of brain waves] that disrupt how the various brain regions communicate. This is an effective way of placing someone in a state of general anesthesia. However, because these oscillations are not natural they are not without consequences. Frequently, patients’ brains do not work after general anesthesia because these oscillations have created a pathological [coma-like] state that does not immediately resolve. This phenomenon, called post-operative cognitive dysfunction, is especially prevalent in patients 60 years and older.

How can neuroscience research improve anesthesia?

While most neuroscientists focus on clinical problems in disorders like Alzheimer’s, ALS, Huntington’s, stroke and epilepsy, creating anesthesia free of side effects is important in and of itself. When we were simply happy with people being alive after surgery, anesthesia was a blessing. Now that’s not good enough.

If you’re throwing up and/or your brain doesn’t work well for days or even months, that’s not okay. What we’d like is for patients to wake up, pain free and have a clear head. We owe this to them. The anesthetics are having their desired and undesired effects by acting in the brain and central nervous system. Therefore, it makes sense that we should use neuroscience to improve upon the current state of anesthesia care.

In this research we will study the entire brain, with a focus on the brainstem. One reason for studying the brainstem (the stem-like part at the base of the brain that is connected to the spinal cord) is that it is where many of the brain’s control centers are located. Our objective is to precisely control the brain circuits so that the anesthetic state exists only for the time it is needed, is rapidly turned off and the patient recovers immediately with a clear head and is pain free. Reaching this objective requires specific strategies to target brain sites, particularly ones in the brainstem.

Emery N. Brown, MD, PhD
Emery N. Brown, MD, PhD

What can be done to improve anesthesia?

Our approach breaks into two categories. Category A includes the things we can do to optimize care now. Category B is developing new approaches.

Category A has four parts, which we are working on now. Part one is finding ways to administer anesthesia care that is less dependent on opioids, to reduce or even eliminate side effects.

Part two is using the EEG to monitor the anesthetic state of the brain to guide drug dosing. An essential feature has been putting in place a web-based educational program so that all anesthesiologists can use our EEG-based approach to brain monitoring during anesthesia.

I believe that helping anesthesiologists acquire this knowledge and getting them to use the EEG-based monitoring will have an impact on anesthesia care akin to the impact on society that the broad distribution of cell phones has had. Once in place the cell phones gave rise to further unanticipated innovations. I anticipate a similar phenomenon with EEG-based monitoring. At present, anesthesiologists do not realize what is possible. The EEG-based monitoring strategy is particularly important for elderly patients who are more likely to be overdosed or to have cognitive dysfunction.

Part three is designing systems to precisely control the state of anesthesia on a second-to-second basis so that the patient does not receive too much or too little anesthesia. Imagine a computer controlling the drug infusion, as opposed to the anesthesiologist having to sit there and turn it up and down by hand. Like the autopilot system in a plane, the computer doesn’t replace the pilot — it helps the pilot be more efficient. This enhanced efficiency is critical when you have complicated surgeries that last for hours.

“Our objective is to precisely control the brain circuits so that the anesthetic state exists only for the time it is needed, is rapidly turned off and the patient recovers immediately with a clear head and is pain free.”

Part four is to actively turn the brain back on after general anesthesia. We have seen very promising results in pre-clinical experiments and our phase 1 trial with Ritalin, the drug commonly used to treat ADHD. This alone could significantly change practice.

What would philanthropy do?

If I had $15 million, I could do Category A, which will change not only anesthesiology but also have a broad impact on the other fields of clinical neuroscience.

That’s a big statement.

It’s true. I can think in very concrete terms. If you were to say, ‘Emery, show me something tomorrow,’ I would show you something tomorrow. We have developed opioid-sparing anesthesia strategies. We can teach better brain monitoring by using the EEG. We have already built and successfully tested in pre-clinical models closed loop anesthesia delivery systems. And we have compelling pre-clinical success and phase 1 success in our Ritalin testing. We simply need the resources to act on these ideas and more.

What could you do in five to ten years?

We would like to establish a Center for Neuroscience Study of Anesthesia that would call on all of the neuroscience expertise we have in our hospital. The compelling fact is that, at Mass General, the place where anesthesia was first publicly demonstrated, we have a world-class group of neuroscience researchers.

Thanks to the work of Dr. Brown’s team, how anesthesia works is no longer a mystery.
Thanks to the work of Dr. Brown’s team, how anesthesia works is no longer a mystery.

For example, since the brainstem is a part of the brain that is directly affected by anesthetics we would want to understand better what its centers are doing. These are exactly the same centers that psychiatrists need to understand to treat anxiety and depression. They are also the same centers that control sleep and regulate the body’s response to pain.

Return of brainstem activity is often critical in coma recovery. Focused study of the brainstem as a major theme of the center would provide new key information that can help all of these areas. This research would benefit directly all of the other fields of clinical neuroscience, which are neurology, psychiatry, neurosurgery and sleep medicine.

There are other groups conducting anesthesiology research. But no other place views anesthesiology as a critical clinical neuroscience discipline. Nowhere else has comparable departments of anesthesiology, neurosurgery, neurology and psychiatry in one institution. Each of our departments is a world leader. By working together, we could have a synergistic effect.

The other inspiring fact is that most of the investigators in our group are young — instructors, assistant professors and associate professors. They trained and stayed at Mass General because they want to do something that’s going to be truly transformative. We would be enabling the careers of people who have the capacity to change medicine.

Any final thoughts?

The bottom line is — we are grateful for anesthesia. Its advent 170 years ago has enabled transformative progress in patient care. However, anesthesia care is critical medical and surgical infrastructure, which unfortunately, like other types of infrastructure is often overlooked.

“Anesthesia care is critical medical and surgical infrastructure, which unfortunately, like other types of infrastructure is often overlooked.”

For example, a door is critical infrastructure for any building. But when you walk in through a door, you don’t say, ‘thank you door, I’m glad you opened up’ — you just walk through. However, without the door you could not civilly enter the building. The door continues to age, but it still opens. At some point the door needs to be replaced along with the other structures that make up the building. This is why we have building campaigns.

We realize that just as hospital buildings or a city subway system becomes old and needs to be replaced, we need to update and innovate our anesthesia care infrastructure. The exciting fact is that we can, for the first time, rebuild the anesthesia care infrastructure by using an entirely new neuroscience-based design. This neuroscience-based anesthesia care will enable the next wave of transformative progress in patient care.

Sixty-thousand people a day have surgery in the United States. Nearly forty thousand surgeries are performed per year at Mass General. These new innovations will have far-reaching impact not only on anesthesiology and surgery, but also on other fields of clinical neuroscience.

For more information, or to support anesthesia research at Mass General, please contact us.