Published by
Stanford Medicine



Anesthesiology, Neuroscience, Research, Stanford News, Surgery

Stanford anesthesiologist explores consciousness – and unconsciousness

Stanford anesthesiologist explores consciousness - and unconsciousness

face-275015_1280Anesthesiologist Divya Chander, MD, PhD, is one of a leading group of neuroscientists and anesthesiologists who are using high-tech monitoring equipment in the operating room to explore the nature of consciousness – which isn’t quite as simple as on or off, asleep or awake.

Stanford Medicine magazine profiled Chander’s work last summer, but I came across it when the title of one of Chander’s recently published papers grabbed my eye: “Electroencephalographic Variation During End Maintenance and Emergence from Surgical Anesthesia.” Okay, that might not pique your curiosity, but when I spotted the words, “for the first time” in the abstract I was hooked. I read on to learn that Chander and her team attach electrodes to the foreheads of patients during surgery, measuring the brain’s electrical signals.

After a bit of scrambling you might expect when trying to get in touch with someone who spends her days in the operating room, I managed to reach Chander on the phone. Our conversation strayed far from the bounds of her paper:

In this work, what did you do for the first time?

It’s not that no one has ever used an EEG during anesthesia. During the middle of the 20th century, several anesthesiologists attempted to record brain activity under increasing levels of anesthesia, just as many neuroscientists were using the EEG to characterize the stages of sleep. The process of recording EEG was really cumbersome back then, unlike today when you can stick a frontal set of leads on a patient’s forehead in the OR in a matter of seconds. Certain general stages of anesthesia were identified, but a formalized staging nomenclature, based on the relative contribution of dominant slow-wave oscillations in the EEG, had never been defined. Non-REM (slow-wave) and REM (rapid eye movement sleep) were staged in this way by sleep neurobiologists, but not anesthesiologists. In our study, we built upon the sleep stage classification system, to define maintenance patterns of general anesthesia. The formalized nomenclature helps us examine the stages of unconsciousness under anesthesia and communicate with other anesthesiologists.

What did you find?

We recorded the frontal EEGs (from the forehead) of 100 patients undergoing routine orthopedic surgeries. We discovered four primary electrical patterns that patients exhibit when they’re unconscious, and also as they’re waking up from anesthesia. The unconscious patterns show variety – not all patients’ brains look the same under anesthesia, despite similar drug exposure, meaning there are ‘neural phenotypes,’ or patterns of neuronal activity. The emergence patterns from anesthesia (pathways people’s brains take to reestablish conscious awareness after the anesthetic is turned off) bear some similarity to those pathways traversed when people are awakening from sleep.

When wakening from anesthesia, some people spend a relatively long time in non slow-wave anesthesia, which is similar to REM, the stage of sleep where dreams occur that usually precedes awakening. Others go straight from deep anesthesia, what we call slow-wave anesthesia (because of its dominant EEG patterns) to awakening. Interestingly, these patients were more likely to experience post-surgical pain, a situation akin to awakening from a deep sleep and experiencing confusion or discomfort; some childhood parasomnias like sleep terrors are characterized by moving abruptly from slow wave sleep to waking.

We began to see some tantalizing suggestions certain patterns of wake-ups from anesthesia might be more preferable. Could paying attention to these emergence trajectories prevent some problematic complications, like post-operative cognitive dysfunction? Could we ‘engineer’ or optimize anesthetic delivery to favor certain types of maintenance and emergence patterns? Can we monitor these patterns in a way that makes delivering anesthesia safer? Recognizing the variety of maintenance and emergence patterns under anesthesia also opens an entirely new possibility in the field of personalized medicine – imagine tailoring anesthetics to a person’s genome? I am trying to develop an initiative that addresses this in collaboration with Stanford’s new GenePool Biobank program.

Continue Reading »

Anesthesiology, Pain, Research, Stanford News

Miniature wireless device aids pain studies

Miniature wireless device aids pain studies

DSC_0053Here’s one thing I didn’t know: For every person who goes to the doctor to be treated for chronic pain, less than a half get their pain reduced even by half. I learned that from anesthesiologist David Clark, MD, who recently received a grant from Stanford Bio-X, which supports interdisciplinary teams working on biomedical problems, to improve those odds.

One of Clark’s collaborators is Scott Delp, PhD, who last spring developed a way of using light to activate and deactivate pain neurons in mice. To be clear, the nerves had to be genetically engineered to allow the light to work – not something that can currently be done in humans.

That work pointed to new ways of studying pain, but had a glitch. The light was delivered through fiber optic cables and the mice couldn’t behave normally in their cages. That’s where engineer Ada Poon, PhD, enters the picture. She’s been developing a variety of devices that work wirelessly in the body, and she’s now working on a wireless device to deliver the light to nerves in mice. Here’s what I wrote in an online story yesterday:

Coupling a wireless technology to optogenetics eliminates the wire and allows a mouse to move freely, use an exercise wheel and socialize. Clark said this combination will allow researchers to design experiments that more closely mirror a patient’s experience.

For example, Clark said that when he sees patients they don’t necessarily complain only about the pain. They complain about not wanting to see friends, not being able to go to work, or not being able to do activities they enjoy.

“What we will be able to look at is a more natural measure of pain relief,” Poon said. They could assess whether a treatment allows mice to return to normal activities by tallying time spent on an exercise wheel or socializing.

Clark went on to tell me the value of working in this team: “When you combine people with different skills you will come up with something with truly high impact.”

Previously: Using light to get muscles moving and Stanford researchers demonstrate feasibility of ultra-small, wirelessly powered cardiac device
Image courtesy of Ada Poon

Anesthesiology, Medicine and Literature, Neuroscience

Exploring the conscious (and unconscious) brain in every day life

Exploring the conscious (and unconscious) brain in every day life

line of peopleThe first time I fainted, I was seven. I passed out while racing my fellow second-graders across the playground. One minute, I was leading the pack in the race; the next thing I knew, I was lying in the nurse’s office with adult faces hovering all around me. My parents explained to me that I’d lost consciousness – it was like falling asleep for a minute, they told me.

It frustrated me to no end- even as a seven year old – that I didn’t know where that time had gone. Why couldn’t I remember those moments where I collapsed onto the grass and got scooped up by a petrified teacher? I ended up fainting a handful of times over the next few years (luckily doctors chalked it up to nothing more than dehydration and a genetic propensity to faint), and each time I was reminded of that frustration of not being able to grasp what was going on in my brain during those lost minutes.

As a seven-year-old, I didn’t have the chance to call up scientists and ask them to explain the brain to me, so when I started working on a feature article on consciousness for the latest issue of Stanford Medicine magazine, I was thrilled that maybe I’d get that chance to finally answer those questions that had been lingering in my head for decades. What makes the brain go from awake and aware to such a blank state, and then back again?

But it’s not that simple, I learned: There’s no single switch that flips the brain from conscious to unconscious. In fact, consciousness isn’t an on-off switch at all; it’s a whole spectrum of states. Anesthesiologist Bruce MacIver, PhD, pointed me toward this handy chart that shows different levels of consciousness. Each state of consciousness has its own unique place on two scales: physical arousal and mental awareness. As I looked at it, I realized that my experience with altered consciousness wasn’t just limited to my childhood fainting episodes – we all go in and out of multiple states of consciousness on a daily basis, and not only when we fall asleep and wake up.

“If you’re an elite athlete and you get in that so-called ‘zone,’ that’s an altered state of consciousness,” anesthesiologist Divya Chander, MD, PhD, explained to me. I’m no elite athlete, but after talking to Chander, I suddenly started paying attention to those not infrequent times when I “zone out” while driving or exercising. And when I woke up to a noise in my house on a recent night, I immediately noticed my heightened senses – that alertness is an altered state of consciousness too.

“What I’m always hoping is that hearing about this kind of work makes people ask more questions about what it means when they themselves enter different states,” Chander said to me when we talked. Her message was not lost on me; I’ve become an active observer of my shifts in attention and awareness.

My Stanford Medicine story delves much deeper than these observations of daily life, to look at how and why anesthesiologists are probing what it means to be conscious – and how their research could lead to better anesthetic drugs. But I hope that in addition to conveying the science, it also helps readers realize that subtle changes in consciousness happen in your brain all the time.

As for the questions I had as a seven-year-old, they’re not fully answered, but I’ve only gotten more intrigued to know how the brain mediates consciousness, and more excited to follow where this research goes in the future.

Sarah C.P. Williams is an award-winning science writer based in Hawaii, covering biology, chemistry, translational research, medicine, ecology, technology and anything else that catches her eye.

Previously: Stanford Medicine magazine opens up the world of surgery, Your secret mind: A Stanford psychiatrist discusses tapping the motivational unconscious and Researchers gain new insights into state of anesthesia
lllustration by Jon Han

Anesthesiology, In the News, Technology

From "abstract" to "visceral": Virtual reality systems could help address pain

From "abstract" to "visceral": Virtual reality systems could help address pain

Can you imagine a world wherein video games are good for your health? A piece on notes that advances in virtual reality (VR) have made headsets more affordable, and that applications for the technology, on the cusp of being available for home use, could extend beyond entertainment and into the realms of health sciences, finance and more.

From the piece:

“Virtual reality transforms relationships that tend to be abstract to become visceral,” says Jeremy Bailenson, [PhD,] director of Stanford University’s Virtual Human Interaction Lab. “Our research has shown that making this cause and effect relationship perceptual, as opposed to theoretical, changes consumer and other behaviors more than other interventions.”

VR can be an effective tool even where cause and effect are not obvious. In a collaboration with Stanford’s Department of Anesthesia, Bailenson used the technology to place children with chronic regional pain syndrome (CRPS) — a disease characterized by severe pain, swelling, and changes in the skin — in virtual simulations that divert their brains from unpleasant physical therapy and treatment. The children use computer-generated doubles known as avatars, a fixture in VR environments, to perform a simple exercise like popping balloons, distracting them from processing pain signals.

University of Washington researchers have developed a similar form of therapy known as SnowWorld, in which patients concentrate on throwing snowballs at penguins and mastodons to the music of Paul Simon, rather than focusing on painful wound and burn treatments. The technique is so effective, the researchers say, that it has reduced the need for strong narcotics and other addictive painkillers.

Previously: Can Joe Six-Pack compete with Sid Cyborg?Ask Stanford Med: Neuroscientist taking questions on pain and love’s analgesic effects and Can behavioral changes in virtual spaces affect material world habits?

Anesthesiology, Neuroscience, Pain, Stanford News

When touch turns into torture: Researchers identify new drug target for chronic, touch-evoked pain

When touch turns into torture: Researchers identify new drug target for chronic, touch-evoked pain

I admit it: I’m a baby when it comes to the smallest bruises. But I do feel guilty about fussing over papercuts when I hear about people with tactile allodynia, a chronic pain condition where the slightest touch can cause searing pain.

Allodynia, meaning “other pain,” refers to pain from things that shouldn’t normally hurt. For people with tactile allodynia, or touch-evoked pain, simple needs like a hug or a soothing breeze can turn into nightmares. Everyday activities such as brushing their hair or putting on a shirt can hurt. They can certainly kiss their NFL dreams goodbye.

Treating such chronic pain is tricky, because the root cause is not a wound that can be patched up with a Band-Aid. The culprit is often a damaged nerve or nerve circuit, leading to a mix-up of pain and touch signals, and fooling the brain into misreading touch as being painful.

Painkillers such as morphine haven’t been very effective at quelling this particular type of pain so far. That’s because they may have been targeting the wrong nerve cells all along, researchers here reveal.

Their recent article in the journal Neuron describing the finding points out that the nerve cells, or neurons, that control this type of pain are different from the usual pain neurons that morphine-based drugs target.

In my Inside Stanford Medicine story, I describe how the finding can help drug companies develop the right drugs to treat this type of chronic pain. Senior author of the Neuron article, assistant professor of anesthesiology and of molecular and cellular physiology Gregory Scherrer, PhD, and colleagues, zero in on specific binding sites on these neurons that drugs can target in order to cut off their signal and numb the pain.

Because the underlying nerves spread through the skin, topical creams or skin patches carrying the right drug would work quite well to reduce the pain, the authors say.

In the story, Scherrer also explains why drug companies gave up on such drugs before, and how his research could now help these companies successfully develop drugs to help patients with this type of pain.

Previously: Do athletes feel pain differently than the rest of us?Toxins in newts lead to new way of locating pain and On being a parent with chronic pain 

Anesthesiology, Pain, Research, Stanford News

Stanford researchers address the complexities of chronic pain

Stanford researchers address the complexities of chronic pain

If you’re in a reading kind of mood today, I highly recommend feeding it with a recent STANFORD Magazine feature on chronic pain and some of the research Stanford scientists are conducting to address it.

Chronic pain is usually defined as lasting longer than six months, the article notes, and may be present in 30 percent of adults in the United States. Owing to causes such as complex regional pain syndrome, arthritis, fibromyalgia, migraines or persistent lower back pain, many people turn to opioid medications, which can be addictive. The article notes some stunning statistics, such as this one – “More Americans are now dying as a result of prescription opioid overdose than from cocaine or heroin overdose.”

And this one: “In addition to the cost in human suffering, chronic pain costs the United States more than half a trillion dollars annually in direct medical expenses and lost productivity, according to a 2011 Institute of Medicine report (chaired by former School of Medicine dean Philip Pizzo, MD). This is more than the cost of heart disease and cancer combined.”

The article details research at Stanford working to understand the location and physiology of certain types of chronic pain, as well as to help patients overcome the lingering negative emotional effects it may produce.

Sean Mackey, MD, PhD, chief of the division of pain management at Stanford and a professor of anesthesia, said in the article, “When pain becomes persistent, it can become a disease in its own right.”

Previously: Retraining the brain to stop the painExploring the mystery of painMore progress in the quest for a “painometer and Ask Stanford Med: Neuroscientist responds to questions on pain and love’s analgesic effects

Anesthesiology, In the News, Technology

Advances in anesthesia make it possible for patients to remain awake and watch TV during surgery

579365935_5547cbdb96_zTired of hearing negative stories about the mind-numbing effects of television? Take heart, and read this BBC News story about the increasing number of patients that are given the option to remain alert and watch TV while they are being operated on.

As the story explains, it’s now possible for patients to receive a spinal anesthetic – so they feel no pain – and remain conscious during surgery. For patients that choose this form of anesthetic for their surgery, television offers a familiar and entertaining distraction from the medical procedure.

From the BBC News story:

“I feel fine, I can’t feel a thing and I’m watching Match of The Day.”

That was the perspective of 57-year-old patient Paul Eaton during his hip replacement operation at the orthopaedic hospital, one of the UK’s leading centres of excellence in its field.

While consultant surgeon Richard Spencer Jones cut, sawed and hammered during the hour-long hip replacement, Mr Eaton watched football highlights on iPlayer, via the hospital’s wi-fi network.

The benefits of using a spinal anesthetic (as described above) over a general anesthetic include: a faster recovery time, fewer instances of post-operative sickness and a shorter hospital stay.

Holly MacCormick is a writing intern in the medical school’s Office of Communication & Public Affairs. She is a graduate student in ecology and evolutionary biology at University of California-Santa Cruz.

Previously: Researchers gain new insights into state of anesthesia
Photo by Kolya

Aging, Anesthesiology, Neuroscience, Orthopedics, Research

Researchers look at brain activity to study falling

Researchers look at brain activity to study falling

5089256378_bb06d1562dFalling down is an inevitable hazard of walking, even for a seasoned runway model. Basketball players practice taking a charge and modern dancers learn fall and recovery techniques, but what about those who are at greater risk of injury upon impact, such as older adults?

Researchers from the University of Michigan School of Kinesiology are working to understand why the elderly suffer more serious falls than younger people. In a recent study published in the Journal of Neurophysiology, scientists used an electroencephalogram to watch the electrical response in different regions of the brain before and during a fall to determine which parts first identify the fall.

The study used EEG on healthy young adults, who walked heel-to-toe on a balance beam attached to a treadmill, and who were able to continue walking without injury if they fell off the beam.

From a release:

[Lead researcher Daniel Ferris, PhD] and colleagues then used a method called independent components analysis to separate and visualize the electrical activity in different parts of the brain. They found that people sense the start of a fall much better with both feet on the ground.

The researchers were surprised that so many different parts of the brain activate during a fall, and they didn’t expect the brain to recognize a loss of balance as early as it does.

Future studies comparing the elderly with younger subjects could determine if the elderly sense falls too late, in which case, pharmaceuticals might help them regain their balance. If it’s a simple motor problem such as muscles not responding properly, strengthening exercises could help.

Photo by aurélien

Anesthesiology, In the News, Neuroscience, Pediatrics, Research

Study suggests early-childhood anesthesia exposure may affect the brain

Study suggests early-childhood anesthesia exposure may affect the brain

Research published this week in Pediatrics takes a newly rigorous approach to investigating whether anesthesia exposure harms young children’s developing brains. The results suggest that even a single anesthesia exposure before age 3 could hurt kids’ language skills and abstract reasoning abilities.

Earlier studies, including those in animals, had suggested that anesthesia drugs harm young brains, but none had taken such a direct approach to the question as the new paper. In the latest study, Columbia University’s Caleb Ing, MD, and colleagues studied a group of 2,608 Australian children, 321 of whom received anesthesia at least once before age 3. At age 10, the children’s cognitive function was rigorously tested. Scores for skill in expressive language (the ability to form words and sentences) and receptive language (understanding what others say) were both lower in children who had been exposed to anesthesia than those never exposed, as were abstract-reasoning scores. Motor skills, behavior, and visual tracking and attention were not different between the groups.

In a Healthland entry on the research, Ing cautioned that more work is needed to clarify the new findings:

While the exposed children showed deficits in language and reasoning, the researchers were not able to determine whether that effect was due to the anesthesia or to the underlying medical condition that required surgery in the first place. But Ing notes that anesthesia was the likely influence on brain development, since most of the infants who were exposed had had relatively minor procedures, including tonsillectomy, insertion of ear tubes to drain infections and circumcision; only a small percentage needed operations for more serious heart problems or neurological conditions.

Still, says Ing, “At this point there is not enough evidence to show a causal link between anesthesia and deficits. It’s concerning in the sense that we should continue to pursue research to answer this question. I don’t think we should change our practice; we still need to do a lot more research before causing too much alarm.”

Although many uses of anesthesia can’t be avoided, the research could help scientists and physicians figure out what cognitive problems to watch for in children who have had anesthesia, as well as how to remedy them, the Healthland post concludes.

Previously: Researchers gain new insights into state of anesthesia

Anesthesiology, Global Health

A brief look at the global anesthesia crisis in developing countries

In a recent entry, Kelly McQueen, MD, discusses the critical shortage of anesthesiologists in developing nations. I know that anesthetics and equipment are in short supply in various parts of the world, but I had no idea how bad the situation could be in low-income nations:

Many are unaware of the global anesthesia crisis in low-income countries around the world. Some countries have less than one physician per 10,000 people and even less than one anesthesiologist per 100,000 people. The ability to provide safe anesthesia for surgery, labor and delivery, and other procedures, as well as for acute and chronic pain, is nearly absent in many countries.

She later writes:

According to a 2010 Lancet article, 2 billion people are without access to emergency and essential surgery worldwide, and 34 million anesthetics are delivered annually in low-income countries without the standard safety equipment needed or a trained provider.

Those are absolutely shocking numbers.

Stanford Medicine Resources: