Awakening

Since its introduction in 1846, anesthesia has allowed for medical miracles. Limbs can be removed, tumors examined, organs replaced—and a patient will feel and remember nothing. Or so we choose to believe. In reality, tens of thousands of patients each year in the United States alone wake up at some point during surgery. Since their eyes are taped shut and their bodies are usually paralyzed, they cannot alert anyone to their condition. In efforts to eradicate this phenomenon, medicine has been forced to confront how little we really know about anesthesia’s effects on the brain. The doctor who may be closest to a solution may also answer a question that has confounded centuries’ worth of scientists and philosophers: What does it mean to be conscious?
More

Doctors began investigating how anesthesia affects consciousness during the 1960s, shortly after the first reports of awareness. One South African researcher was especially curious about whether and how one might recall memories from a surgery. Perhaps a near-death experience? Pushing well beyond the limits of what would today be considered ethical, he collected 10 volunteers undergoing dental surgery. The procedures went along as normal until, midway through, the room went silent and the medical staff reached for scripts.

“Just a moment!” the anesthesiologist would say. “I don’t like the patient’s color. Much too blue. His (or her) lips are very blue. I’m going to give a little more oxygen.”

The anesthesiologist would then act out a medical emergency, rushing to the patient’s bedside to ventilate his or her lungs, as if this action were necessary to save the patient’s life. After several moments, the team would breathe a collective sigh of relief.

“There, that’s better now,” the anesthesiologist would affirm. “You can carry on with the operation.”

A month later, the patients were hypnotized and asked to remember the day of the surgery. One female patient said she could hear someone talking in the operating theater.

“Who is it who’s talking?” the interviewer asked.

“Dr. Viljoen,” she said, referring to the anesthesiologist. “He’s saying my color is gray.”

“Yes?”

“He’s going to give me some oxygen.”

“What are his words?”

A long pause followed.

“He said that I will be all right now.”

“Yes?”

“They’re going to start again now. I can feel him bending close to me.”

Of the 10 volunteers, four remembered the words accurately; four retained vague memories; and two had no recollection of the surgery. The eight patients who did remember it displayed anxiety during the interview, many of them bursting from hypnosis, unable to continue. But when out of hypnosis, it was as though nothing had happened. They had no memory of the incident. The terror and anxiety seemed permanently buried in their subconscious.

This experiment revealed a fundamental problem for the study of awareness, the frequency of which can be measured only through reported accounts. For some victims, it can take weeks for memories to surface. For Linda Campbell, it took 40 years. But what if no memory remains? Did awareness happen? Does it matter?

An anesthesiologist’s job is surprisingly subjective. The same patient could be put under general anesthesia a number of different ways, all to accomplish the same fundamental goal: to render him unconscious and immune to pain. Many methods also induce paralysis and prevent the formation of memory. Getting the patient under, and quickly, is almost always accomplished with propofol, a drug now famous for killing Michael Jackson. It is milky and viscous, almost like yogurt in a fat syringe. When injected, it has a nearly instant hypnotic effect: blood pressure falls, heart rate increases, and breathing stops. (Anesthesiologists use additional drugs, as well as ventilation, to immediately correct for these effects.)

Other drugs in the anesthetic arsenal include fentanyl, which kills pain, and midazolam, which does little for pain but induces sleepiness, relieves anxiety, and interrupts memory formation. Rocuronium disconnects the brain from the muscles, creating a neuromuscular blockade, also known as paralysis. Sevoflurane is a multipurpose gaseous wonder, making it one of the most commonly used general anesthetics in the United States today—even though anesthesiologists are still relatively clueless as to how it produces unconsciousness. It crosses from the lungs into the blood, and from the blood to the brain, but … then what?

Other mysteries have been untangled. Redheads are known to feel pain especially acutely. This confused researchers, until someone realized that the same genetic mutation that causes red hair also increases sensitivity to pain. One study found that redheaded patients require about 20 percent more general anesthesia than brunettes. Like redheads, children also require stronger anesthesia; their youthful livers clear drugs from the system much more quickly than adults’ livers do. Patients with drug or alcohol problems, on the other hand, may be desensitized to anesthesia and require more—unless the patient is intoxicated at that moment, in which case less drug is needed.

After delivering the appropriate cocktail, anesthesiologists carefully monitor a patient’s reactions. One way they do this is by tracking vital signs: blood pressure, heart rate, and temperature; fluid intake and urine output; oxygen saturation in arteries. They also observe muscles, pupils, breathing, and pallor, among many other indicators.

One organ, however, has remained stubbornly beyond their watch. Even though anesthesiologists are not entirely sure how their drugs work, they do know where they go: the brain. All changes in your vital signs are only the peripheral reverberations of anesthetic drugs’ hammering on the soft mass inside your skull. Determining consciousness by measuring anything besides brain activity is like trying to decide whether a friend is angry by studying his or her facial expressions instead of asking directly, “Are you mad?”

In lamenting how little we know about the anesthetized brain, Gregory Crosby, a professor of anesthesiology at Harvard, wrote in The New England Journal of Medicine in 2011, “The astonishing thing is not that awareness occurs, but that it occurs so infrequently.”

This ignorance gap seems almost absurd in the context of today’s dazzling array of medical technologies. Doctors can parse your brain with innumerable X‑ray slices and then collate them into a three-dimensional grayscale image in a process called computed tomography, or CT. They can send you into a tube where powerful magnets flip the spin of protons on water molecules in your brain; when the protons flip back into position, they emit radio waves, and from that information a computer can generate a comprehensive image known as an MRI (for magnetic resonance imaging). Positron-emission-tomography, or PET, scans provide detailed maps of metabolic activity. Yet we are in the dark ages when it comes to determining whether the brain is conscious or not? We can’t figure out whether patients are awake, or what being awake even means?

Due to their hulking size, CT scanners and MRI machines are rarely, if ever, brought into an operating room. But other technologies are more mobile. For example, doctors can measure electrical activity in the brain using a machine that, with the help of a few electrodes attached to your scalp, generates what’s known as an electroencephalogram (EEG)—essentially a snapshot of your brain waves. An EEG is printed in undulating, longitudinal lines, like the scribbled outline of a mountain range: sometimes smooth and regular like the Appalachians, at other times rough and craggy like the Rockies; and in death or deep coma more like the Great Plains.

This technology is regularly used in sleep studies and to diagnose epilepsy and encephalitis, as well as to monitor the brain during certain specialized surgeries. But the problem with an EEG is interpreting it. The data come at a constant, unforgiving pace, with lines stacked one on top of another like on a page of sheet music (high-density versions can have up to 256 lines). Before digitization, EEG printers disgorged paper at 30 millimeters per second, resulting in 324 meters of print for just three hours of surgery. And even today’s machines provide data that are next to impossible to analyze on the fly, at least with any sort of detail or depth.

In 1985, when a 23-year-old doctoral student named Nassib Chamoun first looked at the sheet music of an EEG, he saw a symphony—albeit one he could not yet read. Chamoun was then an electrical engineer doing a research fellowship at the Harvard School of Public Health, working on decoding the circuitry of the human heart. When an anesthesiologist he worked with argued that the brain was much more electrically interesting than the heart, Chamoun agreed to attend a demonstration of EEG, which was then a relatively new technology in the operating room, during a surgery at a Harvard hospital. The EEG printer was an old model, spilling reams of paper that piled near the head of the gurney. As the anesthesiologist injected the patient with drugs, the machine’s pen danced wildly, ink splattering off the page. Chamoun was entranced by the complexity of the patterns he saw that day. He couldn’t stop thinking about how to engineer these data into something that would be more useful for surgeons and anesthesiologists. He left his doctorate program and embarked on a 25-year quest to decode the brain—and, ultimately, to quantify and measure consciousness.

As a child in Lebanon, Chamoun had been fascinated by taking things apart and putting them back together. During the 1970s, as ethnic tensions there boiled into civil war, Chamoun spent a lot of time cooped up at home when school was canceled, or when it was unsafe for him to venture outside. The soldering iron and circuit board became his playground. Family members asked him to fix televisions, tape recorders, and radios. His parents gave him a microscope as a birthday present. He made his way to the United States for college, eager to expand his study beyond home electronics.

As it happened, the mid-’80s were an auspicious time for a young technologist with a promising idea. When Chamoun began working with EEG, he had early access to mainframe computers at Harvard and Boston University. More important, he had access to surgeries. He wheeled his digital EEG machine into Harvard operating rooms, fixed electrodes to patients, and recorded millions of data points. Then, using computers, he began to sift through the oceans of information, searching for a unifying pattern. Meanwhile, he was enlisting his old mentor, a Nobel Prize–winning Harvard professor, and courting venture-capital firms for seed money. The result was Aspect Medical Systems, a biotech firm he founded in 1987 with a singular goal: to build a monitor that anesthesiologists could use to discern their patients’ level of awareness.

Chamoun turned out to have a pivotal ally in a family friend, Charlie Zraket, the CEO of a big defense contractor called Mitre. In the 1960s, mathematicians had developed a statistical method called bispectral analysis, which breaks down waveforms to find underlying patterns. This method was originally used for studying waves in the ocean, but Mitre applied it to voice-recognition software, and later to sonar on war submarines and radar on airplanes. If bispectral analysis could be used to interpret patterns in ocean, radio, and sound waves, Zraket and Chamoun reasoned, why couldn’t it be applied to brain waves?

Chamoun ended up banking everything on the belief that if he collected enough EEG data, he could hack the patterns using bispectral analysis. But by 1995, eight years in, the entire project was collapsing. Chamoun had gathered more than $18 million from investors, credit lines, and friends, and had spent it all, but still his algorithms could not reliably predict a patient’s level of awareness. Just as he was confronting bankruptcy, he secured a $4 million investment from a well-known venture capitalist. This bought the time Chamoun needed. From that point, he and his team achieved a series of breakthroughs that caused them to fundamentally reframe the way they thought about consciousness. Chamoun had never believed that the brain was something with a simple on/off switch, but he had been looking for one master equation—a sort of electrical fingerprint of consciousness—that would connect all the dots. Only when he let go of the idea of a single equation did a new, more viable model come into view: consciousness as a spectrum of discrete phases that flowed one into the next, each marked by a different electrical fingerprint. Fully conscious to lightly sedated was one phase; lightly to moderately sedated was another; and so on. Once he realized this, Chamoun was able to identify at least five separate equations and arrange them in order, like snapping a series of photos and compiling them into a broad panorama shot.

The BIS monitor compressed consciousness into a medical indicator that could be quantified and measured, like blood pressure or body temperature.

The end product was a shoebox-size blue machine that used EEG data to rank a patient’s level of awareness on an index of zero to 100, from coma to fully awake. Chamoun called it the Bispectral Index, or BIS, monitor. To use the BIS, all that anesthesiologists had to do was connect a pair of disposable electrode sensors to the machine, apply them firmly to a patient’s forehead, and wait for a number to appear on the box’s green-and-black digital display. They would then administer anesthesia and watch the number drop from a waking average of 97 to somewhere in the ideal “depth of anesthesia” range—between 40 and 60—at which point they could declare the patient ready for surgery.

The FDA cleared the BIS monitor in 1997. When Time interviewed Chamoun about the revolutionary device, he called it anesthesia’s “Holy Grail.” Two years later, Aspect Medical’s quarterly revenue surpassed $8 million; the company soon went public. In 2000, Ernst & Young named Chamoun the Healthcare and Life Sciences Entrepreneur of the Year for the New England region.

Enthusiasm for the BIS monitor grew in 2004, when The Lancet published a groundbreaking study reporting that the device could reduce the incidence of anesthesia awareness by more than 80 percent. This nearly pushed the BIS into the realm of medical best practices. By July 2007, half of all American operating rooms had a BIS monitor. By 2010, the device had been used almost 40 million times worldwide. At his home in the suburbs of Boston, Chamoun has the 10 millionth sensor memorialized in a sealed plastic case.

The BIS monitor fundamentally changed the way scientists thought about consciousness. It compressed an enigmatic idea that had long mystified researchers into a medical indicator that could be quantified and measured, like blood pressure or body temperature. One effect of the accessibility of Chamoun’s invention was that it was occasionally used outside the operating room, for purposes he had not foreseen. In a 2006 injunction involving a North Carolina death-row inmate named Willie Brown, a federal judge ruled that performing a lethal injection on a conscious prisoner could cause excessive pain. North Carolina requires prisons to anesthetize inmates before killing them, but the judge worried about the possibility of anesthesia awareness. Only when prison officials purchased a BIS monitor did he allow them to proceed with Brown’s execution. So on April 21, 2006, attendants hooked Brown up to the monitor, injected him with a sedative, and watched his BIS value drop. At approximately 2 o’clock in the morning, once the number had fallen below 60, an attendant administered a lethal dose of pancuronium bromide and potassium chloride.

Jump to comments
Presented by
Get Today's Top Stories in Your Inbox (preview)

Sad Desk Lunch: Is This How You Want to Die?

How to avoid working through lunch, and diseases related to social isolation.


Elsewhere on the web

Join the Discussion

After you comment, click Post. If you’re not already logged in you will be asked to log in or register. blog comments powered by Disqus

Video

Where Time Comes From

The clocks that coordinate your cellphone, GPS, and more

Video

Computer Vision Syndrome and You

Save your eyes. Take breaks.

Video

What Happens in 60 Seconds

Quantifying human activity around the world

Writers

Up
Down

More in Health

More back issues, Sept 1995 to present.

Just In