Anesthesia, page 15
Eger knew from recent studies that by measuring the concentration of the gas an anesthetized patient breathed out of her lungs—the “end tidal gas”—he could calculate the concentration of the drug in her brain. That was the easy part. What he needed, though, was an “end-point,” an unambiguous marker by which he could usefully compare the strength of any one vapor with another.
First, he and Merkel practiced on dogs. Then, with another young colleague, Larry Saidman, Eger turned his attention to people. The pair arrived at the starkly simple idea of drugging patients until they no longer responded to commands (“Open your eyes”; “Squeeze my hand”), and then having the surgeon cut them to see if they would move. If they did, Eger increased the concentration of the gas and asked the surgeon to try again and, if necessary, again, until, at the point where the person stopped moving, he recorded the concentration of end-tidal gas they were exhaling. Over the next few years, he and Saidman did this for hundreds of patients, of different ages, with different anesthetics, in different combinations, individually and in small groups. Then, for each permutation, they took the highest concentration at which each patient had moved and the lowest concentration at which they hadn’t; they found the midway point and called it MAC.
In the recondite world of surgical anesthesia this concept made Eger a superstar. MAC—the initials stand for Minimum Alveolar Concentration—revolutionized anesthesia and became the standard by which many anesthesiologists still judge how much of a given drug to give a patient. Importantly, MAC is a measure not of anesthetic depth but of drug potency. It tells doctors what the chances are that a surgical patient will remain safely unconscious at a given dosage of any anesthetic vapor or gas. It also allows doctors to use drugs in precise combinations.
Some observers caution that MAC is only a measure of probability—it cannot tell for sure whether an individual patient is conscious or not—and it also changes with the patient’s age, and depending on what other drugs it is mixed with. Nevertheless, for many doctors MAC remains anesthesia’s gold standard, and Eger, who died as this book went to press, its standard bearer. He was a steadfast believer in its efficacy. “Despite its imperfections and limitations, it remains the standard because nothing thus far invented is better.” As a unit of measurement, he pointed out with pride, MAC is to anesthesia what centimeters are to distance and degrees Celsius to temperature.
And Eger believed in measurement. If you can’t measure it, it doesn’t exist. You might call him an anesthetic rationalist. Certainly he was not in any way convinced by the odd claims being made by an unknown South African psychiatrist.
Then one day in the early 1990s, a quarter of a century or so after Bernard Levinson had published his study, Eger picked up the phone and on the other end was Hank Bennett, then still a young New York psychologist. This was some years after Bennett had successfully persuaded unwitting patients to touch their ears in a postoperative interview—and more than a decade before I met him in Hull. Bennett had never met Eger, but he knew him by reputation. Now he was calling from New York City with a proposition.
“He introduced himself,” recalled Eger, “and said, ‘I understand from things you’ve written that you don’t believe awareness occurs during an adequate level of anesthesia.’
“I said, ‘That’s correct; awareness does not occur at an adequate level of anesthesia, with inhaled anesthetics.’”
Then Bennett asked how he knew.
“And I said, ‘Well I just know these things.’” Eger laughed. “And it was displaying my usual arrogance. And he persisted, like a good scientist would. He said, ‘Dr. Eger, how do you know?’
“And I finally . . . had to say, ‘Well I don’t really know, I don’t know for sure, but I can’t believe that anyone remembers anything under anesthesia; certainly at MAC, nobody remembers anything.’
“He said, ‘Dr. Eger,’ (in a very nice way; Hank is a very nice guy), ‘Dr. Eger, prove it.’”
Ted Eger had a reputation, depending on who you talk to, of being delightful and brilliant or arrogant and brilliant. Sometimes all three. In the early minutes of our interview, as I proceeded through a rambling explanation of my project, he leaned back in his chair with a small and not very comforting smile, as if sizing me up for sport. Later, in the middle of an entertaining and well polished life history, he announced that he had been for two years running the captain of his school’s winning checkers team, and gleefully issued a challenge. The checkers triumph had been, in his telling, the high point in an otherwise unimpressive childhood and early academic career.
“My parents were affluent. I wanted for nothing. I graduated in the lower fifth of my high school class undistinguished in all ways except that I was the captain of the checkers team which for two consecutive years won the all-Chicago championship, an accomplishment about which I am exceedingly vain—and,” he continued with slightly narrowed eyes, “I can beat anyone in this room in checkers. Any time, any place. With my eyes closed, probably.”
From time to time as he talked he cupped his face in his hands and peered from between his palms, almost childlike, as if he were a small boy who had surprised himself by losing his hair and sprouting glasses.
As a bright but disengaged teenager, Eger had once taken a job selling shoes in one of the poorer areas of Chicago. He lasted a day. By the time he got home, he was more tired than he had ever been. It occurred to him that he didn’t want to do this for the rest of his life. “I think you call it an epiphany.” Instead, and inspired, he said, by the books of microbiologist Paul de Kruif, he decided to study medicine and become a country physician.
His second epiphany came the first time he anesthetized a patient. He had just finished his first year in medical school and was on a summer placement with an anesthesiologist. On his first day, the senior anesthesiologist showed him what to do—how to start the drip that delivered drugs into the woman’s bloodstream; how to adjust the dials that released the gases nitrous oxide and oxygen into her lungs; how to hold the mask over her face. He told Eger to watch the rebreathing bag that moved steadily in and out as the woman drew air from the anesthetic machine and then breathed it out again. Then he left the room. Eger was in charge. He watched as the patient lost consciousness. Then he realized she had stopped breathing.
Horrified, he told the surgeon, who immediately began resuscitation. (“So the surgeon is squeezing on the chest of this woman who’s having some minor procedure, and who I’m about to kill.”) And then the bag began to move again. A nurse ran for the anesthesiologist, who explained that all Eger needed to do if the bag stopped moving was to squeeze it, in and out, in and out; this way he could breathe for the patient.
“I finished that day I think more tired than I was trying to sell shoes. I was drained. And I finished, thinking that I had nearly killed a patient, I had nearly killed a human being. And that if I went into anesthesia,” here Eger’s voice dropped to a delighted, theatrical whisper, “I could do that every day! Every day I could take a patient’s life into my hands. Every day. I could do that!” He straightened and took a breath. “Changed my life! The hell with Paul de Kruif, I’m going to be an anesthesiologist!”
In the decades after MAC, Eger cemented his reputation investigating the pharmacology of the numerous vapors used in modern anesthesia. He made his life’s work studying how they get into, move around and then leave the body, and documenting these processes in scientific papers and books that are still standard texts for anesthesiologists the world over. He also became a well-known and often skeptical voice in the debate about awareness and memory in anesthesia.
But Eger, not just a believer in science, was a man who liked a challenge. And Hank Bennett had just challenged him in terms he could not resist.
•
Not long after that phone call, Hank Bennett came to San Francisco, and in a series of carefully controlled experiments the men set out to resolve the matter. With a team of researchers, they played tapes to anesthetized patients with messages such as “yellow banana, green pear,” or just white noise; then, when they woke, asked them to think of a color or a fruit. All to no effect. (The patients who heard yellow and green were no more likely to name those colors than those who heard white noise.) Then they tried with Trivial Pursuit-style questions: what state has an elephant-leash law? (California, as it turns out); what state was Robert Redford born in? (again California); what is the blood pressure of an octopus? (70 mm of mercury when underwater—same as you or me). Afterward they tested the subjects with multiple-choice questions. Nothing.
“So now we are at odds,” recalled Eger, “with those that have a belief—and it is almost like a religion for some of them—at odds with the group that says you can remember things, that you can recall things under anesthesia.”
Finally they rang Bernard Levinson in Johannesburg.
You would be hard pressed to find two men less alike. Eger small and combative with his quick, hungry brain; Levinson tall and charismatic with that resonant, beguiling voice. Eger had heard him speak about his mock-crisis study not long before at a conference and had been impressed, despite himself. “When he describes it, you just sit up and take notice; a) because it’s a fascinating experiment; and b) because he is just so charismatic, a wonderfully charismatic guy who is honest as the day is long . . . So here we are, we’ve got nothing, and he’s got something—that’s impressive!”
But, he added, the experiment had needed bringing “up to date.”
Eger leaned forward as he talked, hands clasped between his knees. “The study was flawed, fatally flawed. For one thing, Bernard knew what script the patients were getting, and for another, there wasn’t a control.”
This time, he said, his team would do it, and do it right. “We’ll repair the flaws.”
The replication study was driven by Ted Eger with nine researchers, including Levinson, Bennett and a young man called Ben Chortkoff, Eger’s fellow at the time. (He looked, Kate Leslie told me much later, “a bit like John Kennedy junior, except less dead.”) It took place in a small operating theater at the UCSF medical school and was conducted with what an observer described as military precision.
It found absolutely nothing.
Well, almost absolutely nothing.
Levinson, Bennett and Chortkoff interviewed one hundred young men, finally selecting the twenty-two they could most easily hypnotize. The men were put to sleep using modern drugs, not ether, and after fifteen minutes at a relatively light anesthetic were given a paralyzing drug. Then the anesthetic was increased, though not to surgical levels, and breathing tubes inserted. This time none of the researchers who would later interview the subjects were in the room, nor would they find out until the end of the study what information the young men had been exposed to under anesthetic.
They were an odd group. Eger the skeptic, Levinson the believer, Bennett, younger than both, excited and more than a little nervous. But they were all scientists, and emotional men, and a sort of love grew between them. In our interviews, Levinson and Bennett both described the time as a highlight of their careers. Chortkoff, too. Levinson for his part recalls one day looking up as he was hypnotizing one of the subjects to see that Bennett, who was standing next to them, had also entered a deep trance. “When he woke up he smiled, and I smiled and we just went on with it.”
At the heart of the study, as with the original, was a fake crisis, with the wording updated for a nineties audience: “Oh shit, who turned off the oxygen? Who disconnected the cylinder? Damn it, he’s turned blue. God, his lips are blue. Get that thing connected again. You got it? OK. I’m going to give him some more oxygen now. [Fifteen-second pause]. Ho boy. OK. He looks better now. I think we can continue.”
Eger recorded the message in his own voice and it was played to the anesthetized subjects on stereo earphones that also allowed in sounds from the operating theater. Here, though, the study departed markedly from the original. Five days later, the men were anesthetized again, this time using a different drug. The order in which they received the two drugs was randomized and balanced so that equal numbers received each drug on each occasion, without the interviewers knowing who got what when.
This time Eger delivered a quite different “drama” through their headphones, varying the order in which the subjects heard the two scenarios. “Hey, Ben, I think this study is going well. This is the best job we’ve done. I think the volunteer is going to be pleased. God, he’s really doing great.” After a fifteen-second pause, Eger continued, laying it on thick: “We’re moving right along. I think we’re going to do a record this time—it’s moving so fast. Things are going so damned smooth. I don’t think we’ve had a volunteer this good.”
The study that was published in 1995 went under the unwieldy title “Subanesthetic Concentrations of Desflurane and Propofol Suppress Recall of Emotionally Charged Information.” It failed to replicate Levinson’s original findings and is generally interpreted as having invalidated the 1965 experiment. Even under hypnosis, none of the subjects remembered the fake crisis.
Eger, modest in victory, said the difference may have been in the drugs used or it may have been in the methodology. By exposing the young men to both threatening and banal dramas, and by ensuring the interviewers had no way of knowing which of these any participant had just experienced, the study design minimized the effects of chance or bias. “And that’s what science is,” Eger said. “It’s the ability to replicate something. If you can’t replicate something it’s not real. I think things do happen by chance, but if you can’t replicate it, if it isn’t robust enough to replicate, it doesn’t exist.”
There were, however, some other intriguing differences between the two studies. Perhaps the most critical of these was the drugs. Instead of ether, Eger’s team alternated between the gas desflurane and the intravenous drug propofol. Given that ether was no longer in use, it made sense to update Levinson’s study with the sorts of drugs that contemporary patients were likely to encounter, although it made it impossible to draw any direct conclusions about the experiences of Miss D, Mr. R or any of the other patients who passed through that South African dental surgery that day in 1965.
Then there was the fact that the subjects were not surgical patients, but paid volunteers. This is the point that Bernard Levinson kept coming back to when I spoke with him in South Africa, and which, he argued, put them in a very different position from the ten men and women he used in 1965. Paid volunteers, he argued, might be prepared to endure without undue stress situations they would not put up with otherwise. Nor were they vulnerable in the way a patient is vulnerable. “It is a very stressful thing,” said Levinson, “entering into an operating theater with some kind of problem: ‘What is going to happen to me now? Am I going to lose a limb? Maybe I am not going to wake up. Will I have pain when I wake up?’ But paid volunteers enter with a whole different feel: ‘This is going to be a job at work, I’m going to be OK, they are not going to harm me, they wouldn’t harm me, and this is what they are going to do because I read the consent form very carefully, and it is OK.’”
Levinson’s paperwork had been primitive by comparison. “My consent forms were a sham. They consented to ‘having an operation’ . . . that’s all. It was just taken for granted that during anesthetics we could expose them to all sorts of things, as long as we didn’t willfully or knowingly damage them.”
And it is this, argues Levinson, that has made his classic experiment impossible to repeat. His study may have been flawed, he said, but so was Eger’s. The young men in Eger’s study knew beforehand that after they were unconscious, they might be presented with “a drama similar to conversations that may occur at any time in an operating room during a real operation.”
“This is the flaw,” said Levinson from Johannesburg, “this is the very flaw of that experiment that Ted Eger and I did. He is going to contest this, but it was a major flaw that every one of these volunteers knew exactly what we were going to do . . . We had told them—so in a real profound sense, they were not patients, they were very sophisticated guinea pigs.”
Eger and Chortkoff have mounted the opposite argument, that informed consent if anything increased the likelihood of the young men remembering the crisis, by alerting them to all the possible risks of anesthesia, including death (information that might, arguably, heighten their anxiety and, with it, their resistance to the anesthetic drugs).
“We repeated the experiment,” said Chortkoff with finality in response to my suggestion that Levinson’s original study was unrepeatable. I had rung him in Salt Lake City, where he was a professor of Anesthesiology at the University of Utah. As the first author on the report, it was Chortkoff’s job to develop and manage the study and write it up. He is adamant that the replication “drama” was every bit as convincing as the original. “Ted’s a phenomenal actor . . . It was quite frightening to listen to.”
There were other differences. For one, the volunteers were not cut—meaning their nervous systems were not subject to the galvanizing effects of incision—making unconscious learning less likely. Offsetting this was the fact that the Eger study used lower concentrations of drugs than would usually be used for surgery, suggesting that the volunteers (“all lovely bright kids,” said Levinson) were less heavily anesthetized than the patients in the original experiment. Certainly that was the aim, said Chortkoff, who insists the team wanted to give the experiment every chance of working.
And, while Eger’s subjects were not opened up, they were each subjected to a “noxious stimulus.” About half an hour into the procedure, ten minutes before the staged “drama” unfolded, anesthesiologists inserted breathing tubes down their airways—an extremely uncomfortable process if you happen to be awake—and, like surgery, known sometimes to rouse patients. Interestingly, while none of the volunteers claimed when questioned after the anesthetic to remember the tubes being put in, the report noted that, “after at least one anesthetic trial, half stated during hypnosis that they felt something in their throats, something that hurt.”
