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Authors: Atul Gawande

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This makes sense when you recall that nausea is a condition that can be triggered by stimuli as different as an unfamiliar motion, a bad smell, a toxic drug, and the hormonal fluctuations of pregnancy. As scientists explain it, the brain has a vomiting program (or “module”) that receives and responds to all kinds of inputs: from chemoreceptors in the nose, the gut, and the brain; from receptors that detect overfilling of the stomach or tickling of the uvula; from motion sensors in the inner ear; and from higher brain centers governing memory, mood, and cognition. Each of our current drugs presumably interferes with some pathways more than with others. Hence the different effects in different conditions.

What’s more, although we often think of nausea and vomiting as part of the same phenomenon, they are quite separate, probably involving separate programs in the brain, and a drug that affects one may not affect the other. Vomiting does not always involve nausea. I can remember a kid in sixth grade who could vomit at will—no finger down the throat or anything—even though he didn’t feel the least bit sick. And people with the rare condition known as rumination syndrome have an unexplained tendency to vomit food up from their stomach into their mouth shortly after every meal—this without any associated nausea. (They either swallow the food again or spit it out, “depending on social circumstances,” as one scientific article put it.) Conversely, even severe nausea does not necessarily produce vomiting. And drugs that stop vomiting do not necessarily stop nausea—a point that many doctors and nurses often fail to recognize. For example, people working in medicine have been highly impressed by Zofran, but patients may be less so. A study led by Gary Morrow, a nausea researcher at the University of Rochester Medical School, found that widespread use of Zofran and its cousins had
reduced vomiting in chemotherapy patients but had produced no improvement in the severity of their nausea. In fact, patients today report having a longer duration of nausea than patients had during the pre-Zofran years.

Researchers studying chemotherapy patients—a sort of captive population for scientists investigating how nausea and vomiting occur—have discovered something even more surprising. These patients actually experience three separate types of nausea and vomiting. An “acute” type occurs within minutes to hours of receiving a dose of a toxic chemotherapy drug and then gradually resolves—exactly the effect we’d predict from a poison. But then in many patients the nausea and vomiting come back after a day or two, an effect called “delayed emesis.” And about a quarter of chemotherapy patients even begin to have “anticipatory nausea and vomiting,” symptoms that occur before the drugs are injected. Morrow has documented some striking characteristics of these types of nausea. The more intense the initial acute nausea, the worse the anticipatory nausea becomes. And the more cycles of chemotherapy that patients receive, the more general the cues for anticipatory nausea become: vomiting may occur first when a patient sees the nurse who administers the drugs, then when he sees any nurse or takes in the smell of the clinic, then when he pulls into the clinic parking lot for his chemotherapy appointment. Morrow had one patient who vomited whenever she saw the highway exit sign for the hospital.

These reactions are, of course, familiar results of psychological conditioning—the “Clockwork Orange” effect in action. Such conditioning probably plays an important role in prolonging nausea in other circumstances, including pregnancy. Once delayed or anticipatory vomiting develops, though, current drugs don’t help. Studies by Morrow and others have found that only behavioral treatments, like hypnosis or deep relaxation techniques, significantly reduce conditioned vomiting, and then only for some patients.

Ultimately, our medical arsenal against nausea and vomiting is still fairly primitive. Given how common these problems are and
how much people are willing to pay to make them go away, pharmaceutical companies are investing millions of dollars in efforts to find more effective drugs. Merck, for example, has developed a promising contender, currently known as MK-869. This is one of a new class of agents called “substance P antagonists.” These drugs attracted a good deal of attention when Merck announced that they seemed to be clinically effective against depression. Less noted, however, were findings published in the
New England Journal of Medicine
that MK-869 was remarkably effective against nausea and vomiting in chemotherapy patients.

The findings were unusual for two reasons. First, the drug substantially reduced both acute and delayed vomiting. Second, MK-869 didn’t just work against vomiting but reduced nausea as well. The proportion of patients reporting anything more than minimal nausea in the five days following chemotherapy dropped from 75 percent to 51 percent with the drug.

All our medications have their limitations, however, and as promising as such new drugs may seem they will fail many patients. Not even MK-869 could stop nausea for half of the chemotherapy patients. (In addition, its safety and effectiveness in pregnant women are likely to remain unknown for some time. Because of both medical and legal hazards, drug companies generally avoid testing drugs on pregnant women.) So there’s no morphine for nausea on the horizon. Uncontrolled nausea remains a persistent problem. Still, a brand-new clinical specialty called “palliative medicine” is pursuing a radical project: the scientific study of suffering. And what’s striking is that they’re finding solutions where others have not.

Palliative specialists are experts in the care of dying patients—specifically in improving the quality of their lives rather than prolonging their lives. One might think we wouldn’t need a specialty for this, but there’s evidence that these specialists really are better at it. Dying patients often have pain. Many have nausea. Some have such poor lung function that, although they take in enough oxygen to survive,
they live with a constant, terrifying breathlessness—a feeling that they are drowning and just cannot get enough air. These are patients with untreatable disease, and yet palliative specialists have been remarkably successful at helping them. The key is simply that they take suffering seriously, as a problem in itself. In medicine, we’re used to seeing such symptoms only as clues in a puzzle about where the disease is and what we can do about it. And, as a rule, fixing what’s physically wrong—taking out the infected appendix, setting the broken bone, treating the pneumonia—is precisely the way to relieve suffering. (I wouldn’t be a surgeon if I thought otherwise.) But not always—and nowhere is this more apparent than with nausea. Most of the time, nausea is not a sign of pathology but a normal response to something like travel or pregnancy—or even to a beneficial treatment like chemotherapy or antibiotics or general anesthesia. The patient, we say, is “fine,” but the suffering is no less.

Consider the significance of vital signs. When a patient is in the hospital, every four hours or so a nurse records the vital signs on a bedside chart to provide caregivers with a measure of how the patient is doing over time. This is done the same way the world over. By convention, the four vital signs are temperature, blood pressure, pulse, and respiratory rate. And these do tell us a lot about whether someone is getting physically better or worse. But they don’t tell us anything about suffering, about something more than just how the body is doing. Palliative specialists are trying to change this. They want to make pain—the level of discomfort a patient reports—the fifth vital sign. The fuss they’ve raised is forcing physicians to recognize how often we undertreat pain. And they are developing better treatment strategies generally. For example, it is now evident that, once symptoms of severe nausea (or, for that matter, pain) develop and progress, they become increasingly resistant to therapies of any kind. The best approach, palliative specialists have learned, is to start treatment when the symptoms are mild—or, in some circumstances, even before they appear—and that proves true whether you’re a passenger about to board a ship or a cancer patient about to start
chemotherapy. (The American Society of Clinical Oncology has announced guidelines endorsing this preventive approach for chemotherapy patients.) Back when doctors didn’t hesitate to prescribe antiemetics for ordinary pregnancy sickness—at least a third of pregnant women were on such drugs in the 1960s and 1970s—hyperemesis was much less common. But doctors changed this practice after lawsuits forced the popular remedy Bendectin off the market alleging it caused birth defects (despite numerous studies showing no evidence of harm). It became standard to avoid prescribing drugs until, as in Fitzpatrick’s case, vomiting had already caused significant dehydration or starvation. Hospital admissions for hyperemesis of pregnancy subsequently doubled.

Perhaps the most striking observation palliative specialists make, however, is that there is a distinction between symptom and suffering. As the physician Eric J. Cassell points out in his book
The Nature of Suffering and the Goals of Medicine
, for some patients simply receiving a measure of understanding—of knowing what the source of the misery is, seeing its meaning in a different way, or just coming to accept that we cannot always tame nature—can be enough to control their suffering. A doctor can still help, even when medications have failed.

Amy Fitzpatrick said that the doctors she liked best were the few who admitted they didn’t know how to explain her nausea or what to do about it. They would say that they had never seen anything like her case, and she could tell that they commiserated with her. She did acknowledge having some contradictory feelings about such admissions. At times, they made her wonder if she had the right doctors, if, somehow, they were missing something. But, for all the treatments she and the doctors tried, the nausea would not let up. It really did seem beyond anyone’s comprehension.

The first months were a terrible, frightening struggle. Gradually, though, she felt a transformation, a toughening of her spirit, and she sometimes even had a thought that things were not so bad after all. She prayed every day and believed that the two children growing
inside her were a gift from God, and, with time, she came to see her trials as simply the price she had to pay for this remarkable joy. She gave up looking for silver bullets. After the twenty-sixth week of pregnancy, she asked for no more experimental therapies. The nausea and the vomiting persisted, but she would not be defeated by them.

Eventually, there was a glimmer of relief. By the thirtieth week, she found that she could eat an odd selection of four things in sliver-size portions: steak, asparagus, tuna, and mint ice cream. And she was able to hold down a protein drink. The nausea remained, but it had eased just a bit. In the thirty-third week, seven weeks early, Fitzpatrick went into active labor. Her husband flew down on the shuttle from LaGuardia in time for the delivery. The doctors warned her that the twins would be small, around three pounds, but on September 12, at 10:52
P.M.
, Linda was born, weighing four pounds twelve ounces, and at 10:57
P.M.
. Jack was born, at five pounds even—both in excellent health.

Shortly after delivery, Fitzpatrick threw up once more. “But that was the last time,” she recalled. The next morning, she drank a big glass of orange juice. And that night she ate a giant hamburger with blue cheese and fries. “It was delicious,” she said.

Crimson Tide

I
n January of 1997, Christine Drury became the overnight anchorwoman for
Channel
13
News
, the local NBC affiliate in Indianapolis. In the realm of television news and talk shows, this is how you get your start. (David Letterman began his career by doing weekend weather at the same station.) Drury worked the 9
P.M.
to 5
A.M.
shift, developing stories and, after midnight, reading a thirty-second and a two-and-a-half-minute bulletin. If she was lucky and there was breaking news in the middle of the night, she could get more airtime, covering the news live, either from the newsroom or in the field. If she was very lucky—like the time a Conrail train derailed in Greencastle—she’d get to stay on for the morning show.

Drury was twenty-six years old when she got the job. From the time she was a girl growing up in Kokomo, Indiana, she had wanted to be on television, and especially to be an anchorwoman. She envied the confidence and poise of the women she saw behind the desk. One day during high school, on a shopping trip to an Indianapolis mall, she spotted Kim Hood, who was then Channel 13’s prime-time anchor. “I wanted to be her,” Drury says, and the encounter somehow made the goal seem attainable. In college, at Purdue University, she majored in telecommunications, and one
summer she did an internship at Channel 13. A year and a half after graduating, she landed a bottom-rung job there as a production assistant. She ran the TelePrompTer, positioned cameras, and generally did whatever she was told. During the next two years, she worked her way up to writing news and then, finally, to the overnight anchor job. Her bosses saw her as an ideal prospect. She wrote fine news scripts, they told her, had a TV-ready voice, and, not incidentally, had “the look”—which is to say that she was pretty in a wholesome, all-American, Meg Ryan way. She had perfect white teeth, blue eyes, blond hair, and an easy smile.

During her broadcasts, however, she found that she could not stop blushing. The most inconsequential event was enough to set it off. She’d be on the set, reading the news, and then she’d stumble over a word or realize that she was talking too fast. Almost instantly, she’d redden. A sensation of electric heat would start in her chest and then surge upward into her neck, her ears, her scalp. In physiological terms, it was a mere redirection of blood flow. The face and neck have an unusual number of veins near the surface, and they can carry more blood than those of similar size elsewhere. Stimulated by certain neurological signals, they will dilate while other peripheral vessels contract: the hands will turn white and clammy even as the face flushes. For Drury, more troubling than the physical reaction was the distress that accompanied it: her mind would go blank; she’d hear herself stammer. She’d have an overwhelming urge to cover her face with her hands, to turn away from the camera, to hide.

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