Complications

by Atul Gawande

  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

  In 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.

  For as long as Drury could remember, she had been a blusher, and, with her pale Irish skin, her blushes stood out. She was the sort of child who almost automatically reddened with embarrassment when called on in class or while searching for a seat in the school lunchroom. As an adult, she could be made to blush by a grocery-store cashier’s holding up the line to get a price on her cornflakes, or by getting honked at while driving. It may seem odd that such a person would place herself in front of a camera. But Drury had always fought past her tendency toward embarrassment. In high school, she had been a cheerleader, played on the tennis team, and been selected for the prom-queen court. At Purdue, she had played intramural tennis, rowed crew with friends, and graduated Phi Beta Kappa. She’d worked as a waitress and as an assistant manager at a Wal-Mart, even leading the staff every morning in the Wal-Mart cheer. Her gregariousness and social grace had always assured her a large circle of friends.

  On the air, though, she was not getting past the blushing. When you look at tapes of her early broadcasts—reporting on an increase in speeding-ticket fines, a hotel food poisoning, a twelve-year-old with an IQ of 325 who graduated from college—the redness is clearly visible. Later, she began wearing turtlenecks and applying to her face a thick layer of Merle Norman Cover Up Green concealer. Over this she would apply MAC Studiofix foundation. Her face ended up a bit dark, but the redness became virtually unnoticeable.

  Still, a viewer could tell that something wasn’t right. Now when she blushed—and eventually she would blush nearly every other broadcast—you could see her stiffen, her eyes fixate, her movements become mechanical. Her voice sped up and rose in pitch. “She was a real deer in the headlights,” one producer at the station said.

  Drury gave up caffeine. She tried breath-control techniques. She bought self-help books for television performers and pretended the camera was her dog, her friend, her mom. For a while, she tried holding her head a certain way, very still, while on camera. Nothing worked.

  Given the hours and the extremely limited exposure, being an overnight anchor is a job without great appeal. People generally do it for about a year, perfect their skills, and move on to a better position. But Drury was going nowhere. “She was definitely not ready to be on during daylight hours,” the producer said. In October of 1998, almost two years into her job, she wrote in her journal, “My feelings of slipping continue. I spent the entire day crying. I’m on my way to work and I feel like I may never use enough Kleenex. I can’t figure out why God would bless me with a job I can’t do. I have to figure out how to do it. I’ll try everything before I give up.”

  What is this peculiar phenomenon called blushing? A skin reaction? An emotion? A kind of vascular expression? Scientists have never been sure how to describe it. The blush is at once physiology and psychology. On the one hand, blushing is involuntary, uncontrollable, and external, like a rash. On the other hand, it requires thought and feeling at the highest order of cerebral function. “Man is the only animal that blushes,” Mark Twain wrote. “Or needs to.”

  Observers have often assumed that blushing is simply the outward manifestation of shame. Freudians, for example, viewed blushing this way, arguing that it is a displaced erection, resulting from repressed sexual desire. But, as Darwin noted and puzzled over in an 1872 essay, it is not shame but the prospect of exposure, of humiliation, that makes us blush. “A man may feel thoroughly ashamed at having told a small falsehood, without blushing,” he wrote, “but if he even suspects that he is detected he will instantly blush, especially if detected by one whom he reveres.”

  But if it is humiliation that we are concerned about, why do we blush when we’re praised? Or when people sing “Happy Birthday” to us? Or when people just look at us? Michael Lewis, a professor of psychiatry at the University of Medicine and Dentistry of New Jersey, routinely demonstrates the effect in classes. He announces that he will randomly point at a student, that the pointing is meaningless and reflects no judgment whatever about the person. Then he closes his eyes and points. Everyone looks to see who it is. And, invariably, that person is overcome by embarrassment. In an odd experiment conducted a couple of years ago, two social psychologists, Janice Templeton and Mark Leary, wired subjects with facial-temperature sensors and put them on one side of a one-way
mirror. The mirror was then removed to reveal an entire audience staring at them from the other side. Half the time the audience members were wearing dark glasses, and half the time they were not. Strangely, subjects blushed only when they could see the audience’s eyes.

  What is perhaps most disturbing about blushing is that it produces secondary effects of its own. It is itself embarrassing, and can cause intense self-consciousness, confusion, and loss of focus. (Darwin, struggling to explain why this might be, conjectured that the greater blood flow to the face drained blood from the brain.)

  Why we have such a reflex is perplexing. One theory is that the blush exists to show embarrassment, just as the smile exists to show happiness. This would explain why the reaction appears only in the visible regions of the body (the face, the neck, and the upper chest). But then why do dark-skinned people blush? Surveys find that nearly everyone blushes, regardless of skin color, despite the fact that in many people it is nearly invisible. And you don’t need to turn red in order for people to recognize that you’re embarrassed. Studies show that people detect embarrassment before you blush. Apparently, blushing takes between fifteen and twenty seconds to reach its peak, yet most people need less than five seconds to recognize that someone is embarrassed—they pick it up from the almost immediate shift in gaze, usually down and to the left, or from the sheepish, self-conscious grin that follows a half second to a second later. So there’s reason to doubt that the purpose of blushing is entirely expressive.