Why Is She So Short of Breath?

Over-the-counter drugs can be risky

By Tony Dajer|Thursday, March 31, 2005
RELATED TAGS: PHARMACEUTICALS

The Emergency Room patient’s voice was as fragile and breathless as a Southern belle’s: “I know you will make me well, doctor,” she said. “But how could I be so weak? This isn’t me.”

The  monitor registered a slightly low blood pressure, 98/65; a normal pulse, 76; and a robust blood oxygen level.

“I’m not worried about you,” I said. “Your vital signs are fine. But I’m still not sure what’s causing this.”

Sandra, the intern, presented the woman’s story: age 67; history of mild hypertension, otherwise healthy; weak and short of breath for four days; couldn’t get out of bed that morning. No signs of infection or heart failure.

“Any recent plane flights?” I asked, thinking the breathlessness might be caused by a blood clot in the lungs.

“No,” Sandra replied. “And no history of thrombophlebitis [clotted and inflamed veins] either. She’s been feeling pins and needles in her hands and feet. What could that be?”

“Too vague,” I replied. “Anything else?”

“Some diarrhea last week. It was black for a while. Her doctor tested it for blood. Negative. He gave her something, and it went away.”

“Was she on Pepto-Bismol? That can color your stools black. Or iron?”

“Yes, I think she was.”

“No other new medications?”

“No, just the blood pressure pills.”

Sandra had taken a thorough history, but the fun of being a senior doctor is taking a second crack at it. The patient’s tale came together quickly: Had she been taking anything else? Well, yes, her doctor had put her on a daily aspirin, a month ago now. A whole one? Yes. How many black stools had she had? Maybe two or three a day. Tarry? Yes. She gave me a worried look. Is that very bad? No, no, but a stool resembling tar may explain why you’re so run down.

I moved out of the patient’s earshot to quiz Sandra. “Aspirin plus tarry stools equals what?”

“Gastrointestinal bleeding?”

“Looks like it. Her hematocrit is probably around 23.” A hematocrit measures the proportion of red blood cells to total blood volume, and the normal amount is over 30 percent.

“But I wonder why her doctor put her on a whole aspirin, instead of a half?”

Aspirin is nature’s gift to an aching humanity. Its parent molecule, salicin, comes from willow bark; although a real stomach burner, it was an old remedy for rheumatism and inflamed joints. Felix Hoffman, trying to spare his arthritic father more heartburn, modified it to acetylsalicylic acid while he was an employee at Bayer. The company trademarked the drug in 1899, and for the next half century, if your knees ached or your head pounded, aspirin was the treatment.

In the 1950s steroids came along. Although powerful pain relievers, they proved too risky for long-term use. In the 1960s the counterinflammation crusade produced more nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, which proved a bit easier on the stomach than aspirin. Then in the 1970s, fear of Reye’s syndrome—a rare, life-threatening condition that can develop after a child with a viral illness takes drugs containing salicylates— knocked aspirin out of the kiddie-fever market. The old warhorse seemed on its last legs. But new battlefields beckoned.

It had long been known that aspirin can cause easy bruising and bleeding gums. That’s because it blocks forms of cyclooxygenase, an enzyme involved in a host of biochemical functions. One function produces a substance that makes the tiny wound-plugging blood cells called platelets clump. That effect helps heal a torn blood vessel, but it proves lethal in a coronary artery covered with platelet-attracting plaque buildup. With heart attacks and strokes killing Americans by the hundreds of thousands, clinicians wondered whether impeding the clotting of blood, or blood thinning, might help.

In 1986 aspirin proved its vascular credentials by heading off second heart attacks or strokes. And in 1988 a 22,000-subject trial among American doctors found that taking a whole aspirin every other day reduced the number of first heart attacks by an impressive 44 percent. By 1996 the FDA had suggested new labeling to state that aspirin could be used to treat patients during heart attacks: Amazingly, it cut mortality by a fifth—the same as $4,000 clot busters. The American Heart Association is clear. Every year, 5,000 to 10,000 lives could be saved if everyone chewed an aspirin at the first sign of a heart attack.

Suddenly, lots of people seemed to think taking an aspirin a day would safeguard their heart. Primary prevention, though, is a tricky business. First, it’s tough to improve on the asymptomatic state. Second, there’s a good reason Hippocrates’ motto was “Above all, do no harm”—and giving a drug to prevent future (but by no means certain) problems means you could incur some harm now. The iron law of medicine is there’s never—ever—a free lunch.

My patient’s hematocrit came back: 18 percent.

“Oh my gosh. How did you know?” Sandra exclaimed.

I shook my head. “My guess was 23. Eighteen? Wow. She’s lost about half her blood volume.”

Back at the patient’s side, Sandra said, “We know what’s wrong,” and then explained the blood loss to her.

“How?” the patient asked, incredulous.

“The aspirin irritates the stomach lining, and an ulcer forms. Then it bleeds. That’s why you had the black stools. Digested blood. I don’t know why it didn’t show up on the earlier test. Maybe the bleeding was intermittent.”

“Am I going to die?”

“Oh, no, no,” Sandra exclaimed. “But we’re going to take you upstairs so the gastroenterologist can look in with an endoscope and fix the ulcer.”

But on the way to the endoscopy suite, the patient turned even paler. Her breathing rate sped up, and her whole body trembled. It dawned on me she would never tolerate sedatives and an endoscopy.

“Let’s get her back down,” I said. “Her tank’s too low. She needs red cells.”

The problem with aspirin and newer NSAIDs is that they inhibit every effect of cyclooxygenase—not just those involved in inflammatory conditions like arthritis. The enzyme’s products have a hand in a slew of biochemical reactions. In the stomach they build bicarbonate and mucus buffers against the organ’s acids (without them, the risk of ulceration can increase 20-fold); they also help blood vessels dilate and cause uteruses to propel babies into the world.

Yet millions of Americans take medications that block cyclooxygenase’s function. Fifty million Americans take a daily aspirin, and 17 million take other NSAIDs every day. The cost is high: Aspirin, after only two years of use, harms one in 100 patients. NSAIDs quintuple the risk of gastrointestinal bleeding overall (of which there are 150,000 cases a year) and push it even higher in people over 65 and those with heart disease or a history of ulcers.

The path to safer alternatives hasn’t been smooth. Platelet inhibitors that bypass the enzyme are now widely used, but at least one, Ticlid, can trigger a potentially fatal clotting disorder. Some “new and improved” NSAIDs have backfired too: One caused fulminant liver failure and was taken off the market; others have been shown to pose such a high risk of gastrointestinal bleeding that they cannot be used for more than five days.

The newest, such as Vioxx and Celebrex, were tailored to stop only COX-2, the form of the enzyme that affects the inflammatory process, not the form involved in gastric protection. But the recent Vioxx recall—sparked by reports of unaccountably high incidences of heart attacks—as well as gloomy news and federal warnings about Celebrex and Bextra, prove how hard it is to pull off the perfect biochemical surgical strike. Two of the enzyme’s products are at work in the circulatory system, and Vioxx nudged each of them in the wrong direction: The drug didn’t tamp down the product that goads platelets to clot, yet it did squelch the product in blood vessel walls that keeps arteries open.

Still, plain old aspirin does prevent heart attacks. The trick is to find the sweet spot where the benefits outweigh the side effects—which has everything to do with adding up one’s cardiac risk factors. To prevent a first heart attack, a doctor must treat anywhere from 65 to 660 people for five years—and run the risk of one to 10 GI bleeds. If you’re free of hypertension, diabetes, high cholesterol, or previous heart disease, an aspirin a day is not for you. But if you have one of those conditions, it might be. As to the ideal dose, no one has proved that taking fewer milligrams drops the chances of bleeding, but going over 162 mg a day (two baby aspirin) doesn’t do more good. My patient’s only risk factor was mild hypertension, so she did not need a whole aspirin (325 mg) a day.

After a two-unit transfusion, my patient pinked up and caught her breath. “I feel like I’ve risen from the dead,” she exclaimed.

The endoscopy showed a stomach ulcer that had stopped bleeding. But it takes about a week for the gastric lining to replenish itself. Later that night, my patient vomited blood. A second scope showed a new duodenal ulcer eroding a blood vessel, which had to be stapled shut. Five units of blood later, she finally stabilized.

Take two aspirin and call me in the morning? Let’s talk it over first.

Tony Dajer is assistant director of the emergency medicine department at New York University Downtown Hospital and a frequent contributor to Vital Signs. The cases described in Vital Signs are true stories, but the authors have changed some details about the patients to protect their privacy.

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