The two young men who showed up retching and wild-eyed in an emergency room in Portland, Ore., last summer insisted they had swallowed nothing but an ordinary soft drink before one collapsed. Yet their odd coloring suggested otherwise. Fifteen minutes after they had downed the drink, their lips and skin turned a startling blue. Their blood was as dark as chocolate.

Eventually one of the men confessed: they had spiked their soda with a bitter liquid they bought online. They meant to order “2C-E,” a man-made hallucinogen that they heard was similar to Ecstasy or LSD. What they received instead from a chemical company in China was aniline, an industrial solvent that ruptured their red blood cells, starved their tissues for oxygen and nearly killed them. Whether the substitution was their mistake or the company's, no one knew. “For quite a while after they got to the ER,” says Zane Horowitz, medical director of the Oregon Poison Center, “we didn't know what exactly they had taken, and neither did they.”

Horowitz and other toxicologists say the range of legal and illegal drugs now available to anyone with a credit card or well-stocked family medicine chest is broader and, in some ways, more dangerous than ever before. Bored teens seeking the latest high are only part of the problem. Patients who double down on long-acting prescription narcotics or mix some medicines with one another or with alcohol are vulnerable, too. The escalating death toll from drug use in the U.S. is startling, as a recent overview from the Centers for Disease Control and Prevention has confirmed. Accidental poisoning has now replaced car crashes as the nation's leading cause of fatal injury, and 89 percent of those poisonings result from drugs.

The magnitude of the problem has legislators, doctors and public health experts searching for solutions. Last July, President Barack Obama signed into law the Synthetic Drug Abuse Prevention Act of 2012, nationally outlawing the manufacture, sale and possession of 2C-E and 25 other “designer” recreational drugs. To try to rein in prescription drug abuse, at least 49 states have authorized funding for electronic databases that ultimately aim to identify physicians who overprescribe narcotics, as well as addicts who “doctor shop” to load up on pain relievers or stimulants.

Meanwhile medical toxicologists have surprising advice for emergency room teams treating overdoses: rely less on standard blood and urine tests when trying to identify drugs of abuse because those lab tests can be grossly misleading. Instead, these medical sleuths say, asking sharper questions will likely save more patients.

New Narcotics

Despite the recent increase in deaths from designer drugs—recreational compounds that are chemically tweaked to stay ahead of the law—a less exotic threat accounts for the most common type of drug poisoning. In the most recent analysis of all overdose deaths in the U.S., more than 40 percent involved prescription narcotics. Sales of these strong painkillers, including oxycodone, hydrocodone and methadone, have climbed, too, jumping by 300 percent between 1998 and 2008, according to the CDC, as doctors have prioritized alleviating the severe pain of cancer, surgery and serious injury.

In the past decade research has firmly demonstrated that a short course of prescription narcotics can safely reduce suffering. But the abuse of these potentially addictive drugs, alone or in combination, is particularly deadly. A 2008 study in the Journal of the American Medical Association profiled the problem in West Virginia: 56 percent of 275 people who overdosed on prescription narcotics had not been prescribed the medication that killed them. Another 21 percent had received prescriptions for narcotics from five or more doctors in the year before they died, a pattern that suggests they had doctor shopped to obtain more pills than any one physician would supply. National statistics underscore the risk: legal narcotics now kill more people every year than heroin and cocaine combined.

Not only are prescription narcotics more widely available than ever before, some also stay in the body longer. High-dose, extended-release pills are convenient for patients seeking uninterrupted relief from severe pain throughout the night, for example, but they also make overdose more likely if taken incorrectly. Some recreational abusers pulverize long-acting 60-milligram pills of oxycodone to snort or smoke it, thereby sending a potentially toxic quantity into the bloodstream all at once.

Well-meaning pain patients run afoul of the pills, too. “I get patients who tell me, ‘I ran out of my medicine, so my neighbor gave me some of his,’” Horowitz says. “But it turned out the neighbor was taking a much higher dose.”

The greater availability of prescription drugs also makes it dangerously easy to mix medications. In the JAMA overdose study, nearly 80 percent of those who died were on a medley of drugs that usually included benzodiazepines (commonly prescribed for anxiety or insomnia) and had sometimes imbibed alcohol as well. That pattern of mixing often bespeaks an underlying addiction, the researchers say. In high-enough doses, each of those drugs can slow breathing, and the combination is particularly dangerous, says Jane Prosser, an emergency medicine physician at Weill Cornell Medical Center in New York City. “This is one of those cases where one plus one equals four.”

An overdose in an older patient, who is more likely to be undergoing treatment for multiple chronic conditions, can be especially tough to diagnose in the emergency room, Prosser says. “A confused elderly person comes to the ER and says, ‘I feel very weak and dizzy.’ Is that their cancer? The chemo? The pain meds? The fact that they're dehydrated because they've been vomiting and have diarrhea? It can be very hard to tell.”

When Lab Tests Go Wrong

Although advanced analytical techniques can selectively identify any drug, they are too expensive and slow to be useful in a medical emergency, says Mark B. Mycyk, a medical toxicologist at John H. Stroger, Jr., Hospital of Cook County in Chicago. And the standard panels of quicker screening tests for drugs in blood and urine have not kept up with shifts in the types of drugs people abuse.

“Those core [toxicology] screens were developed for the war on drugs in the workplace in the mid-1970s and are designed mostly to pick up heroin, cocaine and marijuana use,” Mycyk says. The tests will not detect the increasing number of barely legal or illegal recreational drugs such as 2C-E that come in many slightly rejiggered versions because of creative chemists looking to make a buck. Even many legitimate medicines, including the antianxiety pills Ativan and Xanax and the painkillers methadone and oxycodone, do not show up on the standard hospital drug-screening tests. Relying on lab results, Prosser says, can, in this case, foil diagnosis and misguide treatment.

Say a man addicted to methadone comes into the emergency room unconscious after also taking a hefty dose of Xanax. The doctor, trying to figure out why the patient is unconscious, screens his urine for sedating narcotics. The results come back negative because the screen will pick up neither methadone nor Xanax. Misled by the test results, the doctor does not prescribe a medicine that would blunt symptoms of withdrawal as the narcotic wears off—and that decision has fatal consequences. “Suddenly [the patient] starts vomiting from opiate withdrawal but doesn't wake up, because he has OD'd on benzodiazepines,” Prosser says. Inhaling that vomit could kill him.

Improved testing is not necessarily the answer, Mycyk says. When time is critical, taking note of a telltale constellation of symptoms typically triggered by a certain class of drugs—and treating those symptoms—makes more sense than waiting for chemical confirmation.

Federal organizations have started to work on solutions as well. Last July the Food and Drug Administration began requiring drug companies to start educating doctors about the special risks of such prescription drugs. The CDC has called on states to consider monitoring Medicaid or workers' compensation claims “for signs of inappropriate use of controlled prescription drugs.” To help reduce doctor shopping, the CDC says, these state programs might in some cases consider restricting reimbursement for controlled drugs to scripts that come through only one designated prescriber per patient and one designated pharmacy.

Mycyk has started telling the ER physicians he trains that they might save more lives by asking more specific questions than the ones they learned to ask in medical school. “Don't ask, ‘Do you abuse illegal drugs?’” he says. “Most of the drugs people are using today are not illegal. A lot of them are overdosing on drugs that were prescribed by their doctor.”

Instead, Mycyk says, asking questions such as “Have you ever gotten high on cough syrup?” or “Have you ever taken a friend's or relative's pills?” will put you on the right track to more helpful responses. “Most [patients] will do all they can to help you,” he says. “In most cases, landing in the ER was an accident. They don't want to die.”

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