Jessie A. Leak, M.D.
Committee on Communications

“In Jon’s mind, because it was legal, it had to be safe,” says Greg Frary of his son’s DXM [dextromethorphan] use. “He made a mistake … It’s cheap, it’s legal, and it’s available at any drugstore. DXM, a cough medicine ingredient, is the latest craze for teens who want to get high — or die trying.”

— People Magazine, February 2, 2004

Because of the extensive information available to the practicing anesthesiologist on the dangers of perioperative dietary supplement use by this and many other authors, this article will focus on two substances that have received top billing in the news of late: the new ban on ephedra alkaloid-containing products and the misuse/abuse of dextromethorphan, a well-known cough syrup ingredient available in several hundred over-the-counter medications, including Coricidin™ products.^1-5

Ephedra-Containing Products
It is currently estimated that up to 1 million youths between the ages of 12 and 17 use sports supplements, the most common of which are ephedra and creatine. Fifty-five percent of all adverse events concerning these products involve children 19 or younger. Industry estimates are that 12 to 17 million Americans consume more than 3 billion doses of ephedra products each year. The Food and Drug Administration (FDA) believes that up to 17 percent of all currently marketed dietary supplements contain a form of ephedra.

In June 2002, President Bush ordered the Rand Corporation to perform a safety review on ephedra. The American Medical Association called for a ban on ephedra on October 8, 2002. On October 9, 2002, Health and Human Services (HHS) Secretary Tommy Thompson said that he had asked FDA to recommend the “strongest possible mandatory warning label” for ephedra products. On February 28, 2003, the New York Times quoted Secretary Thompson who was “…..advis[ing] people…not to take the herb. I would not take this, I would not give it to my family, and I don’t know why anyone would take these products. Based on the ongoing Rand survey, why take the risk? Nonetheless [I] want to collect more evidence to meet the law’s tough standards for a ban, which [would] require, at the very least, unreasonable risk that a supplement will inflict injury.”

The results of the Rand study were publicly released by Secretary Thompson on this same day with severe concern about the herb. Four suggestions were made in this report: 1) a “black-box” warning on all ephedra-containing products; 2) that the FDA should send a letter to manufacturers with instructions to remove “unproven” health claims; 3) that if ephedra promotes biologic activity as it seemingly does, it should go through the same steps for FDA approval as any other drug; and 4) legislation was suggested for defining and regulating dietary supplements. A subsequent March 2003 Annals of Internal Medicine study revealed a 100-fold higher chance of causing an adverse reaction with ephedra than any other dietary supplement. In the same month, the government ordered 24 companies to stop advertising ephedra as a way to “build up muscles,” etc.

As a final measure, on December 30, 2003, FDA issued a consumer alert on the safety of dietary supplements containing ephedra. The alert “advised consumers to immediately stop buying and using ephedra products.” Additionally, on the same day, FDA notified manufacturers “that it intends to publish a final rule stating that dietary supplements containing ephedrine alkaloids present an unreasonable risk of illness or injury. The rule would have the effect of banning the sale of these products as soon as it becomes effective, 60 days after publication.” This means that all sales must cease by April 13, 2004.

Dextromethorphan (DXM)
Dextromethorphan, an N-methyl-d-aspartate (NMDA)-antagonist used in limited experimental settings for certain pain syndromes such as phantom limb pain, is a common ingredient in many over-the-counter cough medicines. In experimental models, it can attenuate acute morphine withdrawal in the developing organism. Unfortunately this ingredient is a popular abused substance, particularly to teenagers because of its potent euphoric properties. Signs and symptoms of intentional, excessive intake include tachycardia, hypertension, somnolence, agitation, slurred speech, loss of motor control, seizures, coma, low body temperature, nausea and vomiting, heavy sweating, muscle rigidity, tremor, low body temperature, impaired judgment, confusion, numbness of fingers/toes and even death. Many of the commercially available products with DXM are mixed with ingredients such as acetaminophen, which can further enhance its morbidity, i.e., hepatotoxicity from CoricidinHBP Maximum Strength Flu.™ ²

Typically teenagers seek to induce a “zombie-like” state called “dexing” or “robotripping” by taking medications found in drug stores such as Robitussin™ cough syrup or Coricidin™ cold tablets, known among users as red devils, triple-C's or skittles (the red pills, resembling candy, bear three Cs).³

Conclusion
ASA will keep up with new developments as they become available and disseminate this information to the membership. The educational pamphlets on herbs and dietary supplements that are available through ASA are updated every two years and will be updated within the next year to keep our members and our patients appraised of important new details.

References:

1. Leak JA. Potential hazards of perioperative herb and supplement use. Refresher Courses in Anesthesiology. American Society of Anesthesiologists. 2003; 31:117-126.

2. Kirages TJ, Sule HP, Mycyk MB. Severe manifestations of Coricidin intoxication. Am J Emerg Med. 2003; 21(6):473-475.

3. Fields-Meyer T, Sandra B, Harmel K, et al. Over the counter killer. People. February 2, 2004:48-51.

Jessie A. Leak, M.D., is Clinical Professor, University of Texas Health Science Center at San Antonio, San Antonio, Texas.