Are your patients on fen/phen? You’d better get them to tell you

Anecdotal reports point to cardiac arrest for patients taking diet drug

It started out as an informal preventive medicine study on medication side effects for the University of California at San Diego. About half a dozen hospitals in Southern California were contacted and asked: What has your experience been with side effects related to the combination diet drug fenfluramine/phentermine ("fen/phen")?

While the researchers might have expected answers such as dizziness, headaches, and nausea, they were shocked by what they heard: "Virtually every hospital had reports of life-threatening adverse reactions" when patients were under general anesthesia, says Joe Risser, MD, MPH, one of the researchers and now a staff physician at Lindora Medical Clinics in San Diego. "The most common were heart-related, such things as arrhythmias, MI, strokes, heart attacks — even a few deaths."

And now such anecdotal reports are being heard across the country and have led the American Society of Anesthesiologists (ASA) in Park Ridge, IL, to post a media statement on its Web site regarding fen/phen. (See statement, p. 3.) The statement says the ASA is concerned about reports that patients taking fen/phen are not disclosing this information to their anesthesiologists and "are experiencing adverse and potentially deadly reactions while under general anesthesia." The ASA encourages patients to be forthcoming when talking with their anesthesiologists about any drugs they have taken prior to surgery, including prescriptions and over-the-counter medications such as diet pills, vitamins, and herbal preparations.

What’s the problem?

All of the physicians contacted by Same-Day Surgery for this story want to make one point perfectly clear: There has been no scientific research done on the effect of anesthesia on patients taking fen/phen. The steps that these providers are taking and that are described below are the most conservative approach to what potentially could be life-threatening problems.

The 1996 edition of Physicians’ Desk Reference contains a single case study related to Pondimin tablets, a brand of fenfluramine hydrochloride:

"A fatal cardiac arrest has been reported shortly after the induction of anesthesia in a patient who had been taking fenfluramine prior to surgery. Fenfluramine may have a catecholamine-depleting effect when administered for a prolonged period of time; therefore, potent anesthetic agents should be administered with caution to patients taking fenfluramine. If general anesthesia cannot be avoided, full cardiac monitoring and facilities for instant resuscitative measure are a minimum necessity."1

While that reference is for just one of the drugs in the fen/phen combination, "We don’t know if the combination of the two drugs is better or worse than one alone," says Julian Gold, MD, co-chairman of the department of anesthesiology at Cedars-Sinai Medical Center in Los Angeles.

In fact, the problems with fen/phen could be caused, in part, by the obesity of the patients, Risser says.

Same-day surgery managers need to be prepared for the catecholamine-depleting effect of fenfluramine, warns Asa Lockhart, MD, staff physician at Trinity Mother Francis Hospital and East Texas Medical Center, both in Tyler, TX.

"If patients were to become hypotensive, then you’d need to use a direct acting agent such as Norepinephrine or Neo-synephrine," Lockhart says. "If the patient becomes hypotensive, they would likely be unresponsive to ephedrine."

What should you do?

Same-day surgery managers should take these steps regarding fen/phen, experts advise:

Inform surgeons that you expect patients to be off fen/phen for two weeks when patients come in for surgery.

"The burden is on surgeons," Gold says.

Send a note to your surgeons expressing your concern and advising patients who are having elective surgery to be off phentermine and fenfluramine for at least two weeks prior to the surgery date, which is the tactic Gold used. Tell them surgery will be canceled if they don’t follow this directive.

Surgeons may want to post the note in their offices and highlight the part of the notice about being off the drugs for two weeks, as did one of the surgeons at Cedars-Sinai.

"We want to make sure patients understand we’re serious about this," Gold says.

Ask patients in the preoperative interview whether they are taking any prescription or over-the-counter medications, including diet pills, herbal preparations, vitamins, or recreational drugs.

Keep in mind that many patients are embarrassed to admit they’re taking diet pills, Lockhart says. In addition to asking patients about diet drugs when patients are in the surgeon’s office and in the preoperative interview, Lockhart’s patients are asked for a third time in the surgical holding area.

Be careful how you word your question, he warns. Many patients don’t consider diet pills, even prescription ones, to be "medication," Lockhart says. He says when one patient was asked whether she was taking phen/fen, she became indignant and said, "That’s just a vitamin."

Tell patients about possible interaction

If a patient requires urgent or semi-urgent surgery and is taking fen/phen, notify the patient of the risk.

"We tell patients that it’s a possibility that fenfluramine could interact with anesthesia and cause the blood pressure to be unstable and low and that we will closely monitor them as we do all patients," Lockhart says.

Keep in mind that in the event that the patient becomes hypotensive, it takes some time to mix Neo-synephrine because it has to be administered as an infusion, Lockhart warns. Norepinephrine has to be diluted as a drip.

"It probably would be wise to have Norepinephrine available, if you’re a freestanding facility, to minimize delays and therapy," he suggests.

The half-life of Pondimin, which is the brand name of fenfluramine hydrochloride, is 20 hours. Therefore, phen/fen should be eliminated from the body in approximately five half-lives, or about four days, Lockhart says.

"However, there may be variability in the rate of elimination in different patients," he says. "By the time you let that allowance, you’re in the neighborhood of about a week."

If the drug causes a problem, it is caused by the depletion of catecholamine, Lockhart points out.

"Where conditions permit, we should allow another week for those levels to be replenished," he says. For that reason, Lockhart and others are asking patients to be off the drugs for two weeks before surgery.

"It’s admittedly an overly conservative approach, but when conditions permit it, if a patient wants the most conservative approach, that’s what we recommend," Lockhart says.

Gold concurs. "We’ve just decided until there’s some science to resolve the issue, we’d take the most conservative and safest position," he says.

Reference

1. Medical Economics Co. Physicians’ Desk Reference. 50th edition. Montvale, NJ; 1996.