By Abby S. Van Voorhees, MD, February 01, 2012
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with David Ozog, MD, about his recent Journal of the American Academy of Dermatology article, “Recommendations and current practices for the reconstitution and storage of botulinum toxin type A.”
Dr. Van Voorhees: What are the current recommendations from the Centers for Disease Control and Prevention (CDC) regarding reconstitution and storage of botulinum toxin type A? Are these recommendations different from those recommended by the Centers for Medicare and Medicaid Services (CMS)?
Dr. Ozog: One of the problems that led to our study is that the CDC guidelines differ from Medicare’s. The CDC insists on adherence to the package insert, which includes the labeling “single patient use.” Their rationale developed from some non-dermatologic cases where patients developed infections including hepatitis after multiple patients were injected from various single-use vials. It wasn’t a problem with the vials themselves but with “double-dipping” of needles, where the same needles were used for multiple patients, which isn’t a safe practice in any situation. Dermatologists have safely used multiple use vials, such as lidocaine, for years without issue when adhering to safe, sterile practice. There is no actual safety difference between using a lidocaine vial for multiple patients and using a botulinum toxin vial for multiple patients.
The issue for hospitals, such as Henry Ford where I practice, is that adherence to and compliance with CDC guidelines is necessary for Joint Commission accreditation. So many hospital-based practices are required to discard large quantities of unused toxin after a single patient use, which is adding to the cost of treating patients. Interestingly, CMS encourages the use of botulinum toxin for multiple patients. They’re paying for it in certain circumstances, including hyperhidrosis and neurological conditions, and they’ll reimburse the exact amount used. However, if there’s remaining toxin they’ll reimburse for that as well. But they’d rather not, and they recognize, correctly we believe, that as long as you’re doing safe practices, using sterile needles and not double-dipping, there is no increased risk of infection.
Dr. Van Voorhees: How was this study conducted? Who was surveyed?
Dr. Ozog: We looked at 1,000 physicians who are members of the American Society for Dermatologic Surgery; we chose this group because its members were likely to be highly procedurally based given the nature of the organization. We sent out Internet-based surveys to 1,000 physicians and had a nice response rate of about 32 percent. We ended up using about 31 percent because we had a 1 percent drop-off based on the initial question, “Do you currently use botulinum toxin in your practice?” 10 people dropped out of the survey based on saying they did not. [pagebreak]
Dr. Van Voorhees: What did you ask?
Dr. Ozog: We asked them how they reconstitute their botulinum toxin in their office, how long they keep the vial after reconstitution, whether they were adhering to the CDC guidelines and discarding after a single use or using a vial for multiple uses, if they’d had a patient develop a local infection after a botulinum toxin injection, and how many years they’d been in practice. We wanted to see if there were differences in practice patterns based on the length of time since residency.
Dr. Van Voorhees: What did you find? Were most physicians discarding their reconstituted botulinum toxin after one week? What were the majority actually doing?
Dr. Ozog: The majority of the physicians, more than 68 percent, routinely keep the toxins for one week or greater, and 67 percent felt that the toxins could be safely kept for one to four weeks. No instances of local infection were documented at any time by any of the 312 practices that responded. In fact, we were unable to find any published reports of local infection after botulinum toxin injection.
Dr. Van Voorhees: Were physicians reconstituting their botulinum toxin primarily in sterile saline? If not, what were most using and why?
Dr. Ozog: Just under 80 percent were using bacteriostatic saline. Some were still using sterile water as per the package insert guidelines, and a few were using non-bacteriostatic saline.
Dr. Van Voorhees: Did you ask them why they were choosing different vehicles to reconstitute the product?
Dr. Ozog: We didn’t specifically ask them why but the support for using bacteriostatic saline stems from what was originally anecdotal evidence, but then in 2002 Murad Alam, MD, Jeffrey Dover, MD, and Ken Arndt, MD, did a randomized prospective study and 100 percent of patients in their prospective arm had less pain with the bacteriostatic saline and the difference was more than 50 percent in terms of decrease in pain. (Arch Dermatol. 2002;138:510-514.) They posited, and this was borne out in subsequent studies, that the presence of benzyl alcohol not only acts as a preservative but also a temporary anesthetic. [pagebreak]
Dr. Van Voorhees: It sounds like most physicians were keeping the reconstituted botulinum toxin longer than one week were they using it for the same patient, or for multiple patients?
Dr. Ozog: They were using it for multiple patients. Nearly 70 percent open a vial, treat a patient, and then keep it for one week, two weeks, sometimes longer and use it in multiple patients, obviously adhering to safe practice when it comes to needle use, using fresh sterile needles every time the product is withdrawn.
Dr. Van Voorhees: What are these consensus guidelines then recommending for botulinum toxin reconstitution and storage?
Dr. Ozog: The first recommendation is that reconstituted botulinum toxin A vials that are labeled for single patient use may be administered to multiple patients provided that safe injection techniques are practiced. Second, reconstitution may be performed using bacteriostatic saline as this has been found to decrease pain and increase tolerability upon injection. Third, the reconstituted toxin may be stored for a period of at least two weeks without detrimental effect to its safety, sterility, or efficacy.
Dr. Van Voorhees: Is there any applicability with other toxins?
Dr. Ozog: This would be the same between abobotulinum toxin and onabotulinum toxin. We don’t know if incobotulinumtoxin A will be any different because it’s non-refrigerated, has a smaller particle size, and can be stored for longer periods of time; therefore it is best not to make conclusions until more data is available.
Dr. Van Voorhees: Is the hope that the CDC will revise its guidelines based on these new consensus guidelines?
Dr. Ozog: That would be hoping for too much. I’m hoping that at least a few of the hospital-based systems, such as Henry Ford, can stand up to the regulatory agencies and point out the evidence. However, in general they tend to be very averse to doing anything other than what the Joint Commission dictates. But perhaps after reviewing our data and getting the bill for all of the toxin that’s been thrown away, they’ll reconsider.
Dr.OZOG is an assistant professor in the department of dermatology, division of Mohs micrographic surgery at Henry Ford Hospital. His article was published online in the Journal of the American Academy of Dermatology on Nov. 7, 2011 and is available at www.eblue.org/article/S0190-9622(11)01092-9/fulltext. doi:10.1016/j.jaad.2011.10.008.