Circulation 60,475 • Volume 15, No. 3 • Fall 2000

Anesthesiologist Executive Reports How Abbott Made Sevoflurane Safer

Charles H. McLeskey, MD

Water Stops Formation of Highly Toxic Acid

To the Editor

As reported in previous APSF Newsletter articles, in 1996 and 1997 Abbott recalled specific lots of sevoflurane in the U.S. At that time, we discovered that sevoflurane could degrade in the presence of metal impurities and other environmental contaminants to form hydrogen fluoride. Hydrogen fluoride has the potential to produce an acid burn on contact with mucosa of the respiratory tract, and thus, Abbott embarked on a massive research investigation to identify the source of the contamination and understand the mechanism underlying the degradation. Through these efforts, we learned that the equipment used in manufacturing and shipping of product, the amber glass bottles, and even anesthesia equipment all have the potential to contain metal and environmental impurities which when in contact with sevoflurane could form hydrogen fluoride.

Once the cause and mechanism of this chemical reaction were determined, Abbott scientists next took on the challenge of finding a way to inhibit the degradation reaction, making sevoflurane more stable, and thus, safer. After intensive research efforts, an elegant solution was discovered. When an effective concentration of water is added to sevoflurane, the degradation process resulting in the formation of hydrogen fluoride is inhibited. With the agreement of the FDA and other regulatory agencies, this improvement was quickly implemented. In fact, this discovery was so substantial that sevoflurane containing this effective amount of water was issued a patent by the U. S. Patent office. The water-enhanced sevoflurane product inhibits hydrogen fluoride formation should sevoflurane come in contact with metal and environmental impurities, which are endemic and may be found during manufacturing, transport, storage or even potentially during delivery of the anesthetic.

Abbott took on the next goal of packaging sevoflurane in a plastic container. This container would reduce the possibility of breakage, making the workplace safer. An ideal container should have the following properties: stability in the presence of sevoflurane, no release of extractables, vapor barrier properties that prevent sevoflurane from escaping the container, non-breakable, and durability in the anesthesia environment. Although plastic reduces the level of potential contaminants, water is still required to inhibit the formation of hydrogen fluoride. After an encyclopedic search, the plastic known as PEN, polyethylene napthalate, was found by Abbott scientists to meet all of the above requirements and to be ideal for this purpose. Sevoflurane in the PEN container has now received FDA approval and a patent has been awarded to Abbott Laboratories Inc.

The discovery that an effective concentration of water added to sevoflurane addresses the hydrogen fluoride problem, may appear relatively simple on the surface. However, in actual fact, much sophisticated research and testing were required to identify the solution to a potential problem faced by anesthesia providers. The inclusion of water in sevoflurane and selection of PEN as the ideal plastic container are two important safety enhancements now afforded the anesthesia community. These advances are representative of Abbott’s commitment to and continual search for improvements in anesthetic drugs and techniques.

Charles H. McLeskey, MD
Sr. Director, Clinical Development
Abbott Laboratories – Hospital Products Division
Department 96R, Building AP30
200 Abbott Park Rd
Abbott Park, IL 60064
ph. (847) 938-3950 fax (847) 938-6590
[email protected]