Propofol is an excellent anesthetic, relatively safe with a fast induction time and relatively quick recovery time. It is used in all types of surgical and non-surgical procedures (including intubation and time on a vent if the patient is in distress). With all the COVID 19 cases and the resultant hospitalizations and ICU stays, the increase in use has resulted in the drug product’s placement on the FDA’s shortage list.
Propofol (as noted above) is an excellent anesthetic, but, because of its formulation, it is also serves as an excellent growth media for bacteria and fungi. First approved in 1989, the injectable product was originally approved without containing a preservative. Over the course of a few years, various outbreaks of post-use infection were reported, and, in 1996, the innovator of the brand Diprivan added EDTA to the formulation as a preservative. Over the years, as generics were approved, because of periods of exclusivity and patents associated with the EDTA use in Diprivan, other antibacterial preservative were introduced into the formulations of generic products.
To make a short story long, bacterial and even fungal outbreaks continued post-addition of the preservatives (see history of propofol and outbreaks in an article entitled Infectious Disease Risk Associated with Contaminated Propofol Anesthesia, 1989–2014, by Vaca et. al. here). One of the more notorious outbreaks occurred in 2007, at an endoscopy center in Nevada where providers were re-using single dose vials of propofol for multiple patients. Mishandling and contamination of propofol vials have led to most of the outbreaks because of the high potential for bacterial/fungal growth of the egg lecithin- based formulation.
So where is all this going? Last week, the FDA issued guidance titled Temporary Policy on Repackaging or Combining Propofol Drug Products During the COVID-19 Public Health Emergency (here) permitting, among other things, combining the contents of two or more single use vials of propofol for use on multiple patients. In addition, there are other concerns associated with this practice, as different manufacturers of propofol include different inactive ingredients as their preservatives. FDA provides advice as to which approved products can be combined and which should not be combined. The guidance warns that combining products with different preservatives can effectively lower the concentration of either preservative, thus reducing its ability to inhibit growth of microorganisms.
Propofol is also subject to oxidation, and combining contents of different single use vials could pose a problem as the approved products are filled under a nitrogen blanket to decrease the amount of oxygen the product is exposed to during manufacture to prevent oxidation, and clearly manipulation of the product at pharmacies or hospitals cannot use such precautions. FDA has also provided strict and short “use by” times for these manipulated products in its advice.
A word to the health care industry – it is recognized that propofol is critical for use in treating COVID-19 patients as well as other emergent situations where an anesthetic is required, just be extra vigilant in its use and watch patients closely for signs of infection under these temporary conditions– which may be difficult when your are dealing with a patient that already is infected with COVID 19.
