The Propofol Safety Review

by Tricia A. Meyer, PharmD

On June 15, 2007, the FDA released a safety alert concerning reports over the past few months of cases of fever, chills, and body aches in several clusters of patients shortly after the administration of propofol. These new cases involved patients undergoing procedures in gastrointestinal suites. The FDA noted that the symptoms were similar to those reported when propofol was first introduced in the US. The postoperative infection in these early cases was attributed to lapses in aseptic technique with risk factors that included “batch” preparation of propofol syringes for use throughout the day, reuse of syringes or infusion pump lines on different patients, use of propofol syringes prepared more than 24 hours in advance, transfer of prepared syringes between operating rooms or facilities, failure to wear gloves during insertion of intravenous catheters, and failure to disinfect the stoppers of the propofol vials. It was also noted that 50-ml and 100-ml vials were used as multi-dose vials. The formulation at that time did not contain preservatives.

In the most recently reported cases, investigators also found use of the single-use vials for multiple patients. To date, tests performed on multiple units of propofol vials and lots by the FDA have not identified any units contaminated with bacteria or endotoxins. Testing of other possible sources such as the lidocaine coadminsitered with propofol and the instrumentation sterilization systems have not identified any potentially causative agents.

Propofol is marketed as Diprivan^® and is also available as a generic disodium edetate. Sodium metabisulfite or benzyl alcohol is added to the propofol to retard the rate of microbial growth. Even though the product contains preservatives, microbial growth is still possible and it is not an antimicrobially preserved product under USP standards. The emulsion is capable of supporting microbial growth in the event of contamination during administration due to the level of soybean oil and egg lecithin or egg yolk phospholipids contained in the product.

Recommendations and considerations by the FDA are:

• Both the vial and prefilled syringe formulation must be used on only 1 patient.
• Administration must commence immediately after the vial or syringe has been opened.
• In general anesthesia or procedural sedation: administration from a single vial or syringe must be completed within 6 hours of opening.
• In ICU sedation: propofol administered directly from a vial must be limited to only 1 patient, must commence immediately on opening the vial and must be completed within 12 hrs of opening the vial.

Package Insert Guidelines:

• Strict aseptic technique must always be used during handling, including hand washing prior to use.
• Propofol should be visually inspected prior to use for:
  • particulate matter
  • discoloration
  • evidence of separation of the phases of the emulsion.
• Do not use if contaminated.
• Prepare for use just prior to administration to each patient.
• The vial rubber stopper should be disinfected using 70% isopropyl alcohol.
• Discard unused portions within the required time limits.

The FDA urges individuals to report adverse events to the MedWatch Adverse Event Reporting Program.

Tricia A. Meyer, PharmD, MS, is Director of the Department of Pharmacy and Assistant Professor, Department of Anesthesiology, Scott and White Hospital, Texas A&M Health Science Center, Temple, TX

General References

1. FDA alert/information for healthcare professionals: propofol (marketed as Diprivan and as generic products) Information. U.S. Food and Drug Administration, Center for Drug Evaluation and Research. Available at: http://www.fda.gov/cder/drug/infopage/propofol/default.htm. Accessed June 17, 2007.
2. Bennett SN, McNeil MM, Bland LA, et al. Postoperative infections traced to contamination of an intravenous anesthetic, propofol. N Engl J Med 1995;333:147-54.
3. Infections linked to lax handling of propofol. Am J Health Syst Pharm 1995;52:2061, 2066.
4. Propofol injection. Deerfield, Il., Baxter Healthcare Corporation, Sept. 2004.
5. Propofol injection. Bedford, OH., Bedford Laboratories, July 2005.
6. Diprivan^®. Wilmington, DE, AstraZeneca, 2005 (currently Abraxis).