Any data around combining 20 mL bottles of propofol to create a larger bottle or bag?

Comment by InpharmD Researcher

There is no direct information regarding the pooling or combining of multiple propofol vials, but this practice is generally not recommended. Propofol is especially susceptible to microbial contamination, so the less opportunity of contamination, the better. When not used from the original container, propofol should be used within 6 hours due to the possibility of oxidative degradation to exposed air and the potential for microbial contamination.

Background

Per the Centers for Disease Control and Prevention (CDC), single-use vials should not be pooled or combined. However, this recommendation particularly pertains to saving leftover contents of a single-use vial for later use. There have been outbreaks resulting from pooling of contents of single-dose or single-use vials and/or storage of contents for future use. [1]

A review on the safe administration of propofol by the Association of periOperative Registered Nurses (AORN) advises against pooling or combining propofol vial contents; reusing a syringe or needle to withdraw medication from a multidose vial; and re-entering a single-use vial, ampule, or solution. Doing so can increase the risk of microbial contamination, especially since propofol is a lipid-based emulsion that readily supports bacterial growth. Infusion from prefilled syringes or vials must begin within 6 hours of opening/filling the syringe. Larger volumes that are infused directly must be used within 12 hours. [2]

A retrospective cohort study used epidemiological data and onsite investigations to determine the cause of postoperative systemic inflammatory response syndrome (SIRS) in seven patients. The outbreak of postoperative sepsis diagnosed in seven patients and confirmed in two patients was traced to extrinsically contaminated propofol with K. pneumoniae and S. marcescens. Vials of 100 mL of propofol were used, and separate vials were used for each operating room. From each vial, five aliquots of 20 mL were taken by using the same spike. Interviews and on-site observations of working procedures showed that syringes were filled with propofol not using strict aseptic technique. Spikes were difficult to handle aseptically and more than one syringe was filled from a single vial at a time. During drawing up, the spike-stopper was temporarily put on a non-sterile surface, and occasionally, one spike was used on more than one vial. The use of single-use vials of propofol for multiple patients resulted in the infectious outbreak. [3]

In a 2007 propofol-drug shortage, a Nevada endoscopy clinic used propofol 50-mL single-use vials for multiple doses, against label recommendations. The practice used a clean needle and syringe to draw medication from a propofol single-use vial, which was then injected directly through an intravenous (IV) catheter into the patient's arm. In the case of additional sedation for the same patient, a new needle was placed on the old syringe to draw more medication. It was speculated that IV or needle removal backflow might have contaminated the syringe with HCV and resulted in vial contamination. Medication remaining in the vial was used to sedate the next patient. Vial contamination led to an outbreak of hepatitis C infection (6 patients in July–December 2007). Roughly 40,000 patients were advised to undergo testing for potential hepatitis B, hepatitis C, and HIV infections. [4]

Propofol undergoes oxidative degradation upon air exposure. Therefore, the container headspace is filled with nitrogen to avoid oxygen presence. Upon container penetration, propofol administration should be completed within 12 hours. Remaining propofol, if any, and tubing should be discarded at this time. The administration should be completed within 6 hours if the emulsion is transferred to a different container (e.g. syringe), and remaining propofol and tubing should be discarded. [5], [6], [7]

Relevant Prescribing Information

Strict aseptic technique must always be maintained during handling. Propofol is a single access parenteral product (single patient infusion vial) which contains 0.005% disodium edetate (EDTA) to inhibit the rate of growth of microorganisms, for up to 12 hours, in the event of accidental extrinsic contamination. However, propofol can still support the growth of microorganisms, as it is not an antimicrobially preserved product under USP standards. [8]

There have been reports, in the literature and other public sources, of the transmission of bloodborne pathogens (such as Hepatitis B, Hepatitis C, and HIV) from unsafe injection practices, and use of propofol vials intended for single use on multiple persons. Propofol vials are never to be accessed more than once or used on more than one person. [8]

Diprivan (propofol), with EDTA inhibits microbial growth for up to 12 hours, as demonstrated by test data for representative USP microorganisms. [8]

If propofol is transferred to a syringe prior to administration, it should be drawn into a sterile syringe immediately after a vial is opened. When withdrawing DIPRIVAN from a vial, a sterile vent spike should be used. The syringe should be labeled with appropriate information including the date and time the vial was opened. Administration should commence promptly and be completed within 12 hours after the vial has been opened. DIPRIVAN should be discarded and administration lines changed after 12 hours. [8]

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Wondering if you’ve had any DI requests around combining 20 mL bottles of propofol to create a larger bottle or bag?

Please see Table 1 for your response.

Bacterial contamination of propofol vials used in operating rooms of a third-level hospital
Design	Observational study N=198
Objective	To determine the frequency of bacterial contamination of propofol vials used in operating rooms (ORs) of a high-complexity hospital in Colombia
Study Groups	Propofol samples (n=198)
Methods	Inclusion criteria: all available discarded propofol 20 mL vials used in surgical procedures in the operating rooms of a single hospital Exclusion: none described Staff in the ORs labeled the vials with the date and time of opening and discard and the number of extraction punctures made. The time between opening and discarding each vial was regarded as the time of use. The staff then collected propofol vials after the vials were discarded daily and kept them refrigerated until a researcher took them to the laboratory to make 2 separate aliquots. An aliquot of 1-1000 microliters into a thioglycollate broth and an aliquot of 1-100 microliter on a trypticase soy agar supplemented with 5% sheep blood were made. The plates were examined for bacterial growth and the characteristics were compared. Two separate lots were used during this time, designated here as lot A and B.
Duration	September 2014 to November 2014
Outcome Measures	Comparison of vial characteristics and the growth of bacteria from samples
Baseline Characteristics		All propofol samples (N=198)
	Time of use, h (range)	3.7 (0.1-72.4)
	Residual propofol volume, mL (range)	1.0 (0.1-15.0)
	Number of extraction punctures (range)	2 (1-4)
	Vials punctured once	52 (26.3%)
	Vials punctured more than once	146 (73.7%)
	Propofol lot A B	69 (34.9%) 129 (65.1%)
Results		Bacterial growth
		Yes (n=12)	No (n=186)	P value
	Time of use, h (range)	7.2 (1.0-47.3)	3.5 (0.1-72.4)	0.08
	Residual propofol volume, mL (range)	1.3 (0.5-10.0)	1.0 (0.1-15.0)	0.25
	Number of extraction punctures	2.0 ± 0.95	2.1 ± 0.84	0.76
	Propofol Lot A B	2 (16.7%) 10 (83.3%)	67 (36.0%) 119 (64.0%)	0.22
	Propofol volume cultured in agar, μL (range)	100 (1-100)	100 (1-100)	0.70
	Propofol volume cultured in thioglycollate broth, μL (range)	725 (50-1,000)	200 (1-1,000)	0.24
Study Author Conclusions	In conclusion, bacterial contamination occurred in 6.1% of propofol vials, which is similar to studies elsewhere. We also found that some vials were used for extended periods and that approximately 75% of vials were punctured more than once. Education on the topic should stress that vials are single-patient use and must be immediately discarded after use. Clinical significance of bacterial contamination of propofol vials in our setting should be determined in further epidemiologic studies.
InpharmD Researcher Critique	This is a small observational study from a single center in Colombia that did not have well-defined outcome measures.

References:

Zorrilla-Vaca A, Escandón-vargas K, Brand-giraldo V, León T, Herrera M, Payán A. Bacterial contamination of propofol vials used in operating rooms of a third-level hospital. Am J Infect Control. 2016;44(1):e1-3.