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Bacterial contamination of propofol: the effects of temperature and lidocaine

Aydin, O. N.*; Aydin, N.; Gultekin, B.; Ozgun, S.*; Gurel, A.*

European Journal of Anaesthesiology: June 2002 - Volume 19 - Issue 6 - p 455-458
Original Article

Background and objective: The intravenous anaesthetic propofol may become contaminated once the ampoules have been opened. The effect of lidocaine and cooling was tested on the bacterial contamination of propofol.

Methods: The study was performed in two parts. In Part 1, 1920 aliquots of propofol alone, and of a propofollidocaine mixture, were drawn into sterile syringes and stored at room temperature (24-26°C) or in the refrigerator (12-14°C). In Part 2, 1200 aliquots from opened ampoules of propofol alone, or as a propofol-lidocaine mixture, were stored at room temperature or in the refrigerator. Samples were aerobically cultured at 0, 1, 2, 4, 8 and 12 h.

Results: In Part 1, diphtheroid bacillus was isolated from one aliquot (0.06%). In Part 2, there was bacterial growth in both groups; the number of contaminated ampoules increased with time and it was 20-26% at 12 h. Diphtheroid bacilli and coagulase-negative staphylococci were the most frequent micro-organisms.

Conclusions: When propofol is stored in opened ampoules, the bacterial contamination rate is high. Adding lidocaine, or storing opened ampoules at 12-14°C, does not affect the contamination rate, except during the first few hours. It is advisable to draw propofol aseptically into a syringe in an amount that can be used during one procedure.

Adnan Menderes University, *Department of Anaesthesiology and Reanimation, andDepartment of Microbiology and Clinical Microbiology, Aydın, Turkey

Correspondence to: O. N. Aydin, Adnan Menderes Üniversitesi, Tip Fakültesi, Anesteziyoloji ve Reanimasyon Departmant, 09100 Aydın, Turkey. E-mail:; Tel: +90 256 2124078; Fax: +90 256 2120146

Accepted for publication August 2001 EJA 683

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Propofol (2.6-diisopropylphenol) has the structure of a fat-soluble lipid melt; it contains propofol 10 mg mL−1, soybean oil 100 mg mL−1, glycerol 22.5 mg mL−1, egg lecithin 12 mg mL−1, and water and sodium hydroxide to keep the pH at 6-8.5 [1-5]. The structure of this solution forms a suitable medium for the proliferation of micro-organisms [2,3,6-8]. It has been shown that in absence of added preservatives or antimicrobial agents, micro-organisms may grow in propofol [2,3,6,9-13]. Recently, disodium edetate (EDTA) has been added to propofol for its antimicrobial properties [14,15].

In a report of the Centre for Disease Control (CDC) in the USA in 1990, Carr and colleagues reported on 24 cases of infection after the use of propofol [16]. Subsequently, reports were published on contamination of opened propofol ampoules and of propofol when drawn up into syringes, and even on sepsis and sepsis-related death [10,12,13,17]. It has been stated that strict aseptic requirements are needed for drawing up, storage and use of propofol [1,6,8,18]. It has also been suggested that bacteriological contamination of propofol may be prevented by the addition of lidocaine [5,19].

The aim of the present study was to investigate the effects on contamination of storing propofol at room temperature or in a refrigerator, and of adding lidocaine to propofol.

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The study was carried out at the Medical Faculty of Adnan Menderes University. All aliquots were prepared by research assistants of the Anaesthesiology and Reanimation Department using standard but not sterile techniques in usual daily anaesthetic working conditions. Commercially available propofol without disodium edetate or other antimicrobial agents (200 mg 20 mL−1, Abbott Propofol® 1%, 10 mg mL−1) and lidocaine (2% Aritmal, Biosel 20 mg mL−1) were used. The study was carried out in two parts.

In Part 1, four ampoules of propofol were opened daily and lidocaine was added to two (lidocaine 1 mL 2% added to propofol 20 mL). From each of the four ampoules, 1 mL was then drawn into 18 sterile 2 mL syringes; half of those were kept at room temperature, with the other half being kept in the door of a refrigerator. Group A1 was propofol without lidocaine stored at room temperature; Group B1 was propofol with lidocaine stored at room temperature; Group C1 was propofol without lidocaine stored in the refrigerator; Group D1 was propofol with lidocaine stored in the refrigerator. At 0, 1, 2, 4, 8 and 12 h, three syringes from each group were sent to the laboratory to be cultured. The procedure was completed in 27 working days; 1920 cultures were made.

In Part 2, four ampoules of propofol were opened daily and lidocaine was added to two (lidocaine 1 mL 2% added to propofol 20 mL). Opened ampoules were then stored at room temperature or in the door of a refrigerator. Group A2 was propofol without lidocaine stored at room temperature; Group B2 was propofol with lidocaine stored at room temperature; Group C2 was propofol without lidocaine stored in the refrigerator; Group D2 was propofol with lidocaine stored in the refrigerator. At 0, 1, 2, 4, 8 and 12 h, 2 mL was taken from each ampoule and drawn into sterile syringes to be sent to the laboratory for culture. The procedure was completed in 50 working days; 1200 samples were cultured.

The temperature of the room was kept at 24-26°C and that of the refrigerator was 12-14°C. No other materials were stored in the refrigerator and the door was opened only for the purposes of these investigations. The refrigerator was not cleaned or sterilized specifically. For cultures, 100 μL of each aliquot was inoculated to 5% blood agar and incubated at 35°C for 72 h in an aerobic medium. Grown colonies were counted and the isolated micro-organisms identified according to the types and species by conventional methods.

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Statistical analysis

Statistical analyses were performed using the Pearson's χ2-test for comparisons of the grown micro-organisms. P < 0.05 was regarded as significant.

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In Part 1, there was one positive culture among the 1920 syringes (0.06%). This was diphtheroid bacillus in propofol-lidocaine at room temperature (Group B1). There was no growth in the other samples.

In Part 2, there were two positive cultures in two contaminated ampoules (0.16%) at the beginning of the study (at hour 0). The positive cultures were in Groups A2 and B2. The number of positive cultures increased with time in all groups (Table 1). At 1 h, there was more bacterial growth in Group A2 (propofol at room temperature) compared with the other groups (χ2 = 9.51, P = 0.023). At 2 h, the higher number of contaminated samples from Group A2 compared with the other groups was still borderline statistically significant (χ2 = 7.69, P = 0.052). At 4, 8 and 12 h, there was no difference between the four groups. After 12 h, 20-26% of the samples were contaminated. In Group A2, two species of bacteria grew from one ampoule at zero and 2 h, and from two ampoules at 8 h. In Group B2, growth was seen from one ampoule at 12 h, in Group C2 from one at 8 h, and in Group D2 in one ampoule at 4 h.

Table 1

Table 1

The most frequently cultured micro-organisms among all groups were diphtheroid bacilli (33.3%), coagulase-negative staphylococci (23.5%), and Bacillus spp. (17.6%) (Table 2). Micro-organism counts ranged from 102 to 105 'colony-forming unit' (CFU) mL−1. Counts reached 102-103 CFU mL−1 during the first 4 h, and up to 105 CFU mL−1 at room temperature at the end of 8 h, and in the refrigerator at end of 12 h.

Table 2

Table 2

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When propofol was drawn into sterile syringes immediately after the ampoules had been opened, growth rates were very low (0.06%). Storing propofol at 12-14°C or adding lidocaine 0.1% had no impact on this low contamination rate. This suggests that propofol when drawn into a sterile syringe immediately after the ampoule has been opened may be kept at room temperature for 12 h without an increased risk of contamination. The present data are comparable with those from other investigations [1,9,20-23]. In one study, propofol drawn into sterile syringes was kept sterile for 14 days; it was suggested that propofol might be used safely up to 24 h after its preparation [24]. Others have suggested that propofol when drawn into sterile syringes may be used for 72 h [1,25].

When open ampoules were stored (Part 2), propofol without lidocaine and kept at room temperature (Group A2) was more often contaminated during the first 2 h (Table 1). This indicates that during the first few hours after opening an ampoule, both adding lidocaine and cooling to 12-14°C may have an inhibitory effect on the growth of micro-organisms. The number of contaminated samples increased with time and at 12 h 20-26% of the samples of all four groups were positive. In similar studies, various rates of contamination of propofol samples have been reported, 6.3% at 28 min, 3% at 165 min, or 40% at 1 h [1,18,26].

The count of colonies increased proportionally with time from 102-103 to 105 CFU mL−1. In aliquots stored at room temperature, counts of 105 were reached earlier than in those kept in the refrigerator (8 versus 12 h). Although in the present study cooling was limited to 12-14°C, these data provide some evidence that low temperature may inhibit bacterial growth in opened propofol ampoules. In the operating room, the number of airborne CFU m−2 increases progressively with time [27]. It was reported that CFU numbers were lowest with laminar airflow, moderate with high-efficiency particulate air filter systems, and highest without any of these systems. To prevent contaminated air from reaching the operating theatre, forced ventilation is recommended [28,29]. Diphtheroid bacilli, coagulase-negative staphylococci and Bacillus spp. were the primary micro-organisms that grew in the present study. Four per cent of the samples from open ampoules contained Staphylococcus aureus. In other studies, Staphylococcus epidermis, S. aureus, diphtheroid bacilli and Candida albicans have been identified [6,9,13,18,30].

Bacterial contamination of propofol may occur during opening of the glass ampoules, and it was, therefore, recommended that the neck of the ampoules be wiped with alcohol [1,6,19]. In the present study, the necks of the ampoules were not wiped with any disinfectant to reproduce usual daily working conditions. The fact that diphtheroid bacilli were among the most frequently isolated micro-organisms suggested that skin-related contamination during opening of the ampoules may have happened. To avoid the risk of contamination during drawing up propofol into a syringe, wiping the neck of the propofol ampoules with antiseptic solutions and wearing sterile gloves during drawing the drug into syringes has been recommended [1,2,9]. Other potential reasons for contamination of propofol are the breaking of the neck of a glass ampoule (i.e. glass splints may fall into the ampoule), administration of the drug directly through a rubber tube, and sharing syringes among several patients [8,11,30-32].

It has been suggested that lidocaine should be added to propofol, administrated through a 0.2 μm filter, and that the propofol-lidocaine should then be kept in a refrigerator [6,19,21,23,33]. This, however, is contentious. In one study, lidocaine in propofol 0.2% had no bactericidal or fungicidal effects [3]. In addition, lidocaine 10-20 mg added to propofol 200 mg may cause moderate impairment of the stability of propofol [4]. When even higher doses of lidocaine were added to propofol and the mixture was stored at room temperature, both microscopic and macroscopic impairment of the stability of propofol was seen [4].

To prevent contamination of propofol, hands should be washed before any manipulation; the neck of the ampoule should be wiped with 70% alcohol; syringes and pumps should be prepared in aseptic conditions immediately before the use of propofol; ampoules and syringes should be labelled with the date and hour of preparation; propofol should be drawn into syringes in amounts that can be used at one time and the residual, if any, should be discarded; and finally, disposable devices such as syringes, infusion sets and triple manifolds should be used for a single patient only [2,3,6,9,22,26].

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