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Departments of
*Anesthesiology and
Pathology, Northwestern University Medical School, Chicago, Illinois
Address correspondence and reprint requests to Mladen I. Vidovich, MD, Passavant Pavilion, Suite 360, 303 East Superior St., Chicago, IL 60611. Address e-mail to miv909{at}nwu.edu
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Abstract |
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Implications: The addition of lidocaine to propofol in concentrations clinically effective in reducing pain on injection had no effect on microbial growth. Adherence to strict aseptic technique is further emphasized.
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Introduction |
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To reduce the rate of microbial growth in the event of accidental extrinsic contamination, a new formulation of propofol containing disodium edeteate has been introduced in the American market (4).
Local anesthetics are often added to propofol to reduce the pain associated with IV administration (5–7). Although local anesthetics can be bacteriocidal at high concentrations (lidocaine 2%), such activity has not been investigated at low concentrations (8–10). Of the local anesthetics, lidocaine has been most commonly used and extensively studied (5–7).
The purpose to this laboratory study was to determine the effect of lidocaine 0.1% on the growth rates of four common microorganisms in the formulation of propofol with disodium edeteate.
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Methods |
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A few colonies from each of the isolates were plated on blood agar plates and incubated overnight at 35°C. On the morning of the experiment four to five well isolated colonies from these plates were inoculated into 3 mL of Mueller Hinton broth (cation supplemented) and incubated at 35°C in a shaking incubator for 2–4 h until turbid. The cultures were then adjusted to a 0.5 McFarland standard concentration by diluting a few drops in 0.9% saline. This inoculum was further diluted in saline so that the final concentration of bacteria was approximately 5 x 105 colony-forming units (CFU)/mL. Preservative-free lidocaine HCl 1% (Abbott Laboratories, North Chicago, IL) was added to propofol (Diprivan 1%; Zeneca Pharmaceuticals, Wilmington, DE) or nonbacteriostatic saline 0.9% to a final concentration of 0.1%. Sterile test tubes (13 x 100 mL) were set up, in duplicate, with 2 mL each of propofol, propofol + lidocaine, saline, and saline + lidocaine. Within approximately 15 min of preparation, 100 µL of the adjusted inoculum suspension was carefully added to each tube, making sure there was no splash-over on the sides of the tubes. The tubes were then mixed gently and left at room temperature. The initial inoculum density was determined for each isolate by plating 100 µL from the inoculum suspension (0 h) on blood agar plates (5% sheep blood, trypticase soy agar; DiMED Corporation, St. Paul, MN). At 2, 5, and 24 h, 100 µL of the sample was removed from each tube and plated. These plates were incubated at 37°C for 24 h, and the colonies were counted. For each organism, 14 samples were plated in duplicate for each time period. Plates were also set up to check for sterility of all the preparations used in the experiment.
Analysis of variance (ANOVA) with a post hoc t-test with Bonferroni correction was used for data analysis. A P value of <0.05 was considered significant.
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Results |
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Compared with saline, the number of CFU in propofol 2 and 5 h after inoculation was significantly lower, except for Serratia marcescens (in propofol with lidocaine) and Pseudomonas aeruginosa (in propofol alone).
Twenty-four hours after inoculation, there was a significant increase in CFU in all saline and propofol preparations, with two exceptions. There were significantly fewer CFU of Staphylococcus aureus in both propofol preparations, and the number of CFU of Candida albicans in propofol alone was unchanged.
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Discussion |
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The original formulation of propofol contained no preservative. Previous studies have examined the growth of various microorganisms in this formulation (11–16). Propofol was shown to support rapid growth of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Moraxella osloensis, as well as endotoxin production. Outbreaks of postoperative surgical site infections have been traced to extrinsically contaminated propofol (1–3).
In 1996, a modified formulation containing 0.005% disodium edeteate was introduced in the hope of retarding the rate of microbial growth in the event of accidental extrinsic contamination (4). We designed the present study to examine this premise while simulating a possible clinical scenario: an ampule of propofol is opened, accidentally contaminated, drawn into a syringe, and premixed with lidocaine. Because the prescribing information specifies that propofol should be used within 6 h of opening, this syringe may be left at room temperature for up to 6 h before use. Therefore, the extent of bacterial growth 2 and 5 h after inoculation was examined.
We examined four common bacteria, three of which were involved in the clinically described infection epidemics (1–3).
Several studies have tried to determine the concentration of lidocaine that most efficiently diminishes or eliminates pain on propofol injection (5–7). There seems to be a dose-effect relationship, and increasing the concentration of lidocaine is more effective in reducing the pain of injection.
However, with >20 mg of lidocaine added to 200 mg of propofol, the emulsion can be destabilized. Lipid droplets in the emulsion may flocculate or coalesce and form an oily surface layer (17). We therefore selected the concentration of 0.1% lidocaine for the study given that the emulsion stability is preserved and that it is clinically very effective in reducing the pain of injection.
We found no difference in bacterial growth between propofol and propofol with lidocaine at time intervals up to 6 h. Therefore, it seems that this concentration of lidocaine does not reduce the rate of microbial growth in propofol. The difference found in some preparations 24 h after inoculation may be attributed, at least in part, to the effect of lidocaine that increases with the length of exposure.
Most preparations with propofol exhibited a lower number of CFU compared with saline. Pure 2,6-diisopropylphenol is bacteriocidal (12) and saline controls did not contain disodium edeteate, which may account for faster growth in saline. Furthermore, disodium edeteate does not prevent propofol from supporting microbial growth, and this product should not be considered an antimicrobially preserved product.
In summary, based on our laboratory study, there was no clinically significant difference in microbial growth in propofol with and without lidocaine, which further emphasizes the need for strict adherence to manufacturer’s recommendations for the use of this induction drug.
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Acknowledgments |
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This article has been cited by other articles:
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  Y. Masaki, M. Tanaka, and T. Nishikawa Physicochemical Compatibility of Propofol-Lidocaine Mixture Anesth. Analg., December 1, 2003; 97(6): 1646 - 1651. [Abstract] [Full Text] [PDF]
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 I. H. Lorenz, C. Kolbitsch, C. Lass-Florl, I. Gritznig, B. Vollert, W. Lingnau, P. L Moser, and A. Benzer Routine handling of propofol prevents contamination as effectively as does strict adherence to the manufacturer's recommendations: [Le maniement d'usage du propofol previent la contamination aussi effectivement que la stricte adhesion aux recommandations du fabricant] Can J Anesth, April 1, 2002; 49(4): 347 - 352. [Abstract] [Full Text] [PDF]
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R. P. Driver Jr., D. T. Jolly, I. Wachowski, J. Hrazdil, and J. C. Galbraith Conclusions Regarding Propofol/Lidocaine Admixture May Be Misleading • Response Anesth. Analg., November 1, 1999; 89(5): 1331 - 1331. [Full Text] [PDF]
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