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Is it safe to re-access sodium bicarbonate bottles for use in minor surgery?
Accepted Manuscript Is it safe to re-access sodium bicarbonate bottles for use in minor surgery?
Lindsay Bjornson, Marija Bucevska, Peter Tilley, Cynthia Verchere PII: DOI: Reference:
S0022-3468(18)30244-6 doi:10.1016/j.jpedsurg.2018.04.005 YJPSU 58645
To appear in: Received date: Revised date: Accepted date:
21 December 2017 20 March 2018 2 April 2018
Please cite this article as: Lindsay Bjornson, Marija Bucevska, Peter Tilley, Cynthia Verchere , Is it safe to re-access sodium bicarbonate bottles for use in minor surgery?. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Yjpsu(2018), doi:10.1016/j.jpedsurg.2018.04.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Bjornson Is it safe to re-access sodium bicarbonate bottles for use in minor surgery? Running title: Sodium bicarb A
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Lindsay Bjornson MSc , Marija Bucevska MD , Peter Tilley MD FRCPC MD FRCSC
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Queen’s University, Kingston, ON, Canada
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, Cynthia Verchere
Department of Surgery, University of British Columbia
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Department of Pathology & Lab Medicine, University of British Columbia BC Children’s Hospital, Vancouver, BC, Canada
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Institution: University of British Columbia
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Corresponding Author: Lindsay Bjornson K3-131 – 4480 Oak Street, Vancouver, BC V6H 3V4, Canada Tel: (604) 875-3758 Fax: (604) 875-2749 [email protected]
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Abstract: Background/Purpose: Sodium bicarbonate is added to lidocaine to reduce injection pain. In Canada, it is available in vials exceeding the injection volume 100-fold. These are single-use vials that should be disposed of after one access. Some surgeons re-use vials to reduce waste, potentially causing contamination. This study aims to review the safety of sodium bicarbonate and assess alternatives to current practice. Methods: Strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Burkholderia cepacia were used to assess bacterial growth in vials of sodium bicarbonate. Each pathogen was inoculated into a vial for 14 days at room temperature. At several time points, 1 mL of solution was removed and diluted. One hundred microliters were transferred to blood agar plates and incubated at 35ºC. Colony counts were calculated, averaged and plotted onto a logarithmic graph. Results: Colony counts of all strains fell below observational threshold after 7 days in sodium bicarbonate. Conclusions: Although all strains were reduced, bacteria can survive in sodium bicarbonate for several days, during which transmission may occur. Sodium bicarbonate vials should be treated as single-dose, as indicated by the manufacturers. To reduce waste, hospital pharmacies can repackage sodium bicarbonate into smaller vials or pre-alkalize lidocaine with sodium bicarbonate.
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KEY WORDS: sodium bicarbonate; single-dose vials; minor surgery; contamination.
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1. Introduction: When local anesthetics, such as lidocaine, are administered, many patients experience a painful burning sensation, which may be attributed to the acidic nature of these solutions [1–4] Common anesthetics are usually maintained at a relatively low pH in order to maximize the stability and therefore the shelf-life of the product [1,4]. Solutions of lidocaine without epinephrine have been found to have a pH of approximately six, while those containing epinephrine were found to have a pH of approximately four [1,3]. When compared to the pH of the subcutaneous tissue into which these anesthetics are injected, which is between 7.3 and 7.6, these solutions are markedly more acidic [3,4]. The painful stinging or burning sensation is likely due to the increase in hydrogen ions in the tissue upon injection [1]. It is possible to reduce the pain associated with the administration of local anesthetics by elevating the pH to the physiological level [1]. This can be achieved through the addition of sodium bicarbonate, which acts as an alkalizing agent of lidocaine [1–5]. In solution, sodium bicarbonate dissociates into a sodium cation and a bicarbonate anion. This anion binds to the free hydrogen cations in the solution, thereby reducing the hydrogen ion concentration and increasing the pH. Titration studies have shown that the optimal ratio of sodium bicarbonate to lidocaine is one milliliter to ten milliliters [3,4]. Using these volumes, the pH of lidocaine reaches the physiological level. Many studies have demonstrated that the addition of sodium bicarbonate to lidocaine is effective in decreasing patient discomfort upon injection [1–5]. In Canada, sodium bicarbonate is only available in single-dose vials. The Centers for Disease Control and Prevention (CDC) outline the regulations surrounding single- and multipledose vials [6,7]. As the names suggest, single-dose vials should be disposed of after one needle access, whereas multiple-dose vials may be re-accessed multiple times at the manufacturer’s instruction. The key distinguishing characteristic between the two is that the contents of multiple-dose vials possess antibacterial properties, which may be a result of either added preservatives or inherent properties of the solution itself. It is important to note that contamination may occur if aseptic technique is neglected, irrespective of the vial type. Failure to follow procedures such as the use of a new, sterile needle and syringe for each vial access has been shown to lead to contamination events [8–13]. A challenge associated with the use of single-dose vials is the accompanying wastage of materials. Some single-dose vials provide volumes that are far greater than those required for a single use. For example, sodium bicarbonate for injection is only available in Canada in 50 mL single-dose vials. When the plastic surgeons at British Columbia Children’s Hospital access these vials, they use an average of half a milliliter of sodium bicarbonate at a time for each administration of local anesthetic, leaving nearly an entire 50-mL vial of sodium bicarbonate. Although sodium bicarbonate is not a particularly expensive compound, often costing between five and ten dollars per vial, the waste produced by disposing countless glass vials containing the majority of their contents is concerning. Furthermore, current national and global shortages make sodium bicarbonate a limited commodity which should be conserved [14]. Anecdotally, some surgeons choose to re-use sodium bicarbonate vials. Although this does prevent excessive wastage, it is a risky and potentially dangerous practice, given the potential for contamination. Currently, there is limited information published in the literature about the viability of bacteria in sodium bicarbonate. Previous studies have demonstrated that sodium bicarbonate enhances the antimicrobial effect of lidocaine [1,15]. Another study suggested that sodium bicarbonate develops an increased ability to inhibit the growth of Pseudomonas aeruginosa and Staphylococcus aureus with increased time and increased sodium
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bicarbonate concentration [16]. Despite these promising findings, it remains unclear if the re-use of sodium bicarbonate vials might be considered a safe practice, particularly when considering that the current sodium bicarbonate shortage resulted from a manufacturer recall due to possible microbial contamination [14]. Understanding the safety of re-using sodium bicarbonate vials is particularly important during the current shortage, as clinicians may feel pressured to re-use vials in order to conserve available supplies. The purpose of this study was to review the safety of sodium bicarbonate by testing the viability of certain common bacterial strains in sodium bicarbonate and by assessing alternatives to the current practice. This article aims to generate awareness among surgeons of the potential dangers of re-using sodium bicarbonate, and of the available options to minimize these risks. We hypothesized that the risk of bacterial growth would be low, but needed to find evidence in typical clinical practice.
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2. Material and Methods: The study was exempt from REB review based on regulatory and institutional criteria. Strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Burkholderia cepacia were isolated and used to assess bacterial growth in 50 mL single-dose vials of 8.4% sodium bicarbonate. The procedure used for each of the four bacterial strains is illustrated in Figure 1, and described in more detail below. A 0.5 McFarland cell suspension of the organism was prepared in sterile saline. This suspension was then further diluted in saline to form a test suspension containing 105 colonyforming units per milliliter. One milliliter of sodium bicarbonate was removed from a new 50 mL vial of 8.4% sodium bicarbonate and discarded, and one milliliter of the test suspension was subsequently added to the vial. The contents of the vial were then mixed thoroughly. The pathogen was exposed to the solution for a total of fourteen days at room temperature. In order to assess bacterial growth in sodium bicarbonate, the solution was sampled at time points of 0 hours, 4 hours, 24 hours, 48 hours, 4 days, 7 days, and 14 days. At each of these time points, one milliliter of solution was removed from the vial and was serially diluted in saline to give three concentrations of solution: neat, 1/10, and 1/100. One hundred microliters of each resulting suspension were transferred to Columbia blood agar plates in triplicate and incubated at 35ºC. After a minimum of eighteen hours, colony counts were performed. Once all plates of a certain time point lacked colonies, subsequent time points were omitted. A control suspension was prepared for the 0-hour time point by adding the test inoculum to sterile saline and following the aforementioned procedure. The colony counts were noted for each time point, and an average value was calculated for each set of triplicates. These values were then plotted onto a logarithmic graph of number of colonies as a function of time. Figure 1. Schematic diagram of general experimental procedure 3. Results: Viability data for Staphylococcus aureus, Staphylococcus epidermidis, Burkholderia cepacia, and Pseudomonas aeruginosa injected in sodium bicarbonate vials can be found in Figure 2. The results of the experiment using Staphylococcus aureus, shown in Figure 2, indicate an initial increase in colonies per milliliter at the four-hour time point. Following this growth, the
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number of colonies fell to below the threshold of detection by day seven of the experiment. Staphylococcus aureus was the only organism to demonstrate an initial increase in colony numbers after exposure to sodium bicarbonate. The counts of Staphylococcus epidermidis, found in Figure 2, show a decrease in colony numbers at every time point. By day seven, no colonies were observed. Similarly, Burkholderia cepacia experienced a drop in colony counts at each time point. As shown in Figure 2, no colonies were recovered by day four. Finally, the results of the experiment using Pseudomonas aeruginosa, found in Figure 2, demonstrate a decline in colonies per milliliter from the zero-hour time point until day seven, when no colonies were counted.
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Figure 2. Viability data for Staphylococcus aureus, Staphylococcus epidermidis, Burkholderia cepacia, and Pseudomonas aeruginosa in sodium bicarbonate 8.4%
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4. Discussion: Sodium bicarbonate reduced the viable colonies of all four bacterial strains tested at our institution. The U.S. Pharmacopoeia (USP) General Chapter 51, Antimicrobial Effectiveness Testing, outlines the procedures for testing the effectiveness of an antimicrobial [17]. One criterion of an effective antimicrobial is a minimum reduction of 1.0 log from the initial colony count by day seven. All four of the bacterial strains in this study were reduced by more than 1.0 log by the seventh day. These results confirm some measure of anti-bacterial activity in 8.4% sodium bicarbonate, but over a period of time which is too long to be clinically helpful. The current procedure differed in some regards from that of the USP; nevertheless, it may be worth investigating the possible antimicrobial effectiveness of sodium bicarbonate further. Although sodium bicarbonate is widely accepted as an effective alkalizing agent of lidocaine, it is only available in Canada in volumes one hundred times larger than required for the 1:10 ratio of sodium bicarbonate to lidocaine [3,4]. Although all four bacterial strains were reduced by the seventh day in the present study, it is clear that bacteria can survive in the sodium bicarbonate vials for several days, and there is a risk of transmission during that time period. Therefore, sodium bicarbonate should continue to be treated as a single-dose vial, as instructed by the manufacturers. As such, all vials and their leftover contents should be disposed of immediately following opening. In Canada, this leads to excessive wastage of sodium bicarbonate, which is already in short supply, and glass vials. We investigated the ways in which surgeons can use sodium bicarbonate more efficiently in order to conserve limited resources and decrease the wastefulness of the current practice. One option is to use smaller vials of sodium bicarbonate. Given that sodium bicarbonate should be accessed only once, there would be less wastage if it were provided in smaller sizes. These volumes are not available on the Canadian market; however, it is possible to repackage larger unopened vials under ISO Class 5 conditions in accordance with USP General Chapter 797, Pharmaceutical Compounding – Sterile Preparations [18]. Most hospital pharmacies meet these standards. Thus, they may be able to repackage the 50 mL sodium bicarbonate vials into more useful volumes for the alkalization of lidocaine, depending on the availability of smaller containers. Glass containers are preferable, as they are the medium in which sodium bicarbonate is typically provided; however, a 2010 study showed that sodium bicarbonate is also stable in polyolefin for up to seven days when refrigerated [19].
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The alternative solution is to use a pre-alkalized lidocaine solution [3]. Again, this must be prepared under ISO Class 5 conditions in accordance with USP General Chapter 797. As before, glass containers are preferable; however, evidence suggests that alkalized lidocaine is stable in a plastic syringe for up to 28 days with refrigeration, while alkalized lidocaine with epinephrine is stable in a plastic syringe for up to 7 days with refrigeration [20,21]. Thompson et al. (1993) suggested that sodium bicarbonate can actually enhance the bacteria-killing effect of lidocaine [15]. This data, in combination with the antimicrobial activity of the lidocaine solution and its methylparaben and sodium metabisulfite preservatives, suggests that the alkalized lidocaine will remain sterile and can be used as a multi-dose vial. The Plastic Surgery Clinic at British Columbia Children’s Hospital has investigated the latter option. Our hospital prepares mixtures of sodium bicarbonate with lidocaine with or without epinephrine; however, lidocaine with epinephrine is preferred [3]. The pharmacy can provide these 20 mL vials at a set time each week in preparation for the following week’s minor surgeries in all parts of the hospital. Each 20 mL vial of buffered lidocaine with epinephrine costs about $7. While this solution may not necessarily be more cost-effective than continuing to use the 50 mL single-dose vials, it addresses the concern for waste reduction of the glass vials and sodium bicarbonate. We are unable to pursue an in-depth cost analysis, but data from a previous publication arising from our institution show approximately 110 minor surgery procedures undertaken by a single surgeon in a one-year period; the cost of selecting one vial type over another would be multiplied by this factor [22]. In having the pharmacists prepare the alkalized lidocaine solution under sterile conditions, the number of sodium bicarbonate vials that must be discarded is far less; however, the process of preparing individual plastic syringes may also create extra waste. Nevertheless, it eliminates the potential risks associated with reaccessing a single-dose vial multiple times. It must be said, however, that neither of the proposed options is ideal, practical, or sustainable for use in local anesthesia. If manufacturers would consider supplying sodium bicarbonate in 1mL single-use glass ampules, there would be an overall reduction in cost, a decrease in plastic and mixed waste, more efficient shipping and less discarded sodium bicarbonate in times of shortage.
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Acknowledgments: The authors would like to gratefully acknowledge Mary-Jane Margach and Lori Willis for their technical assistance, and Rebecca Courtemanche for her editorial assistance in this study. Lindsay Bjornson would like to acknowledge the BC Patient Safety & Quality Council for funding her studentship.
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ACCEPTED MANUSCRIPT Bjornson References: [1]
Cepeda M, Tzortzopoulou A, Thackrey M, Hudcova J, P AG, Schumann R. Adjusting the pH of lidocaine for reducing pain on injection ( Review ). Cochrane Libr 2010.
[2]
Strazar R, Lalonde D. Minimizing injection pain in local anesthesia. Can Med Assoc J
Frank SG, Lalonde DH. How acidic is the lidocaine we are injecting, and how much
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[3]
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2012;184:2016. doi:10.1503/cmaj.111780.
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bicarbonate should we add? Can J Plast Surg 2012;20:71–4.
Matsumoto AH, Reifsnyder AC, Hartwell GD, Angle JF, Selby JB, Tegtmeyer CJ.
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Reducing the discomfort of lidocaine administration through pH buffering. J Vasc Interv
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Radiol 1994;5:171–5.
Lee HJ, Cho YJ, Gong HS, Rhee SH, Park HS, Baek GH. The effect of buffered lidocaine
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in local anesthesia: a prospective, randomized, double-blind study. J Hand Surg Am
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2013;38:971–5. doi:10.1016/j.jhsa.2013.02.016. Centres for Disease Control and Prevention. Frequently asked questions (FAQs) regarding
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safe practices for medical injections: Questions about single-dose/single-use vials,
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https://www.cdc.gov/injectionsafety/providers/provider_faqs_singlevials.html; n.d. (accessed July 20, 2017). Centres for Disease Control and Prevention. Frequently asked questions (FAQs) regarding
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[7]
safe practices for medical injections: Questions about multi-dose vials, https://www.cdc.gov/injectionsafety/providers/provider_faqs_multivials.html; n.d. (accessed July 20, 2017). [8]
Sakuragi T, Yanagisawa K, Shirai Y, Dan K. Growth of Escherichia coli in propofol, lidocaine, and mixtures of propofol and lidocaine. Acta Anaesthesiol Scand 1999;43:476–
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Plott RT, Wagner RF, Tyring SK. Iatrogenic contamination of multidose vials in simulated use: A reassessment of current patient injection technique. Arch Dermatol 1990;126:1441–4.
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[10] Kirschke DL, Jones TF, Stratton CW, Barnett JA, Schaffner W. Outbreak of Joint and
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Soft-Tissue Infections Associated with Injections from a Multiple-Dose Medication Vial.
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Clin Infect Dis 2003;36:1369–73.
[11] Sheth NK, Post GT, Wisniewski TR, Uttech B V. Multidose vials versus single-dose vials:
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a study in sterility and cost-effectiveness. J Clin Microbiol 1983;17:377–9.
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[12] Longfield R, Longfield J, Smith LP, Hyams KC, Strohmer ME. Multidose Medication Vial Sterility: An IN-Use Study and a Review of the Literature. Infect Control
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1984;5:165–9.
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[13] Anderson S, Rigler J, Oberoi V, Christ C, Eggers P, Lemp J, et al. Invasive Staphylococcus aureus infections associated with pain injections and reuse of single-dose
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vials-Arizona and Delaware, 2012. Morb Mortal Wkly Rep 2012;61:501–4.
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[14] Government of Canada. Information update - Health Canada provides information on shortage of injectable sodium bicarbonate products in Canada,
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http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/63654a-eng.php; 2017 (accessed July 20, 2017). [15] Thompson KD, Welykyj S, Massa MC. Antibacterial activity of lidocaine in combination with a bicarbonate buffer. J Dermatol Surg Oncol 1993;19:216–20. [16] Williams BJ, Hanke CW, Bartlett M. Antimicrobial effects of lidocaine, bicarbonate, and epinephrine. J Am Acad Dermatol 1997;37:662–4.
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http://www.pharmacopeia.cn/v29240/usp29nf24s0_c797.html; n.d. (accessed July 20,
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2017).
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[19] Wear J, McPherson TB, Kolling WM. Stability of sodium bicarbonate solutions in polyolefin bags. Am J Heal Syst Pharm 2010;67:1026–9.
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[20] Pascuet E, Donnelly RF, Garceau D, Vaillancourt R. Buffered lidocaine hydrochloride
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solution with and without epinephrine: Stability in polypropylene syringes. Can J Hosp Pharm 2009;62:375–80.
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[21] Donnelly RF. Stability of buffered lidocaine in glass vials. Can J Hosp Pharm
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2011;64:289–90.
[22] Chan E, Bucevska M, Verchere C. Minor surgery procedures: A retrospective review and
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prospective survey in a pediatric population. Plast Surg 2015;23:189-194.
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Lindsay Bjornson, Marija Bucevska, Peter Tilley, Cynthia Verchere PII: DOI: Reference:
S0022-3468(18)30244-6 doi:10.1016/j.jpedsurg.2018.04.005 YJPSU 58645
To appear in: Received date: Revised date: Accepted date:
21 December 2017 20 March 2018 2 April 2018
Please cite this article as: Lindsay Bjornson, Marija Bucevska, Peter Tilley, Cynthia Verchere , Is it safe to re-access sodium bicarbonate bottles for use in minor surgery?. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Yjpsu(2018), doi:10.1016/j.jpedsurg.2018.04.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Bjornson Is it safe to re-access sodium bicarbonate bottles for use in minor surgery? Running title: Sodium bicarb A
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Lindsay Bjornson MSc , Marija Bucevska MD , Peter Tilley MD FRCPC MD FRCSC
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Queen’s University, Kingston, ON, Canada
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Department of Surgery, University of British Columbia
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Department of Pathology & Lab Medicine, University of British Columbia BC Children’s Hospital, Vancouver, BC, Canada
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Institution: University of British Columbia
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Corresponding Author: Lindsay Bjornson K3-131 – 4480 Oak Street, Vancouver, BC V6H 3V4, Canada Tel: (604) 875-3758 Fax: (604) 875-2749 [email protected]
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Abstract: Background/Purpose: Sodium bicarbonate is added to lidocaine to reduce injection pain. In Canada, it is available in vials exceeding the injection volume 100-fold. These are single-use vials that should be disposed of after one access. Some surgeons re-use vials to reduce waste, potentially causing contamination. This study aims to review the safety of sodium bicarbonate and assess alternatives to current practice. Methods: Strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Burkholderia cepacia were used to assess bacterial growth in vials of sodium bicarbonate. Each pathogen was inoculated into a vial for 14 days at room temperature. At several time points, 1 mL of solution was removed and diluted. One hundred microliters were transferred to blood agar plates and incubated at 35ºC. Colony counts were calculated, averaged and plotted onto a logarithmic graph. Results: Colony counts of all strains fell below observational threshold after 7 days in sodium bicarbonate. Conclusions: Although all strains were reduced, bacteria can survive in sodium bicarbonate for several days, during which transmission may occur. Sodium bicarbonate vials should be treated as single-dose, as indicated by the manufacturers. To reduce waste, hospital pharmacies can repackage sodium bicarbonate into smaller vials or pre-alkalize lidocaine with sodium bicarbonate.
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KEY WORDS: sodium bicarbonate; single-dose vials; minor surgery; contamination.
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1. Introduction: When local anesthetics, such as lidocaine, are administered, many patients experience a painful burning sensation, which may be attributed to the acidic nature of these solutions [1–4] Common anesthetics are usually maintained at a relatively low pH in order to maximize the stability and therefore the shelf-life of the product [1,4]. Solutions of lidocaine without epinephrine have been found to have a pH of approximately six, while those containing epinephrine were found to have a pH of approximately four [1,3]. When compared to the pH of the subcutaneous tissue into which these anesthetics are injected, which is between 7.3 and 7.6, these solutions are markedly more acidic [3,4]. The painful stinging or burning sensation is likely due to the increase in hydrogen ions in the tissue upon injection [1]. It is possible to reduce the pain associated with the administration of local anesthetics by elevating the pH to the physiological level [1]. This can be achieved through the addition of sodium bicarbonate, which acts as an alkalizing agent of lidocaine [1–5]. In solution, sodium bicarbonate dissociates into a sodium cation and a bicarbonate anion. This anion binds to the free hydrogen cations in the solution, thereby reducing the hydrogen ion concentration and increasing the pH. Titration studies have shown that the optimal ratio of sodium bicarbonate to lidocaine is one milliliter to ten milliliters [3,4]. Using these volumes, the pH of lidocaine reaches the physiological level. Many studies have demonstrated that the addition of sodium bicarbonate to lidocaine is effective in decreasing patient discomfort upon injection [1–5]. In Canada, sodium bicarbonate is only available in single-dose vials. The Centers for Disease Control and Prevention (CDC) outline the regulations surrounding single- and multipledose vials [6,7]. As the names suggest, single-dose vials should be disposed of after one needle access, whereas multiple-dose vials may be re-accessed multiple times at the manufacturer’s instruction. The key distinguishing characteristic between the two is that the contents of multiple-dose vials possess antibacterial properties, which may be a result of either added preservatives or inherent properties of the solution itself. It is important to note that contamination may occur if aseptic technique is neglected, irrespective of the vial type. Failure to follow procedures such as the use of a new, sterile needle and syringe for each vial access has been shown to lead to contamination events [8–13]. A challenge associated with the use of single-dose vials is the accompanying wastage of materials. Some single-dose vials provide volumes that are far greater than those required for a single use. For example, sodium bicarbonate for injection is only available in Canada in 50 mL single-dose vials. When the plastic surgeons at British Columbia Children’s Hospital access these vials, they use an average of half a milliliter of sodium bicarbonate at a time for each administration of local anesthetic, leaving nearly an entire 50-mL vial of sodium bicarbonate. Although sodium bicarbonate is not a particularly expensive compound, often costing between five and ten dollars per vial, the waste produced by disposing countless glass vials containing the majority of their contents is concerning. Furthermore, current national and global shortages make sodium bicarbonate a limited commodity which should be conserved [14]. Anecdotally, some surgeons choose to re-use sodium bicarbonate vials. Although this does prevent excessive wastage, it is a risky and potentially dangerous practice, given the potential for contamination. Currently, there is limited information published in the literature about the viability of bacteria in sodium bicarbonate. Previous studies have demonstrated that sodium bicarbonate enhances the antimicrobial effect of lidocaine [1,15]. Another study suggested that sodium bicarbonate develops an increased ability to inhibit the growth of Pseudomonas aeruginosa and Staphylococcus aureus with increased time and increased sodium
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bicarbonate concentration [16]. Despite these promising findings, it remains unclear if the re-use of sodium bicarbonate vials might be considered a safe practice, particularly when considering that the current sodium bicarbonate shortage resulted from a manufacturer recall due to possible microbial contamination [14]. Understanding the safety of re-using sodium bicarbonate vials is particularly important during the current shortage, as clinicians may feel pressured to re-use vials in order to conserve available supplies. The purpose of this study was to review the safety of sodium bicarbonate by testing the viability of certain common bacterial strains in sodium bicarbonate and by assessing alternatives to the current practice. This article aims to generate awareness among surgeons of the potential dangers of re-using sodium bicarbonate, and of the available options to minimize these risks. We hypothesized that the risk of bacterial growth would be low, but needed to find evidence in typical clinical practice.
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2. Material and Methods: The study was exempt from REB review based on regulatory and institutional criteria. Strains of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Burkholderia cepacia were isolated and used to assess bacterial growth in 50 mL single-dose vials of 8.4% sodium bicarbonate. The procedure used for each of the four bacterial strains is illustrated in Figure 1, and described in more detail below. A 0.5 McFarland cell suspension of the organism was prepared in sterile saline. This suspension was then further diluted in saline to form a test suspension containing 105 colonyforming units per milliliter. One milliliter of sodium bicarbonate was removed from a new 50 mL vial of 8.4% sodium bicarbonate and discarded, and one milliliter of the test suspension was subsequently added to the vial. The contents of the vial were then mixed thoroughly. The pathogen was exposed to the solution for a total of fourteen days at room temperature. In order to assess bacterial growth in sodium bicarbonate, the solution was sampled at time points of 0 hours, 4 hours, 24 hours, 48 hours, 4 days, 7 days, and 14 days. At each of these time points, one milliliter of solution was removed from the vial and was serially diluted in saline to give three concentrations of solution: neat, 1/10, and 1/100. One hundred microliters of each resulting suspension were transferred to Columbia blood agar plates in triplicate and incubated at 35ºC. After a minimum of eighteen hours, colony counts were performed. Once all plates of a certain time point lacked colonies, subsequent time points were omitted. A control suspension was prepared for the 0-hour time point by adding the test inoculum to sterile saline and following the aforementioned procedure. The colony counts were noted for each time point, and an average value was calculated for each set of triplicates. These values were then plotted onto a logarithmic graph of number of colonies as a function of time. Figure 1. Schematic diagram of general experimental procedure 3. Results: Viability data for Staphylococcus aureus, Staphylococcus epidermidis, Burkholderia cepacia, and Pseudomonas aeruginosa injected in sodium bicarbonate vials can be found in Figure 2. The results of the experiment using Staphylococcus aureus, shown in Figure 2, indicate an initial increase in colonies per milliliter at the four-hour time point. Following this growth, the
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number of colonies fell to below the threshold of detection by day seven of the experiment. Staphylococcus aureus was the only organism to demonstrate an initial increase in colony numbers after exposure to sodium bicarbonate. The counts of Staphylococcus epidermidis, found in Figure 2, show a decrease in colony numbers at every time point. By day seven, no colonies were observed. Similarly, Burkholderia cepacia experienced a drop in colony counts at each time point. As shown in Figure 2, no colonies were recovered by day four. Finally, the results of the experiment using Pseudomonas aeruginosa, found in Figure 2, demonstrate a decline in colonies per milliliter from the zero-hour time point until day seven, when no colonies were counted.
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Figure 2. Viability data for Staphylococcus aureus, Staphylococcus epidermidis, Burkholderia cepacia, and Pseudomonas aeruginosa in sodium bicarbonate 8.4%
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4. Discussion: Sodium bicarbonate reduced the viable colonies of all four bacterial strains tested at our institution. The U.S. Pharmacopoeia (USP) General Chapter 51, Antimicrobial Effectiveness Testing, outlines the procedures for testing the effectiveness of an antimicrobial [17]. One criterion of an effective antimicrobial is a minimum reduction of 1.0 log from the initial colony count by day seven. All four of the bacterial strains in this study were reduced by more than 1.0 log by the seventh day. These results confirm some measure of anti-bacterial activity in 8.4% sodium bicarbonate, but over a period of time which is too long to be clinically helpful. The current procedure differed in some regards from that of the USP; nevertheless, it may be worth investigating the possible antimicrobial effectiveness of sodium bicarbonate further. Although sodium bicarbonate is widely accepted as an effective alkalizing agent of lidocaine, it is only available in Canada in volumes one hundred times larger than required for the 1:10 ratio of sodium bicarbonate to lidocaine [3,4]. Although all four bacterial strains were reduced by the seventh day in the present study, it is clear that bacteria can survive in the sodium bicarbonate vials for several days, and there is a risk of transmission during that time period. Therefore, sodium bicarbonate should continue to be treated as a single-dose vial, as instructed by the manufacturers. As such, all vials and their leftover contents should be disposed of immediately following opening. In Canada, this leads to excessive wastage of sodium bicarbonate, which is already in short supply, and glass vials. We investigated the ways in which surgeons can use sodium bicarbonate more efficiently in order to conserve limited resources and decrease the wastefulness of the current practice. One option is to use smaller vials of sodium bicarbonate. Given that sodium bicarbonate should be accessed only once, there would be less wastage if it were provided in smaller sizes. These volumes are not available on the Canadian market; however, it is possible to repackage larger unopened vials under ISO Class 5 conditions in accordance with USP General Chapter 797, Pharmaceutical Compounding – Sterile Preparations [18]. Most hospital pharmacies meet these standards. Thus, they may be able to repackage the 50 mL sodium bicarbonate vials into more useful volumes for the alkalization of lidocaine, depending on the availability of smaller containers. Glass containers are preferable, as they are the medium in which sodium bicarbonate is typically provided; however, a 2010 study showed that sodium bicarbonate is also stable in polyolefin for up to seven days when refrigerated [19].
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The alternative solution is to use a pre-alkalized lidocaine solution [3]. Again, this must be prepared under ISO Class 5 conditions in accordance with USP General Chapter 797. As before, glass containers are preferable; however, evidence suggests that alkalized lidocaine is stable in a plastic syringe for up to 28 days with refrigeration, while alkalized lidocaine with epinephrine is stable in a plastic syringe for up to 7 days with refrigeration [20,21]. Thompson et al. (1993) suggested that sodium bicarbonate can actually enhance the bacteria-killing effect of lidocaine [15]. This data, in combination with the antimicrobial activity of the lidocaine solution and its methylparaben and sodium metabisulfite preservatives, suggests that the alkalized lidocaine will remain sterile and can be used as a multi-dose vial. The Plastic Surgery Clinic at British Columbia Children’s Hospital has investigated the latter option. Our hospital prepares mixtures of sodium bicarbonate with lidocaine with or without epinephrine; however, lidocaine with epinephrine is preferred [3]. The pharmacy can provide these 20 mL vials at a set time each week in preparation for the following week’s minor surgeries in all parts of the hospital. Each 20 mL vial of buffered lidocaine with epinephrine costs about $7. While this solution may not necessarily be more cost-effective than continuing to use the 50 mL single-dose vials, it addresses the concern for waste reduction of the glass vials and sodium bicarbonate. We are unable to pursue an in-depth cost analysis, but data from a previous publication arising from our institution show approximately 110 minor surgery procedures undertaken by a single surgeon in a one-year period; the cost of selecting one vial type over another would be multiplied by this factor [22]. In having the pharmacists prepare the alkalized lidocaine solution under sterile conditions, the number of sodium bicarbonate vials that must be discarded is far less; however, the process of preparing individual plastic syringes may also create extra waste. Nevertheless, it eliminates the potential risks associated with reaccessing a single-dose vial multiple times. It must be said, however, that neither of the proposed options is ideal, practical, or sustainable for use in local anesthesia. If manufacturers would consider supplying sodium bicarbonate in 1mL single-use glass ampules, there would be an overall reduction in cost, a decrease in plastic and mixed waste, more efficient shipping and less discarded sodium bicarbonate in times of shortage.
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Acknowledgments: The authors would like to gratefully acknowledge Mary-Jane Margach and Lori Willis for their technical assistance, and Rebecca Courtemanche for her editorial assistance in this study. Lindsay Bjornson would like to acknowledge the BC Patient Safety & Quality Council for funding her studentship.
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Figure 1
Figure 2