Skin Sterility After Application of a Vapocoolant Spray William F. Schleicher, MD,* Bryson G. Richards, MD,* Franziska Huettner, MD, PhD,* Cemile Ozturk, MD,† Patricia Zuccaro, BS,‡ and James E. Zins, MD, FACS*

BACKGROUND Refrigerant sprays have been widely used to reduce pain in the office setting. However, more recently, their use has been limited by both concern regarding flammability and questions of bacterial contamination. OBJECTIVE We investigated the microbiological effect of 1,1,1,3,3 pentafluoropropane and 1,1,1,2tetrafluoroethane when sprayed after povidone–iodine application in 50 volunteers. MATERIALS AND METHODS In 50 volunteers, 3 cultures were taken (1) at time 0 before antiseptic application, (2) after povidone–iodine topical antiseptic, and (3) after spraying with vapocoolant. Cultures at 3 time intervals were analyzed in a blinded fashion, and Gram stains obtained when cultures were positive. RESULTS Bacterial growth was found in 98% of cultures taken before antiseptic was applied (Group 1), in 28 cultures (56%) after povidone–iodine was applied, and in 24 cultures (48%) after spraying with vapocoolant. There was a statistically significant difference found between Group 1 (no antiseptic) and both Group 2 (after antiseptic but before vapocoolant) and Group 3 (after vapocoolant) (p < .001). CONCLUSION The topical antiseptic povidone–iodine significantly reduces skin colonization when compared with unprepared skin (p < .001). The vapocoolant 1,1,1,3,3 pentafluoropropane and 1,1,1,2-tetrafluoroethane is sprayed on skin prepared with povidone–iodine; there is no statistically significant increase in bacterial colonization.

apocoolant sprays (skin refrigerants) are widely used topical agents frequently used to diminish pain caused by needle injections or minor surgical procedures.1–13 Tetrafluoroethane is a vapocoolant skin refrigerant spray, which acts by immediate vaporization, creating a cooling effect and has been shown to reduce discomfort when used immediately before injections of local anesthetic or even botulinum toxin and soft-tissue fillers.1

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composed of 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane, which are nonflammable substances, making it usable in the surgical setting. However, little clinical data exist regarding the microbiology of the vapocoolant sprays in general and 1,1,1,3,3-pentafluoropropane and 1,1,1,2tetrafluoroethane in particular.15,16 Because the product is labeled nonsterile, this is a deterrent to its office and minor procedure use.

Other skin refrigerants such as ethyl chloride and alkanes have also been used to reduce pain.4,5,7,8,10 However, these compounds are highly flammable and therefore precluded from use in the operating room setting.14 Pain Ease (Gebauer Co., Cleveland, OH) could potentially be a safe alternative because it is

The purpose of this study was to determine whether the application of 1,1,1,3,3-pentafluoropropane and 1,1,1,2tetrafluoroethane vapocoolant spray, after standard skin preparation, alters the sterility of the injection site in healthy volunteers. Such results either positive or negative would support or discourage the use of the product.

*Department of Plastic Surgery, Cleveland Clinic, Cleveland, Ohio; †Plastic and Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo, New York; ‡Northeast Ohio Medical University, Rootstown, Ohio This study was funded by the Gebauer Co., Cleveland, OH.

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© 2014 by the American Society for Dermatologic Surgery, Inc. Published by Lippincott Williams & Wilkins ISSN: 1076-0512 Dermatol Surg 2014;40:1103–1107 DOI: 10.1097/01.DSS.0000452654.29636.56

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APPLICATION OF A VAPOCOOLANT SPRAY

Materials and Methods A prospective, blinded, controlled study was performed including 50 healthy adult volunteers. This included 35 women and 15 men aged 23 to 72 years. Volunteer subjects were allowed to participate if they were healthy and older than 18 years. Subjects were excluded from the study if they had a known hypersensitivity to 1,1,1,3,3-pentafluoropropane or 1,1,1,2-tetrafluoroethane or povidone–iodine solution. Informed consent was obtained and our institutional review board (IRB) approved the protocol. No injections or procedures were actually performed. The dorsum of the hand was first sprayed to familiarize the patient with the sensation of the vapocoolant spray. Three swab cultures were obtained from the subject’s face using a single, dry, dual-tip cotton swab (Copan, Copan Diagnostics Inc., Murrieta, CA). The subject’s cheek was used as the test site. The first culture was obtained before skin preparation. The skin at the same site was then cleansed with 3 passes of a Povidone–Iodine Swabstick (Professional Disposables International, Orangeburg, NY), and the site was allowed to dry for 1 minute. We chose povidone–iodine solution as the skin preparation to mimic operating room conditions for those patients undergoing minor procedures on the face. After the povidone–iodine was allowed to dry, a second culture was then obtained over the cleansed skin. The study area was then sprayed using the vapocoolant from a distance of 8 to 10 cm continuously for a time of 4 to 8 seconds until the skin just turned white. The third culture was then obtained. The same nonsterile canister of 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane was used for each subject without additional cleansing of the canister or the spray valve to simulate common practice in a clinical setting.

Microbial growth was reported as none (0 microbial growth), rare (#15 colonies), few (16–20 colonies), moderate (21–25 colonies), and many (>25 colonies). No further speciation was determined because of financial constraints of the study. Study data were collected and managed using REDCap16 electronic data capture tools hosted at the Cleveland Clinic. Patient characteristics were described using medians and quartiles and mean values and standard deviations for all continuous variables and counts and percentages for all categorical variables. McNemar test was used to determine whether positive and negative Gram stains occurred at the same rate within preparation stages. The Wilcoxon signed-rank test was used to determine whether any changes in the amount of growth observed between within-preparation stages. All analyses were 2-tailed and performed at a significance level of .05.

Results Of the 50 subjects mock treated (Table 1), bacterial growth before skin preparation was applied and found in 49 patients (98%; Table 2). The most common pathogen found was gram-positive cocci (98%; Table 1). Growth was found after antiseptic preparation but before spray with vapocoolant in 28 specimens (56%). The reduction in cultures positive for bacteria after antiseptic application was statistically significant (p < .001). Finally, growth occurred in 24 specimens (48%) after povidone–iodine swab and vapocoolant spray. There TABLE 1. Descriptive Summaries for all Variables Total (N = 50)

All microbiology specimens were treated in a blinded fashion regarding the nature and sequence of the culture swabs. A standard 5-day incubation period was used for all aerobic and anaerobic cultures. A qualitative analysis of growth as described by Polishchuk and colleagues15 was performed along with basic gram staining in cases where growth was noted.

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Age N Mean (SD) Range Gender

50 44.3 (13.2) 23.0–72.0

Male

15 (30.0%)

Female

35 (70.0%)

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SCHLEICHER ET AL

TABLE 2. Distribution of Growth Amounts Amount Growth

Before Preparation

After Preparation

After Spray

p value None

1 (2.0%)

22 (44.0%)

26 (52.0%)

Rare

5 (10.0%)

22 (44.0%)

18 (36.0%)

18 (36.0%) 18 (36.0%)

2 (4.0%) 4 (8.0%)

5 (10.0%) 1 (2.0%)

Few Moderate Many

8 (16.0%)

0 (0.0%)

Before Preparation vs After Preparation

After Preparation vs After Spray

10-year period with no known clinical infections.

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APPLICATION OF A VAPOCOOLANT SPRAY

We chose to use povidone–iodine as our antiseptic agent of choice because we were attempting to simulate the use of vapocoolant for minor operating room procedures. The choice of alcohol as an antiseptic was also considered because this would simulate office conditions when injecting botulinum toxin or soft-tissue fillers. Whether similar results would have been found had we used alcohol cannot be determined by this study. This is currently under review. The strengths of this study include its prospective blinded nature. In addition, the selection of the skin site and skin preparation was chosen to be clinically relevant. Povidone–iodine swabs were used as our method of cleansing the test site because this is the standard skin preparation used for facial cases at our institution. There are acknowledged limitations in this study. Our sample size was small (n = 50), and our results are applicable only to the use of 1,1,1,3,3 pentafluoropropane and 1,1,1,2-tetrafluoroethane on the face, specifically the cheeks, as this was the only site tested for microbial growth. Our results would need to be replicated at other injection sites using different types of preparation material to allow for broader application of our findings. We chose not to directly culture the product itself. The vapocoolant product is subject to independent laboratory testing outside the manufacturer to meet microbiological acceptance criteria, which include total aerobic microbial count, total yeast and mold counts, and presence/absence of Staphylococcus aureus and Pseudomonas aeruginosa. Although culturing the product may either support or contradict our findings, the goal of this study was to evaluate the skin sterility before and after vapocoolant application in a clinically relevant method. 1,1,1,3,3 pentafluoropropane and 1,1,1,2tetrafluoroethane are an ideal product to establish preinjection analgesia before botulinum toxin and dermal fillers. Our decision to use povidone–iodine as the antiseptic solution limits our ability to generalize this study’s application for those who use alcohol as an antiseptic preparation before aesthetic injectable therapies.

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Our findings provide potential clinical relevance for the safe use of 1,1,1,3.3-pentafluoropropane and 1,1,1,2tetrafluoroethane in the clinic and minor operating room setting from an antimicrobial standpoint.

Conclusion In summary, the lack of microbiological data regarding the effect of the topical refrigerant 1,1,1,3,3 pentafluoropropane and 1,1,1,2-tetrafluoroethane on the skin treated with a topical antiseptic may be limiting the use of an otherwise effective product. We present prospective blinded data using a mock injection clinical model in 50 subjects documenting no increase in pathogens after a topical antiseptic followed by refrigerant spray compared with a topical antiseptic alone.

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12. Mantha S, Thisted R, Foss J, Ellis JE, et al. A proposal to use confidence intervals for visual analog scale data for pain measurement to determine clinical significance. Anesth Analg 1993;77:1041–7. 13. Reis EC, Jacobson RM, Tarbell S, Weniger BG. Taking the sting out of shots: control of vaccination-associated pain and adverse reactions. Pediatr Ann 1998;27:375–86. 14. Gebauer Company, P.E.F.S. Available from: http://www. gebauerspainease.com Accessed March 2012. 15. Polishchuk D, Gehrmann R, Tan V. Skin sterility after application of ethyl chloride spray. J Bone Joint Surg Am 2012;94:118–20.

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Address correspondence and reprint requests to: James E. Zins, MD, FACS, Department of Plastic Surgery, Cleveland Clinic, 9500 Euclid Avenue, Desk A60, Cleveland, OH 44195, or e-mail: [email protected]

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