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Licensed Unlicensed Requires Authentication Published by De Gruyter October 1, 2017

Prospective, double blind, randomized, controlled trial comparing vapocoolant spray versus placebo spray in adults undergoing intravenous cannulation

  • Sharon E. Mace EMAIL logo



Painful diagnostic and therapeutic procedures are common in the health care setting. Eliminating, or at least, minimizing the pain associated with various procedures should be a priority. Although there are many benefits of providing local/topical anesthesia prior to performing painful procedures, ranging from greater patient/family satisfaction to increased procedural success rates; local/topical anesthetics are frequently not used. Reasons include the need for a needlestick to administer local anesthetics such as lidocaine and the long onset for topical anesthetics. Vapocoolants eliminate the risks associated with needlesticks, avoids the tissue distortion with intradermal local anesthetics, eliminates needlestick pain, have a quick almost instantaneous onset, are easy to apply, require no skills or devices to apply, are convenient, and inexpensive. The aims of this study were to ascertain if peripheral intravenous (PIV) cannulation pain would be significantly decreased by using a vapocoolant (V) versus sterile water placebo (S) spray, as determined by a reduction of at least >1.8 points on numerical rating scale (NRS) after vapocoolant versus placebo spray, the side effects and incidence of side effects from a vapocoolant spray; and whether there were any long term visible skin abnormalities associated with the use of a vapocoolant spray.

Materials and methods

Prospective, randomized, double-blind controlled trial of 300 adults (ages 18-80) requiring PIV placement in a hospital ED, randomized to S(N = 150)or V(N = 150) prior to PIV. Efficacy outcome was the difference in PIV pain: NRS from 0 (none) to worst (10). Safety outcomes included a skin checklist for local adverse effects (i.e., redness, blanching, edema, ecchymosis, itching, changes in skin pigmentation), vital sign (VS) changes, and before/after photographs of the PIV site.


Patient demographics (age, gender, race), comorbidity, medications, and vital signs; and PIV procedure variables (e.g., IV needle size, location, number of IV attempts, type and experience of healthcare provider performing the IV) were not significantly different for the two groups. Median (interquartile range) PIV pain was 4 (2,7) (S) and 2 (0,4) (V) (P< 0.001). Skin checklist revealed minimal erythema: S 0% (N = 0/150), V: 2.7% (4/150), which resolved within 5min, and no blanching, skin pigmentation changes, itching, edema, or ecchymosis. Photographs at 5-10 min revealed no visible skin changes in any patient (N=300), vapocoolant (N = 150) or placebo groups (N = 150). Complaints (N = 26) were coolness/cold feeling S 8.7% (N = 13), V 7.3% (N = 11), coolness/numbness S 0% (N =0), V 0.7% (N =1), and burning S 0.7% (N =1), V 0 (0%). Patient acceptance of the vapocoolant spray was high: 82% (123/150) of the patients stated they would use the spray in the future, while only 40.7% (61/150) of the placebo group stated they would use the placebo spray in the future.

Conclusions and Implications

Vapocoolant spray significantly decreased peripheral intravenous cannulation pain in adults versus placebo spray and was well tolerated with minor adverse effects that resolved quickly. There were no significant differences in vital signs and no visible skin changes documented by photographs taken within 5-10 min postspray/PIV.

Department of Emergency Medicine, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Faculty MetroHealth Medical Center/Cleveland Clinic Emergency Medicine Residency, Cleveland, OH, United States

☆ Presentations: American College of Emergency Physicians, October 2013, Seattle, WA. American Society of Regional Anesthesia and Pain Medicine, April 2014, Chicago, IL.Society of Academic Emergency Medicine, May 2014, Dallas, TX. American College of Emergency Physicians, October 2014, Chicago, IL. International Conference on EmergencyMedicine, April 2016, Capetown, South Africa. Society of Academic Emergency Medicine, May 2016, New Orleans, LA.

  1. Ethical issues: The study was approved by the Institutional Review Board (IRB).

    Written informed consent was obtained from all subjects.

    The study protocol was registered at (NCT01670487).

  2. Conflict of interest: Thus study was an investigator-initiated study supported by a research grant from the Gebauer Company. The sponsor had no involvement in the study other than funding and supplying the spray cans used for the administration of the placebo spray and the vapocoolant spray.


I would like to thank Mr. Benjamin Nutter, the Section of Biostatistics, Quantitative Health Sciences for his statistical analysis of the data.


[1] Zempsky WT. Pharmacologic approaches for reducing venous access pain in children. Pediatrics 2008;122:S140–53.10.1542/peds.2008-1055gSearch in Google Scholar PubMed

[2] Singer AJ, Richman PB, Kowalska AL, Thode Jr HC. Comparison of patient and practitioner assessments of pain from commonly performed emergency department procedures. Ann Emerg Med 1999;33:652–8.Search in Google Scholar

[3] Todd KH, Ducharme J, Choiniere M, Crandall CS, Fosnocht DE, Homel P, Tanabe P, PEMI Study Group. Pain in the emergency department: results of the Pain and Emergency Medicine Initiative (PEMI) multicenterstudy. J Pain 2007;8:460–6.10.1016/j.jpain.2006.12.005Search in Google Scholar PubMed

[4] Emergency Nurses Association (ENA) Position Statement.Pediatric procedural pain management. Emergency Nurses Association; 2010 [last accessed March 2017].Search in Google Scholar

[5] Kennedy RM, Luhmann J, Zempsky WT. Clinical implications of unmanaged needle-insertion pain and distress in children. Pediatrics 2008;122:S130–3.10.1542/peds.2008-1055eSearch in Google Scholar PubMed

[6] Fosnocht DE, Swanson ER, Bossart P. Patient expectations for pain medication delivery. AmJ Emerg Med 2001;19:399–402.10.1053/ajem.2001.24462Search in Google Scholar PubMed

[7] Reyes-Gibby CC, Todd KH. Oligo-evidence for oligoanesthesia: a non sequitur? Ann Emerg Med 2013;612:373–4.10.1016/j.annemergmed.2012.09.018Search in Google Scholar PubMed

[8] Todd KH, Sloan E, Chen C, Eder S, Wamstad K. Survey of Pain etiology, management practices and patient satisfaction in two urban emergency departments. CJEM 2002;4:252–6.10.1017/S1481803500007478Search in Google Scholar PubMed

[9] Fein JA, Zempsky WT, Cravero JP, Committee on Pediatric Emergency Medicine and Section on Anesthesiology and Pain Medicine, American Academy of Pediatrics.Relief of pain and anxiety in pediatric patients in emergency medical systems. Pediatrics 2012;130:e1391–405.10.1542/peds.2012-2536Search in Google Scholar PubMed

[10] Young KD. Pediatric procedural pain. Ann Emerg Med 2005;45:160–71.10.1016/j.annemergmed.2004.09.019Search in Google Scholar PubMed

[11] MacLean S, Obispo J, Young KD. The gap between pediatric emergency department procedural pain management treatments available and actual practice. Pediatr Emerg Care 2007;23:87–93.10.1097/PEC.0b013e31803Search in Google Scholar PubMed

[12] American Academy Pediatrics Committee on Psychosocial Aspects of Child and Family Health, American Pain Society Task Force on Pain in Infants, Children, and Adolescents. The assessment and management of acute pain in infants, children, and adolescents. Pediatrics 2001;108:793–7.10.1542/peds.108.3.793Search in Google Scholar PubMed

[13] Zempsky WT. Optimizing the management of peripheral venous access pain in children: evidence, impact, and implementation. Pediatrics 2008;122:S121–4.10.1542/peds.2008-1055cSearch in Google Scholar

[14] Czarnecki ML, Turner HN, Collins PM, Doellman D, Wrona S, Reynolds J. Procedural pain management: a clinical statement with practice implications. Pain Manag Nurs 2011;12:95–111.10.1016/j.pmn.2011.02.003Search in Google Scholar

[15] Taddio A, Lord A, Hogan ME, Kikutu A, Yiu A, Darra E, Bruinse B, Keogh T, Stephens D. A randomized controlled trial of analgesia during vaccination in adults. Vaccine 2010;28:5365–9.10.1016/j.vaccine.2010.05.015Search in Google Scholar

[16] Farion KJ, Splinter KL, Newhook K, Gaboury I, Splinter WM. The effect of vapocoolant spray on pain due to intravenous cannulation in children: a randomized controlled trial. CMAJ 2008;179:31–6.10.1503/cmaj.070874Search in Google Scholar

[17] Mace SE. Topical anesthesia. In: Mace SE, Ducharme J, Murphy MF, editors. Pain management and sedation, New York, NY. 2006. p. 195-202 [Chapter 26].Search in Google Scholar

[18] Armstrong P, Young C, McKeown D. Ethyl chloride and venipuncture pain: a comparison with intradermal lidocaine. Can J Anaesth 1990;37:656–8.10.1007/BF03006485Search in Google Scholar

[19] Page DF, Taylor DM. Vapocoolant spray vs. subcutaneous lidocaine injection for reducing the pain of intravenous cannulation: a randomized, controlled, clinical trial.BrJ Anaesth 2010;105:519–25.10.1093/bja/aeq198Search in Google Scholar

[20] Parent du Chatelet I, Lang J, Schlumberger M, Vidor E, Soula G, Genet A, Standaert SM, Saliou P. Clinical immunogenicity and tolerance studies of liquid vaccines delivered byjet-injectorand a new single-use cartridge (Imule): comparison with standard syringe injection. Vaccine 1997;15:449–58.10.1016/S0264-410X(96)00173-9Search in Google Scholar

[21] Mace SE. Prospective, randomized, double-blind controlled trial comparing vapocoolant spray vs.placebo spray in adults. Am J Emerg Med 2016;34:798–804.10.1016/j.ajem.2016.01.002Search in Google Scholar PubMed

[22] Kelly AM. Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Acad Emerg Med 1998;5:1086–90.10.1111/j.1553-2712.1998.tb02667.xSearch in Google Scholar PubMed

[23] Todd KH, Funk JP. The minimum clinically important difference in physicianassigned visual analog pain scores. Acad Emerg Med 1996;3:142–6.10.1111/j.1553-2712.1996.tb03402.xSearch in Google Scholar PubMed

[24] Galdyn I, Swanson E, Gordon C, Kwiecien G, Bena J, Siemionow M, Zins J. Microcirculatory effect of topical vapocoolants. Plast Surg 2015;23:71–6.10.1177/229255031502300211Search in Google Scholar

[25] Evans JG, Taylor DM, Hurren F, Ward P, Yeoh M, Hoiwden BP. Effects of vapocoolant spray on skin sterility prior to intravenous cannulation. J Hosp Infect 2015;90:333–7.10.1016/j.jhin.2015.03.010Search in Google Scholar

[26] Schleicher WF, Richards BG, Huetther F, Ozturk C, Zuccaro P, Zins JE. Skin sterility after application of a vapocoolant spray. Dermatol Surg 2014;40:1103–7.10.1097/01.DSS.0000452654.29636.56Search in Google Scholar

[27] Burke D, Mogyoros I, Vagg R, Kierman MC. Temperature dependence of excitability indices of human cutaneous afferents. Muscle Nerve 1999;22:51–60.10.1002/(SICI)1097-4598(199901)22:1<51::AID-MUS9>3.0.CO;2-QSearch in Google Scholar

[28] Griffith RJ, Jordan V, Herd D, Reed PW, Dalziel SR. Vapocoolants (cold spray) for pain treatment during intravenous cannulation (review). Cochrane Database Syst Rev 2016. ANCD009484.10.1002/14651858.CD009484.pub2Search in Google Scholar

[29] Algafly AA, George KP. The effect of cryotherapy on nerve conduction velocity, pain threshold and pain tolerance. BrJ Sports Med 2007;41:365–9.10.1136/bjsm.2006.031237Search in Google Scholar

[30] Malanga GA, Yan N, Stark J. Mechanisms and efficacy of heat and cold therapies for musculoskeletal injuries. Postgrad Med 2015;127:57–65.10.1080/00325481.2015.992719Search in Google Scholar

[31] Fossum K, Love SL, April MD. Topical ethyl chloride to reduce pain associated with venous catheterization: a randomized crossover trial. Am J Emerg Med 2016;34:845–50.10.1016/j.ajem.2016.01.039Search in Google Scholar

[32] Reis Cohen E, Holubkov R. Vapocoolant spray is equally effective as EMLA cream in reducing immunization pain in school-aged children. Pediatrics 1997;100 in Google Scholar

[33] Mawhorter S, Daugherty L, Ford A, Hughes R, Metzger D, Easley K. Topical vapocoolant quickly and effectively reduces vaccine-associated pain: results ofa randomized, single-blinded, placebo controlled study. J Travel Med 2004;11:267–72.10.2310/7060.2004.19101Search in Google Scholar

[34] Weiss RA, Lavin PT. Reduction of pain and anxiety prior to botulinum toxin injections with a new topical anesthestic method. Ophthal Plast Reconstr Surg 2009;25:173–7.10.1097/IOP.0b013e3181a145caSearch in Google Scholar

[35] Kosaraju A, Vanewallie KS. A comparison of a refrigerant and a topical anesthetic gel as preinjection anesthetics: a clinical evaluation. JSADA 2009;140:68–72.Search in Google Scholar

[36] Selby IR, Bowles BJ. Analgesia for venous cannulation: a comparison of EMLA (5 minute application), lignocaine, ethyl chloride and nothing. J R Soc Med 1995;88:264–7.Search in Google Scholar

[37] Hijazi R, Taylor D. Effect of topical alkane vapocoolant spray on pain with intravenous cannulation n patients in emergency departments: randomized double blind placebo controlled trial. BMJ 2009;338:b215, in Google Scholar

[38] Celik G, Ozbek O, Yilmaz M, Dunman I, Ozbek S, Apiliogullaris S. Vapocoolant spray vs lidocaine/prilocaine cream for reducing the pain of venipuncture in hemodialysis patients: a randomized, placebo controlled trial. Int J Med Sci 2011;8:623–7.10.7150/ijms.8.623Search in Google Scholar

[39] Ramsook C, Kozinetz CA, Moro-Sutherland D. Efficacy of ethyl vinyl chloride as a local anesthetic for venipuncture and catheter insertion in a pediatric emergency department. Pediatr Emerg Care 2001;17:341–3.10.1097/00006565-200110000-00005Search in Google Scholar

[40] Costello M, Ramundo M, Christopher N, Powell KR. Ethyl chloride vapocoolant spray fails to decrease pain associate with intravenous cannulation in children. Clin Pediatr(Phila) 2006;45:628–32.10.1177/0009922806291013Search in Google Scholar

[41] Biro P, Meier T, Cummins AS. Comparison of topical anesthesia methods for venous cannulation in adults. EurJ Pain 1997;1:37–42.10.1016/S1090-3801(97)90051-3Search in Google Scholar

[42] Hogan ME, Smart S, Shah V, Taddio A. A systematic review of vapocoolants for reducing pain from venipuncture and venous cannulation in children and adults. J Emerg Med 2014;47:736–49.10.1016/j.jemermed.2014.06.028Search in Google Scholar PubMed

Received: 2017-04-29
Revised: 2017-06-07
Accepted: 2017-06-10
Published Online: 2017-10-01
Published in Print: 2017-10-01

© 2017 Scandinavian Association for the Study of Pain

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