Topical vapocoolant quickly and effectively reduces vaccine-associated pain: results of a randomized, single-blinded, placebo-controlled study

J Travel Med. Sep-Oct 2004;11(5):267-72. doi: 10.2310/7060.2004.19101.


Background: Comprehensive international travel preparation often requires several vaccines. Up to 90% of adults have some fear of injections, mostly due to injection-related pain. Pediatric studies with routine vaccines have shown topical anesthetic EMLA cream (lidocaine and prilocaine, Astra Pharmaceuticals, Inc.) and the topical vapocoolant Fluori-Methane (dichlorodifluoromethane and trichlorodifluoromethane, Gebauer Co.) to be equally effective in reducing pain from vaccinations. EMLA cream is expensive and requires a 60-min application, while Fluori-Methane (FM) is immediate in onset of action and inexpensive. Skin anesthesia begins at 10 degrees C. Fluori-Methane can briefly cool the skin to 0 degrees C.

Methods: We studied the effectiveness of topical vapocoolant on adult clients at our international travel clinic in a randomized, controlled trial of topical FM vs. cold (4 degrees C) saline placebo. Using a preset randomization table, participants served as their own controls, receiving placebo/control or active agent (participant blinded) in one arm (left or right), and a similar number of vaccines in the untreated arm. Vaccines were administered according to a set protocol per arm to minimize the risk of bias. Pain was measured using a modified McGill present pain intensity (PPI) pain index. Subjects rated their pain immediately and at 5 min on a six-level scale, noting treated and untreated arms separately. A questionnaire was completed on intervention preferences. Sample size was predetermined to achieve 90% statistical power estimating 25% efficacy (minimum n=172).

Results: One hundred and eighty-five participants were enrolled; 93 FM and 92 cold saline placebo. FM-treated arms had a significant reduction in immediate pain compared to untreated arms (pain scale mean 2.2 vs. 3.1; p<.0001), and compared to placebo (mean 2.2 vs. 2.8; p<.01). Delayed pain at 5 min was not affected by FM or control (mean 1.9 vs. 2.0) compared to no intervention (pain scale 1.9). The intervention preference questionnaire indicated that participants did not find FM therapy uncomfortable. They would choose FM therapy in the future, over a cream, especially if a wait was involved.

Conclusion: The topical vapocoolant Fluori-Methane is an effective, quick, preferred, inexpensive agent for reducing vaccine-associated injection pain for international travel clients.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Adult
  • Chlorofluorocarbons, Methane / therapeutic use*
  • Female
  • Humans
  • Injections / adverse effects*
  • Linear Models
  • Male
  • Pain / etiology
  • Pain / prevention & control*
  • Single-Blind Method
  • Travel*
  • Vaccination / adverse effects*


  • Chlorofluorocarbons, Methane
  • fluori-methane