In recent years, alternative methods for topical anesthesia prior to injections have been investigated.1 Vapocoolant sprays, typically used to provide temporary relief from minor sports injuries, are also marketed as topical anesthetic agents for use prior to injections or minor surgical procedures in humans. Commonly used products include ethyl chloride, fluorohydrocarbons, and alkane mixtures, all of which provide rapid but transient skin anesthesia via evaporation-induced skin cooling. The local anesthetic effect is believed to occur through desensitization of nociceptors2 or by means of activation of ion channels involved in transmission of cold-specific afferent input.3
Vapocoolant sprays have been proven effective in reducing pain and anxiety associated with vaccinations4 and botulinum toxin injections in humans.5 Conflicting reports exist concerning the use of these products for reduction of pain associated with IV catheterization. No effect was reported in 2 studies6,7 in which investigators were not blinded to the type of treatment used, whereas a significant reduction of pain associated with IV cannulation was demonstrated in 2 recent double-blinded, placebo-controlled studies in juvenile8 and adult9 humans. To the authors' knowledge, no reports have been published on the efficacy of such products in animals.
Intra-articular injections are essential for diagnosis of lameness in horses. Multiple injections may be necessary during a lameness examination, and the nature of such examination prohibits use of systemic analgesic or sedative agents. Although most horses tolerate diagnostic injections well, there are substantial interindividual differences in response to this procedure. Some horses resist the stimulus from needle penetration to such an extent that performing diagnostic injections in the unsedated animal is unsafe. Also, some horses tend to react more throughout an examination that requires multiple injections, perhaps because of anxiety and anticipatory stress.
The objective of the study reported here was to evaluate the efficacy of a commercially available topical vapocoolant spray to reduce responses to commonly performed clinical procedures in unsedated horses. We sought to evaluate the effect of this product on responses to subsequent MC and MCP joint arthrocentesis and jugular vein catheterization. Our hypothesis was that the vapocoolant spray treatment would significantly reduce horses' responses to these procedures, compared with responses after a placebo treatment.
Materials and Methods
Preliminary experiments—Optimal spraying time for the vapocoolant product,a which contained 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluorethane, was investigated. Briefly, 2 Standardbred horses from the teaching herd of the Norwegian School of Veterinary Science that were not enrolled in the trial were selected for preliminary testing of the vapocoolant spray. The horses were determined to be healthy on the basis of a clinical examination conducted immediately prior to the experiment. Three sites on the neck of each horse were clipped and aseptically prepared. The vapocoolant was then sprayed onto a prepared site from a distance of 10 cm for 5, 10, or 15 seconds. The site chosen for each duration of spray was randomly selected. Response to skin pricking (insertion of a 21-gauge needle to a depth of approx 2 to 3 mm, repeated 5 times) immediately following application of the vapocoolant spray was assessed by use of a 6-point categorical scale (0 = no response [ie, no movement of the skin, head, or neck], 1 = minimal response [eg, a few cutaneous muscle contractions at the needle placement site], 2 = mild response [eg, multiple cutaneous muscle contractions at the needle placement site], 3 = moderate response [eg, multiple cutaneous muscle contractions at the needle placement site and vertical head movement] 4 = marked response [eg, horizontal head and neck movement away from the needle], and 5 = severe response [eg, body movement away from the needle]). Each of the needle-prick tests was scored, and the mean value for each site for each horse was used in the evaluation. To evaluate safety regarding use of the spray on an aseptically prepared site, each sprayed site was subsequently swabbed with commercial swabsb within 2 minutes of spray application and the swabs were submitted to our institution's laboratory for aerobic and anaerobic microbial culture. Bacterial culture was also performed on blood agar plates that were directly sprayed with the vapocoolant product.
Placebo-controlled trial—Eight mares (6 Standardbreds and 2 Norwegian Coldblooded Trotters; mean age, 15 years [range, 9 to 22 years]) from the teaching herd of the Norwegian School of Veterinary Science were enrolled in the study. The horses were determined to be healthy on the basis of a clinical examination conducted immediately prior to commencement of the study. The number of horses was determined on the basis of a preliminary power analysis with the intention of including 8 additional horses if needed in accordance with methods described elsewhere regarding the use of animals in research.10 All procedures, including preliminary experiments to optimize vapocoolant spraying time, were approved by the Norwegian Animal Research Authority.
Spray application, arthrocentesis, and IV catheterization—A total of 6 sites/horse (bilateral MC joints, bilateral MCP joints, and bilateral jugular grooves) were clipped and scrubbed according to standard hospital methods for arthrocentesis and for placement of an IV catheter, respectively. This included a 3-minute scrub with a chlorhexidine-based detergent solution, followed by 1 minute of swabbing with chlorhexidinealcohol—soaked gauze sponges.
Spray application followed by needle or IV catheter placement (21-gauge hypodermic needles for arthrocentesis of the MC and MCP joints; 14-gauge IV catheters for placement in jugular veins) was performed in the following predetermined order: left MC joint, right MC joint, left MCP joint, right MCP joint, left jugular vein, and right jugular vein. The sites were paired with respect to application of the vapocoolant spraya (intervention) to one joint or vein and application of a commercially available bacteriologically pure water sprayc (placebo) to the contralateral joint or vein immediately prior to needle placement. This design gave 8 possible sequences (left vs right) for application of the placebo and intervention treatments among the tested sites, and the 8 horses were randomly assigned to the various orders of treatments. The spray products were applied to each prepared needle or catheter placement site for 15 seconds on the basis of results of the described preliminary experiments. A spray distance of 15 cm was chosen because it was near the far end of the range recommended by the manufacturer of the vapocoolant product (8 to 18 cm). This reduced the likelihood of inadvertently touching the horse with the canister if movement occurred. All spray canisters were stored at room temperature.
Spray applications and needle placements were performed on unsedated horses by 1 investigator (CTF). A twitch was not used. Arthrocentesis was performed according to standard aseptic methods, with an assistant lifting up the limb and holding it in place. A dorsolateral approach was used for MC joints, and a proximal palmarolateral approach was used for MCP joints.11 For catheterization of jugular veins, the horses' ipsilateral eye was covered by the assistant's hand for the duration of spray application and venipuncture.
Horses were observed for signs of potential adverse effects such as jugular vein phlebitis or septic arthritis during the 48 hours after procedures were performed. The horses were also reexamined 4 and 8 weeks after the spray products were used for any evidence of skin reactions (ie, skin thickening, scaling, crusting, or abnormal regrowth of hair) or frostbite.
Response scoring—All procedures were filmed with a digital video camera. Each video clip was reviewed by one of the authors (HAH), who was familiar with use of the VAS12 and was unaware of which spray product was used at each site. This observer scored the horses' responses to each procedure independently of other procedures. Aversive behavior, including whole body movement away from the investigators and vertical or horizontal movement of the body part being manipulated, was interpreted as a response to nociceptive stimulus. The total response was graded by use of a 6-point categorical scale (0 = no response [ie, no limb movement during needle placement], 1 = minimal response [eg, slight limb movement during needle placement], 2 = mild response [eg, 1 jerk of the limb during needle placement], 3 = moderate response [eg, several jerks of the limb during needle placement], 4 = marked response [eg, several jerks of the limb during needle placement and leaning away from the investigators], 5 = severe response [eg, strong movement of the limb during needle placement and body movement away from the investigators]) as well as a VAS. For jugular venipuncture, categorical scores were assessed as described for the preliminary experiment.
The VAS consisted of a 100-mm horizontal line printed on a 21 × 29.7-cm piece of paper; a separate VAS was used for each procedure. The left end of the horizontal line was labeled “no response”, and the right end was labeled “worst possible response”. The observer placed a vertical mark on the horizontal line, corresponding to the perception of the total aversive response of the horse to each procedure. The distance from the end of the line labeled “no response” to the mark placed by the observer was subsequently measured in millimeters, and this value was used for statistical analysis. Descriptive statistical analysis was performed. A 2-sided Student t test was used for paired observations, and values of P < 0.05 were accepted as significant.
Results
Preliminary experiments—Results of response scoring by use of the 6-point categorical scale indicated that the 2 horses used in preliminary experiments reacted less to skin pricking with a 21-gauge needle after a vapocoolant spraying time of 15 seconds, compared with spraying times of 5 and 10 seconds. Therefore, a spraying time of 15 seconds was elected for use in the placebo-controlled trial. Aerobic and anaerobic cultures of samples from skin sites swabbed after vapocoolant spray treatment and of blood agar plates sprayed directly with the vapocoolant did not yield any microbial growth.
Placebo-controlled trial—Arthrocentesis of the MC joints and jugular vein catheterization procedures were completed for all horses in the study. However, 1 horse was excluded from MCP joint arthrocentesis because of uncooperative behavior (ie, spraying and MCP joint arthrocentesis was not attempted). Therefore, data for responses at this site were obtained from only 7 horses, and a total of 46 procedures (16 jugular vein catheterizations and arthrocentesis of 16 MC joints and 14 MCP joints) were performed.
For the intervention and placebo spray treatments, skin at the sprayed site appeared wet but not blanched or frosted after spraying. No adverse effects were observed from any of the described procedures.
Categorical scale response scores—Response scores for MC and MCP joint arthrocentesis and jugular vein catheterization in most horses were in the range of 0 (no response) to 2 (mild response), regardless of treatment (Figure 1). For MC joint arthrocentesis, 4 of 8 horses had lower scores (indicative of less response) after intervention treatment than after placebo treatment. In 3 of 8 horses, scores for this procedure after intervention treatment were identical to those recorded after placebo treatment, and 1 horse had a higher score after intervention treatment than after placebo treatment. For MCP joint arthrocentesis, 5 of 7 horses had lower response scores after intervention treatment than after placebo treatment, whereas in 2 of 7 horses, scores for this procedure after intervention treatment were identical to their scores after the placebo treatment. For jugular vein catheterization, 3 of 8 horses had lower response scores after intervention treatment than after placebo treatment; in 3 of 8 horses, scores after the intervention treatment were identical to those recorded after the placebo treatment, and in 2 of 8 horses, scores were higher after the intervention treatment than after the placebo treatment. Statistical analysis of the categorical data was not performed because of the low power of such tests when performed on a data set with few categories. The categorical scale is, however, more clinically applicable than the VAS and was therefore used to better illustrate the magnitude of the horses' responses to the nociceptive stimulus.
Categorical scores of responses to MC (A) and MCP joint (B) arthrocentesis and to jugular vein catheterization (C) in 8 unsedated horses after treatment with a vapocoolant spray (intervention treatment; white bars) or bacteriologically pure water spray (placebo treatment; black bars) at the needle placement site. One observer who was blinded to the type of spray used scored the responses by use of a 6-point categorical scale (0 = no response, 1 = minimal response, 2 = mild response, 3 = moderate response, 4 = marked response, and 5 = severe response). For safety reasons, MCP joint arthrocentesis was not performed in 1 horse that had uncooperative behavior.
Citation: American Journal of Veterinary Research 72, 6; 10.2460/ajvr.72.6.746
Categorical scores of responses to MC (A) and MCP joint (B) arthrocentesis and to jugular vein catheterization (C) in 8 unsedated horses after treatment with a vapocoolant spray (intervention treatment; white bars) or bacteriologically pure water spray (placebo treatment; black bars) at the needle placement site. One observer who was blinded to the type of spray used scored the responses by use of a 6-point categorical scale (0 = no response, 1 = minimal response, 2 = mild response, 3 = moderate response, 4 = marked response, and 5 = severe response). For safety reasons, MCP joint arthrocentesis was not performed in 1 horse that had uncooperative behavior.
Citation: American Journal of Veterinary Research 72, 6; 10.2460/ajvr.72.6.746
Categorical scores of responses to MC (A) and MCP joint (B) arthrocentesis and to jugular vein catheterization (C) in 8 unsedated horses after treatment with a vapocoolant spray (intervention treatment; white bars) or bacteriologically pure water spray (placebo treatment; black bars) at the needle placement site. One observer who was blinded to the type of spray used scored the responses by use of a 6-point categorical scale (0 = no response, 1 = minimal response, 2 = mild response, 3 = moderate response, 4 = marked response, and 5 = severe response). For safety reasons, MCP joint arthrocentesis was not performed in 1 horse that had uncooperative behavior.
Citation: American Journal of Veterinary Research 72, 6; 10.2460/ajvr.72.6.746
VAS response scores—For MC joint arthrocentesis, the mean response score determined by use of the VAS after intervention treatment was 15.9 mm (median, 6.0 mm [range, 0 to 65.0 mm]), compared with 21.8 mm (median, 18.0 mm [range, 2.0 to 65.0 mm]) after the placebo was used; 7 of 8 horses had lower response scores (indicative of less response) after intervention treatment, compared with the scores after placebo treatment, whereas 1 horse had identical response scores after both treatments. For MCP joint arthrocentesis, mean response scores were 9.4 mm (median, 4.0 mm [range, 1.0 to 20.0 mm]) and 23.4 mm (median, 25 mm [range, 6.0 to 39.0 mm]) after treatment with the intervention and placebo products, respectively. At this site, scores were lower for all horses after intervention treatment, compared with scores after placebo treatment. For jugular vein catheterization, the mean response score after intervention treatment was 27.3 mm (median, 23.5 mm [range, 1.0 to 86.0 mm]), compared with 34.0 mm (median, 29.0 mm [range, 18.0 to 72.0 mm]) after placebo treatment; scores were lower for 4 of 8 horses and were higher for the remaining 4 horses after intervention treatment, compared with scores after placebo treatment. In Student t test analysis, mean response scores were significantly lower after intervention treatment, compared with scores after placebo treatment, for MC joint (P = 0.007) and MCP joint (P = 0.01) arthrocentesis. Response scores for jugular vein catheterization were not significantly different after use of the intervention product, compared with scores after use of the placebo.
Discussion
Treatment with the vapocoolant spray (intervention) in the study reported here significantly reduced mean responses to MC and MCP joint arthrocentesis but not to jugular vein catheterization in unsedated horses, compared with use of a bacteriologically pure water spray (placebo treatment). In practice, sudden limb movement during arthrocentesis may not only jeopardize the procedure, but may be a safety hazard for personnel involved. Safety of the individuals involved in diagnostic injection procedures should be a concern in equine practice, especially during examination of anxious horses and horses known to have exaggerated responses to injections. Unwanted limb movement during arthrocentesis may be avoided by topical use of a local anesthetic prior to needle placement. However, the time-dependent effect of topical lidocaine-prilocaine cream, which necessitates application 45 to 60 minutes before the procedure13 to have a clinical effect, precludes routine use of this product in equine practice. The fact that the vapocoolant spray has an immediate effect, which lasts for 30 to 60 seconds,8 makes it applicable for use in lameness examinations. Duration of effect was not evaluated in the present study; however, all needle placements were done immediately after the spray was applied. Therefore, any anesthetic effect should have taken place when the needles were inserted. Care must be taken, however, in targeting the fine, concentrated vapocoolant jet precisely to the proposed needle placement site. Because the spray does not leave any visible residue on the skin, the sprayed area may be missed when the needle is inserted, resulting in a lack of the intended effect. Therefore, the authors recommend that vapocoolant spray application and needle placement are performed by the same individual to avoid this potential error.
The VAS proved useful in the present study, which is not surprising as it is a continuous scale and therefore sensitive in detecting differences. The VAS scale has been validated as a highly discriminant method of assessing pain in humans.14 Adaptation to veterinary use is not straightforward, as the animal experiencing the noxious stimulus must have a response that is detectable and quantifiable by the observer. Horses commonly move their limbs or neck away from a nociceptive stimulus such as a penetrating needle. In the present study, this type of aversive behavior was interpreted to indicate nociception caused by needle placement and was easily detectable. The fact that the VAS can be poorly repeatable was not considered an important weakness of the study because we sought to achieve our objective via detection of intraindividual differences in horses' responses to various procedures after intervention and placebo treatment and because only 1 observer (HAH) scored all responses to procedures.
The study reported here revealed clear differences among individual horses in response to common clinical procedures such as arthrocentesis and jugular vein catheterization. In evaluation of the responses to arthrocentesis, low scores on the categorical scale (1 and 2, corresponding to minimal and mild responses, respectively) were most commonly assigned. However, 1 horse had response scores of 4 and 5 (corresponding to marked and severe responses) for arthrocentesis of the MC joints after placebo and intervention treatments. Further arthrocentesis was not attempted in this horse because of safety concerns. In a clinical setting, use of a twitch or light sedation may have allowed completion of the planned procedures. For purposes of the present study, chemical restraint and the use of a twitch were not allowed because of concerns that these might mask or reduce the response to needle or catheter placement. Blindfolding of horses was also not allowed, to minimize interference with the horses' typical behavior during the procedures.
The finding that the spray did not have the hypothesized effect on responses to jugular vein catheterization concurs with results of several studies in humans.6,7 By increasing the power of the study, a difference may have been detected as has been revealed in recent studies in children8 and adult humans.9 We chose not to include additional horses, as part of the hypothesis of the study was accepted. The use of a larger-gauge needle for IV catheterization than for arthrocentesis (14 gauge vs 21 gauge, respectively), evoking a greater nociceptive response, may explain why the intervention treatment did not have any detectable effect on the response to jugular vein catheterization.
An effect interpreted as anticipatory distress was also observed, in which horses tended to react more during the second procedure if the first site had the placebo treatment applied. This was particularly obvious during jugular vein catheterizations, when 3 of 4 horses that had a greater response to the intervention treatment had received the placebo treatment for the first catheterization procedure. Thus, a potential effect of the vapocoolant spray on responses to jugular vein catheterization may have been masked by this effect. A washout time could have been allowed between the placebo procedure and the intervention procedure to avoid such an effect. The differences in effect of the intervention treatment may also be related to regional differences in skin thickness. However, according to Talukdar et al,15 skin thickness at the dorsal surface of the MC joint (extensor surface) and in the jugular groove should be fairly similar. Skin thickness at the palmarolateral pouch of the MCP joint (flexor surface) is, however, thinner than that of the other penetration sites15 in this study. As the effect of the intervention treatment at the MC joints and MCP joints was quite similar, we believe that skin thickness was not a major factor in the observed regional differences in the effect of intervention treatment.
The vapocoolant spray used in the study reported here was odorless, nontoxic, and nonflammable. It did not leave a skin residue and was easy to use. The spray is marketed as a so-called clean product, and the canisters are filled in a controlled environment. Burney et al16 demonstrated the antimicrobial effect of the vapocoolant ethyl chloride; this effect was believed to result from the sudden drop in skin temperature. If this assumption is true, a degree of antimicrobial effect might also be expected from other vapocoolants, such as that used in the present study. Our preliminary experiments yielded no microbial growth from skin swab samples or on blood agar plates directly sprayed with the vapocoolant product. Therefore, there was no extra concern regarding its use prior to arthrocentesis or venipuncture after aseptic skin preparation. Application of the spray did not delay the clinical procedures for more than the 15 seconds of spraying time, and the horses tolerated the sprays well.
The product used in the present study is recommended to be sprayed for 4 to 10 seconds to avoid frostbite in humans, although up to 15 seconds of spraying time has been used for similar products.4 None of the horses in the present study showed any evidence of skin blanching during the study, and no signs of skin lesions or frostbite were detected during reexamination 4 and 8 weeks later. Therefore, 15 seconds of spraying time appears to be safe on these regions in horses. Until further experience with use of vapocoolant products in horses is gained, however, the authors recommend a shorter duration of spraying time (10 seconds) in thin-skinned animals.
Use of the vapocoolant spray in the present study proved efficient in reducing responses to arthrocentesis in unsedated horses. Use of such a product may improve the safety of personnel performing diagnostic joint injections in unsedated horses; also, the ease of using the spray, lack of adverse effects, and relatively low cost may add to its value in equine practice.
ABBREVIATIONS
| MC | Middle carpal |
| MCP | Metacarpophalangeal |
| VAS | Visual analog scale |
Gebauer's Pain Ease Medium Stream Spray, Gebauer Co, Cleveland, Ohio.
Culturette, Becton Dickinson Microbiology Systems, Cockeysville, Md.
Avène Thermal Spring Water Spray, Pierre Fabre Dermo-Cosmetique, Winchester, Hampshire, England.
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