Anesthesiology, Article

Prospective, randomized, double-blind controlled trial comparing vapocoolant spray vs placebo spray in adults undergoing venipuncture

a b s t r a c t

Introduction: Topical anesthetics are used to decrease procedural pain such as venipuncture. Advantages of vapocoolants include rapid onset, ease of application, low cost, and lack of associated pain of injection and other needlestick-related risks. We hypothesized that the pain of venipuncture would be reduced by at least

1.8 points on a 10-point numerical rating scale after application of a vapocoolant compared with placebo. Methods: We conducted a prospective, randomized, double-blind controlled trial of vapocoolant vs placebo spray in 100 adults (ages 18-80) requiring venipuncture in a hospital emergency department or observation unit. The primary efficacy outcome was the difference in pain scores immediately after venipuncture, measured on a 10-point verbal Numeric rating scale from 0 (none) to worst (10). Safety outcomes included local adverse effects (edema, erythema, blanching) and changes in vital signs (VS). Results: Patient characteristics and venipuncture procedure were not significantly different for the 2 groups. The median (interquartile range) pain of venipuncture was 3 (1.2-5) in the placebo group and 1 (0-3) in the vapocoolant group, P b .001. Skin checklist revealed the following: vapocoolant–minimal blanching 4%, minimal erythema 18% which resolved within 5 minutes; placebo–no visible skin changes. Photographs at 5 to 10 minutes revealed no visible skin changes in any patient. There were 2 complaints: “very wet and cold on skin” (placebo) and “felt burning on skin” (vapocoolant).

Conclusion: The vapocoolant significantly decreased venipuncture pain in adults compared with placebo and was well tolerated with minor adverse effects that resolved quickly. There were no significant differences in VS and no visible skin changes documented at the site by photographs taken within 5 to 10 minutes postspray/venipuncture.

(C) 2016

Introduction

Background

Painful medical procedures, including needlestick procedures, are frequently done in the emergency department (ED) [1-4]. Pain is the most common reason for ED visits, and oligoanesthesia is common,

? Presentations: American Society of regional anesthesia and Pain, November 2012, Miami, FL; Society of Academic Emergency Medicine, May 2012, Atlanta, GA; American College of Emergency Physicians Scientific Assembly, October 2011, San Francisco, CA.

?? Supported by a grant from the Gebauer Company.

? The funding source had no involvement in study design; collection, analysis, and

interpretation of the data; writing of the report; and the decision to submit the article for publication.

?? The trial is registered at ClinicalTrials.gov NCT01712776.

* Cleveland Clinic, Emergency Services Institute, 9500 Euclid Ave, E- 19, Cleveland, Ohio 44195. Tel.: +1 216 445 4598, +1 216 444 1748 (administrative assistant, Mimi);

fax: 1 216 445 4552.

E-mail address: [email protected].

with practitioners frequently failing to provide adequate analgesia for patients with painful medical conditions [5]. Oligoanesthesia also applies to painful medical procedures, with health care providers failing to use anesthetics before performing painful procedures even though patients indicate that they would like to receive analgesia before a painful procedure [6-9].

local anesthetics including topical anesthetics are a method of de- creasing the pain of procedures [7-11]. The Vapocoolant sprays offer many potential advantages over other topical or local infiltrative anes- thetics including avoidance of painful injections, local tissue distortion, and health care provider risks of a needlestick. Vapocoolants are also low cost and result in more rapid onset, less administration time, great- er staff convenience, and decreases in ED length of stay [4,7,10-17].

The objective of the study is to evaluate the efficacy and safety of a vapocoolant spray in adults in the ED undergoing venipuncture. We hypothesized that the pain of venipuncture would be at least 1.8 points lower after vapocoolant vs placebo spray and that there would be no permanent skin changes associated with the use of a vapocoolant spray [12,18,19].

http://dx.doi.org/10.1016/j.ajem.2016.01.002

0735-6757/(C) 2016

Methods

Study design and setting

This is a prospective, double-blind, randomized, placebo-controlled efficacy and safety trial conducted at an urban, academic, tertiary care referral hospital conducted from June 2011 to 2012. The study was ap- proved by the institutional review board, and all patients gave written informed consent.

Study population

Adults (ages 18-80 years) undergoing venipuncture in the ED or ED observation unit (OU) were eligible for enrollment in the study. Inclu- sion criteria were as follows: patient undergoing venipuncture, mental- ly competent patient able to understand the consent form, and clinically stable. Patients were excluded from the study if any of the following criteria were met: allergy to the spray components (eg, 1,1,1,3,3- pentafluoropropane or 1,1,1,2-tetrafluoroethane), critically ill or unsta- ble, extremes of age (pediatric b 18 years or elderly geriatric N 80 years), pregnant, previous experience with any vapocoolant spray, venipunc- ture site located in area of compromised Blood supply, venipuncture site located in area of insensate skin, patient intolerant of cold or with hypersensitivity to cold, and patient unwilling to give consent. Examples of venipuncture sites located in areas of compromised blood supply would include patients with peripheral vascular disease, gangrene, Raynaud disease or Buerger disease. Examples of patients with insensate or abnormal sensation of the skin would include patients with a peripheral neuropathy. None of the patients recently received an analgesic (such as an opioid) before the venipuncture. Informed written consent was obtained from all subjects.

This was a convenience sample because patients were enrolled when the ED Research staff was available, eg, day and evening shifts on weekdays and weekends. The ED research staff members conducting the study were not involved in the care of the patient or in the actual Blood draw. The primary researcher was not present and not involved in patient enrollment or data analysis.

The medical history including comorbidities, current medications, and characteristics of the venipuncture itself was listed to determine if the patient populations for the 2 groups were well matched at baseline because comorbidity and medication use, and the venipuncture itself (eg, needle size, location) could possibility affect the difficulty of the ve- nipuncture procedure and the response to the pain of the venipuncture. Patients were randomized to either sterile water placebo spray (Nature’s Tears) or to vapocoolant spray (1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane) (Gebauer’s Pain Ease Medium Stream). The application of the spray in all patients was completed by 1 of 2 trained research assistants whose job was to enroll patients and to standardize administration of the topical spray. After prepping and cleansing the venipuncture site per protocol, the spray was applied in the same manner for all patients, both control and vapocoolant subjects, as recommended by the manufacturer. The specific technique of spray application for both the placebo spray and the vapocoolant spray was as follows: hold the can 3 to 7 in from the venipuncture site; spray onto the venipuncture site steadily for 4 to 10 seconds or until the skin begins turning white, whichever comes first (the anesthetic effect is complete at this time); then immediately perform the venipuncture.

There is about a 1-minute time frame to complete the venipuncture because the topical anesthetic lasts only about 1 minute.

The spray cans were not identified as to whether they were the placebo spray or the vapocoolant spray and thus were blinded to the subjects, the research assistants applying the spray, and the health care providers performing the venipuncture. The actual blood draw was done by the ED staff and not by the 2 research associates. All the blood draws were obtained using a Vacutainer with a size 21-gauge needle.

Randomization was accomplished using a computer random num- ber generator with block randomization using randomly varied block sizes of 20 or 30. The spray cans were supplied from outside the ED in varied block sizes such that the randomization was not done by or knowledgeable to the ED research staff performing the actual patient enrollment and data collection to maintain allocation concealment.

Data collection and processing

All data were collected by trained research associates who had no patient care duties. Their research duties included patient enrollment, data recording, and application of the spray. They recorded on standard- ized case report forms the demographic data, vital signs (completed by ED nursing staff), clinical variables (from the electronic medical record), all adverse effects/complications, and pain scales (eg, numeric rating scale [NRS]) as reported verbally by the patients: NRS immediately postspray/prevenipuncture and NRS for the pain of venipuncture. They completed the standardized checklist and took before-and-after photographs of the venipuncture site to document any visible skin changes.

All data were entered into a REDCap database and then analyzed using R software (version 2.15.0) by a biostatistician. Continuous vari- ables were summarized using means with variability assessed using standard deviations. Categorical variables were summarized as counts and percentages. Tests for differences of continuous variables were done using Welch 2-sample t tests or Wilcoxon rank sum tests. Tests on categorical variables were done using either Pearson ?2 tests with Yates continuity correction or Fisher exact test for count data. Signifi- cance was at P b .05, and the results of testing were given by P values and/or confidence intervals (CIs).

Outcome measures

The primary outcome was the pain of venipuncture on a 10-point NRS scale ranging from 0 (none) to 10 (worst). The primary safety mea- sures were the documentation of any and all adverse effects/complica- tions and vital signs. Secondary Safety measures included a checklist for any changes of the skin: redness, blanching or pallor, itching, edema, or changes in skin pigmentation done immediately post spray/ postvenipuncture, NRS postspray/prevenipuncture, and photographs of the venipuncture site done preapplication and 5-10 minutes postapplication of the spray/postprocedure for any visible skin changes. According to previous studies, a change in NRS of 1.3 or greater is deemed clinically significant [18,19]. A pediatric study found a decrease of 19 mm for the pain of intravenous (IV) cannulation on a 0-100 VAS scale with the use of a vapocoolant spray [12]. Therefore, we decided to use a decrease of >= 1.8 on the NRS because this would include the meaningful difference and was similar to the earlier pediatric study findings. To detect a clinically important decrease of 1.8 on the NRS [18,19], a sample size of 90 adults (45 per treatment group) was chosen, assuming a 2-tailed test, power of 90%, and type I error rate of 0.05. The sample size was increased to 100 (50 per group) to compensate for

potential dropouts or Protocol deviations.

Results

Study subjects

Of the 136 patients screened for the study, 100 were randomized and received their allocated treatment: 50 patients received sterile water spray (placebo arm), and 50 patients received vapocoolant spray (treat- ment arm) (Fig. 1). For all 100 study subjects, the mean age (+- SD) was

52. 2 (+- 12.4) years (range, 19-75 years), with 46 men and 54 women and 62 African Americans and 38 Caucasians. The patients in the 2 study arms had similar baseline characteristics with no significant differ- ences in any of the demographic variables (age, sex, race) or clinical

Placebo N= 50

Vapocoolant N = 50

Randomized Patients

N = 100

Excluded

  • Age (? 81 years old) N = 19
  • Declined to participate N = 14
  • Getting IV line N = 2
  • Dementia N = 1

Patients eligible for study N = 136

Fig. 1. Participant flow diagram according to the Consolidated Standards of Reporting Trial guidelines.

characteristics (comorbidities or medications) (Table 1). The characteris- tics of the venipuncture itself were similar between the 2 groups, with no significant differences in needle size (21-gauge Vacutainer in all patients), location of the blood draw, number of blood draw attempts, difficulty of blood draw, or the health care providers performing the venipuncture (years of experience and role in ED). The procedure (eg, venipuncture) was performed in b 1 minute in all patients (Table 2).

Results: efficacy

The median NRS (IQR) for the pain of venipuncture was 3 (1.2-5) for the placebo spray group vs 1 (0-3) for the vapocoolant spray group (P b .001) (Fig. 2).

Results: safety

There were no significant differences in vital signs between the 2 groups (Table 1). There were 2 complaints: 1 patient in the placebo group said the spray “was very wet and cold on the skin,” and 1 patient in the vapocoolant group “felt burning on the skin”. There were no seri- ous adverse effects/events or complications, and minor adverse effects, such as erythema and blanching of the skin, resolved in b 5 minutes.

The skin checklist completed immediately postspray/venipuncture revealed minimal blanching in 2 patients (4%) and minimal redness in 9 patients (18%) in the vapocoolant spray group which resolved within 5 minutes, and no visible skin changes were noted in the placebo spray group. There was no edema, pruritus, or other visible skin changes re- ported for either group (Table 3). The median NRS (IQR) postspray/ prevenipuncture was between 0 and 0 for the placebo spray vs 0.0 (0.0-1.8) for vapocoolant spray (P b .001). Patients were asked, “Would you want to use a spray for future blood draws?” Of the vapocoolant group, 80% (40/50) responded affirmatively vs 20% (10/ 50) of the placebo group (P b .001). Before-and-after photographs of the venipuncture site taken within 5-10 minutes of the spray/venipunc- ture revealed no visible skin changes in any of the patients no matter the location of the venipuncture, skin pigmentation, or sex.

Discussion

Discussion: efficacy

The vapocoolant spray significantly decreased the acute pain of venipuncture in adults when compared with placebo spray. Our find- ings are similar to previous studies with other needlestick procedures using this formulation of vapocoolant spray Pain Ease (1,1,1,3,3 pentafluoropropane and 1,1,1,2 tetrafluoroethane) (PT). In a random- ized paired (split face) study by Weiss et al [20] in adults undergoing botulinum toxin facial injections in a plastic surgery outpatient setting, there was a significant (P b .001) decrease in pain with vapocoolant

Pain Ease PT compared with the control. Farion et al [12] in a double- blind, randomized controlled trial at a Canadian children’s hospital pe- diatric ED comparing vapocoolant Pain Ease PT with a placebo spray for IV cannulation in pediatric patients reported a significant reduction in pain with the use of the vapocoolant Pain Ease PT (mean difference, 19 mm; 95% CI, 6-32 mm; P b .01) and greater first-attempt IV cannula- tion success rate (vapocoolant 85% vs 62.5% placebo; 95% CI, 3.2%-39.9%; P = .03).

Studies with a different vapocoolant spray, ethyl chloride (EC), also documented decreases in pain from needlestick procedures. In a crossover-design, randomized controlled trial, there was a significant (P = .00) drop in pain in adult patients undergoing puncture of the ar- teriovenous fistula before hemodialysis when EC was used vs placebo, with a mean Visual analogue scale (VAS) pain score of 33.4 for placebo vs 14.0 for EC [21]. In adult women needing an IV before gynecologic surgery, the median VAS post-IV cannulation was 23.5 for the control group vs 4.0 for the EC group (P b .01) [15].

Cohen Reis and Houbkov [22] performed a randomized controlled study of immunization pain in school-aged children that compared Fluori-Methane (FM) vapocoolant spray with lidocaine-prilocaine (EMLA) cream and control plus distraction in all 3 groups. There were no significant differences between the EMLA and FM groups, but there were significant differences (P b .05) between the control and the EMLA or FM groups. The mean scores were as follows: linear VAS: con- trol 38.9, EMLA 14.9, and FM 15.4; faces VAS: control 2.4, EMLA 1.1, and FM 1.0; and observational scale of behavioral distress: control 3.1, EMLA 1.3, and FM 1.2.

There have been a few studies that did not find a significant reduc- tion in the pain of a needlestick procedure with the use of a vapocoolant spray [23-26]. In these earlier studies, the exact spray time was not measured or less than recommended, and whether or not the procedure was performed in <= 1 minute was not noted [12,14]. The importance of proper technique in the application of the vapopcoolant spray (eg, cor- rect distance from the procedure site, using a steady spray, covering the specific area with the spray, and spray time) as well as performing the procedure within 1 minute following the end of the spray application is critical for the vapocoolant spray to be effective [12,14]. Methodolog- ical problems with these studies, including small sample size, have also been noted by other researchers [12,14].

Our mean NRS scores (+-SD) for venipuncture pain with the placebo spray of 3.72 (+- 2.9) (95% CI, 2.98 to -4.52) vs 1.76 (+- 2.3) (95% CI,

1.18 to -2.46) for vapocoolant spray are analogous to previous reports [21,27]. Without any anesthetic, the mean pain of arteriovenous fistula puncture in adults on a 0-100 VAS scale was 33.4 [21], and the mean ve- nipuncture pain in 6 adult volunteers on a 0-10 VAS scale was 3.3 [27].

Discussion: safety

In our study, there were no significant differences in vital signs post- spray application and no major adverse effects or complications in any patients. Minor transient skin irritation, for example, redness and blanching, did occur in a few patients. Our incidence of visible skin changes 18% minimal erythema, 4% minimal blanching, no edema, no pruritius, and no hemorrhages/petechiae–is relatively low when com- pared with reports of other topical anesthetics. Moreover, these visible skin changes occurred immediately post-spray application and re- solved within 5 minutes. Before-and-after photographs taken between 5 and 10 minute postspray in all patients also documented no lasting visible skin changes.

Only 4% of our patients in the vapocoolant group had blanching of the skin. This is a considerably lower incidence than for EMLA cream as reported by others: 32%, 61.5%, and 76.4%, respectively, for Koren et al [27], Choy et al [28], and Bisha et al [29]. Transient local reactions (eg, blanching followed by transient local numbness, or erythema) can occur in up to 56% of patients with EMLA cream [30].

Table 1

Patient demographics, clinical variables, vital signs

Demographics

Placebo spray

n = 50 patients

Vapocoolant spray n = 50 patients

P value

All 100 patients

Age (years) mean (+- standard deviation) (+- SD)

51.5 (+-11.5)

53.0 (+- 13.4)

.55

52,2 (+- 12.4)

Sex

Male 27 (54%)

Male 19 (38%)

.16

Male 46 (46%)

Number. of patients (%)

Female 23 (46%)

Female 31 (62%)

Female 54 (54%)

Race

African American 29 (58%)

African American 33 (66%)

.54

African American 62 (62%)

Number of patients (%)

White 21 (42%)

White 17 (34%)

White 38 (38%)

Comorbidity

Hypertension

28 (56%)

24 (48%)

.55

52 (52%)

Diabetes

11 (22%)

8(16%)

.61

19 (19%)

Chronic obstructive pulmonary disease (COPD)

6 (12%)

2 (4%)

.27

8 (8%)

Cancer

2 (4%)

3 (6%)

N.99

5 (5%)

Status post (s/p) radiation therapy

0 (0%)

1 (2%)

N.99

1 (1%)

Status post (s/p) mastectomy

0 (0%)

2 (4%)

.49

2 (2%)

Obesity

6 (12%)

2 (4%)

.27

8 (8%)

Renal disease

3(6%)

1 (2%)

.62

4 (4%)

Dialysis (hemodialysis)

2 (4%)

0 (0%)

2 (2%)

Sickle cell disease

0 (0%)

1 (2%)

N.99

1 (1%)

History of blood clot in upper extremity

0 (0%)

1 (2%)

N.99

1 (1%)

Gout

0 (0%)

3 (6%)

.24

3 (3%)

Thyroid disease

0 (0%)

1 (2%)

N.99

1 (1%)

Medicationsa

Number of patients (%) Acetaminophen

10 (20%)

13 (26%)

.28

23 (23%)

Opioids (acetaminophen-oxycodone or

9 (18%)

9 (18%)

.83

18 (18%)

acetaminophen-hydrocodone) Antidepressants

6 (12%)

6 (12%)

.79

12 (12%)

Nonsteroidal anti-inflammatory drugs

3 (6%)

7 (14%)

.20

10 (10%)

Benzodiazepine

4 (8%)

2 (4%)

.68

6 (6%)

Anticonvulsants

1 (2%)

3 (6%)

.36

4 (4%)

Corticosteroids (eg, prednisone)

1 (2%)

2 (4%)

.62

3 (3%)

Vital signs: mean (+- standard deviation) (+- SD)

Blood pressure systolic

146.8 (+- 28.3)

137.7 (+- 20.8)

.072

142.2 (+- 25.1)

Blood pressure diastolic

80.3 (+- 15.3)

74.9 (+- 12.4)

.052

77.6 (+- 14.1)

Heart rate

80.1 (+- 17.1)

79.1 (+- 15.7)

.76

79.6 (+- 16.4)

Respiratory rate

18.2 (+- 3.1)

18.2 (+- 2.1)

N.99

18.2 (+- 2.6)

a Medications listed were obtained from the electronic medical record and verified by the ED hospital pharmacist. The analgesics were prn and were generally for musculoskeletal conditions other than why the patient(s) were in the emergency department observation unit (EDOU), which was for a chest pain rule-out. Any patient who received any analgesic <=4 hours from the time of venipuncture was excluded from the study.

Erythema was reported in 37%, 48.7%, or 76.4% for Tetracaine 4% gel in various studies [28,29,31], whereas we had only an 18% incidence documented in our study. A study by Arrowsmith and Campbell [32] found that EMLA had significantly greater (P b .001) blanching than AMETOP, whereas AMETOP had significantly greater erythema (P b

.01). The exact incidence of the local skin adverse effects and the dura- tion were not reported in this study. Similarly, a study by Van Kan et al [33] noted erythema when tetracaine was applied and skin blanching when lidocaine-prilocaine was applied. Again, the exact inci- dence of these local dermatologic adverse effects was not mentioned.

We also found no instances of edema, pruritus, needle marks, hyper- pigmentation, bruising/bleeding, or petechiae/hemorrhage that have been reported with use of other topical agents/devices [34-38]. After 5 minutes, we had no visible skin changes. This compares favorably with the Zempsky et al [34] study evaluating a needle-free delivery device which delivered powdered lidocaine or sham placebo. At 30 minutes in those receiving the powdered lidocaine, the following skin abnormalities were still present: erythema 56.2%, edema 9.2%, pruritus 0.7%, and pete- chiae 45.9%. In another study using a needle-free delivery device to ad- minister powdered lidocaine into the dermis, telephone survey follow- up at 2 and 4 days reported that 12.5% of patients still had a local skin re- action (erythema, swelling, pruritus, and contusion) [35]. Another study also confirmed the occurrence of erythema and hemorrhage/petechiae with a needle-free delivery system that delivered powdered lidocaine into the dermis, but they did not report the incidence of these adverse ef- fects [36]. A recent study that used a J-tip device instead of a needle to push lidocaine into the skin reported that 1 child immediately after

venipuncture developed “excess bleeding that was controlled with pres- sure” [37]. In this study, at next-day telephone follow-up, bruising was re- ported in 13.7% and redness in 1.1% [37]. Another study that evaluated the topical delivery of lidocaine found that “all subjects who underwent IP (iontophoresis) experienced mild skin irritation that completely resolved by the next treatment period (1 week)” [38]. As noted, the incidence of skin irritation reported in the literature with other topical delivery devices and topical agents can be high and is reported at 100% for iontophoresis in 1 study [38]. Burns of the skin are another complication that has been re- ported with iontophoresis [10].

Our findings are similar to other studies that used different vapocoolant formulations (eg, FM, ethyl chloride, or a propane/bu- tane/pentane blend) that also did not report any major discomfort or lasting skin abnormalities [13-15]. Celik et al [21] stated, “Our patients were also comfortable during vapocoolant application and did not report any pain during cooling of the skin.” Armstrong et al reported that none of their patients experienced pain with vapocoolant applica- tion. Our study found that 80% of vapocoolant patients vs only 20% of the placebo spray would use the spray for future blood draws, indicating that the vapocoolant spray was well tolerated. This is similar to a prior study comparing the Pain Ease vapocoolant (1,1,1,3,3 pentafluoropropane and 1,1,1,2 tetrafluoroethane) with ice in which 76% of subjects in the vapocoolant group felt that their treatment worked well [39]. In this study, they concluded that “vapocoolant spray may be more effective than ice as an analgesic for IV insertion. Subjects were more satisfied with vapocoolant spray. Neither agent caused a decrease in successful IV insertion rates” [39].

Table 2

Characteristics of the venipuncture procedure

Placebo spray (n = 50)

Vapocoolant Spray (n = 50)

P value

All 100 patients

Needle size

21-gauge Vacutainer (n = 50)

21-gauge Vacutainer (n = 50)

NA

100 (100%)

Location of venipuncture

.86

Hand

29 (58%)

25 (50%)

54 (54%)

antecubital fossa

13 (26%)

15 (30%)

28 (28%)

Forearm

7 (14%)

8 (16%)

15 (15%)

Wrist

Total # of blood draw attempts 1

1 (2%)

50 (100%)

2 (4%)

48 (96%)

.48

3 (3%)

98 (98%)

2

0 (0%)

2 (4%)

2 (2%)

Job description of healthcare provider drawing the blood

>= 0.99

Clinical technician

43 (86%)

44 (88%)

87 (87%)

EMT

3 (6%)

6 (12%)

9 (9%)

Paramedic

1 (2%)

0

1 (1%)

RN

3 (6%)

0

3 (3%)

Years of experience of individual performing the venipuncture {mean (+- SD)} [95% CI]

11.7 (+-4.4) [10.5-13.0]

11.3 (+-3.5) [10.3-12.2]

.80

11.5 (+-4) [10.75-12.24]

Patient questions

Would you consider yourself a difficult blood draw?

Yes 3 (6%)

Yes 6 (12%)

.49

Yes 9 (9%)

Would you want to use a spray for future blood draws?

No 47 (94%)

Yes 10 (20%)

No 40 (80%)

No 44 (88%)

Yes 40 (80%)

No 10 (20%)

b.001

No 91 (91%)

Health care provider question

Would you consider this patient a difficult blood draw?

Yes 2 (4%)

No 48 (96%)

Yes 9 (18%)

No 41 (82%)

.55

Yes 11 (11%)

No 89 (89%)

Spray time

Seconds (mean) [95% CI]

8.5 [8.2-8.5]

9.1 [8.8-9.3]

8.78 [8.57-8.97]

Our results indicating no visible lasting skin abnormalities are consistent with a recent study looking at the microcirculatory effects of the Pain Ease vapocoolant (1,1,1,3,3 pentafluoropropane and 1,1,1,2 tetrafluoroethane) spray. This study reported no statistically significant changes in vessel diameter and inflammatory markers, a “lack of significant or long-lasting vascular changes,” and histologic evaluation showing “no permanent muscular changes.” They concluded

Venipuncture Pain

10

P 75

P 75

P 25

P 25

= median

= mean

9

8

Numeric rating scale

7

6

5

4

3

2

1

0

that vapocoolant, specifically Pain Ease (1,1,1,3,3 pentafluoropropane and 1,1,1,2 tetrafluoroethane), is “safe in all age populations “[40].

Limitations

This study has several limitations. Because this study was performed in low-risk, relatively healthy, clinically stable adults, almost all of whom were undergoing a rule-out myocardial infarction in the ED OU, with a 98% first-attempt success rate of venipuncture, we did not eval- uate procedure success rates. Other research suggests that the use of a vapocoolant spray may increase procedural success rates [12-15].

This study was performed in a wide age range from young adults to Geriatric patients (ages 19-75) (Table 1) but did not include pediatric patients, which could theoretically limit the generalizability. However, prior studies in pediatric patients also demonstrated a significant de- crease in procedural pain from various needlestick procedures including venipuncture with the use of a vapocoolant spray, which indicates that the results are likely to be applicable to a wide age range, not just adults but also children and the elderly [12,22]. This clinical trial was limited to 1 ED, which also could limit its generalizability. However, other studies from other EDs that evaluated a different needlestick procedure, IV in- sertion, also reported significant decreases in the procedural pain. The Page and Taylor [14] study of adults with a different vapocoolant spray in an ED and the Farion et al [12] study in a pediatric ED both found that vapocoolant significantly decreased the pain of IV insertion. This study evaluated only 1 procedure, venipuncture, which could again restrict the generalizability. However, other studies using a vapocoolant spray for various needlestick procedures also documented significantly less procedural pain when a vapocoolant spray was used for immunizations, IV catheter insertions, puncture for hemodialysis,

Placebo Spray

Vapocoolant Spray

and insertion of botulinum toxin injections, which implies that a vapocoolant spray could be used to decrease the pain of any needlestick

Fig. 2. The pain of venipuncture on NRS: box and whisker plots of NRS for the placebo spray and the vapocoolant spray. The median is the center line, the boxes are the 25th to 75th percentile, and the triangle is the mean.

procedure involving the skin [12-15,20-22,41-43].

Although the spray cans were identical in appearance and thus blinded, there is a difference in the sensation on the skin between the

Table 3

Skin checklist: immediately postspray/postvenipuncture and at 5 to <=10 minutes postspray/postvenipuncture

Placebo spray (n = 50 patients) immediately postspray/ postvenipuncture

Placebo spray (n = 50 patients) 5 to

<= 10 min postspray/postvenipuncture

Vapocoolant spray (n = 50 patients) immediately postspray/ postvenipuncture

Vapocoolant spray (n = 50 patients) 5 to <= 10 min postspray/postvenipuncture

Redness

None

50 (100%)

50 (100%)

41 (82%)

50 (100%)

Minimal

0

0

9 (18%)

0

Moderate

0

0

0

0

Severe

0

0

0

0

Blanching

None

50

50

48 (96%)

50 (100%)

Minimal

0

0

2 (4%)

0

Moderate

0

0

0

0

Severe

0

0

0

0

Changes in skin pigmentation

None

50

50

50

50

Minimal

0

0

0

0

Moderate

0

0

0

0

Severe

0

0

0

0

Itching

0

0

0

0

None

50

50

50

50

Minimal

0

0

0

0

Moderate

0

0

0

0

Severe

0

0

0

0

Edema

None

50

50

50

50

Minimal

0

0

0

0

Moderate

0

0

0

0

Severe

0

0

0

0

Other

None

50

50

50

50

Minimal

0

0

0

0

Moderate

0

0

0

0

Severe

0

0

0

0

placebo sterile water spray and the vapocoolant spray, which may have led to a bias. However, because the patients never had a vapocoolant (or a placebo spray) as a topical anesthetic in the past, they would not know what a vapocoolant (or placebo spray) would feel like, so it is likely that their responses would not be biased. Patients could only be enrolled once in the study to avoid prior experience with a topical spray. We did not want to influence the patients’ response, so we did not give pa- tients any preinformation about the sprays except that one was a place- bo spray and one was the treatment spray. The spray cans were masked and labeled A and B and stored together at the same temperature. Because of variances in the characteristics of the spray itself, a difference might be noted over time by those applying the spray that A and B were different. However, the unmasking of the spray cans A and B was not done until after enrollment and all data collection were complete.

We used only 1 formulation of a vapocoolant spray (1,1,1,3,3 pentafluoropropane and 1,1,1,2 tetrafluoroethane), so we do not know if our findings apply to the other formulations (ethyl chloride, FM, or a propane/butane/pentane blend). However, the results of other studies with these formulations–ethyl chloride for venipuncture, IV cannulation, or puncture of a dialysis fistula [13,15,21]; a propane/ butane/pentane blend for IV cannulation [14,39]; or an FM [22,43] for immunization–also found a decrease in pain with the use of the respec- tive vapocoolant sprays for needlestick procedures. The only vapocoolant sprays approved by the Food and Drug Administration for needlestick procedures are Pain Ease and ethyl chloride. The advantage of Pain Ease is that it is nonflammable and can be used on minor open wounds.

Improper application of the spray or a delay (eg, greater than 1 min- ute) in performing the procedure likely negates the efficacy of the top- ical vapocoolant. It may be difficult in the real world to perform a given procedure within this short time frame. However, this should not be problematic because Pain Ease can be reapplied as often as needed.

Conclusions

Compared with a placebo spray, there was a significant decrease in the pain of venipuncture on an NRS scale in adult patients undergoing blood draws. There were no differences in vital signs between the 2 groups, and there were no complications or major adverse effects. The vapocoolant spray (Pain Ease) was well tolerated with minor adverse effects that resolved quickly. There were no visible skin changes docu- mented at the site by photographs taken within 5-10 minutes postapplication of the vapocoolant spray.

Acknowledgments

I would like to thank the following individuals for their participation in the IMPACT PAIN Trial (IMproved patient comfort Trial: Pain Assess- ment In VeiNipuncture): Mr Colin O?Rourke from the Department of Quantitative Health Sciences for the statistical analysis; Elizabeth Gaul, RN, Michael Zeleny, and Tracy Barbour from the Emergency Services Research Department for the data collection and entry; and Terri Obrian of the Department of Art and Photography for the graphs and figures.

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