Ethyl chloride spray, a local anesthetic in arterial blood gas sampling: A randomized, controlled, double-blinded study

a b s t r a c t

Aim: arterial blood gas sampling provides useful information on respiratory parameters and acid-base balance. However, this procedure is painful and uncomfortable for the patient. Therefore, this study aimed to examine the Analgesic efficacy of ethyl chloride spray compared to a placebo during radial artery blood gas sampling.

Method: This randomized, double-blind, placebo-controlled study was conducted at the emergency department

of a tertiary hospital. A total of 202 patients were randomly divided into two groups: ethyl chloride spray (n = 101) and placebo (n = 101). The analgesic efficacy of ethyl chloride spray was compared with the placebo using the Visual analog scale .

Results: The VAS score was determined to be 4 [interquartile range (IQR): 1.0] for the ethyl chloride spray group and 5 (IQR: 1.0) for the placebo group. The analgesic efficacy of ethyl chloride spray in reducing pain was statis- tically significantly higher compared to the placebo (p = 0.000).

Conclusion: Ethyl chloride spray has analgesic efficacy in arterial blood gas sampling. Therefore, the use of this spray provides an analgesic effect on patients during arterial blood gas sampling performed in the emergency department.

(C) 2022

  1. Introduction

Arterial blood gas sampling provides useful information on respira- tory parameters and acid-base balance. However, this procedure is painful and uncomfortable for the patient [1]. Therefore, chest diseases and thoracic surgery associations recommend local anesthesia (subcu- taneous lidocaine or mepivacaine) to patients prior to arterial blood gas sampling [2]. However, even local anesthesia to be applied may cause pain and anxiety in patients. Furthermore, since patients need to wait for a few minutes after interventional local anesthesia at the emergency department, non-invasive local Anesthetic agents should be preferred in these cases. For the efficacy of non-invasive topical anes- thetic preparations, 30-60 min are required after the application, and it has been stated that these agents have no effect on arterial blood gas sampling [3,4].

It is a Topical anesthetic used before rapid invasive techniques in minor surgery and sports medicine. When applied to the skin surface with aerosol, its rapid evaporation causes tissue cooling down to -20

* Corresponding author at: Ataturk Universitesi Saglik Arastirma ve Uygulama Merkezi, Mudurlugu Universite Kampusu Yakutiye, Erzurum 25040, Turkey.

E-mail address: [email protected] (A. Gur).

?C, resulting in the insensitivity of peripheral nerves. A 10-s application of ethyl chloride spray produces an immediate local anesthetic effect of 30 s [5]. Therefore, it is an easy-to-use, fast and non-invasive method for pain relief.

The aim of this study was to determine whether ethyl chloride spray had an analgesic effect on the intensity of pain caused by arterial blood gas sampling compared to a placebo at the emergency department.

  1. Material and method
    1. Study design and setting

This study was conducted between January 1, 2022, and February 25, 2022, with a randomized, double-blinded, placebo-controlled de- sign at the emergency department of a tertiary hospital. For arterial blood gas sampling, 150 mL of ethyl chloride spray (Clorethyl Cooling Spray, EBT health services, Bursa, Turkey) was compared with a pla- cebo (distilled cold water). The study was initiated following the approval of the local ethics committee (number: E-37732058- 514.99-6029). Written informed consent was obtained from all the volunteers participating in the study. The study complied with the principles of Good Clinical Practices of the Declaration of Helsinki and the CONSORT directive.

0735-6757/(C) 2022

    1. Sample size and patients

G-Power 3.1 software was used to calculate the sample size required for the study. During this calculation, the medium effect size was taken as 0.5, type 1 error as 0.05, and power as 0.80. 15 mm VAS difference was expected between groups. The sample size for the study was calcu- lated as a minimum of 64 patients (128 patients with the 1:1 allocation ratio) in each group considering a possible loss of 10%. To better repre- sent this calculated population in the %95 Confidence interval (CI), we increased the sample size to 101 patients in each group (202 patients with the 1:1 allocation ratio).

Conscious and cooperative patients aged 18-70 years, who required arterial blood gas sampling for respiratory or metabolic evaluation at the emergency department according to medical criteria, were included in the study. Patients with a low level of consciousness (Glasgow Coma Scale score < 15), those with an allergy to ethyl chloride, pregnant or breastfeeding women, patients that had taken analgesics within the past 24 h, those that had problems in verbal communication, those with peripheral neuropathies, those with a diagnosis of Raynaud’s phe- nomenon diagnosis, those with skin abrasions, and those with an infec- tion in the sampling area were excluded from the study.

    1. Randomization and primary outcome

Ethyl chloride spray and sterile water were separately placed in enclosed boxes numbered 1 and 2 and kept at +4 degrees. Only the per- son who prepared the drugs knew which was in which box. The person administering the drugs was blinded to the groups. The patient groups were sequentially determined according to the randomization table prepared using the website Accordingly, the drug to be administered to each patient was allocated. Interventional blood gas sampling was performed by the same physi- cian in all the patients. The outcome of the study was pain score evalu- ated using the visual analog scale in patients who underwent arterial blood gas sampling.

    1. Study variables and intervention

After obtaining consent form from the patients for arterial blood gas sampling, the radial artery or femoral artery was evaluated as

intervention sites according to the preference of the person to perform the intervention. The area was first cleaned with 10% povidone iodine with cotton. Then, the spray numbered 1 or 2 according to the random- ization table was applied to the area three times from a distance of 15 cm, according to the manufacturer’s recommendation. After waiting for one to two minutes, Arterial puncture was performed preferably with a 25-gauge needle attached to a standard 5 mL heparinized sy- ringe. All the interventions were undertaken by a single physician who was an emergency medicine specialist. For the patients who under- went the radial intervention, wrist movement was observed during the procedure. All the interventions were performed at the emergency de- partment. Following the procedure, the patients’ age, gender, region of intervention, and wrist movement were recorded in a previously cre- ated form. The patients were followed up for bleeding, swelling, and redness. After the procedure, the patients were asked to mark the level of pain they felt during the procedure on a 10-cm horizontal VAS scale, ranging from 0 (no pain) to 10 (worst pain ever experienced). In addition, the patients were asked to rate pain character as 0 (no pain), 1 (oppressive), 2 (dull), and 3 (sharp). These data were then recorded on patient forms.

    1. Statistical analysis

Statistical analysis was performed using SPSS software version 25.0 (IBM Corp., Armonk, New York, USA). The distribution of variables was evaluated for normality using the Kolmogorov-Smirnov test. De- scriptive statistics were given as frequency (n) and percentage (%) values for categorical variables. The comparison of groups for variables with a normal distribution was made with Student’s t-test, and group comparisons for variables that did not have a normal distribution were undertaken with the Mann-Whitney U test. P < 0.05 was consid- ered statistically significant.

  1. Results
    1. Patient population and characteristics

A total of 239 patients were initially evaluated, and 37 that did not meet the inclusion criteria were excluded. The remaining 202 patients were included in the sample (Fig. 1). Data from all the 202 patients

Image of Fig. 1

Fig. 1. CONSORT flow diagram of the study.

Table 1

Demographic data and other characteristics of the study groups.



Ethyl chloride


(n = 101)

(n = 101)

Age (years), Median (IQR)

65 (29)

62 (23)




Male, n (%)

64 (63.3%)

49 (48.5%)

Female, n (%)

37 (36.9%)

52 (51.5%)

Attempt number


First, n (%)

75 (74.2%)

90 (89.1%)

Second, n (%)

26 (28.8%)

11 (10.9%)

Wrist movement


No, n (%)s

92 (91.0%)

86 (85.1%)

Little, n (%)

9 (9.0%)

15 (14.9%)

Region of intervention


Radial, n (%)

96 (95.1%)

91 (90.1%)

Femoral, n (%)

5 (4.9%)

10 (9.9%)

* Mann-Whitney U test.

?? Chi-square test.

were analyzed using SPSS, and no other patients were excluded during the study period.

The demographic data and other characteristics of the patients are given in Table 1. The mean age of the placebo group was 65 [inter- quartile range (IQR): 29] years, and that of the ethyl chloride spray group was 62 (IQR: 23) years, with no significant difference between the two groups (p = 0.552).

The rate of male patients was 63.3% and 48.5% in the placebo and ethyl chloride spray groups, respectively, and there was a significant dif- ference between the groups (p = 0.046). An arterial blood gas sample was successfully taken at the first attempt in 74.2% of the patients in the placebo group and 89.1% of those in the ethyl chloride spray group. The success rate at the first attempt was significantly higher in the ethyl chloride spray group compared to the placebo group (p = 0.007). In the placebo group, wrist movement was absent in 91.1% of the patients and reduced in 9.0%, while these rates were 85.1% and 14.9%, respectively, revealing no statistically significant difference (p = 0.216). The preferred region of intervention was the radial artery in both groups (95.1% for the placebo group and 90.1% for the ethyl chlo- ride spray group), which was not statistically significant (p = 0.155).

    1. Comparison of groups

The median VAS score was 4 (IQR: 1.0) in the ethyl chloride spray group and 5 (IQR: 1.0) in the placebo group. The efficacy of ethyl chlo- ride spray in reducing pain was statistically significantly higher com- pared to the placebo (p = 0.001) (Fig. 2). In the evaluation of pain character, there was no patient who did not feel pain in the placebo group, while 6.9% of the patients in the ethyl chloride spray group did not feel any pain. Pain character statistically significantly differed between the two groups (p = 0.001) (Table 2).

  1. Discussion

In this study, it was shown that ethyl chloride spray reduced the in- tensity of pain in patients compared to the placebo group during arterial blood gas sampling. The blood gas sampling procedure is painful for the patient, which causes concern for both the patient and the practitioner. This reduces the practitioner’s chance of success in a single attempt. Therefore, further attempts are required for the procedure to be suc- cessful, resulting in more pain in the patient. It is necessary to ensure that the patient feels no or very little pain during the procedure. To achieve this, non-invasive cryoanalgesic and lidocaine spray applica- tions have been investigated in the literature in terms of their efficacy in reducing pain during arterial puncture as an alternative to local anesthetic agents [6-8]. These applications also bring to mind the

Image of Fig. 2

Fig. 2. Primary outcome: Assessment of pain intensity using a 10-cm Visual Analog Scale in the ethyl chloride and placebo groups.

Table 2

Assessment of pain intensity in the study groups.

Variables Placebo (n = 101) Ethyl chloride (n = 101) p-value VAS score (Median, IQR) 5 (1.0) 4 (1.0) 0.000?

Pain character, n (%) 0.000??

No pain 0 (0%) 7 (6.9%)


4 (3.9%)

18 (17.8%)


3 (2.9%)

57 (56.4%)


94 (93.2%)

19 (18.8%)

VAS: Visual Analog Scale. IQR: Interquartile range.

* Mann-Whitney U test.

?? Chi-square test.

possibility of using ethyl chloride spray for this purpose in arterial blood gas sampling.

Unlike our results, there are studies reporting no significant differ- ence in patients’ self-perceived pain between the arterial blood gas anal- ysis procedures performed with and without ethyl chloride [9,10]. Similarly, some studies suggest that subcutaneous amines and vaporized ethyl chloride have no significant difference as anesthetic agents in pain perception during arterial blood gas sampling [11,12]. We consider that the reason why our results were different from previous studies is that the effect of cryoanalgesic applications is more superficial and involves individual differences due to cold application. Because the cryoanesthetic effect of ice should be less effective and result in a long time [13].

To date, other therapeutic strategies have also been explored to re- duce iatrogenic pain associated with arterial puncture [8,14-16]. Among these strategies, it is mentioned that subcutaneous amines and lidocaine spray have anesthetic effects. All of these strategies are studies aimed at reducing patient pain for anesthesia purposes in arterial blood gas sampling. Because reducing the pain of patients is important for pa- tient comfort. Therefore, the use of ethyl chloride spray as an anesthetic in residual blood gas sampling can be added to these strategies.

Most patients experience sharp pain during interventions per- formed on the skin [17]. In our study, the patients in the placebo group mostly reported feeling sharp pain while those in the ethyl chlo- ride spray mostly experienced dull pain. This once again proves the an- algesia effect of ethyl chloride spray.

  1. Conclusion

In this study, the topical anesthetic effect of ethyl chloride spray was demonstrated in arterial blood gas sampling compared to a placebo.

Therefore, the use of ethyl chloride spray can both increase comfort and reduce pain in patients undergoing arterial blood gas sampling at the emergency department.

  1. Limitation

There are some limitations to our study. First concerns the measure- ment tool used to assess pain. Although the VAS scale is accepted as a valid and reliable tool, since pain perception varies from one patient to another, the VAS scores obtained from the study were patient- dependent. In other words, patients with different pain thresholds were questioned. Second, arterial blood gas sampling procedures that were successful at the first or second attempt were included in the study. There may have been a difference in pain experiences of patients for whom the procedure was successful at the first or second attempt.



Credit authorship contribution statement

Fatma Cakmak: Writing – review & editing, Visualization, Resources, Data curation. Ali Gur: Writing – review & editing, Writing – original draft, Visualization, Supervision, Methodology, Conceptualization.

Declaration of Competing Interest

The authors declare no conflicts of interest.


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