Pain is one of the most significant and universal human experiences that prompts individuals of all ages to seek medical attention1. In healthcare settings, this fundamental human experience is not only a primary concern but can be further complicated by various medical procedures and interventions. The experience of pain during medical procedures represents a critical challenge in modern healthcare, affecting both patient experience and treatment outcome2. Healthcare providers must navigate the delicate balance between necessary medical interventions and patient comfort, recognizing that procedural pain can have lasting impact on patient attitude toward healthcare and treatment compliance. The complexity of pain as a physiological and psychological phenomenon cannot be overstated. The International Association for the Study of Pain’s definition of pain as “an unpleasant sensory or emotional experience associated with actual or potential tissue damage” only begins to capture its multifaceted nature3. Venepuncture is a routine yet painful procedure that can cause discomfort and anxiety for patients. Ethyl chloride, a vapocoolant spray, is commonly used to provide rapid pain relief by cooling the skin and temporarily numbing the area. However, there is limited research on whether a second spray enhances its analgesic effect compared to a single application. This study aims to determine if an additional spray significantly improves patient comfort and reduces pain perception. The search for ideal pain management solutions in vascular access procedures has led to extensive research into various interventions. The optimal solution should meet several critical criteria: it must be rapid in onset, easy to administer, cost-effective and minimally invasive. Additionally, it should not interfere with the procedure itself or cause complications that might affect patient safety or procedural success. Vapocoolant sprays, for example, work through rapid evaporation of volatile liquid on the skin surface, causing brief interruption of pain sensation through desensitization of pain receptors or activation of ion channels involved in pain transmission. While these sprays offer advantages such as immediate onset and ease of application, research has shown varying degrees of effectiveness across different procedures and patient populations4. Despite the fact that a single application is frequently employed in standard practice, there is little and conflicting data regarding whether adding another spray improves the analgesic effect. Particularly in nervous or pain-sensitive people, a stronger effect with repeated application may enhance patient comfort and procedural success. The purpose of this study is to investigate and compare the analgesic effectiveness of one versus two ethyl chloride sprays in patients undergoing anesthesia requiring intravenous cannulation before surgery. The results could be helpful in enhancing patient satisfaction, enhancing pain management procedures and advancing evidence-based clinical procedures for venepuncture analgesia.

This hospital-based, prospective, randomized, comparative study was conducted in the Department of Anaesthesia at SMS Medical College, Jaipur, after obtaining approval from the Institutional Ethics Committee(Ref. No: 328 MC/EC/2023, Date: 12-10-2023). Patients aged 18-60 years, either sex, ASA physical status I and II, scheduled for elective surgeries requiring IV cannulation were included in the study and patients with local infection at puncture site, known hypersensitivity to ethyl chloride, psychiatric illness, or those unwilling to participate were excluded from the study. A total of 64 patients were randomized using a computer-generated sequence into two equal groups (n=32 each): Group A: Received one spray of ethyl chloride for 5 seconds from 5 cm distance. Group B: Received two consecutive sprays, each for 5 seconds, from the same distance. After approval from the Institute Ethics Committee and written and informed consent, 64 patients requiring IV cannulation before surgery under anaesthesia, satisfying the inclusion criteria were included in the study. NBM status, PAC and consent were checked in the operating room. Routine vital monitors were attached for ECG ,SPO2 ,NIBP .They were randomized pre- operatively into two groups by computer generated random number table. Following the Ethyl Chloride spray, venipuncture was done by anaesthesiologist on the forearm using 25G cannula after wiping with 70% alcohol. Patients in Group A received spray of Ethyl Chloride once for 5 seconds perpendicular to the skin from a distance of 5 cm and patients of Group B received spray of Ethyl Chloride twice each over 5 seconds perpendicular to the skin.All patients reported the procedure related pain following 0-10 VAS score where 0 means no pain and 10 means worst pain imaginable. Pain analysis was done immediately after cannulation, at 3 minutes and at 5 minutes. Anaesthesia was given as per standard protocol.Data were analyzed using SPSS version 26.0. Continuous variables were expressed as mean ± SD and analyzed using t-tests. Categorical data were expressed aspercentages and compared using chi-square tests. A p-value <0.05 was considered statistically significant.

A total of 64 patients aged between 18 and 60 years were enrolled in the study and randomized equally into two groups: Group A (one spray of ethyl chloride) and Group B (two sprays). Baseline characteristics were comparable between the two groups. The mean age in Group A was 39.19 ± 13.25 years, while in Group B it was 40.44 ± 13.64 years (p = 0.711). The average weight was 62.38 ± 6.97 kg in Group A and 62.88 ± 8.59 kg in Group B (p = 0.799). Gender distribution was also similar, with Group A comprising 18 males and 14 females, and Group B comprising 22 males and 10 females (p = 0.439). None of these differences were statistically significant (Table 1). The incidence of pain during IV cannulation was significantly lower in Group B compared to Group A. In Group A, 59.38% of patients reported experiencing pain, whereas only 31.25% of patients in Group B reported pain. Conversely, 68.75% of Group B reported no pain compared to 40.63% in Group A. This difference was statistically significant (Chi-square = 4.035, p = 0.045), indicating the effectiveness of the two-spray technique in reducing the occurrence of pain (Table 2, Figure 2). When assessing the severity of pain, significant differences were also observed between the groups. In Group B, 56.25% of patients reported mild pain (VAS score 0–3), compared to 28.13% in Group A. Moderate pain (VAS 4–6) was reported in 34.38% of patients in Group B and 40.63% in Group A. Notably, severe pain (VAS 7–10) was much more common in Group A (31.25%) than in Group B (9.375%). This distribution showed a statistically significant difference (Chi-square = 6.936, p = 0.031), suggesting that two sprays provided better pain control by shifting the distribution towards lower pain severity (Table 3, Figure 3). The Visual Analog Scale (VAS) scores at various time points after IV cannulation further supported these findings. Immediately after cannulation, the mean VAS score in Group A was 5.09 ± 2.48, significantly higher than in Group B, which recorded a mean of 3.22 ± 2.24 (p = 0.002). At 3 minutes post-cannulation, the scores were 3.31 ± 2.09 in Group A and 1.81 ± 1.64 in Group B (p = 0.002). Even at 5 minutes, pain scores remained significantly lower in Group B (1.00 ± 1.30) compared to Group A (1.91 ± 1.57) (p = 0.014). These consistent differences across all time points confirmed the superior analgesic efficacy of the two-spray technique (Table 4, Figure 4). No adverse events were reported in either group during the study. Table 1: Baseline Characteristics Parameter Group A (n=32) Group B (n=32) p-value Significance Age (years) 39.19 ± 13.25 40.44 ± 13.64 0.711 NS Weight (kg) 62.38 ± 6.97 62.88 ± 8.59 0.799 NS Gender (M/F) 18/14 22/10 0.439 NS Table 2: Comparison of incidence of pain on IV Cannulation between the study groups Pain on IV Cannulation Group A Group B Total P Value Significance N % N % N % 0.045 S No 13 40.63 22 68.75 35 54.69 Yes 19 59.38 10 31.25 29 45.31 Total 32 100 32 100 64 100 Chi-square = 4.035 with 1 degree of freedom S = Significant NS = Non Significant Figure 2: Comparison of incidence of pain on IV Cannulation between the study groups Table 3: Comparison of severity of pain on IV Cannulation Pain severity Group A Group B Total P Value Significance N % N % N % 0.031 S Mild (0-3) 9 28.13 18 56.25 27 42.19 Moderate (4-6) 13 40.63 11 34.38 24 37.5 Severe (7-10) 10 31.25 3 9.375 13 20.31 Total 32 100 32 100 64 100 Chi-square = 6.936 with 2 degrees of freedom S = Significant NS = Non Significant Figure 3: Comparison of severity of pain on IV Cannulation   Table 4: Comparison of VAS score between the study groups Time Group A Group B P value Significance Immediately after IV Cannulation 5.09 ± 2.48 3.22 ± 2.24 0.002 S 3 min after IV Cannulation 3.31 ± 2.09 1.81 ± 1.64 0.002 S 5 min after IV Cannulation 1.91 ± 1.57 1 ± 1.3 0.014 S S = Significant NS = Non Significant Figure 4: Comparison of VAS score between the study groups Ethical Approval This study was approved by the Institutional Ethics Committee of SMS Medical College, Jaipur (Ref. No: 328 MC/EC/2023, Date: 12-10-2023). Funding of the Study The study did not receive any external funding. It was self-funded by the investigators. Conflict of Interest Declaration The authors declare no conflicts of interest related to this study. Acknowledgments We acknowledge the support of the Department of Anaesthesia, SMS Medical College, Jaipur, and the cooperation of all patients who participated in the study.

Venepuncture is a routine but often painful procedure required for intravenous (IV) cannulation, especially before surgery under anesthesia. Pain and anxiety associated with venepuncture can lead to patient discomfort and distress. Various pharmacological and non-pharmacological methods have been used to minimize this pain. Local anesthetics, such as the eutectic mixture of local anesthetics (EMLA) cream, require application time and may cause injection-related discomfort. Vapocoolants like Ethyl Chloride, on the other hand, act rapidly by cooling the skin and numbing the nociceptors, providing immediate and transient analgesia. Ethyl Chloride is widely used in minor procedures, including venepuncture, due to its ease of application, rapid onset and cost-effectiveness. However, there is limited research comparing the effectiveness of a single spray versus two sprays in reducing venepuncture-related pain. The results of our study demonstrated a statistically significant reduction in pain incidence during intravenous (IV) cannulation when two sprays of ethyl chloride were used instead of one (p = 0.045). The nearly 50% reduction in pain incidence with two sprays represents a clinically significant improvement in patient comfort during IV cannulation as second spray ensures more uniform and sustained cooling of the skin surface and the underlying superficial nerve endings. Ethyl chloride works through a mechanism known as cryoanalgesia, which relies on rapid evaporation and subsequent heat extraction from the skin. This cooling decreases the excitability of peripheral nerve endings by reducing sodium channel activity and temporarily blocks the conduction of sensory signals. The repeated application allows for a deeper and more homogenous reduction in skin temperature, likely resulting in more complete inhibition of nociceptive transmission. Additionally to the local neural effects, psychological modulation of pain perception also plays a role. The pronounced cold sensation following the second spray may act as a distracting stimulus, temporarily shifting the patient’s attention away from the pain-inducing stimulus of the venipuncture. This concept aligns with the gate control theory of pain, where non-painful input (cold sensation) closes the “gates” to painful input, thereby suppressing pain perception.Similarly, Shah et al. (2018)5 reported a significant reduction in needle electromyography pain and higher patient satisfaction when ethyl chloride spray was used versus placebo .Rao et al. (2019)6 also demonstrated a significant difference in venipuncture pain scores between control, single-spray, and double-spray groups, with twice-applied ethyl chloride yielding the greatest analgesic benefit Fareeda et al. (2025)7 observed a significant analgesic effect of ethyl chloride spray in children, with a substantial proportion reporting no or mild pain compared to severe pain in the control group. The VAS scores were consistently lower in Group B at all time points. Immediately after injection, Group B recorded an average VAS score of 3.22 ± 2.24 compared to 5.09 ± 2.48 in Group A, with a statistically significant difference (p = 0.002). This trend persisted at 3 minutes (Group B: 1.81 ± 1.64 vs. Group A: 3.31 ± 2.09, p = 0.002) and at 5 minutes (Group B: 1 ± 1.3 vs. Group A: 1.91 ± 1.57, p = 0.014). The consistently lower VAS scores in Group B suggest that applying two sprays of ethyl chloride provides more sustained pain relief compared to a single spray. The sustained pain reduction over time is observed, as it suggests that the enhanced analgesic effect of two sprays is not merely transient but provides meaningful pain relief throughout the critical period of the procedure. This sustained relief may be due to a longer residual cooling effect that results in extended inhibition of nociceptive signals, especially from A-delta and C fibers responsible for transmitting sharp and dull pain respectively. By lowering local skin temperature beyond a certain threshold, the nerve fibers may take longer to return to their baseline excitability after the procedure, hence explaining the significant difference observed even 5 minutes after cannulation8. Moreover, the increased duration and intensity of skin cooling could be associated with a larger dermatome area being effectively anesthetized. A single spray may not uniformly cover the venipuncture zone, leaving some sensory nerve endings unaffected. The second application ensures a more consistent spread, reinforcing the anesthetic field. The temporal pattern of pain scores in our study provides valuable insights into the duration of analgesic effect. The significant difference maintained at 3 and 5 minutes post-procedure suggests that two sprays not only provide better immediate pain relief but also extend the duration of analgesia. This finding has important clinical implications, particularly for procedures that may require multiple attempts or take longer to complete. The sustained analgesic effect could potentially reduce the need for additional pain management interventions and improve overall patient satisfaction with the procedure. The double spray mechanism amplified the degree and duration of anesthesia achieved by temporarily numbing of the nerve endings. When categorizing pain severity there was a notable difference between the two groups. These observations reinforces the hypothesis that cooling intensity and coverage directly correlate with pain modulation. The transient blockade of nociceptive fibers is likely more robust in the double-spray group, preventing escalation of minor discomfort into more severe pain perception. Furthermore, vapocoolant sprays may also reduce neurogenic inflammation by constricting local capillaries, limiting the release of pain-enhancing inflammatory mediators at the site of needle entry. The second spray may also optimize patient readiness both psychologically and physiologically before the process of venipuncture. The perceived attention to comfort and the second cooling stimulus may lead to reduced anxiety and sympathetic activation, indirectly affecting pain severity. Physiologically, the dual application amplifies the depth and extent of cooling, resulting in greater suppression of peripheral nociceptor activity. The superficial nerve endings, once cooled below a certain threshold, become temporarily inactive due to membrane depolarization failure, inhibiting the transmission of pain impulses9. Across all participants, there were no instances of rash, cutaneous flushing, hematoma, or excessive bleeding. This complete absence of side effects supports the safety profile of ethyl chloride vapocoolant spray, reinforcing its suitability for routine clinical use, particularly for pain relief during procedures like venipuncture or cannulation. These findings are consistent with previous literature that highlights the generally well-tolerated nature of vapocoolant sprays. The findings of the present study indicate that two sprays of ethyl chloride provide better pain relief than one spray, likely due to the increased intensity and duration of skin cooling. The additional spray prolongs the numbing effect, making the venepuncture procedure more tolerable for patients. The results of our study have significant implications for clinical practice, suggesting that the use of two sprays of ethyl chloride can provide better pain relief than a single spray during venepuncture procedures. This finding can inform the development of standardized protocols for vapocoolant spray application, potentially improving patient comfort and satisfaction during these common medical procedures. Furthermore, the study's focus on the optimization of vapocoolant spray dosage contributes to the growing body of literature on pain management strategies, highlighting the importance of considering both the effectiveness and practicality of different interventions in clinical decision-making.

When it comes to minimizing pain during venepuncture, two ethyl chloride vapocoolant sprays are far more effective than one. It provides prolonged analgesia, improved patient comfort and outstanding safety without changing critical parameters. Its cost-effectiveness and simplicity of use encourage its acceptance as a standard procedure in clinical settings, especially those where a rapid onset of action is crucial. Our study demonstrates that the use of two sprays of ethyl chloride provides superior and sustained analgesia during venipuncture compared to a single spray, without compromising patient safety . The double spray technique appears to prolong the duration and depth of skin anesthesia, making it a simple, effective and well-tolerated intervention for reducing procedural pain. These findings advocate for the broader use of this approach in clinical settings, particularly in patients with anxiety or repeated cannulation needs. Future studies with larger, multi-center samples and long-term follow-up could help further refine the optimal usage strategy and assess broader clinical benefits.

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