局部麻醉劑在減少周邊靜脈插管疼痛的療效比較 : 一項隨機試驗

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1 Hong Kong Journal of Emergency Medicine Comparison of the efficacies of topical anaesthetics in the reduction of the pain during peripheral intravenous cannulation: a randomised trial 局部麻醉劑在減少周邊靜脈插管疼痛的療效比較 : 一項隨機試驗 E Armagan, E Kocabas, O Koksal, G Simsek, H Bal Objective: This study aimed to compare the efficacies of two different topical anesthetic agents and placebo in the reduction of the pain observed during intravenous (IV) cannulation. Methods: Study enrolled a total of 129 healthy male donors and IV cannulation was performed to antecubital region. The donors were assigned into three groups. Prilocaine-lidocaine mixture cream (E), lidocaine spray (X) and Placebo cream (P) were given to patients. After the administration the donors were waited for approximately 45 minutes. The pain experienced by the donors after the insertion of 16 gauge cannula in arms was recorded as "pain experienced at minute 0, 5 and 15" on 100 mm visual analog scale (VAS). Results: In the first group, there was no significant difference between mean VAS scores recorded after the administration of prilocainelidocaine mixture cream and lidocaine spray before IV cannulation. Mean VAS value was 9.1 mm with prilocaine-lidocaine mixture cream and 9.3 mm with lidocaine spray. In the second group, we detected significant difference between mean VAS scores recorded after the administration of lidocaine spray and placebo cream. Mean VAS value was 9.8 mm with lidocaine spray and 24.3 mm with placebo (p<0.05). In the third group, we found statistically significant difference between VAS scores recorded after the administration of prilocaine-lidocaine mixture cream and placebo cream. Mean VAS value was 8.8 mm with prilocaine-lidocaine mixture cream and 33.0 mm with placebo cream (p<0.05). Conclusion: Although both agents administrated before IV cannulation were superior to placebo in adult patients in this study, we can state that these drugs were not superior to each other and showed similar efficacy. (Hong Kong j.emerg. med. 2012;19: ) 目的 : 本研究的目的是比較兩種不同的局部麻醉劑和安慰劑, 在減少靜脈注射 (IV) 插管過程中產生的痛楚的療效 方法 : 研究對象共 129 名, 是接受在肘部靜脈穿刺的健康男性獻血者 捐助者分為三組, 分別接受普魯卡因 / 利多卡因混合霜 (E) 利多卡因噴霧 (X) 和安慰劑霜 (P ) 捐助者用藥後等待約 45 分鐘 捐助者接受 16 號導管插入後, 在 0, 5 和 15 分鐘的痛楚程度, 是使用 100 毫米的視覺模擬評分 (VAS) 量表作記錄 結果 : 在第一組中, 靜脈置管前有接受普魯卡因 / 利多卡因混合霜和利多卡因噴霧的捐助者, 錄得的平均 VAS 評分之間無顯著差別 普魯卡因 / 利多卡因混合霜組平均 VAS 評分為 9.3 毫米, 利多卡因噴霧組平均 VAS 評分為 9.1 毫米 在第二組中, 我們發現利多卡因噴霧與安慰劑霜 2 組之間的平均 VAS 評分有顯著性差異 利多卡因噴霧組平均 VAS 評分為 9.8 毫米, 而 Correspondence to: Ozlem Koksal, MD, PhD Uludag University Faculty of Medicine, Department of Emergency, Gorukle Bursa, Turkey koksalozlem@gmail.com Uludag University Faculty of Medicine, Blood and Blood Products Center, Gorukle Bursa, Turkey Haldun Bal, MD Erol Armagan, MD Egemen Kocabas, MD Gozde Simsek, MD

2 184 Hong Kong j. emerg. med. Vol. 19(3) May 2012 安慰劑組為 24.3 毫米 (p<0.05) 在第三組中, 我們發現普魯卡因 / 利多卡因混合霜和安慰劑霜 2 組的 VAS 評分有統計學意義的差別 普魯卡因 / 利多卡因混合霜組平均 VAS 值是 8.8 毫米, 安慰劑霜組是 33.0 毫米 (p<0.05) 結論 : 在這項成年患者的研究中, 靜脈置管前給這兩種藥物雖然均優於安慰劑, 但這兩種藥物並不優於對方, 而表現出類似的療效 Keywords: Efficacy, infiltration anesthesia, peripheral catheterization 關鍵詞 : 功效 浸潤麻醉 外周導管 Introduction Peripheral intravenous (IV) cannulation is an invasive method, which is commonly used in the hospitals. Major limitations of this method include its painful nature and anxiety. Although using topical anaesthetics before the cannulation can reduce the pain, the most effective method is unknown. 1 There are many alternative ways to reduce the pain occurred during IV cannulation. One of these ways is intradermal injection of Lidocaine, which, as a source of pain and anxiety, limits the use. 2 In IV cannulation, the use of topical anaesthetics, such as lidocaine, tetracaine and prilocaine-lidocaine mixture, is a commonly used technique. Prilocaine-lidocaine mixture is the first commercially available topical agent that provides adequate analgesic effect. The literature shows that the studies for the use of topical agents before IV cannulation were most commonly conducted in paediatric population. 1,3-5 Studies performed on adults are more commonly performed in healthy volunteers 6 and the studies conducted in emergency department (ED) are limited. 1,7-9 As intact skin is an important barrier for topical agents, topical agents must be applied minutes before the cannulation, for which the time is mostly inadequate in ED. IV cannulas used for blood and blood product transfusion have a larger diameter and cause more pain. There is enough time to apply local anaesthetic agents to ED patients, for whom blood and blood product transfusion is planned before the transfusion. Our study was conducted in Blood and Blood Products Center, with the donors who donated whole blood sample to obtain platelet suspension required for the patients, which were planned to be given the transfusion of platelet suspension in ED. In Uludag University Faculty of Medicine (UUFM) Blood and Blood Products Center, platelet suspension was obtained using apheresis method from approximately 3500 donors annually. In this method, whole blood sample obtained from the donor is anticoagulated with citrate-containing solution using apheresis device and the platelets are collected. IV cannulation is administrated to both arms of the donor. This study aimed to compare the efficacies of two different topical anaesthetic agents (prilocaine-lidocaine mixture cream and lidocaine spray) and placebo in the reduction of the pain observed during IV cannulation. Subjects and methods Study was designed as a prospective and placebocontrolled study and was approved by Uludag University Ethical Committee. Study enrolled a total of 132 healthy male donors, which presented to UUFM Blood and Blood Products Center as a volunteer and were planned to receive platelet suspension. While three donors were excluded from the study due to various reasons (declined to participate or other reasons), 129 donors completed the study (Figure 1). In our Blood and Blood Products Center, platelet suspension was obtained using apheresis. In this method, IV cannulation was applied to the antecubital fossa of both arms of the donor. Whole blood sample obtained from the donor was anticoagulated with citrate-containing solution using apheresis device and the platelets were collected. Thereafter, the components, which remain after the dissociation of the platelets, were given to other arm of the donor.

3 Armagan et al./efficacies of topical anesthetics 185 (A) Figure 1. Flow diagram. In all donors, IV cannulation was performed to antecubital region. Drug 1 was an eutectic mixture of lidocaine (2.5%) prilocaine (2.5%) cream (E) and two gram was applied. Drug 2 contained 10% lidocaine spray (X) and five doses were applied. Drug 3 was the placebo (P) cream and two gram was applied. The donors were assigned into three groups and included in these groups respectively. In the first group, Drug 1 (E) was given to right arms and Drug 2 (X) was given to left arms of 40 patients. In the second group, Drug 2 (X) was given to right arms and Drug 3 (P) was given to left arms of 46 patients. In the third group, Drug 1 (E) was given to right arms and Drug 3 (P) was given to left arms of 43 patients. Randomisation was performed using a randomnumber generator. The physician on duty in the blood center generated the random allocation sequence, an emergency physician enrolled participants, and another emergency physician assigned par ticipants to interventions. After the administration, the relevant site of administration was covered using a transparent and non-absorbent wrapping and the donors were waited for approximately 45 minutes. IV cannulations were performed 45 minutes after the application of the intervention i.e. drug either E, X or placebo. At the end of this period, the pain experienced by the donors after the insertion of 16 gauge cannula was recorded as "pain experienced at minute 0, 5 and 15" on 100 mm visual analog scale (VAS) by blinded assessor. Statistical methods Statistical analysis was performed using SPSS 13.0 for Windows. Paired samples t-test was used to compare VAS scores of IV cannulation at minute 0, 5 and 15. To compare VAS scores and age between the three groups, ANOVA test was used. "Independent samples t-test" was used to evaluate the statistical differences between the two drug groups in terms of VAS scores. Results Intravenous cannulation was applied to 129 donors. All donors enrolled to the study were men and mean age was 33.2±8.7. No statistical difference was observed between three groups in terms of mean age (p>0.05). All d ono rs u nder went IV can nulatio n in t he antecubital region. In the first group, there was no significant difference between mean VAS scores recorded at minute 0, after the administration of prilocaine-lidocaine mixture cream to right arms and lidocaine spray to left arms after IV cannulation. Mean VAS value was 9.1 mm with prilocaine-lidocaine mixture cream and 9.3 mm with lidocaine spray (p>0.05) (Figure 2). In the second group, we detected significant difference between mean VAS scores recorded at minute 0, after the

4 186 Hong Kong j. emerg. med. Vol. 19(3) May 2012 administration of lidocaine spray to right arms and placebo cream to left arms. Mean VAS value was 9.8 mm with lidocaine spray and 24.3 mm with placebo (p<0.05) (Figure 3). In the third group, we found statistically significant difference between VAS scores recorded at minute 0, after the administration of prilocaine-lidocaine mixture cream to right arms and placebo cream to left arms of the donors. Mean VAS value was 8.8 mm with prilocaine-lidocaine mixture cream and 33.0 mm with placebo cream (p<0.05) (Figure 4). Finally, we compared the mean VAS scores recorded at minute 0, 5 and 15 between prilocaine-lidocaine mixture cream and lidocaine spray administrated before IV cannulation. While there was no statistically significant difference between two groups (p>0.05), efficacy of both drugs (E and X) markedly increased over time (p<0.05). Mean VAS value was 9.3 mm at minute 0, 2.9 mm at minute 5, and 2.3 mm at minute 15 with prilocaine-lidocaine mixture cream and 9.1 mm at minute 0, 2.6 mm at minute 5, and 2.2 mm at minute 15 with lidocaine spray (Figure 5). Figure 2. The mean VAS scores at minute 0 in the first group [prilocaine-lidocaine mixture (E) and lidocaine (X)]. Statistically insignificant (p>0.05). Figure 4. The mean VAS scores at minute 0 obtained with the drugs administrated in the third group [prilocaine-lidocaine mixture (E) and placebo (P)]. Statistically significant (p<0.05). Figure 3. The mean VAS scores at minute 0 in the second group [lidocaine (X) and placebo (P)]. Statistically significant (p<0.05). Figure 5. The mean VAS scores of prilocaine-lidocaine mixture (E) cream and lidocaine (X) spray (in the first group) at minute 0, 5 and 15. No statistically significant difference between the two groups (p>0.05). The efficacies of both drugs (E and X) significantly increased after the administration over time (p<0.05).

5 Armagan et al./efficacies of topical anesthetics 187 Discussion In this study, we demonstrated that the both local anaesthetic agents, which were administrated before IV cannulation, have a similar efficacy, and better analgesic efficacy compared to placebo in healthy volunteers from whom platelet suspension had been taken. Pain and anxiety, which occur during IV cannulation, is significantly reduced with locally administrated lidocaine. In addition, although lidocaine produces vasoconstriction, many studies showed that it did not prevent IV cannulation Similarly, our study revealed a significant difference of mean VAS scores, which favoured lidocaine, when comparing with placebo cream. In the literature, many studies demonstrated that the pain observed during IV cannulation was reduced with the administration of prilocaine-lidocaine mixture cream Following the administration of prilocainelidocaine mixture cream, a biphasic vasoactive response, which is consisted of vasoconstriction followed by a vasodilatation, occurs. 16,17 However, prilocainelidocaine mixture cream shows its vasodilatation effect in long-term (>180 minutes). 17,18 Although, we did not mention long-term effect of prilocaine-lidocaine mixture cream, we found a significant difference of mean VAS scores, which favoured prilocaine-lidocaine mixture cream when comparing with placebo cream. In a study that compared prilocaine-lidocaine mixture cream and topical tetracain used during IV cannulation in adults, it was demonstrated that tetracain provided a better analgesia. 18 In another study, in which prilocaine-lidocaine mixture cream and tetracain were compared in paediatric patients, tetracain was found to be superior. 19 Moreover, a study which compared LidoDin, a lidocain-based local anaesthetic, and prilocaine-lidocaine mixture cream in years old children, showed that both agents had equivalent topical anaesthetic efficacy and safety during IV cannulation. 20 Similarly, in our study, the absence of statistically significant difference of mean VAS scores between prilocaine-lidocaine mixture cream and lidocaine spray, indicated that both agents were not superior to each other. Only difference was that, while tetracain used in these studies was esteric local anaesthetic agent, lidocain used in our study was an amide local anaesthetic agent. This study has several limitations. Participants in this study were healthy male adult and the IV cannulation was performed only in the antecubital region. Results from this population may not be generalisable to other populations. Also this study has a limitation on methodology; the routes of administration topical anaesthetics agents are not similar. Additionally, operators had varying experience in placing IV cannulations and this situation may affect VAS levels. Consequently, although both agents administrated before IV cannulation were superior to placebo in adult patients in this study, we can state that these drugs were not superior to each other and showed similar efficacy. Especially in ED patients or triage three to five patients for whom blood and blood product transfusion was decided, given that there is enough time to use the topical agents before IV cannulation, their use may be considered in terms of patient's comfort. However, given the limitations of the study, more studies, which will be conducted with IV cannulation in various patient populations, with different agents and on different localisations, especially in emergency departments, are warranted. References 1. McNaughton C, Zhou C, Robert L, Storrow A, Kennedy R. A randomized, crossover comparison of injected buffered lidocaine, lidocaine cream, and no analgesia for peripheral intravenous cannula insertion. Ann Emerg Med 2009;54(2): Fetzer SJ. Reducing the pain of venipuncture. J Perianesth Nurs 1999;14(2):95-101, 112. Review. 3. Costello M, Ramundo M, Christopher NC, Powell KR. Ethyl vinyl chloride vapocoolant spray fails to decrease pain associated with intravenous cannulation in children. Clin Pediatr (Phila) 2006;45(7): Pershad J, Steinberg SC, Waters TM. Cost-effectiveness analysis of anesthetic agents during peripheral intravenous cannulation in the pediatric emergency

6 188 Hong Kong j. emerg. med. Vol. 19(3) May 2012 department. Arch Pediatr Adolesc Med 2008;162(10): Arendts G, Stevens M, Fry M. Topical anaesthesia and intravenous cannulation success in paediatric patients: a randomized double-blind trial. Br J Anaesth 2008; 100(4): Dutta A, Puri GD, Wig J. Piroxicam gel, compared to EMLA cream is associated with less pain after venous cannulation in volunteers. Can J Anaesth 2003;50(8): Valdovinos NC, Reddin C, Bernard C, Shafer B, Tanabe P. The use of topical anesthesia during intravenous catheter insertion in adults: a comparison of pain scores using LMX-4 versus placebo. J Emerg Nurs 2009;35 (4): Robinson PA, Carr S, Pearson S, Frampton C. Lignocaine is a better analgesic than either ethyl chloride or nitrous oxide for peripheral intravenous cannulation. Emerg Med Australas 2007;19(5): Singer AJ, Shallat J, Valentine SM, Doyle L, Sayage V, Thode HC Jr. Cutaneous tape stripping to accelerate the anesthetic effects of EMLA cream: a randomized, controlled trial. Acad Emerg Med 1998;5(11): Evans GR, Gherardini G, Gürlek A, Langstein H, Joly GA, Cromeens DM, et al. Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery. Plast Reconstr Surg 1997;100(6): Burgher SW, McGuirk TD. Subcutaneous buffered lidocaine for intravenous cannulation: is there a role in emergency medicine? Acad Emerg Med 1998;5(11): Sacchetti AD, Carraccio C. Subcutaneous lidocaine does not affect the success rate of intravenous access in children less than 24 months of age. Acad Emerg Med 1996;3(11): Hallen B, Olsson GL, Uppfeldt A. Pain-free venepuncture. Effect of timing of application of local anaesthetic cream. Anaesthesia 1984;39(10): Hopkins CS, Buckley CJ, Bush GH. Pain-free injection in infants. Use of a lignocaine prilocaine cream to prevent pain at intravenous induction of general anaesthesia in 1-5-year-old children. Anaesthesia 1988; 43(3): Cordoni A, Cordoni LE. Eutectic mixture of local anesthetics reduces pain during intravenous catheter insertion in the pediatric patient. Clin J Pain 2001;17 (2): Lander JA, Weltman BJ, So SS. EMLA and amethocaine for reduction of children's pain associated with needle insertion. Cochrane Database Syst Rev 2006; 3: CD Bjerring P, Andersen PH, Arendt-Nielsen L. Vascular response of human skin after analgesia with EMLA cream. Br J Anaesth 1989;63(6): Browne J, Awad I, Plant R, McAdoo J, Shorten G. Topical amethocaine (Ametop) is superior to EMLA for intravenous cannulation. Eutectic mixture of local anesthetics. Can J Anaesth 1999;46(11): Romsing J, Henneberg SW, Walther-Larsen S, Kjeldsen C. Tetracaine gel vs EMLA cream for percutaneous anaesthesia in children. Br J Anaesth 1999;82(4): Shavit I, Hadash A, Knaani-Levinz H, Shachor- Meyouhas Y, Kassis I. Lidocaine-based topical anesthetic with disinfectant (LidoDin) versus EMLA for venipuncture: a randomized controlled trial. Clin J Pain 2009;25(8):711-4.