TITLE: Lidocaine-prilocaine cream (EMLA) versus amethocaine/tetracaine gel (Ametop) and Maxeline for Patients Requiring Local Anesthetic: Clinical-Effectiveness, Cost-Effectiveness, and Guidelines DATE: 13 May 2009 RESEARCH QUESTIONS: 1. What is the clinical-effectiveness of EMLA, Ametop, and Maxeline for patients requiring local anesthetic? 2. What is the cost-effectiveness of EMLA, Ametop, and Maxeline for patients requiring local anesthetic? 3. What are the guidelines for best use of EMLA, Ametop, and Maxeline for patients requiring local anesthetic? METHODS: A limited literature search was conducted on key health technology assessment resources, including PubMed, the Cochrane Library (Issue 2, 2009), University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, international HTA agencies, and a focused Internet search. Results include articles published between 2004 and May 2009 and are limited to English language publications only. Filters were applied to limit the retrieval to health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, controlled clinical trials, economic studies, and guidelines. Internet links are provided, where available. RESULTS: HTIS reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessment reports, systematic reviews, and meta-analyses are presented first. These are followed by randomized controlled trials, controlled clinical trials, economic evaluations, and evidence-based guidelines. Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in which a third party owns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a web site, redistributed by email or stored on an electronic system without the prior written permission of CADTH or applicable copyright owner. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.
Two systematic reviews and 15 randomized controlled trials were identified regarding the clinical-effectiveness of EMLA, and Ametop for patients requiring local anesthetic; no relevant health technology assessments or controlled clinical trials were identified. One economic evaluation was identified regarding the cost-effectiveness of EMLA and Ametop for patients requiring local anesthetic. No relevant guidelines for the best use of EMLA or Ametop for patients requiring local anesthetic were identified from the literature search results. No evidence of any type was identified regarding Maxeline. Additional articles of interest may be found in the appendix. Health technology assessments No literature identified Systematic reviews and meta-analyses 1. Kappelou O. Blood sampling in infants (reducing pain and morbidity). London: BMJ Clinical Evidence; 2007. Article available for purchase at http://clinicalevidence.bmj.com Note: see Topical Anesthetics, page 5 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. PubMed: PM16856039 Randomized controlled trials 3. Shaikh FM, Naqvi SA, Grace PA. The Influence of a Eutectic Mixture of Lidocaine and Prilocaine on Minor Surgical Procedures: A Randomized Controlled Double-Blind Trial. Dermatol Surg 2009. PubMed: PM19397664 4. 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):521-4. PubMed: PM18292082 5. Demirci H, Erdamar H, Karakoc A, Arslan M. Thyroid fine needle aspiration biopsy: is topical local anaesthesia beneficial? Int J Clin Pract 2008. PubMed: PM18803557 6. Nichani J, Camilleri AE, Broomfield S, Saeed S. Optimizing local anesthesia for grommet insertion: eutectic mixture of local anaesthetics versus Ametop: a randomized clinical trial. Otol Neurotol 2008;29(5):658-60. PubMed: PM18665031 7. Shiau JM, Su HP, Chen HS, Hung KC, Lin SE, Tseng CC. Use of a topical anesthetic cream (EMLA) to reduce pain after hemorrhoidectomy. Reg Anesth Pain Med 2008;33(1):30-5. PubMed: PM18155054 8. Choy L, Collier J, Watson AR. Comparison of lignocaine-prilocaine cream and amethocaine gel for local analgesia before venepuncture in children. Acta Paediatrica 2007;88(9): 961-964. Abstract available: http://www3.interscience.wiley.com/journal/119937715/abstract (accessed 10 May 2009) EMLA versus Ametop and Maxeline 2
9. Liberty G, Gal M, Halevy-Shalem T, Michaelson-Cohen R, Galoyan N, Hyman J, et al. Lidocaine-prilocaine (EMLA) cream as analgesia for hysterosalpingography: a prospective, randomized, controlled, double blinded study. Hum Reprod 2007;22(5):1335-9. PubMed: PM17234675 10. Pongrojpaw D, Somprasit C, Chanthasenanont A. The efficacy of lidocaine-prilocaine cream to reduce pain in genetic amniocentesis. J Med Assoc Thai 2007;90(10):1992-6. PubMed: PM18041414 11. Samson D, Minville V, Chassery C, Nguyen L, Pianezza A, Fourcade O, et al. Eutectic mixture of local anesthetic (EMLA) decreases pain during humeral block placement in nonsedated patients. Anesth Analg 2007;105(2):512-5. PubMed: PM17646514 12. De Maria M, Mogorovich A, Giannarini G, Manassero F, Selli C. Lidocaine-prilocaine administration during transrectal ultrasound-guided prostatic biopsy: a randomized, singleblind, placebo-controlled trial. J Endourol 2006;20(7):525-9. PubMed: PM16859470 13. Langan SM, Collins P. Randomized, double-blind, placebo-controlled prospective study of the efficacy of topical anaesthesia with a eutetic mixture of lignocaine 2.5% and prilocaine 2.5% for topical 5-aminolaevulinic acid-photodynamic therapy for extensive scalp actinic keratoses. Br J Dermatol 2006;154(1):146-9. PubMed: PM16403108 14. Leloudis DH, Kittleson MM, Felker GM, Rosenberg PB, Hernandez AF, Yager JE, et al. Topical anesthesia with EMLA reduces pain during endomyocardial biopsy: a randomized trial. J Heart Lung Transplant 2006;25(9):1164-6. PubMed: PM16962481 15. Raber M, Scattoni V, Roscigno M, Rigatti P, Montorsi F. Perianal and intrarectal anaesthesia for transrectal biopsy of the prostate: a prospective randomized study comparing lidocaine-prilocaine cream and placebo. BJU Int 2005;96(9):1264-7. PubMed: PM16287442 16. Bloch Y, Levkovitz Y, Atshuler A, Dvoretzki V, Fenning S, Ratzoni G. Use of topical application of lidocaine-prilocaine cream to reduce injection-site pain of depot antipsychotics. Psychiatr Serv 2004;55(8):940-1. PubMed: PM15292547 17. Sarifakioglu N, Terzioglu A, Cigsar B, Aslan G. EMLA and ear surgery: is it possible to achieve full-thickness anesthesia with EMLA? Dermatol Surg 2004;30(3):395-8. PubMed: PM15008868 Controlled clinical trials No literature identified Economic evaluations 18. Pershad J, Steinberg SC, Waters TM. Cost-effectiveness analysis of anesthetic agents during peripheral intravenous cannulation in the pediatric emergency department. Arch Pediatr Adolesc Med 2008;162(10):952-61. PubMed: PM18838648 EMLA versus Ametop and Maxeline 3
Guidelines and recommendations No literature identified PREPARED BY: Michelle Clark, BSc, Research Assistant Charlene Argáez, MLIS, Information Specialist Health Technology Inquiry Service Email: htis@cadth.ca Tel: 1-866-898-8439 EMLA versus Ametop and Maxeline 4
APPENDIX FURTHER INFORMATION: Observational studies 19. Berná-Serna JD, Redondo MV, Durán I, Berná-Mestre JD. Galactography without discomfort using lidocaine/prilocaine anesthetic cream. Acta Radiol 2008;49(1):22-4. PubMed: PM18210310 20. Fetzer S, Holmes S. Relieving the pain of sentinel lymph node biopsy tracer injection. Clin J Oncol Nurs 2008;12(4):668-70. PubMed: PM18676334 21. Thomas AA, Nguyen CT, Dhar NB, Sabanegh ES, Jones JS. Topical anesthesia with EMLA does not decrease pain during vasectomy. J Urol 2008;180(1):271-3. PubMed: PM18499175 22. Cracowski JL, Lorenzo S, Minson CT. Effects of local anaesthesia on subdermal needle insertion pain and subsequent tests of microvascular function in human. Eur J Pharmacol 2007;559(2-3):150-4. PubMed: PM17229423 23. Kim JY, Yoon J, Yoo BS, Lee SH, Choe KH. The effect of a eutectic mixture of local anesthetic cream on wrist pain during transradial coronary procedures. J Invasive Cardiol 2007;19(1):6-9. PubMed: PM17297176 24. Buhse M. Efficacy of EMLA cream to reduce fear and pain associated with interferon beta- 1a injection in patients with multiple sclerosis. J Neurosci Nurs 2006;38(4):222-6. PubMed: PM16924997 25. Tak JH, van Bon WH. Pain- and distress-reducing interventions for venepuncture in children. Child Care Health Dev 2006;32(3):257-68. PubMed: PM16634971 Review articles 26. Stinson J, Yamada J, Dickson A, Lamba J, Stevens B. Review of systematic reviews on acute procedural pain in children in the hospital setting. Pain Res Manag 2008;13(1):51-7. PubMed: PM18301816 27. Ernst DJ. Pain reduction during infant and pediatric phlebotomy. MLO Med Lab Obs 2007;39(7):19-22, 24. PubMed: PM17695967. Full-text available: http://www.mlo-online.com/articles/0707/0707cover_bonus.pdf (accessed 08 May 2009) Note: see Topical Anesthetics, page 20 28. O'Brien L, Taddio A, Lyszkiewicz DA, Koren G. A critical review of the topical local anesthetic amethocaine (Ametop) for pediatric pain. Paediatr Drugs 2005;7(1):41-54. PubMed: PM15777110 29. Rogers TL, Ostrow CL. The use of EMLA cream to decrease venipuncture pain in children. J Pediatr Nurs 2004;19(1):33-9. PubMed: PM14963868 EMLA versus Ametop and Maxeline 5
Additional references 30. Association of topical anesthetics with serious adverse events [important safety information]. Ottawa: Health Canada; 2009. Available: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/emla_ametop_hpccps-eng.pdf (accessed 11 May 2009) EMLA versus Ametop and Maxeline 6