A Comparison of Amethocaine and Liposomal Lidocaine Cream as a Pain Reliever Before Venipuncture in Children A Randomized Control Trial Naveen Poonai, MD,*Þ Khalid Alawi, MD,* Michael Rieder, MD, PhD,*þ Tim Lynch, MD,*Þ and Rodrick Lim, MD*Þ Objective: Although the use of anesthetic creams before intravenous (IV) insertion has been shown to be both safe and effective in decreasing pain during IV cannulation, the use of any single agent based on efficacy is not yet considered the standard of care in children. We sought to com- pare a commonly used preparation, 4% liposomal lidocaine (Maxilene), with 4% amethocaine (Ametop), a newer agent with reportedly good efficacy and an intrinsic vasodilatory effect. Methods: A total of 60 children aged 5 to 12 years were randomized to receive topically either 4% amethocaine or 4% liposomal lidocaine before IV cannulation. The primary outcome variable was the child’s rating of pain using the Faces Pain Scale Y Revised. Secondary outcomes included success rate on first IV cannulation attempt, cannulation dif- ficulty ratings by the nurses, and adverse skin reactions. Results: We found no statistically significant differences in self- reported scores in the Faces Pain ScaleYRevised with the use of 4% amethocaine versus 4% lidocaine before IV cannulation. There was a trend toward fewer IV cannulation attempts in the 4% amethocaine group. Adverse skin reactions were uncommon, and there were no sta- tistically significant differences between groups. Discussion: This study demonstrates that there is no difference be- tween 4% amethocaine and 4% liposomal lidocaine in reducing pain associated with IV cannulation in children. Amethocaine confers no advantage in improving IV cannulation success rate over lidocaine. Both agents are associated with few local adverse skin reactions. Key Words: amethocaine, lidocaine, topical anesthesia, venipuncture (Pediatr Emer Care 2012;28: 104Y108) P eripheral intravenous (IV) insertion in pediatric patients is often necessary to deliver resuscitative fluids, antibiotics, and other therapies. However, the pain associated with IV in- sertion is a source of great distress to both children and their caregivers. Current guidelines issued by the American Academy of Pediatrics recommend that adequate analgesia be provided for nonurgent painful procedures. 1 Given ample evidence of adverse long-term consequences of untreated pain in childhood such as anxiety, hyperesthesia, and needle phobia, 2 there is a need for the development of interventions to decrease pain among children undergoing painful procedures. Intravenous cannulation is a common procedure performed in the pediatric emergency department (ED) for resuscitative fluids and parental drug therapy. Currently, in such settings, the use of topical anesthesia to lessen the discomfort of IV inser- tion is uncommon. 3 There are several reasons for this. The first commercially available topical agent that provided adequate analgesia was a eutectic mixture of lidocaine-prilocaine cream (EMLA). Although EMLA is the most frequently used agent, it requires a 60-minute application time and causes vasoconstric- tion, often obscuring anatomical landmarks necessary for suc- cessful IV insertion. EMLA penetrates poorly through intact skin, and methemoglobinemia has been reported with signifi- cant application in younger patients. 4 These factors often pre- clude the use of EMLA in most busy EDs. Liposomal lidocaine 4% (Maxilene; Ferndale Laborato- ries, Inc, Ferndale, Mich), formerly known as ELA-Max, is a liposome-encapsulated formulation that has enhanced efficacy and onset of action likely owing to its lipophilicity. 5 Liposomal encapsulation provides a higher concentration of local anesthetic at peripheral sensory nerves than conventional topical anesthe- sia. 6 It has the advantage of a shorter onset of action compared with EMLA, minimal vasoactive properties, and no reports of methemoglobinemia. The latter benefit is thought to be because liposomal lidocaine lacks prilocaine, whose metabolite oxidizes hemoglobin to methemoglobin, potentially causing methemo- globinemia, a rare adverse effect of EMLA. 7 The recommended use of lidocaine is a 30-minute application time without occlu- sion. 7 Lidocaine has been shown to be as effective as EMLA in decreasing pain from venipuncture 7Y9 and superior to placebo in increasing IV success rate, decreasing procedure time, and reducing pain in children undergoing IV cannulation. 10 In a meta-analysis, Eidelman et al 11 found that, according to pooled 100-mm visual analog scale (VAS) pain scores, liposomal lido- caine is favored to have greater analgesic activity over EMLA, although the difference may not be clinically detectable. Amethocaine (4% tetracaine or Ametop) has been shown in several studies to be an effective topical anesthetic agent before venipuncture and IV cannulation. 12,13 It has been used safely in children as young as term neonates. 14 There are conflicting literature reports as to whether it has improved efficacy over EMLA. 12Y18 However, it is reported to have a longer duration of anesthesia. 19 Although amethocaine is considered to have higher systemic toxicity, 20 it has the advantage of an intrinsic vaso- dilatory effect, thereby theoretically facilitating easier IV inser- tion. 20 A recent Cochrane review included 6 pediatric trials that demonstrated amethocaine to have superior efficacy over EMLA in reducing pain. 20 Two studies have demonstrated that amethocaine requires a shorter application time than lidocaine (30 vs 60 minutes), likely owing to former’s lipophilicity. 21,22 The recommended application time is 30 to 45 minutes. 23 Im- proved efficacy is achieved with a longer application time. 21 Reported adverse effects include transient erythema due to its ORIGINAL ARTICLE 104 www.pec-online.com Pediatric Emergency Care & Volume 28, Number 2, February 2012 From the Departments of *Pediatrics, and †Medicine, Division of Emergency Medicine, Schulich School of Medicine, University of Western Ontario; and ‡Departments of Physiology and Pharmacology, Children’s Health Research Institute, Children’s Hospital of Western Ontario, London, Ontario, Canada. Disclosure: The authors declare no conflict of interest. Reprints: Naveen Poonai, MD, Children’s Hospital at London Health Sciences Centre, 800 Commissioners Rd E, London, Ontario, Canada N6A 2V5 (e-mail: poonai@hotmail.com). The authors did not receive funding for this study. Copyright * 2012 by Lippincott Williams & Wilkins ISSN: 0749-5161 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.