Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Systematic Review
  • Published:

Eutectic mixture of local anesthetics and amethocaine as topical anesthetics in pediatrics: a meta-analysis

Pediatric Research volume 96, pages 51–56 (2024)Cite this article

Abstract

Background

Pediatric patients often receive topical anesthesia before skin procedures in the Emergency Department, with EMLA cream and amethocaine gel being common choices. The most effective option remains a subject of debate.

Objective

Our goal was to compare EMLA cream with amethocaine gel in pediatric patients undergoing topical anesthesia, focusing on outcomes: first-attempt cannulation success, child-reported visual analogue scale (VAS) score, parent-reported VAS score, observed pain score, child-reported absence of pain, and child-reported acceptable anesthesia.

Methods

A database search for studies comparing EMLA cream and amethocaine gel in pediatric topical anesthesia was conducted. Two reviewers extracted and cross-verified data, with a third ensuring accuracy. Using R software, a pairwise meta-analysis was performed via the Mantel-Haenszel method. Outcomes were pooled as risk ratios or standard mean differences with 95% confidence intervals using the random-effects model.

Results

Amethocaine gel surpasses EMLA cream in child-reported pain absence and first cannulation success. No significant differences were found in child-reported acceptable anesthesia or observed pain scores. Similarly, child- and parent-reported VAS scores showed no variations between EMLA and amethocaine.

Conclusion

This analysis favors amethocaine gel for pediatric topical anesthesia. Further large randomized trials comparing EMLA cream and amethocaine gel in pediatric patients are warranted.

Impact

Procedural pain is a major concern for pediatric patients, their families, and physicians. Topical anesthesia is routinely given prior to children undergoing skin-related procedures in the Emergency Department. In pediatric patients, topical anesthetics such as eutectic mixture of local anesthetics cream and amethocaine gel have proved to be pioneering in pain reduction, but the most effective method is often disputed. Presently, this is the most comprehensive pooled analysis of trials comparing EMLA cream and amethocaine gel in pediatric patients undergoing topical anesthesia. Amethocaine performed better with regards to child-reported absence of pain and first attempt cannulation success.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Forest plot comparing Eutectic mixture of local anesthetics (EMLA) cream with amethocaine gel for first attempt cannulation success rate.
Fig. 2: Forest plot comparing Eutectic mixture of local anesthetics (EMLA) cream with amethocaine gel for child-reported absence of pain.
Fig. 3: Forest plot comparing Eutectic mixture of local anesthetics (EMLA) cream with amethocaine gel for child-reported visual analogue scale (VAS) score.
Fig. 4: Forest plot comparing Eutectic mixture of local anesthetics (EMLA) cream with amethocaine gel for parent-reported visual analogue scale (VAS) score.
Fig. 5: Forest plot comparing Eutectic mixture of local anesthetics (EMLA) cream with amethocaine gel for observed pain score.
Fig. 6: Forest plot comparing Eutectic mixture of local anesthetics (EMLA) cream with amethocaine gel for child-reported acceptable anesthesia.

Similar content being viewed by others

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

References

  1. Fein, J. A., Zempsky, W. T. & Cravero, J. P. Relief of Pain and Anxiety in Pediatric Patients in Emergency Medical Systems. Pediatrics 130, e1391–e1405 (2012).

    Article  PubMed  Google Scholar 

  2. Hallen, B. & Uppfeldt, A. Does Lidocaine-Prilocaine Cream Permit Painfree Insertion of IV Catheters in Children? Anesthesiology 57, 340–342 (1982).

    Article  CAS  PubMed  Google Scholar 

  3. Hallén, B., Olsson, G. L. & Uppfeldt, A. Pain-free venepuncture. Anaesthesia 39, 969–972 (1984).

    Article  PubMed  Google Scholar 

  4. Maunuksela, E. L. & Korpela, R. Double-blind evaluation of a lignocaine-prilocaine cream (EMLA) in children. Effect on the pain associated with venous cannulation. Br. J. Anaesth. 58, 1242–1245 (1986).

    Article  CAS  PubMed  Google Scholar 

  5. Cooper, C. M., Gerrish, S. P., Hardwick, M. & Kay, R. EMLA cream reduces the pain of venepuncture in children. Eur. J. Anaesthesiol. 4, 441–448 (1987).

    CAS  PubMed  Google Scholar 

  6. Reduction of pain at venous cannulation in children with a eu tec tic mixture of lidocaine and prilocaine (EMLA® cream): comparison with placebo cream and no local premedication - Manner - 1987 - Acta Anaesthesiologica Scandinavica - Wiley Online Library. Accessed April 21, 2023. https://onlinelibrary-wiley-com.ezproxy.med.nyu.edu/doi/abs/10.1111/j.1399-6576.1987.tb02655.x?sid=nlm%3Apubmed.

  7. Assessing pain and analgesia with a lidocaine-prilocaine emulsion in infants and toddlers during venipuncture - ScienceDirect. Accessed April 21, 2023. https://www-sciencedirect-com.ezproxy.med.nyu.edu/science/article/pii/S0022347605822206?via%3Dihub.

  8. Lander, J. et al. Determinants of success and failure of EMLA. Pain 64, 89–97 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Soliman, I. E., Broadman, L. M., Hannallah, R. S. & Mcgill, W. A. Comparison of the Analgesic Effects of EMLA (Eutectic Mixture of Local Anesthetics) to Intradermal Lidocaine Infiltration Prior to Venous Cannulation in Unpremedicated Children. Anesthesiology 68, 804–806 (1988).

    Article  CAS  PubMed  Google Scholar 

  10. Gajraj, N. M., Pennant, J. H. & Watcha, M. F. Eutectic Mixture of Local Anesthetics (EMLA®) Cream. Anesth. Analg. 78, 574 (1994).

    Article  CAS  PubMed  Google Scholar 

  11. Sawyer, J. et al. Heated lidocaine/tetracaine patch (SyneraTM, RapydanTM) compared with lidocaine/prilocaine cream (EMLA®) for topical anaesthesia before vascular access. Br. J. Anaesth. 102, 210–215 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Browne, J., Awad, I., Plant, R., McAdoo, J. & Shorten, G. Topical amethocaine (AmetopTM) is superior to EMLA for intravenous cannulation. Can. J. Anesth. 46, 1014–1018 (1999).

    Article  CAS  PubMed  Google Scholar 

  13. O’Connor, B. & Tomlinson, A. A. Evaluation of the efficacy and safety of amethocaine gel applied topically before venous cannulation in adults. Br. J. Anaesth. 74, 706–708 (1995).

    Article  PubMed  Google Scholar 

  14. Molodecka, J., Stenhouse, C., Jones, J. M. & Tomlinson, A. Comparison of percutaneous anaesthesia for venous cannulation after topical application of either amethocaine or EMLA cream. Br. J. Anaesth. 72, 174–176 (1994).

    Article  CAS  PubMed  Google Scholar 

  15. van Kan, H. J., Egberts, A. C., Rijnvos, W. P., ter Pelkwijk, N. J. & Lenderink, A. W. Tetracaine versus lidocaine-prilocaine for preventing venipuncture-induced pain in children. Am. J. Health-Syst. Pharm. AJHP J. Am. Soc. Health-Syst. Pharm. 54, 388–392 (1997).

    Article  Google Scholar 

  16. Small, J., Wallace, R. G., Millar, R., Woolfson, A. D. & McCafferty, D. F. Pain-free cutting of split skin grafts by application of a percutaneous local anaesthetic cream. Br. J. Plast. Surg. 41, 539–543 (1988).

    Article  CAS  PubMed  Google Scholar 

  17. Woolfson, A. D., McCafferty, D. F. & Boston, V. Clinical experiences with a novel percutaneous amethocaine preparation: prevention of pain due to venepuncture in children. Br. J. Clin. Pharm. 30, 273–279 (1990).

    Article  CAS  Google Scholar 

  18. Doyle, E., Freeman, J., Im, N. T. & Morton, N. S. An evaluation of a new self-adhesive patch preparation of amethocaine for topical anaesthesia prior to venous cannulation in children. Anaesthesia 48, 1050–1052 (1993).

    Article  CAS  PubMed  Google Scholar 

  19. Bjerring, P., Andersen, P. H. & Arendt-Nielsen, L. Vascular Response Of Human Skin After Analgesia With Emla Cream. Br. J. Anaesth. 63, 655–660 (1989).

    Article  CAS  PubMed  Google Scholar 

  20. Meta-analysis of Observational Studies in Epidemiology: A Proposal for Reporting | Public Health | JAMA | JAMA Network. Accessed May 10, 2023. https://jamanetwork.com/journals/jama/fullarticle/192614.

  21. Ottawa Hospital Research Institute. Accessed May 10, 2023. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

  22. Homepage [The metafor Package]. Accessed May 10, 2023. https://www.metafor-project.org/doku.php.

  23. Higgins, J. P. T. et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343, d5928 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mace, S. E. et al. Local and Topical Anesthetics for Pediatric Patients in the Emergency Department. Pediatr. Emerg. Care 36, 593 (2020).

    Article  PubMed  Google Scholar 

  25. Hsu D. Clinical use of topical anesthetics in children. UpToDate. https://www-uptodate-com.ezproxy.med.nyu.edu/contents/clinical-use-of-topical-anesthetics-in-children#.

  26. Pywell, A. & Xyrichis, A. Does topical Amethocaine cream increase first-time successful cannulation in children compared with a eutectic mixture of local anaesthetics (EMLA) cream? A systematic review and meta-analysis of randomised controlled trials. Emerg. Med J. 32, 733–737 (2015).

    Article  PubMed  Google Scholar 

  27. Taddio, A., Gurguis, M. G. Y. & Koren, G. Lidocaine-prilocaine cream versus tetracaine gel for procedural pain in children. Ann. Pharmacother. 36, 687–692 (2002).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Kathryn S. Varghese, Adham Ahmed.

Authors and Affiliations

  1. CUNY School of Medicine, New York, NY, USA

    Kathryn S. Varghese, Adham Ahmed, Dave M. Mathew & Peter J. Fusco

  2. The Feinstein Institutes for Medical Research, New Hyde Park, NY, USA

    Mabel N. Abraham

Authors
  1. Kathryn S. Varghese
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adham Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dave M. Mathew
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter J. Fusco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mabel N. Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Two authors (K.V. & A.A.) reviewed 1438 titles and abstracts after eliminating duplicate citations. Two investigators (A.A. & D.M.) reviewed the full texts of the remaining articles for eligibility, with disagreements being resolved by a third investigator (P.F.). After reviewing the articles, two authors (K.V. and A.A.) independently extracted data from the studies that were included. If there were any disagreements, a third author (M.A.) reviewed them. To ensure accuracy and fairness, two separate authors (A.A. & D.M.) evaluated the quality of each study using the Newcastle Ottawa Scale for observational studies, which rates observational studies quality via asterisk score in three domains: up to four asterisks for patient selection, up to two for comparability of study arms, and up to three asterisks for sufficient outcome follow-up duration/assessment. In cases where there were discrepancies, a third author (P.F.) was consulted and a group discussion was held to reach a consensus. One author (M.A.) oversaw the editing and development of the manuscript.

Corresponding author

Correspondence to Kathryn S. Varghese.

Ethics declarations

Competing interests

The authors declare no competing interests.

Patient Consent

Patient consent was not required due to the structure of the study or type of submission.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Varghese, K.S., Ahmed, A., Mathew, D.M. et al. Eutectic mixture of local anesthetics and amethocaine as topical anesthetics in pediatrics: a meta-analysis. Pediatr Res 96, 51–56 (2024). https://doi.org/10.1038/s41390-024-03113-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-024-03113-7

Search

Advanced search

Quick links