Toxicity of local application of a mixture of anesthetics: Lidocaine and prilocaine cream in an experimental model

Article type: Research Article

Authors: Lemus-Varela, M.L. | López-Salazar, H. | Gómez-Meda, B.C. | Zamora-Perez, A.L. | Sola, A. | Perea-Díaz, J. | Zúñiga-González, G.M.

Affiliations: Neonatal Intensive Care Unit, Tertiary Pediatric Hospital, Western National Medical Center, Mexican Social Security Institute (IMSS), Guadalajara, Jalisco, México | Department of Molecular Biology and Genomics, Institute for Molecular Biology and Gene Therapy, University Center for Health Sciences, University of Guadalajara, Guadalajara, Jalisco, México | Department of Integral Dental Clinics, Dental Research Institute, University Center for Health Sciences, University of Guadalajara, Guadalajara, Jalisco, México | Iberoamerican Society of Neonatology, Masimo, Irvine, CA, USA | Laboratory of Biochemistry II, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco, México | Laboratory of Mutagenesis, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, Jalisco, México

Note: [] Corresponding author: Augusto Sola, Laboratorio de Mutagénesis, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Colonia Independencia, C.P. 44340, Guadalajara, Jalisco, México. Tel.: +52 36683000; ext.: 31937; +52 36189410; Fax: +52 36181756; E-mail: [email protected], [email protected]

Abstract: Objective: To determine genotoxicity, cytotoxicity and methemoglobinemia of a mixture of lidocaine (LD) and prilocaine (PL) (EMLA®) in an experimental model. Study design: Newborn hairless rats were studied in a prospective random and masked design. Groups I–III received topically LD-PL mixtures at 5, 10 or 20% respectively, group IV: petrolatum (negative control); group V: 5-fluorouracil 5% (genotoxicity and cytotoxicity positive control); and group VI: aniline (methemoglobinemia positive control). Blood samples were collected every 24 h from 0–144 hours. Genotoxicity and cytotoxicity were assessed by the micronucleus assay. Changes in micronucleated erythrocytes and micronucleated polychromatic erythrocytes evaluated genotoxicity, and polychromatic erythrocytes in 1,000 total erythrocytes were used to determine cytotoxicity. Methemoglobin values were quantified by spectrophotometry. Results: The micronucleated erythrocytes number increased proportionally to the LD-PL mixture dose (p = 0.04), from 60% in group II until 90% in group III in relation to their basal value; however, no cytotoxicity effect was observed. Methemoglobin values increased in groups II, III, V and VI from the second day (p < 0.05). Conclusion: Topical administration of LD-PL mixture (10% and 20%) to neonatal rats show genotoxic effects and produces methemoglobinemia. Clinical implications of these findings require urgent further investigation before continuing to use LD-PL mixture routinely.

Keywords: Local anesthetics, neonatal, genotoxicity, pain

DOI: 10.3233/NPM-2011-51011

Journal: Journal of Neonatal-Perinatal Medicine, vol. 4, no. 4, pp. 333-339, 2011