title: Topical anesthetic-induced methemoglobinemia in sheep: a comparison of benzocaine and lidocaine.
abstract: Benzocaine induces methemoglobin (MHb) in several species, whereas lidocaine may increase MHb in cats and human. Elevated MHb (greater than 20%) in sheep after benzocaine exposure was recently recognized. MHb decreases blood oxygen-carrying capacity which can complicate interpretation of experimental data. Sheep are used in research which requires tracheal intubation and blood gas analysis. Since benzocaine and lidocaine are used to provide local anesthesia prior to intubation, we compared MHb production by sheep after exposure to these drugs. A dose-response relationship between benzocaine and MHb was investigated. Eight crossbred Dorset ewes were dosed intranasally with benzocaine for 2 sec or with 40 mg of lidocaine in a randomized crossover design. Sheep with elevated MHb after the 2-sec benzocaine dose were later dosed with benzocaine intranasally for 10 sec. MHb levels were measured periodically on a CO-Oximeter. A quantitative MHb response to an indirect MHb former, p-aminopropiophenone (PAPP), by each sheep was determined 15 min after PAPP (0.6 mg/kg iv). MHb levels remained at baseline (1-2%) after lidocaine exposure in all sheep, as well as in four sheep (nonresponders) after the 2-sec benzocaine dose. Four sheep (responders) demonstrated 16.5-26.4% MHb after the 2-sec benzocaine dose. The responders formed 38.2-50.5% MHb after the 10-sec benzocaine dose. All responders developed high MHb after PAPP, while nonresponders developed slightly elevated MHb after PAPP. An N-hydroxy metabolite of benzocaine is the likely active MHb-forming substance. Benzocaine should be replaced by lidocaine when local anesthesia of the nasal or oropharyngeal region in sheep is required.
authors.affiliation: Department of Respiratory Research, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
authors.forename: A T
authors.initials: AT
authors.lastname: Guertler
authors.forename: M S
authors.initials: MS
authors.lastname: Lagutchik
authors.forename: D G
authors.initials: DG
authors.lastname: Martin
mesh_terms: D000287:Administration, Topical; D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D001566:Benzocaine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D008012:Lidocaine / Q000633:toxicity*; D008706:Methemoglobin / Q000378:metabolism; D008708:Methemoglobinemia / Q000139:chemically induced*; D011427:Propiophenones / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D012756:Sheep
chemical_list: D006454:Hemoglobins; D011427:Propiophenones; D011837:Radiation-Protective Agents; C029564:4-aminopropiophenone; D008706:Methemoglobin; D008012:Lidocaine; D001566:Benzocaine