A Kortgen1, U Janneck, A Vetsch, M Bauer. 1. Klinik für Anaesthesiologie und Intensivmedizin, Universitätskliniken des Saarlandes, Homburg/Saar. aiakor@uniklinik-saarland.de
Abstract
OBJECTIVE: This study investigated in vivo and in vitro kinetics of o-toluidine-induced methemoglobinemia and the influence of ascorbic acid on resulting methemoglobin concentrations. o-Toluidine is a metabolite of prilocaline and ascorbic acid is recommended for treatment of methemoglobinemia as an alternative to methylene blue. METHODS: We measured the formation of methemoglobin in vitro in a whole blood culture system of 8 healthy individuals 30, 60, and 360 min after the addition of different concentrations of o-toluidine (0.5, 5, 50 micrograms/ml) with and without addition ofascorbic acid (0.5 and 5 mg/ml). In a prospective randomized clinical study, a total of 72 patients of ASA risk I-III were investigated. The 3 groups of 24 patients received either an axillary, an infraclavicular vertical brachial plexus, or a combined femoral and ischiadic blockade. In each plexus anesthesia group, 12 patients were given 2,000 mg ascorbic acid intravenously before applying the local anesthetics. For surgery of the upper limb the patients received 40 ml 1% prilocaine and 10 ml 0.5% bupivacaine, for surgery of the lower limb they received 60 ml 1% prilocaine and 0.25 mg adrenaline. Blood samples for measurement of methemoglobin concentrations were taken before and 30, 60, 120, 180 and 360 min after the injection of the regional anesthetic. A p < 0.05 was considered to be significant. RESULTS: There was a dose-dependent increase of methemoglobin due to addition of o-toluidine after 360 min in vitro. The application of 0.5 mg/ml ascorbic acid to the whole blood samples with 0.5 and 5 micrograms/ml o-toluidine resulted in a further increase of methemoglobin formation whereas there was no difference in the samples with 50 micrograms/ml. The higher concentration of 5 mg/ml ascorbic acid attenuated the methemoglobin formation only with 50 micrograms/ml o-toluidine. No effect was observed with lower concentrations of o-toluidine. In the in vivo study plexus anesthesia with prilocaine resulted in an increase of the methemoglobin concentration with a maximum after 120-180 min. The highest measured methemoglobin concentration found was 11.3%. The methemoglobin concentration already showed a decrease 360 min after the application of the regional anesthetic 2,000 mg ascorbic acid given intravenously before plexus anesthesia was not able to influence the resulting methemoglobin concentrations. CONCLUSIONS: In vitro high concentrations of ascorbic acid are able to reduce the resulting methemoglobin concentration 360 min after addition of 50 micrograms/ml o-toluidine. The application of 2,000 mg ascorbic acid i.v. before plexus anesthesia with prilocaine does not reduce the concentration of methemoglobin.
RCT Entities:
OBJECTIVE: This study investigated in vivo and in vitro kinetics of o-toluidine-induced methemoglobinemia and the influence of ascorbic acid on resulting methemoglobin concentrations. o-Toluidine is a metabolite of prilocaline and ascorbic acid is recommended for treatment of methemoglobinemia as an alternative to methylene blue. METHODS: We measured the formation of methemoglobin in vitro in a whole blood culture system of 8 healthy individuals 30, 60, and 360 min after the addition of different concentrations of o-toluidine (0.5, 5, 50 micrograms/ml) with and without addition of ascorbic acid (0.5 and 5 mg/ml). In a prospective randomized clinical study, a total of 72 patients of ASA risk I-III were investigated. The 3 groups of 24 patients received either an axillary, an infraclavicular vertical brachial plexus, or a combined femoral and ischiadic blockade. In each plexus anesthesia group, 12 patients were given 2,000 mg ascorbic acid intravenously before applying the local anesthetics. For surgery of the upper limb the patients received 40 ml 1% prilocaine and 10 ml 0.5% bupivacaine, for surgery of the lower limb they received 60 ml 1% prilocaine and 0.25 mg adrenaline. Blood samples for measurement of methemoglobin concentrations were taken before and 30, 60, 120, 180 and 360 min after the injection of the regional anesthetic. A p < 0.05 was considered to be significant. RESULTS: There was a dose-dependent increase of methemoglobin due to addition of o-toluidine after 360 min in vitro. The application of 0.5 mg/ml ascorbic acid to the whole blood samples with 0.5 and 5 micrograms/ml o-toluidine resulted in a further increase of methemoglobin formation whereas there was no difference in the samples with 50 micrograms/ml. The higher concentration of 5 mg/ml ascorbic acid attenuated the methemoglobin formation only with 50 micrograms/ml o-toluidine. No effect was observed with lower concentrations of o-toluidine. In the in vivo study plexus anesthesia with prilocaine resulted in an increase of the methemoglobin concentration with a maximum after 120-180 min. The highest measured methemoglobin concentration found was 11.3%. The methemoglobin concentration already showed a decrease 360 min after the application of the regional anesthetic 2,000 mg ascorbic acid given intravenously before plexus anesthesia was not able to influence the resulting methemoglobin concentrations. CONCLUSIONS: In vitro high concentrations of ascorbic acid are able to reduce the resulting methemoglobin concentration 360 min after addition of 50 micrograms/ml o-toluidine. The application of 2,000 mg ascorbic acid i.v. before plexus anesthesia with prilocaine does not reduce the concentration of methemoglobin.