Life-threatening toxic methemoglobinemia induced by prilocaine

Kreutz, Randall W.; Kinni, Mark E.

doi:10.1016/0030-4220(83)90092-0

Cited by 40 publications

(13 citation statements)

References 4 publications

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“…For example, when 288 mg of prilocaine was used in a 19-year-old white woman, her Met-Hb levels were observed to be 37.8% of total hemoglobin levels approximately 4 hours after injection (Kreutz and Kinni, 1983). Fetuses and infants under 6 months of age seem to be more susceptible.…”

Section: Introductionmentioning

confidence: 99%

Prilocaine- and Lidocaine-Induced Methemoglobinemia Is Caused by Human Carboxylesterase-, CYP2E1-, and CYP3A4-Mediated Metabolic Activation

et al. 2013

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Prilocaine and lidocaine are classified as amide-type local anesthetics for which serious adverse effects include methemoglobinemia. Although the hydrolyzed metabolites of prilocaine (o-toluidine) and lidocaine (2,6-xylidine) have been suspected to induce methemoglobinemia, the metabolic enzymes that are involved remain uncharacterized. In the present study, we aimed to identify the human enzymes that are responsible for prilocaine-and lidocaine-induced methemoglobinemia. Our experiments revealed that prilocaine was hydrolyzed by recombinant human carboxylesterase (CES) 1A and CES2, whereas lidocaine was hydrolyzed by only human CES1A. When the parent compounds (prilocaine and lidocaine) were incubated with human liver microsomes (HLM), methemoglobin (MetHb) formation was lower than when the hydrolyzed metabolites were incubated with HLM. In addition, Met-Hb formation when prilocaine and o-toluidine were incubated with HLM was higher than that when lidocaine and 2,6-xylidine were incubated with HLM. Incubation with diisopropyl fluorophosphate and bis-(4-nitrophenyl) phosphate, which are general inhibitors of CES, significantly decreased Met-Hb formation when prilocaine and lidocaine were incubated with HLM. An anti-CYP3A4 antibody further decreased the residual formation of Met-Hb. Met-Hb formation after the incubation of o-toluidine and 2,6-xylidine with HLM was only markedly decreased by incubation with an anti-CYP2E1 antibody. o-Toluidine and 2,6-xylidine were further metabolized by CYP2E1 to 4-and 6-hydroxy-o-toluidine and 4-hydroxy-2,6-xylidine, respectively, and these metabolites were shown to more efficiently induce Met-Hb formation than the parent compounds. Collectively, we found that the metabolites produced by human CES-, CYP2E1-, and CYP3A4-mediated metabolism were involved in prilocaine-and lidocaineinduced methemoglobinemia.

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Section: Introductionmentioning

confidence: 99%

Prilocaine- and Lidocaine-Induced Methemoglobinemia Is Caused by Human Carboxylesterase-, CYP2E1-, and CYP3A4-Mediated Metabolic Activation

et al. 2013

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“…Lokal anestezik ilaçlardan klinikte yaygın kullanım alanına sahip olan prilokain kolaylıkla methemoglobinemiye neden olabilmektedir 8 . Prilokain otoluidin metaboliti ile methemoglobinemiye neden olmaktadır 9 . Tedavi edici dozlarda (1-2mg/kg) kullanılan prilokain genelde siyanoza yol açmayacak kadar düşük düzeylerde methemoglobinemiye neden olur, doz arttıkça methemoglobinemi riski de artar 10 .…”

Section: Discussionunclassified

Intravenous Ascorbic Acid and Oral Methylene Blue Treatment in Prilocaine-induced Methemoglobinemia: A Case Report

Elmas¹,

Koçer²,

Özdemir³

2016

Sakarya Med J

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Methemoglobinemi; kanda methemoglobin (iki değerli ferröz hemoglobin yerine üç değerli ferrik demir içeren türü) düzeyinin normalden daha yüksek olmasına bağlı gelişen klinik tablodur. Methemoglobinemi konjenital/genetik ve edinsel nedenlere bağlı gelişebilir. Konjenital methemoglobinemiler, yapısal hemoglobin bozuklukları ve methemoglobin redüksiyon enzimlerindeki eksikliklere bağlı olarak gelişir. Edinsel methemoglobinemiler ise oksidan özelliğe sahip ilaç, kimyasal madde ve gıdalara maruziyet yanında süt çocukluğu döneminde görülen bazı hastalıklara bağlı gelişebilir. Prilokain içeren lokal anestezik kullanılarak sünnet yapıldıktan sonra solunum sıkıntısı ve siyanozu başlayan 3.5 aylık erkek bebek hastanemize yatırıldı. Kan methemoglobin düzeyi %31.5 bulundu ve methemoglobinemi tanısı konuldu. İntravenöz askorbik asid ile birlikte oral metilen mavisi uygulanan hastanın 3. saatinde klinik bulgularında düzelme izlendi ve 12. saatinde methemoglobin düzeyi normal olarak bulundu. Methemoglobinemi vakalarında intravenöz askorbik asid ile birlikte oral metilen mavisi de tedavi seçenekleri arasında değerlendirilebilir. Abstract Methemoglobinemia is a disorder characterized by the presence of a higher than normal level of methemoglobin (is a form of hemoglobin that contains ferric

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“…Bu yaş grubunda bu komplikasyon akılda tutulmalıdır. Yaşamın ilk üç ayında methemoglobin redük-taz aktivitesi düşük olduğundan toksik maddelere bağlı methemoglobinemi riski artar [10][11][12]. Methemoglobin düzeyi %20'den düşükse sıklıkla neden olan ilacın kesilmesi tedavi için yeterli iken %40'tan yüksekse intravenöz olarak 1-2 mg/kg %1'lik metilen mavisi ve askorbik asit uygulanabilir.…”

Section: Discussionunclassified

Comparison of the Use of Prilocaine and Lidocaine Gel During the Cystoscopy

Geçit¹

2012

Ann Clin Anal Med

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ÖzetAmaç: Bu çalışmada üroloji pratiğinde çok sık olarak kullanılan sistoskopi sı-rasında hastanın ağrısını azaltmak ve işlemin konforunu arttırmak için üret-ra içine prilokain ile lidokain jel instilasyonu arasındaki etkinlik farkı araştırıl- Anahtar KelimelerPrilokain Jel; Lidokain Jel; Sistoskopi Abstract Aim: In this study, the difference of the activity between the prilocaine and lidocaine gel instillation into the urethra was investigated in order to reduce the patient's pain and to increase the comfort of the procedure during the cystoscopy which was commonly used in the practice of urology. Material and Method: 134 patients who were decided to be performed the cystoscopy for various reasons between the years of 2008 and 2011 were randomly divided into two groups2% of lidocaine gel to the first group and 20 cc of 2% of prilocaine to the second group were given from the urethral route 5 minutes before the cystoscopy. Visual Analog Scale (VAS) was used in the assessment of the pain levels of the patients during the cystoscopy. The discomforts of the patients during the process were assessed with the question like "would you have the process done again if necessary". In patients in both groups, the levels of the pain and the hemodynamic changes were recorded at the beginning of the procedure, during the procedure and after the procedure. Results: There was no significant difference in terms of the hemodynamic changes between the two groups. If it is necessary to repeat the cystoscopy, while the average score of VAS for prilocaine was 3.8 and the rate of the performance was 80%, these values for lidocaine were about 5 and 70% respectively. Cystoscopy was viewed as more comfortable both for the doctor and for the patient in the group used prilocaine. It was understood that the majority of the patients would be able to perform the cystoscopy again if necessary. Discussion: Reducing the sense of the pain in the urethra, urethral instillation of the prilocaine has provided less pain during the rigid cystoscopy especially for the outpatients and has prevented the formation of the bad memories about the process. Prilocaine has drawn its score of VAS down 1.2 points compared to lidocaine and has increased the rate of doing cystoscopy again of patient by 10% when required.

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Life-threatening toxic methemoglobinemia induced by prilocaine

Cited by 40 publications

References 4 publications

Prilocaine- and Lidocaine-Induced Methemoglobinemia Is Caused by Human Carboxylesterase-, CYP2E1-, and CYP3A4-Mediated Metabolic Activation

Prilocaine- and Lidocaine-Induced Methemoglobinemia Is Caused by Human Carboxylesterase-, CYP2E1-, and CYP3A4-Mediated Metabolic Activation

Intravenous Ascorbic Acid and Oral Methylene Blue Treatment in Prilocaine-induced Methemoglobinemia: A Case Report

Comparison of the Use of Prilocaine and Lidocaine Gel During the Cystoscopy

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