Methylene blue implicated in potentially fatal serotonin toxicity
2006; Wiley; Volume: 61; Issue: 10 Linguagem: Inglês
10.1111/j.1365-2044.2006.04808.x
ISSN1365-2044
Autores Tópico(s)Anesthesia and Sedative Agents
ResumoAnaesthesiaVolume 61, Issue 10 p. 1013-1014 Free Access Methylene blue implicated in potentially fatal serotonin toxicity P. K. Gillman, P. K. Gillman Bucasia Queensland 4750, Australia E-mail: kg@matilda.net.auSearch for more papers by this author P. K. Gillman, P. K. Gillman Bucasia Queensland 4750, Australia E-mail: kg@matilda.net.auSearch for more papers by this author First published: 11 September 2006 https://doi.org/10.1111/j.1365-2044.2006.04808.xCitations: 63 A response to a previously published article or letter can be submitted to the Online Correspondence section at http://www.anaesthesiacorrespondence.com. A selection of this correspondence is published several times a year in Anaesthesia. All correspondence intended for publication in Anaesthesia should be addressed to Dr David Bogod, Editor-in-Chief, and submitted as an e-mail attachment to anaesthesia@nottingham.ac.uk. For multi-author letters, a covering letter signed by all authors must be submitted either by post, fax (44 (0) 115 962 7670) or by e-mail as a scanned document before correspondence can be published. Alternatively, letters may be submitted typewritten on one side of paper, double spaced with wide margins to Anaesthesia, 1st Floor, Maternity Unit, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK. All paper submissions must include a signed covering letter, a disc or CD-ROM with a Word for Windows or .rtf version of the letter and an email address for the corresponding author. Copy should be prepared in the usual style of the Correspondence section. Authors must follow the advice about references and other matters contained in the Author Guidelines at http://www.blackwellpublishing.com/journals/ana/submiss.htm. Correspondence presented in any other style or format will be returned to the author for revision. AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat This journal recently published an interesting case report on neurological sequelae following use of methylene blue during a parathyroidectomy [1]. Subsequently, there has been a similar and equally intriguing report by Rosenbaum [2], who suggested that the symptoms and signs observed might be serotonin toxicity resulting from an interaction between methylene blue and a serotonin re-uptake inhibitor (SRI). Another case of possible serotonin toxicity with methylene blue and an SRI (citalopram) has now been reported [3]. In all instances the patient was receiving an SRI prior to the procedure and exhibited typical signs of serotonin toxicity. SRIs do not induce serotonin toxicity of such severe degree by themselves, even in overdose, as discussed in my recent editorial [4]. Severe degrees of serotonin toxicity involving therapeutic doses of SRIs occur only following combination with monoamine oxidase inhibitors (MAOIs) [5], and not with other serotonergic drugs (with other mechanisms of action). These two cases suggest that methylene blue has clinically significant potency as an MAOI. A search of the existing standard pharmacological texts reveals no information or suggestion that methylene blue is an MAOI, but other recent literature does support an MAOI effect of uncertain potency [6-8]. Further corroboration and quantification of the potency of methylene blue is in progress to establish the degree of effect in the doses used in surgery. SRIs have been in use for more than three decades (clomipramine has been in use since 1968, well before fluoxetine (1988)). It would be astonishing if substantial numbers of patients taking them had not been operated on with procedures that utilise an infusion of methylene blue. If it was a potent MAOI there would probably be a number of reports of life-threatening toxicity, and there are not. That leads to the supposition that it is a relatively weak MAOI, and the risk of serotonin toxicity is low. This is similar to the situation with linezolid, the antibiotic with MAOI effects [9, 10]. It is perhaps only when large doses are infused, or in susceptible individuals (for example cytochrome P450 2D6 poor metabolisers), or as a result of pharmacokinetic drug–drug interactions (raising methylene blue levels) that an interaction might occur. It is probably significant that in one case the SRI concerned, fluoxetine, is a potent inhibitor of several cytochrome P450 subtypes. It may be that moderate and significant serotonin toxicity symptoms have occurred, the relevance of which has not been appreciated (such as with pethidine and linezolid) [11]. It would be most interesting to know if, in retrospect, experienced practitioners recognise that they have indeed seen serotonergic symptoms (particularly clonus, hyperreflexia, pyrexia and altered mental state) in such cases. Please let me know at the e-mail address below. Until the evidence is clearer, adherence to the lower dose range (< 5 mg.kg−1) of methylene blue and ceasing to use the SRIs, especially paroxetine and fluoxetine, and other potent cytochrome P450 2D6 inhibitors, is probably sufficient precaution. References 1 Martindale SJ, Stedeford JC. Neurological sequelae following methylene blue injection for parathyroidectomy. Anaesthesia 2003; 58: 1041– 2. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 2 Rosenbaum H. http://wwwmhausorg/indexcfm/fuseaction/ContentDisplay/PagePK/Jan06CaseOfTheMonth13cfm[accessed 1 June 2006]. Google Scholar 3 Mathew S, Linhartova L, Raghuraman G. Hyperpyrexia and prolonged postoperative disorientation following methylene blue infusion during parathyroidectomy. Anaesthesia 2006; 61: 580– 3. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 4 Gillman PK. Extracting value from case reports: lessons from serotonin toxicity (serotonin syndrome). Anaesthesia 2006; 61: 419– 22. Wiley Online LibraryPubMedWeb of Science®Google Scholar 5 Gillman PK. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biological Psychiatry 2006; 59: 1046– 51. CrossrefCASPubMedWeb of Science®Google Scholar 6 Wegener G, Volke V, Rosenberg R. Endogenous nitric oxide decreases hippocampal levels of serotonin and dopamine in vivo. British Journal of Pharmacology 2000; 130: 575– 80. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 7 Oxenkrug GF, Requintina PJ. Melatonin and jet lag syndrome. Experimental model and clinical implications. CNS Spectrums 2003; 8: 139– 48. CrossrefPubMedWeb of Science®Google Scholar 8 Lerch S, Kupfer A, Idle JR, Lauterburg BH. Cerebral formation in situ of S-carboxymethylcysteine after ifosfamide administration to mice: a further clue to the mechanism of ifosfamide encephalopathy. Toxicology Letters 2006; 161: 188– 94. CrossrefCASPubMedWeb of Science®Google Scholar 9 Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: a review of postmarketing data. Clinical Infectious Diseases 2006; 42: 1578– 83. CrossrefCASPubMedWeb of Science®Google Scholar 10 Gillman PK. Linezolid and serotonin toxicity. Clinical Infectious Diseases 2003; 37: 1274– 5. CrossrefPubMedWeb of Science®Google Scholar 11 Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia 2005; 95: 434– 41. CrossrefCASPubMedWeb of Science®Google Scholar Citing Literature Volume61, Issue10October 2006Pages 1013-1014 ReferencesRelatedInformation
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