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Greenish-blue discoloration of the brain and heart after treatment with methylene blue

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Abstract

Greenish-blue discoloration of the brain and heart was observed during the autopsy of a 63-year-old woman who had been treated with methylene blue for septic shock following a traffic accident. This “pistachio” or “avatar” discoloration occurs when the colorless metabolite leucomethylene blue is oxidized to methylene blue upon exposure to atmospheric oxygen. Other clinically documented adverse effects of methylene blue include greenish-blue urine and bluish discoloration of the skin and mucosa. In medicine, methylene blue is an inhibitor of nitric oxide synthase and guanylate cyclase with different clinical applications, namely, rapid reversal of circulatory shock that is refractory to fluid administration, inotropic agents, and vasoconstrictors. Postmortem differential diagnosis with putrefaction and hydrogen sulfide poisoning should be made, and forensic pathologists should be aware of methylene blue-related greenish-blue discoloration to avoid unnecessary workup and investigations.

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References

  1. Ginimuge PR, Jyothi SD. Methylene blue: revisited. J Anaesthesiol Clin Pharmacol. 2010;26:517–20.

    PubMed  PubMed Central  Google Scholar 

  2. Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue. Biochem Pharmacol. 1993;45:367–74.

    Article  CAS  Google Scholar 

  3. Snuderl M, Wirth D, Sheth SA, Bourne SK, Kwon CS, Ancukiewicz M, et al. Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors. Brain Pathol. 2013;23:73–81.

    Article  Google Scholar 

  4. Miclescu A, Sharma HS, Martijn C, Wiklund L. Methylene blue protects the cortical blood-brain barrier against ischemia/reperfusion-induced disruptions. Crit Care Med. 2010;38:2199–206.

    Article  CAS  Google Scholar 

  5. Gura T. Hope in Alzheimer’s fight emerges from unexpected places. Nat Med. 2008;14:894.

    Article  CAS  Google Scholar 

  6. Sontag EM, Lotz GP, Agrawal N, Tran A, Aron R, Yang G, et al. Methylene blue modulates huntingtin aggregation intermediates and is protective in Huntington’s disease models. J Neurosci. 2012;32:11109–19.

    Article  CAS  Google Scholar 

  7. Osterwald A, Scholz J, Gehl A, Püschel K. Differential diagnosis: blue gastric mucosa. Post-mortem staining of the gastric mucosa with methylene blue. Arch Kriminol. 2012;230:35–41.

    PubMed  Google Scholar 

  8. Lummus S, Kleinschmidt-Demasters BK. Methylene blue “avatar” brain. J Neuropathol Exp Neurol. 2013;72:263–5.

    Article  Google Scholar 

  9. Prayson RA, Douglas EA. Pistachio green brain discolouration associated with methylene blue use: an autopsy series. Pathology. 2010;42:681–3.

    Article  Google Scholar 

  10. DiSanto AR, Wagner JG. Pharmacokinetics of highly ionized drugs. II. Methylene blue—absorption, metabolism, and excretion in man and dog after oral administration. J Pharm Sci. 1972;61:1086–90.

    Article  CAS  Google Scholar 

  11. Tan CD, Rodriguez ER. Blue dye, green heart. Cardiovasc Pathol. 2010;19:125–6.

    Article  Google Scholar 

  12. Szymanski LJ, Hurth K. “pistachio” and “avatar” green-blue discoloration of the brain. Ac Forensic Pathol. 2016;6:150–2.

    Article  Google Scholar 

  13. Warth A, Goeppert B, Bopp C, Schirmacher P, Flechtenmacher C, Burhenne J. Turquoise to dark green organs at autopsy. Virchows Arch. 2009;454:341–4.

    Article  Google Scholar 

  14. Dumbarton TC, Gorman SK, Minor S, Loubani O, White F, Green R. Local cutaneous necrosis secondary to a prolonged peripheral infusion of methylene blue in vasodilatory shock. Ann Pharmacother. 2012;46:e6.

    Article  Google Scholar 

  15. Gillman PK. Methylene blue implicated in potentially fatal serotonin toxicity. Anaesthesia. 2006;61:1013–4.

    Article  CAS  Google Scholar 

  16. Dinis-Oliveira RJ, Carvalho F, Magalhães T, Santos A. Postmortem changes in carbon monoxide poisoning. Clin Toxicol (Phila). 2010;48:762–3.

    Article  Google Scholar 

  17. Valente-Aguiar MS, Magalhães T, Dinis-Oliveira RJ. Suicide by inhalation of carbon monoxide of car exhausts fumes. Curr Drug Res Rev. 2019;11:145–7.

    Article  Google Scholar 

  18. Lansdown AB. Critical observations on the neurotoxicity of silver. Crit Rev Toxicol. 2007;37:237–50.

    Article  CAS  Google Scholar 

  19. Merchant F, Carpenter T. Blue-gray discoloration of the skin. Am Fam Physician. 2011;84:821–2.

    PubMed  Google Scholar 

  20. Murphy RP, Canavan M. Skin discoloration from amiodarone. N Engl J Med. 2020;382:e5.

    Article  Google Scholar 

  21. Hugar SB, Shulman J, Yanta J, Nine J. Ochronosis presenting as methemoglobinemia. J Forensic Sci. 2019;64:913–6.

    Article  Google Scholar 

  22. Durão C, Pedrosa F, Dinis-Oliveira RJ. A fatal case by a suicide kit containing sodium nitrite ordered on the internet. J Forensic Legal Med. 2020;73:101989.

    Article  Google Scholar 

  23. Piraccini BM, Alessandrini A. Drug-related nail disease. Clin Dermatol. 2013;31:618–26.

    Article  Google Scholar 

  24. Dinis-Oliveira RJ, Carvalho F, Moreira R, Proença JB, Santos A, Duarte JA, et al. Clinical and forensic signs related to chemical burns: a mechanistic approach. Burns. 2015;41:658–79.

    Article  Google Scholar 

  25. Christia-Lotter A, Bartoli C, Piercecchi-Marti MD, Demory D, Pelissier-Alicot AL, Sanvoisin A, et al. Fatal occupational inhalation of hydrogen sulfide. Forensic Sci Int. 2007;169:206–9.

    Article  CAS  Google Scholar 

  26. Sams RN, Carver HW 2nd, Catanese C, Gilson T. Suicide with hydrogen sulfide. Am J Forensic Med Pathol. 2013;34:81–2.

    Article  Google Scholar 

  27. Knight LD, Presnell SE. Death by sewer gas: case report of a double fatality and review of the literature. Am J Forensic Med Pathol. 2005;26:181–5.

    PubMed  Google Scholar 

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Funding

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, and royalties.

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Authors and Affiliations

  1. Portuguese National Institute of Legal Medicine and Forensic Sciences, Lisbon, Portugal

    Carlos Durão & Frederico Pedrosa

  2. Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal

    Carlos Durão

  3. Department of Sciences, IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116, Gandra, Portugal

    Ricardo Jorge Dinis-Oliveira

  4. Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal

    Ricardo Jorge Dinis-Oliveira

  5. UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

    Ricardo Jorge Dinis-Oliveira

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  1. Carlos Durão
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  2. Frederico Pedrosa
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  3. Ricardo Jorge Dinis-Oliveira
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Correspondence to Ricardo Jorge Dinis-Oliveira.

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Durão, C., Pedrosa, F. & Dinis-Oliveira, R.J. Greenish-blue discoloration of the brain and heart after treatment with methylene blue. Forensic Sci Med Pathol 17, 148–151 (2021). https://doi.org/10.1007/s12024-020-00316-2

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  • DOI: https://doi.org/10.1007/s12024-020-00316-2

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