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


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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

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

    PubMed  PubMed Central  Google Scholar 

  2. 2.

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

    PubMed  CAS  Article  Google Scholar 

  3. 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.

    PubMed  Article  Google Scholar 

  4. 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.

    PubMed  CAS  Article  Google Scholar 

  5. 5.

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

    PubMed  CAS  Article  Google Scholar 

  6. 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.

    PubMed  PubMed Central  CAS  Article  Google Scholar 

  7. 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. 8.

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

    PubMed  Article  Google Scholar 

  9. 9.

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

    PubMed  Article  Google Scholar 

  10. 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.

    PubMed  CAS  Article  Google Scholar 

  11. 11.

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

    PubMed  Article  Google Scholar 

  12. 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. 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.

    PubMed  Article  Google Scholar 

  14. 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.

    PubMed  Article  Google Scholar 

  15. 15.

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

    PubMed  CAS  Article  Google Scholar 

  16. 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. 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.

    PubMed  Article  Google Scholar 

  18. 18.

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

    PubMed  CAS  Article  Google Scholar 

  19. 19.

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

    PubMed  Google Scholar 

  20. 20.

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

    PubMed  Article  Google Scholar 

  21. 21.

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

    PubMed  Article  Google Scholar 

  22. 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. 23.

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

    PubMed  Article  Google Scholar 

  24. 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.

    PubMed  Article  Google Scholar 

  25. 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.

    PubMed  CAS  Article  Google Scholar 

  26. 26.

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

    PubMed  Article  Google Scholar 

  27. 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 

Download references


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.

Author information



Corresponding author

Correspondence to Ricardo Jorge Dinis-Oliveira.

Ethics declarations

Conflict of interests

The authors declare that they have no conflict of interest. No writing assistance was used in the production of this manuscript.

Ethical approval

All procedures were performed according to the ethical and legal standards of the institution.

Informed consent

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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 (2020).

Download citation


  • Methylene blue
  • Greenish-blue discoloration
  • Heart
  • Brain
  • Forensic autopsy