The blue coma: The role of methylene blue in unexplained coma after cardiac surgery

Enrico Antonio Martino, Dario Winterton, Pasquale Nardelli, Laura Pasin, Maria Grazia Calabrò, Tiziana Bove, Giovanna Fanelli, Alberto Zangrillo, Giovanni Landoni

Research output: Contribution to journalArticlepeer-review


Objectives Methylene blue commonly is used as a dye or an antidote, but also can be used off label as a vasopressor. Serotonin toxicity is a potentially lethal and often misdiagnosed condition that can result from drug interaction. Mild serotonin toxicity previously was reported in settings in which methylene blue was used as a dye. The authors report 3 cases of life-threatening serotonin toxicity in patients undergoing chronic selective serotonin reuptake inhibitor (SSRI) therapy who also underwent cardiac surgery and received methylene blue to treat vasoplegic syndrome. Design An observational study. Setting A cardiothoracic intensive care unit (ICU) in a teaching hospital. Participants Three patients who received methylene blue after cardiac surgery, later discovered to be undergoing chronic SSRI therapy. Interventions None. Measurements and Main Results All 3 patients received high doses of fentanyl during general anesthesia. They all developed vasoplegic syndrome and consequently were given methylene blue in the ICU. All 3 patients developed serotonin toxicity, including coma, after this administration and diagnostic tests were negative for acute intracranial pathology. Coma lasted between 1 and 5 days. Two patients were discharged from the ICU shortly after awakening, whereas the third patient experienced a complicated postoperative course for concomitant refractory low-cardiac-output syndrome. Conclusions Patients undergoing chronic SSRI therapy should not be administered methylene blue to treat vasoplegic syndrome.
Original languageEnglish
Pages (from-to)423 - 427
Number of pages5
JournalJournal of Cardiothoracic and Vascular Anesthesia
Issue number2
Publication statusPublished - Apr 1 2016


  • Anesthesia
  • Coma
  • Intensive care
  • Methylene blue
  • Selective serotonin reuptake inhibitors
  • Serotonin syndrome
  • Thoracic surgery
  • Vasoplegic syndrome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine


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