The Blue Coma: The Role of Methylene Blue in Unexplained Coma After Cardiac Surgery: A Case Series

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
JournalJournal of Cardiothoracic and Vascular Anesthesia
Publication statusAccepted/In press - 2015


  • 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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