Original Article
The Blue Coma: The Role of Methylene Blue in Unexplained Coma After Cardiac Surgery

https://doi.org/10.1053/j.jvca.2015.09.011Get rights and content

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.

Section snippets

Materials and Methods

Three women undergoing chronic SSRI therapy with paroxetine, citalopram, and sertraline, respectively, underwent cardiac surgery with cardiopulmonary bypass. Anesthesia was induced with propofol, rocuronium, and fentanyl. Anesthesia was maintained with a combination of propofol, rocuronium, sevoflurane, and high doses of fentanyl. Details on the patients are reported in Table 1.

Serotonin toxicity was diagnosed retrospectively in all 3 patients using the Hunter criteria (reported in Table 2).13

Results

All 3 patients (described in Table 3) developed vasoplegic syndrome while sedated with propofol in the intensive care unit (ICU) after surgery and received a continuous infusion of norepinephrine and/or epinephrine. Methylene blue (100 mg over 20 minutes) was administered to reduce the dose of vasoconstrictors and was repeated after a few hours in all patients.

All 3 patients developed coma, for which they underwent neurologic investigation. Their brain computed tomography scans were negative

Discussion

The importance of this case series is that the authors have described, for the first time, 3 cases of unexplained postoperative coma caused by rarely diagnosed, but possibly common, life-threatening serotonin toxicity. The common features among the patients were the regular use of SSRI medication, the administration of methylene blue, and neurologic signs and symptoms.

Conclusions

The off-label use of methylene blue in vasoplegic cardiac surgery patients undergoing chronic SSRI therapy or in those taking other serotonergic drugs must be avoided. In the setting of a postoperative “blue coma,” SSRI therapy should not be restarted and serotonergic drugs should not be added.1, 27

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      Citation Excerpt :

      One magic bullet in this scenario is methylene blue.13-15 This agent decreases endothelial production of nitric oxide to enhance systemic vascular tone and thereafter to restore organ perfusion.16-19 Methylene blue can be dramatically effective and has been discussed extensively in the journal.11-17

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    E.A.M and D.W. contributed equally to this work.

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