April 22, 2022: How do you treat refractory methemoglobinermia? Can methylene blue cause Serotonin Syndrome?


(Last abstract from the American College of Medical Toxicology meeting).


This was a case discussion regarding refractory methemoglobinemia (Methb). I learned a lot from it and thought you might be interested.

Sodium Nitrite exposures have markedly increased over the last two years. It is readily available on the internet as a white crystalline material resembling table salt that easily dissolves in water. Nitrites oxidize the iron in hemoglobin from Fe+2 to Fe+3 yielding Methb which reduces the oxygen carrying capacity of the blood.

A 29 year-old male injected sodium nitrite. He arrived in the ED with a Methb concentration of 73.3% (this concentration is associated with a >70% mortality) and a lactate of 4. He was cyanotic, in shock and rapidly intubated.

The antidote, Methylene Blue(MB) (1 mg/kg), was administered twice (usual dose is 1-2 mg/kg) as well as vasopressors. At high doses, MB will induce a hemolytic anemia. 

The patient developed clonus and hyperreflexia to touch after the second administration of MB. There was concern that MB had caused a serotonin syndrome (SS) *although cerebral hypoxia has many clinical signs consistent with SS. (MB is a MAO inhibitor, which like SSRI and SNRI block the extracellular clearance of serotonin).

Exchange transfusion and ECMO were considered. HD catheter placement failed so a thoracotomy was performed in the ED and a cannulae was placed in the right atrium and aorta. BC exchange was performed by exsanguination and repletion of 3 units of RBC. Subsequently 4 more units were administered via exchange. Following ECMO initiation, vasopressors were able to be weaned. Methemoglobinemia resolved in 19 hours. The patient was discharged neurologically intact.

*Comment: Although toxicologists think of MB as an antidote for methemoglobinemia, it is also used in cardiothoracic surgeries to treat vasoplegia as MB reverses refractory hypotension through nitric oxide-mediating pathways. There are case report from the cardiac/thoracic literature of SS following the administration of MB. *However, these patients are also receiving a number of other drugs. If MB is administered to a patient already receiving a serotonergic drug (such as an SSRI) the risk is certainly higher of causing a SS.  

This is clearly not a case you deal with every day. 


Call the Poison Center when caring for patients with unusual toxicologic presentations. 






Question prepared by Donna Seger, MD

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Department of Medicine, VUMC

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