Methylene Blue is a medication that was initially developed in the late 1800s and was the first fully synthetic drug ever used to treat malaria. It was also one of the first medications used in the treatment of psychosis, which ultimately led to the development of phenothiazine antipsychotic drugs such as compazine and thorazine. Since then it has been shown to have quite a few uses, and yes…as the name suggests it is blue in color.

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Uses for methylene blue

Its standard, FDA-approved use is to treat methemoglobinemia, a rare blood disorder that affects how RBCs deliver oxygen to the tissues. In methemoglobinemia, the ferrous component of the heme molecule has oxidized to what is called a ferric state. Methylene blue reacts within the red blood cell to essentially reverse that oxidation and convert the ferric ion back to its ferrous state so the heme molecule can carry and deliver oxygen.

But there are other uses, too. Though not FDA-approved, you could still see them utilized or discussed in the clinical setting: 

Methylene blue can be used to evaluate the presence of a leak after surgeries that affect the bladder and adjacent structures such as the prostate or uterus. A Foley catheter is placed and the blue dye is instilled into the bladder through the catheter. The catheter is clamped and the dye is allowed to dwell for a short period of time. If there are any leaks in the bladder, the surgeon can easily see them because of the distinctive blue color of the dye which shows in the abdominal cavity. Note that a patient who had methylene blue instilled in this way will have blue colored urine in the immediate post-op period. 

A study published in the journal Critical Care in March 2023 showed that in septic shock, the use of methylene blue reduced vasopressor use and length of stay. Note that methylene blue is not part of the Surviving Sepsis guidelines for recommended treatments, but it will be interesting to see if more research is done in this area.

Another current use of methylene blue is to treat neurotoxicity and encephalopathy caused by ifosfamide, a medication used in the treatment of cancer. It works by preventing the formation of neurotoxic metabolites when this chemotherapeutic agent is used.

Another cancer related use is in patients undergoing a mastectomy or lumpectomy with sentinel node biopsy. The blue dye helps map out and identify lymph nodes showing signs of malignancy.

Methylene blue may also be used to treat vasoplegic syndrome, which is a type of distributive shock that occurs during coronary artery bypass graft surgery. If the patient doesn’t respond adequately to a traditional vasopressor, methylene blue has shown to be effective in increasing systemic vascular resistance. 

The medication may be used to prevent the pain associated with propofol administration when administered IV approximately 45 seconds before the propofol is injected.

And lastly, it is also shown to be effective in treating malaria in areas that have developed resistance to the more traditional medications, chloroquine and pyrimethamine-sulfadoxine.

Adverse effects of methylene blue

However methylene blue is used, it can cause adverse effects. The most common is a bluish-green discoloration of the urine and it can contribute to serotonin syndrome if administered in patients also taking other serotonergic drugs such as SSRIs, MAOIs, and TCAs. And, though rare, anaphylaxis can also occur. Toxicity can occur at high doses and cause cardiac arrhythmias, decreased cardiac output, decreased renal and mesenteric blood flow, increased pulmonary vascular resistance and decreased gas exchange. There is no antidote for methylene blue toxicity and care is supportive. 

So, if you’ve ever heard of methylene blue and thought, “What is that?”…well now you know!

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