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Methylene Blue Myths: Science, Hype, and Unknowns

Methylene blue has been hailed to improve cognitive function, act as an anti-ageing agent, and even a cancer fighter. But is it really the wonder compound it’s made out to be, or just another biohacking fad lacking evidence? In this article, we explore what the science actually says, highlight common misconceptions, and examine the unanswered questions around methylene blue and human health. Methylene blue has a history of diverse applications spanning 120 years. It is both a dye for bodily tissue and a form of medical treatment.

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Featured

 Methylene Blue: A Therapeutic Trifecta?

Methylene blue (MB) has the unique potential to be a therapeutic trifecta in advanced cardiovascular life support (ACLS). Trifecta, a horse racing betting term coined in the 1970s, describes a wager to select the top three finishers in the correct order. The available evidence suggests that MB could potentially bring a trifecta of critical therapeutic benefits to cardiac arrest patients.

 The Right Chemistry: Methylene blue shakes up the medical world

Our story takes us to the Victorian era, basically the second half of the 19th century, one of the most colourful in history. Literally.

Articles of Interest

Methylene Blue IV

In 1891, German physician and Noble Prize recipient Paul Ehrlich pioneered the use of Methylene Blue in the treatment of malaria. Ehrlich discovered that MB would quickly concentrate in the brain and selectively target diseased tissues in the body. Methylene Blue is called “Magic Bullet” for this unique action.

Are Methylene Blue Infusions Safe?

Methylene blue is the antidote for a serious disease called methemoglobinemia but has also been studied for other medical uses. Since it has significant side effects and may interact with many medications, the routine use of methylene blue should be avoided.

Be careful with methylene blue

Methylene blue acts as an MAO inhibitor. Monoamine oxidase, or MAO, regulates dopamine, norepinephrine, and serotonin neurotransmitters by removing them when the brain determines that there are excess amounts of any of them. And this is why we need to be very careful in people who suffer from conditions associated with elevated levels of any of those neurotransmitters.

Methylene Blue use in the ED

Uses include methemeglobinemia and vasoplegia. There is also some evidence supporting its use in angioedema. Dose for methemeglobinemia is 1.5mg/kg over 1-2min

Adjunctive Methylene Blue in Septic Shock?

Clinical Take Home Point: This small, single-center RCT found that adjunctive MB administered within 24hrs of septic shock reduced time to vasopressor discontinuation. The study was too small to make strong conclusions about adverse events. Without larger studies and a patient centered outcome, the addition of methylene blue within 24 hours of septic shock should still not be part of a general approach but rather an adjunct in specific circumstances (i.e. Septic shock and significant vasopressor requirements).

Core Cast 90.0 – Methemoglobinemia

Methemoglobinemia can result from exposure to a number of different medications. The most common are dapsone and topical anesthetic agents (i.e. benzocaine) Consider the diagnosis in any patient with cyanosis and hypoxia that doesn’t respond to oxygen administration

Critical Care Alert: Methylene Blue in Septic Shock

Methylene blue led to earlier vasopressor discontinuation and shorter ICU and hospital lengths of stay in patients with septic shock in this RCT, though this did not translate to a decrease in mortality. Consider its use early in patients with septic shock who have escalating pressor requirements.

Episode 110. The use of Methylene Blue for Refractory Hypotension with Rosa Malloy-Post, MD

Dose Methaemoglobinaemia 1-2mg/kg IV over 5 minutes followed by saline flush; repeat at 30-60 min if MetHb levels not falling repeat dose every 6-8h when MetHb continues for days, e.g. dapsone toxicity Vasoplegia 1.5-2 mg/kg IV over 30-60min

Methylene Blue

Methylene blue is one of the oldest organic dyes. It was first prepared in 1876 by H. Caro—BASF’s research director at the time—for use as a cotton dye. In 1880, microbiologist R. Koch established it as a medical stain. It is also used as an indicator for redox reactions, a photosensitizer for generating singlet oxygen, and a drug to treat methemoglobinemia, among other conditions. Until recently, dyestuff-grade methylene blue was used in medicine, but a pharmaceutical grade is now under development.

Methylene Blue in Septic Shock

Recent evidence suggests that methylene blue decreases the time spent on vasopressors but does not improve mortality. At this time, the data is not strong enough to recommend the use of methylene blue routinely in vasopressor refractory septic shock, but it can be considered as an adjunct in certain clinical contexts, and our ICU colleagues may be requesting us to administer it, underlying the importance of being familiar with it for this indication.

Methylene Blue: Revisited

Methylene Blue was till now known mainly as a dye but is now entering into the field of cardiac surgery and critical care as a very important therapeutic agent with diverse applications. The evidence for its use in methemoglobinemia is well established but that for its use in vasoplegia, septic shock, hepatopulmonary syndrome, malaria, ifosfamide neurotoxicity etc is limited but promising and commands more research.

Methylene Blue: The Little-Known Disinfectant

MB is useful in a variety of hospital and laboratory settings, and across disciplines such as hematology, immunohematology and clinical microbiology. In hospital settings, MB is commonly used to treat the blood disorder methemoglobinemia.

The Toxic Shelf: A Blue Patient

A depressed person saying that they are "blue" can mean they are emotionally blue or it can open the door to all of the crazy poisons. A blue patient is one that could potentially be poisoned with...

Resources

StatPearls

Methylene blue is a medication used in the management and treatment of methemoglobinemia, a condition in which hemoglobin decreases its ability to carry oxygen. This activity reviews the indications, action, adverse effects, and contraindications for methylene blue as a valuable agent in the therapy of methemoglobinemia, vasoplegic syndrome, Plasmodium falciparum, and ifosfamide-induced encephalopathy, as well as for diagnostic purposes such as sentinel lymph node mapping during breast procedures and parathyroid gland mapping during parathyroidectomies.