One may ask what is methylene blue ? Methylene blue is a water-soluble blue thiazine dye used most commonly as a treatment for methemoglobinemia or as an indicator dye.
Its utility as an indicator dye has been applied to several clinical situations including identification of aspiration or placement of nasogastric tubes in critically ill patients; localization of parathyroid adenomas; testing of the integrity of the biliary system during hepatic surgery; and testing of the integrity of ureteral or bladder anastomoses.
Additional applications of methylene blue include its use as a urinary antiseptic, reversal for chemotherapy-induced encephalopathy, a topical agent to photoinactivate viruses, an experimental cytotoxic agent for tumor cells, and a vasopressor in patients with septic or anaphylactic shock or for patients undergoing the reperfusion phase of liver transplantation.
Treatment of methemoglobinemia is the most common clinical use of methylene blue. Methemoglobin is the oxidized form of hemoglobin, created when the iron moiety changes from Fe2+ to Fe3+.
This form of hemoglobin cannot bind O2 or CO2 and therefore loses its oxygen-carrying capacity and transport function, predisposing the patient to hypoxemia.
Drug-induced causes of methemoglobinemia include local anesthetics (e.g., prilocaine and benzocaine) and nitrates (e.g., nitroglycerin and nitroprusside).
Methylene blue, administered slowly at a dose of 1 to 2 mg/kg intravenously (IV) with a maximum dose of 7 mg/kg, is converted in vivo to leukomethylene blue, which reduces methemoglobin back to hemoglobin.
Nicotinamide adenine dinucleotide phosphate (NADPH) is essential in the conversion to leukomethylene blue and thus, IV methylene blue administration is contraindicated in those with low endogenous NADPH (i.e., glucose-6-phosphate dehydrogenase [G6PD] deficiency).
Without this NADPH-dependent conversion, the use of methylene blue can lead to hemolytic anemia and exacerbation of methemoglobinemia.
Similarly, if too high a dose of methylene blue is given or it is given too quickly, high concentrations can accumulate and saturate the reducing pathway such that methylene blue will act as an oxidizing agent and paradoxically create more methemoglobin.
Signs and Symptoms
Although the risks of IV administration of methylene blue were well known, the use of this substance enterally was thought to be relatively benign. However, the U.S. Food and Drug Administration (FDA) has recently become concerned about enteral exposure to methylene blue and has issued a warning against using it in this situation.
This is based, in part, on the reported cases of toxicity (including death) associated with enteral exposure of a very similar dye, FD&C Blue No.1 (Blue 1). In most of these cases, the patients had a history of sepsis. The FDA concluded that patients at risk of increased intestinal permeability (e.g., patients with cancer, sepsis, burns, renal failure, celiac sprue, or inflammatory bowel disease) were at risk for mitochondrial toxicity.
Signs and symptoms of mitochondrial toxicity include nausea, vomiting, abdominal pain, fever, sudden weight loss, dizziness, headache, precordial pain, tachycardia, hypertension, dyspnea, profuse sweating, restlessness, tremors, and confusion.
Untreated, mitochondrial toxicity can result in myopathy, neuropathy, lipoatrophy, hemolytic anemia, hypoxemia, arrhythmias, hepatic steatosis, liver failure, lactic acidosis, and refractory hypotension.
Now we know what is methylene blue and also its uses.