Remember that Not All Blue-Colored Compounds are the Same

Chauncey T. Jones MD

There are many blue dye compounds, and each is used for a variety of purposes. Their uses include food coloring, dye for materials, antiseptics, tissue stains, chemical reaction indicators, and to treat diseased aquarium life. Blue dyes are also used in humans for both diagnostic and therapeutic purposes. These dyes include methylene blue, patent blue, isosulfan blue, and indigo carmine. While these substances are all blue in color, they are distinct compounds and have widely varying properties, uses, and adverse effects (Table 56.1).

METHYLENE BLUE

Synonyms: Methylthionium chloride, tetramethylthionine chloride, urolene blue, swiss blue, solvent blue

Molecular formula: C₁₆H₁₈ClN₃S

Molecular weight: 319.85

Structure:

Methylene blue has been used in many clinical situations in humans. It is used primarily as an antidote for both chronic methemoglobinemia (e.g., occurring with dapsone therapy) and acute methemoglobinemia. At low concentrations it promotes the reduction of methemoglobin (the ferric form of hemoglobin) to hemoglobin by acting as a cofactor for the enzyme NADPH-methemoglobin reductase. The recommended dose is 1 to 2 mg/kg administered intravenously (IV). The dose may be repeated after 1 hour if symptoms persist.

Methylene blue has been used as a sentinel lymph node tracer for breast cancer and may be as efficacious and have fewer side effects than other blue dyes more traditionally used for this purpose. It has also been used as a genitourinary antiseptic and for topical virus therapy. The antimicrobial effect is presumed to be secondary to its oxidative/reduction properties.

TABLE 56.1 BLUE DYE COMPOUNDS

BLUE COMPOUND

COMMON USES

ADVERSE EFFECTS

Methylene blue

Antidote for metHgb

Sentinel lymph node tracing

Genitourinary antiseptic

Septic shock

Cyanide toxicity

Hypertension

Chest pain

Anemia

Bladder irritation

Transient, false SpO₂ decrease

Headaches, diaphoresis, abdominal pain

Patent blue

Sentinel lymph node tracing

Breast cancer
Melanoma
Endometrial cancer
Colon cancer

Severe anaphylaxis

Prolonged, false SpO₂ decrease

Isosulphan blue

Tumor marking

Lymphangiography

Urticarial reactions

Anaphylaxis

Transient, false SpO₂ decrease

Indigo carmine

Urology

Locate ureteral orifices during cystoscopy
Test anastomoses
Identify transected ureters intraoperatively

Mild elevation of blood pressure

Relatively low side-effect profile

Transient, false SpO₂ decrease

Indocyanine green

Ophthalmology

Macular surgery
Cataract surgery

Blood volume, cardiac output determinations

Infrared therapy for colon cancer

Can be toxic to eye unless thoroughly washed out

Transient, false SpO₂ decrease

Blue #1

FDA black box warning against use in enteral feeds for detecting aspiration

Refractory hypotension

Metabolic acidosis (acts as a mitochondrial toxin)

Worse in patient with increased gastrointestinal permeability

Death

Although it is not the treatment of first choice, at high concentrations methylene blue can be used to treat cyanide toxicity by converting ferrous hemoglobin to ferric methemoglobin. Methemoglobin combines with cyanide to form cyanmethemoglobin. This serves as an alternative pathway for cyanide and prevents it from combining with cytochrome oxidase, which results in cyanide toxicity.

Possible side effects of methylene blue include hypertension; chest pain; headache; confusion; dizziness; diaphoresis; anemia; discoloration of skin, urine, and feces; nausea; vomiting; abdominal pain; and bladder irritation. The increase in blood pressure caused by methylene blue is so pronounced that it was historically used as a treatment for septic shock, before the era of modern-day vasopressors.

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