Methylene Blue
ProvayBlue
Vital dye / NO synthase inhibitor / metHb reducer
Inhibits guanylate cyclase + nitric oxide synthase → reverses NO-mediated vasodilation. At low dose, reduces methemoglobin (Fe³⁺) → hemoglobin (Fe²⁺) via NADPH-methemoglobin reductase pathway.
Indications
- •Methemoglobinemia (1-2 mg/kg IV over 5 min, may repeat)
- •Vasoplegic syndrome post-cardiopulmonary bypass
- •Refractory anaphylactic shock unresponsive to epi + vasopressin
- •Ifosfamide-induced encephalopathy
- •Surgical marker for parathyroid, sentinel lymph node, ureteral identification
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Methemoglobinemia | 1-2 mg/kg IV over 5 min; may repeat in 1 hour to max 7 mg/kg | — |
| Vasoplegia | 1-2 mg/kg IV bolus over 20-30 min; can repeat ×1 | — |
| Surgical marker | 0.5-1 mL of 1% solution at injection site | — |
Pharmacokinetics
Onset 30-60 min IV; half-life ~5 hr; metabolized to leucomethylene blue (active reducer); renal/biliary excretion.
Hemodynamic effects
Causes increased SVR + MAP via NO inhibition. Transient decrease possible at infusion start.
Side effects
- !Pulse oximetry artifact (falsely low SpO2 — duration ~2 hrs)
- !Blue/green discoloration of urine + skin
- !Serotonin syndrome with serotonergic agents (potent MAOI activity)
- !Hemolytic anemia in G6PD deficiency
- !Methemoglobinemia paradox at high doses (>7 mg/kg)
Contraindications
- ×G6PD deficiency (causes hemolysis)
- ×Severe renal impairment (eGFR <30)
- ×Concurrent serotonergic medications (SSRIs, MAOIs, TCAs, fentanyl, methadone)
- ×Pregnancy (fetal hemolysis)
Clinical pearls
- ★Most common cause of acquired methemoglobinemia in OR: BENZOCAINE topical (Hurricane spray for awake intubation), prilocaine, dapsone, nitrites. Suspect when SpO2 reads 85% in a comfortable patient with normal PaO2.
- ★VASOPLEGIC SYNDROME post-CPB: low SVR + normal/high CO + refractory to NE. Methylene blue 1.5 mg/kg IV often dramatic responder. ATHOS-3 era: also consider angiotensin II as alternative.
- ★DRUG INTERACTION CRITICAL: many anesthesia drugs are serotonergic (fentanyl, methadone, tramadol, ondansetron). Methylene blue is a potent reversible MAOI → serotonin syndrome can be fatal. Plan accordingly.
- ★Pulse ox artifact persists ~2 hours — co-oximetry (ABG with metHb) is the gold standard.
Other drugs in Blue Dyes
- Isosulfan Blue (lymphatic mapping)
Selectively absorbed into lymphatic capillaries after subdermal/peritumoral injection. Tracks to first-station lymph node → blue staining identifies the sentinel node for biopsy in breast, melanoma, and gynecologic cancers.
- Indocyanine Green (ICG)
After IV or interstitial injection, ICG binds plasma proteins (mostly albumin) and fluoresces at 805–835 nm under near-infrared (NIR) imaging. Used for real-time vascular and lymphatic visualization, hepatic function testing, and tissue perfusion assessment.
- Indigo Carmine
Blue dye rapidly excreted by the kidneys → visualizes ureteral efflux/urine flow. Mild α-agonist activity → transient hypertension.
- Fluorescein
Fluoresces under blue/UV light → visualizes vasculature + perfusion + epithelial defects. Not blue, but grouped with surgical/diagnostic dyes.
Browse all classes: /reference/drugs
Suggested reading
- •Miller's Anesthesia, 9e
- •FDA package insert
