Antidotes & Toxicology Pregnancy: Avoid — methylene blue has been associated with foetal intestinal atresia when used intra-amniotically; IV use in emergency acceptable if life-threatening methaemoglobinaemia

Methylene Blue

Brand names: ProvayBlue, Methylene Blue Injection

Adult dose

Dose: 1–2 mg/kg IV over 5 minutes

Route: IV

Frequency: May repeat 1 mg/kg after 30–60 minutes if symptoms persist

Max: 7 mg/kg total cumulative dose

Dilute in 50–100 mL glucose 5%. Will cause blue discolouration of urine and skin — warn patient. For vasoplegic shock: 1–2 mg/kg bolus or 0.25–2 mg/kg/hour infusion

Paediatric dose

Dose: 1–2 mg/kg mg/kg

Route: IV

Frequency: Over 5 minutes; repeat once if needed

Max: 7 mg/kg total

Same as adult dosing; G6PD deficiency is an absolute contraindication — screen before use if non-urgent

Dose adjustments

Renal

No specific dose adjustment; monitor for haemolysis in renal impairment

Hepatic

No specific adjustment

Paediatric weight-based calculator

Patient weight (kg)

Same as adult dosing; G6PD deficiency is an absolute contraindication — screen before use if non-urgent

Clinical pearls

Mechanism: methylene blue is reduced to leucomethylene blue by NADPH-dependent methaemoglobin reductase — leucomethylene blue then reduces methaemoglobin (Fe3+) back to haemoglobin (Fe2+); requires intact G6PD pathway for efficacy
G6PD CRITICAL: G6PD deficiency means NADPH cannot be generated — methylene blue is INEFFECTIVE AND HARMFUL; paradoxically increases methaemoglobin; exchange transfusion or hyperbaric oxygen required instead
Causes of methaemoglobinaemia: dapsone, prilocaine/benzocaine (topical anaesthetics), nitrites, nitrates, chloroquine, primaquine — always check drug history
SpO2 ARTEFACT: methylene blue causes pulse oximeter readings to drop transiently to 65–70% regardless of actual saturation — this is NOT TRUE hypoxia; confirm with co-oximetry (ABG)
MHRA 2008 — SEROTONIN SYNDROME WARNING: methylene blue given to patients on SSRIs, SNRIs, or other serotonergic drugs can cause fatal serotonin syndrome — take full drug history before administering; if urgent, choose alternative (ascorbic acid 1000 mg IV, exchange transfusion)
Vasoplegic syndrome: methylene blue 1–2 mg/kg used off-label for refractory vasoplegia post-cardiopulmonary bypass or septic shock — inhibits guanylyl cyclase pathway (NO signalling); reduces vasopressor requirements

Contraindications

G6PD deficiency — ABSOLUTE: methylene blue causes severe haemolytic anaemia and paradoxically WORSENS methaemoglobinaemia
Known hypersensitivity to methylene blue
Serotonin syndrome or concurrent serotonergic drugs (MAO inhibitors, SSRIs, linezolid) — methylene blue inhibits MAO-A: MHRA 2008 warning — FATAL serotonin syndrome
Intrathecal administration (neurotoxic)

Side effects

Blue discolouration of urine, stool, and skin (inevitable and harmless — warn patient)
SpO2 pulse oximeter readings falsely low (methylene blue absorbs at 660 nm)
Nausea, vomiting, abdominal pain
Headache
Haemolytic anaemia (dose-dependent; especially G6PD deficiency)
High-dose: paradoxical methaemoglobinaemia
Serotonin syndrome with serotonergic drugs

Interactions

MAO inhibitors, SSRIs, SNRIs, triptans, fentanyl, linezolid, tramadol — MHRA 2008: methylene blue is a potent MAO inhibitor — FATAL serotonin syndrome reported; avoid concurrent use or ensure 2-week washout
All serotonergic drugs (additive serotonin toxicity)

Monitoring

Co-oximetry (ABG) — pulse oximeter is UNRELIABLE during methylene blue use
Methaemoglobin level 30–60 minutes after dose
G6PD status (if non-urgent or if not responding — confirms contraindication)
Signs of haemolysis: haematocrit, bilirubin, LDH
Serotonin toxicity signs: hyperthermia, clonus, agitation (if serotonergic drugs present)

Reference: BNFc; BNF 90; NPIS Toxbase; MHRA DSU 2008 (serotonin syndrome); BMJ 2011;342:d3076; Anaesthesia 2015;70(10):1142-1153. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

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