What is the dosing of methylene blue in septic shock?

Methylene Blue Dosing in Septic Shock

The recommended dosing for methylene blue in refractory septic shock is an intravenous bolus of 2 mg/kg followed by a continuous infusion of 0.5 mg/kg/h for up to 48 hours. 1

Indications and Mechanism

• Methylene blue is considered a third-line therapy for refractory vasoplegic shock after first-line α1-adrenergic agonists (norepinephrine) and second-line vasopressin/terlipressin 2
• It works by inhibiting guanylate cyclase, blocking nitric oxide-mediated vasodilation that contributes to refractory shock 3

Dosing Strategies

Three main dosing strategies have been identified, with the bolus followed by continuous infusion showing superior outcomes:

1. Bolus + Continuous Infusion (Preferred)

   • Initial bolus: 2 mg/kg IV over 3-5 minutes
   • Followed by: 0.5 mg/kg/h continuous infusion for up to 48 hours
   • This approach has been associated with reduced 28-day mortality 4

2. Bolus Only

   • 1-2 mg/kg IV over 3-5 minutes
   • Less effective than combined approach 4

3. Continuous Infusion Only

   • 0.25-2 mg/kg/h
   • Less studied than combined approach

Monitoring During Administration

• Monitor mean arterial pressure (target 70-90 mmHg)
• Track vasopressor requirements (expect reduction by up to 87% for norepinephrine, 81% for epinephrine) 5
• Assess oxygen delivery and hemodynamic parameters
• Monitor methemoglobin levels to avoid toxicity 2
• Ensure adequate glucose availability as it's essential for methylene blue effectiveness 2

Contraindications and Precautions

• Absolute contraindications:
  • G6PD deficiency (risk of hemolytic anemia and paradoxical worsening of methemoglobinemia)
  • Concurrent SSRI therapy (risk of serotonin syndrome)
• If G6PD status is unknown in emergency situations, attempt to obtain family history before administration 2

Clinical Pearls

• Methylene blue can be used for prolonged periods in refractory cases (up to 120 hours reported) 6
• Multiple attempts to discontinue may result in hemodynamic instability requiring reinitiation 6
• Methylene blue maintains stroke volume and left-ventricular stroke work indices while increasing mean arterial pressure 5
• No significant adverse effects on organ function have been observed at recommended doses 5

Alternatives for Contraindicated Patients

If methylene blue is contraindicated (G6PD deficiency):

• Consider exchange transfusion for severe cases
• Hyperbaric oxygen therapy may be an alternative
• Ascorbic acid (vitamin C) at 0.5-1g every 12 hours may be used 2

While methylene blue shows promise in improving hemodynamics and reducing vasopressor requirements in septic shock, further research is needed to definitively establish its impact on mortality outcomes.