From the Guidelines
Methylene blue can be used as a rescue therapy for refractory septic or cardiogenic shock when conventional treatments fail, as suggested by a study published in Intensive Care Medicine in 2018 1. For septic shock, methylene blue is typically administered as an intravenous bolus of 1-2 mg/kg over 10-20 minutes, followed by a continuous infusion of 0.25-0.5 mg/kg/hour for up to 48 hours if needed. For cardiogenic shock, similar dosing may be used, though evidence is more limited. Methylene blue works by inhibiting nitric oxide synthase and guanylate cyclase, thereby reducing vasodilation and improving vascular tone when excessive nitric oxide production contributes to refractory hypotension. Important considerations include monitoring for potential side effects such as serotonin syndrome (especially in patients on serotonergic medications), pulmonary vasoconstriction, interference with pulse oximetry readings, and blue discoloration of skin and urine. Methylene blue should be used cautiously in patients with G6PD deficiency due to risk of hemolysis, and in those with renal impairment as dose adjustments may be necessary. This therapy should be considered only after standard vasopressors (norepinephrine, vasopressin, epinephrine) have proven insufficient, and ideally in consultation with critical care specialists, as recommended by the Surviving Sepsis Campaign guidelines published in Critical Care Medicine in 2017 1. Additionally, the ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008, published in the European Heart Journal and European Journal of Heart Failure in 2008, provide guidance on the use of vasopressors in cardiogenic shock 1. Key points to consider when using methylene blue include:
- Monitoring for potential side effects
- Cautious use in patients with G6PD deficiency or renal impairment
- Consideration of standard vasopressors before use
- Consultation with critical care specialists
- Use as a rescue therapy for refractory septic or cardiogenic shock.
From the Research
Role of Methylene Blue in Treating Septic or Cardiogenic Shock
- Methylene blue has been used to treat refractory shock resulting from various causes, including septicaemia and post-cardiac surgery, by inhibiting the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, decreasing vasodilation and increasing responsiveness to vasopressors 2.
- In septic shock patients, methylene blue may contribute to an earlier resolution of shock compared to standard treatment, by acting on guanylate cyclase and nitric oxide synthase 3, 4.
- Studies have shown that early administration of methylene blue in combination with standard treatment for septic shock can reduce vasopressor dosage, improve hemodynamic parameters, and increase vasopressor-free days 4, 5.
- Methylene blue has also been used as an adjuvant therapy in patients with refractory septic shock, resulting in significant improvement in mean arterial blood pressure and decrease in vasopressor requirement 6.
Mechanism of Action
- Methylene blue inhibits the NO-cGMP pathway, which leads to decreased vasodilation and increased responsiveness to vasopressors 2.
- Methylene blue acts on guanylate cyclase and nitric oxide synthase, which contributes to its effect on hemodynamic parameters in septic shock patients 3, 4.
Clinical Evidence
- A randomized controlled trial found that early adjunctive methylene blue reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days in patients with septic shock 5.
- An observational study found that intravenous methylene blue infusion improved hemodynamic parameters and decreased vasopressor requirement in patients with refractory septic shock 6.
- Another study found that methylene blue therapy in addition to standard treatment for acute-phase septic shock reduced vasopressor dosage and improved hemodynamic parameters 4.