From the Guidelines
Methylene blue works as a vasopressor by inhibiting nitric oxide synthase and guanylate cyclase, which are enzymes involved in vasodilation, and its use is described in case series and case reports as an effective adjunct to treat refractory vasodilatory shock after calcium channel blocker overdose. When administered intravenously at doses of 1-2 mg/kg, methylene blue prevents the production and action of nitric oxide, a potent vasodilator. This mechanism is particularly useful in vasoplegic shock states, such as septic shock or post-cardiopulmonary bypass vasoplegia, where excessive nitric oxide production leads to pathological vasodilation and hypotension. By blocking the nitric oxide pathway, methylene blue helps restore vascular tone and increase blood pressure. Some key points to consider when using methylene blue as a vasopressor include:
- It is typically administered as a slow intravenous infusion over 15-30 minutes, with effects beginning within 1-2 hours
- Important considerations include its potential to cause serotonin syndrome when combined with serotonergic drugs, interference with pulse oximetry readings, and temporary blue-green discoloration of urine and skin
- Methylene blue is generally considered a second or third-line vasopressor option when traditional vasopressors like norepinephrine, vasopressin, or phenylephrine have failed to adequately maintain blood pressure, as noted in the 2023 American Heart Association guidelines 1. The most recent and highest quality study on this topic is from 2023, which describes the use of methylene blue as an effective adjunct to treat refractory vasodilatory shock after calcium channel blocker overdose 1.
From the Research
Mechanism of Action
- Methylene blue works as a vasopressor by inhibiting the enzyme nitric oxide synthase, which prevents smooth muscle dilation and ultimately increases blood pressure 2.
- It also inhibits guanylate cyclase, decreasing the production of cyclic guanosine monophosphate, which inhibits vascular smooth muscle relaxation and can be an effective method for refractory hypotension 3.
Clinical Use
- Methylene blue has been used to treat refractory hypotension in various clinical settings, including anaphylaxis, overdose, and cardiac surgery requiring cardiopulmonary bypass 2, 4, 3, 5.
- It has been shown to increase systemic vascular resistance and mean arterial pressure, and decrease vasopressor requirements, making it a valuable adjunct in the treatment of refractory hypotension 2, 4, 3, 5.
Benefits and Safety
- Methylene blue has a favorable safety profile and can be used to reduce the cumulative dose of other vasoactive agents, potentially reducing adverse effects such as peripheral and mesenteric ischemia 6, 5.
- Its use has been associated with improved hemodynamic stability and reduced need for other vasopressors, making it a useful alternative to standard therapy in certain situations 2, 4, 3, 6, 5.