Q: How Methylene blue worked in Nor-epinephrine refractory vasoplegia? 

 Answer: Via inhibition of guanylate cyclase 

 Refractory vasoplegia reflect a dysregulation of nitric oxide synthesis and vascular smooth muscle cell guanylate cyclase activation. Release of proinflammatory mediators may act through the induction of the final commonpathway of nitric oxide, which is the activation of the guanylate cyclase, leading to vasodilation. Hyporesponsiveness to norepinephrine is due to the activation of the soluble guanylate cyclase.

Dose is 2 mg/kg administered intravenously over 20 minutes for one time.