Takeaway

• Methylene Blue offers an adjunctive therapy for severe, resistant hypotension when traditional vasopressors are insufficient.
• “Effective dosages ranged from a 1.5- to 2.0-mg/kg bolus and/or infusion. The clinical responses occurred within 20 minutes.“
• MB may also effectively treat protamine induced vasoplegia

Key Points

Role of Nitric Oxide (NO): Allergens trigger mast cell degranulation, releasing histamine and cytokines that stimulate NO production via inducible nitric oxide synthase (iNOS). Excessive NO production inhibits the release and activity of catecholamines and is a major contributor to vasodilation and severe hypotension.

Mechanism: NO overproduction leads to vascular smooth muscle relaxation, making it challenging to maintain blood pressure during anaphylactic shock.

Therapeutic Potential of Methylene Blue (MB): MB acts as a guanylate cyclase inhibitor, counteracting the effects of NO by stabilizing vascular tone and improving blood pressure.

Excerpts

Epinephrine is indicated for the initial treatment of anaphylaxis.¹ Vasopressin⁶¹ and glucagon⁶²have been advocated as adjunctive treatment for anaphylaxis in patients who have not responded to epinephrine.

Glucagon inhibits production of inducible nitric oxide synthase and nitric oxide.⁶³ 

Catecholamines activate adenyl cyclase, which results in increased cyclic adenosine monophosphate (cAMP).⁶⁴ Vasopressin⁶⁵ and glucagon⁶⁴ also cause increases in cAMP.

cAMP inhibits inducible nitric oxide synthase and nitric oxide production.66, 67 

Nitric oxide, in turn, decreases release of catecholamines68, 69 and the biological activity of norepinephrine.⁷⁰ Nitric oxide synthase inhibition also increases catecholamine and the biological activity of norepinephrine.⁷⁰ 

Full Article

Citation

Evora PR, Simon MR. Role of nitric oxide production in anaphylaxis and its relevance for the treatment of anaphylactic hypotension with methylene blue. Ann Allergy Asthma Immunol. 2007 Oct;99(4):306-13. doi: 10.1016/S1081-1206(10)60545-5. PMID: 17941276.