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Methylene blue treatment of anaphylaxis

Methylene blue treatment of anaphylaxis, Θεραπεία αναφυλαξίας με κυανούν του μεθυλενίου. Histamine along with other mediators, such as leukotrienes, tumor necrosis factor, and platelet-activating factor, induce the production of nitric oxide. Nitric oxide can inhibit the release and effects of catecholamines. Sympathetic amines may inhibit production of nitric oxide. Studies in animals have demonstrated the generation of nitric oxide during anaphylaxis. Inhibition of nitric oxide synthase improves survival in an animal model of anaphylaxis. Nitric oxide causes vasodilation indirectly by increasing the activation of guanylyl cyclase, which then causes smooth muscle relaxation by increasing the concentration of smooth muscle cyclic guanosine monophosphate. Methylene blue is an inhibitor of guanylyl cyclase, which increases systemic vascular resistance and reverses shock in animal studies[1]. This results in reduced responsiveness of the vasculature to cyclic guanosine monophosphate-mediated vasodilators, such as nitric oxide[3].

methylene blue has been administered as a lifesaving alternative drug for the treatment of contrast-induced anaphylaxis[2]. Oliveira Neto AM, et al (2003) ued a cardiovascular catheterization laboratory invasive hemodynamic monitoring , in order to document the lifesaving effect of IV bolus injections of 1.5-2 mg/Kg methylene blue solution to treat three patients for anaphylactic shock following radiocontrast injection during coronary angiography. Methylene blue administration was followed by prompt circulatory improvement, leading to hemodynamic stabilization and relief of other anaphylactic symptoms in each case. There were no deaths[2].

Del Duca D, (2009) presented two cases of catecholamine-refractory and vasopressin-refractory vasoplegic syndrome associated with intraoperative anaphylaxis during cardiac surgery. One case was related to the administration of protamine and the other case to the administration of aprotinin. Both cases were successfully managed using intravenous methylene blue[3].

Among mechanisms thought to be contributory to vasoplegia, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway appears to play a prominent role. In search of effective treatment for vasoplegia, methylene blue (MB), an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase (GC), has been found to improve the refractory hypotension associated with endothelial dysfunction of vasoplegia . There is evidence that methylene blue  may indeed be effective in improving systemic hemodynamics in the setting of vasoplegia, with reportedly few side effects[4].


1. 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.

2. Oliveira Neto AM, Duarte NM, Vicente WV, Viaro F, Evora PR. Methylene blue: an effective treatment for contrast medium-induced anaphylaxis. Med Sci Monit. 2003 Nov;9(11):CS102-6.

3. Del Duca D, Sheth SS, Clarke AE, Lachapelle KJ, Ergina PL. Use of methylene blue for catecholamine-refractory vasoplegia from protamine and aprotinin.
4. Stawicki SP, Sims C, Sarani B, Grossman MD, Gracias VH. Methylene blue and vasoplegia: who, when, and how? Ann Thorac Surg. 2009 Feb;87(2):640-2.
Mini Rev Med Chem. 2008 May;8(5):472-90.

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