2016, Number 2
PDF size: 236.71 Kb.
ABSTRACTBackground: Generalized vasodilation with nonresponding hypotension is present in half of death cases due to septicemia. Methylene blue could be used as a valuable adjuvant in the treatment of refractory hypotension. The aim of this study was to determine the effectiveness of methylene blue as a contributory treatment in patients with septic shock.
Material and methods: A controlled, randomized, double-blinded, clinical trial was performed. Sixty patients were divided in two groups. Group A received a single dose of methylene blue calculated 2 mg/kg per body weight diluted in 100 cm3 of 5% dextrose infused in 60 minutes, and group C (control) received 100 cm3 of 5% dextrose infused in 60 minutes. Basal measurements of the study variables were taken (MBP, lactate, base deficit, central venous saturation and CO2 delta) prior to the administration of methylene blue and every hour afterwards, until MBP › 65 mmHg without vasopressor or 72 hours had passed after shock began. Data about total noradrenaline dose in mg, length of stay, length of mechanical ventilation and mortality was recorded.
Results: MBP increased progressively the first six hours after the methylene blue infusion in group A, 22%, and in group C, 9.2% (p: ‹ 0.05), steadily during the 72-hour follow-up. The noradrenaline dose decreased in the first six hours, in group A 86%, in group C, 56% (p: ‹ 0.05). Lactate clearance in the first six hours was 62% in group A; in contrast, group C had a 33% clearance (p: ‹ 0.05). Mortality at ICU discharge on group A was 20.0% and on group C was 36.6% (p: ‹ 0.05), without variation on 21 days.
Conclusion: Methylene blue is effective as an adjuvant in the treatment of septic shock.
Edmund S, Kwok M, Daniel H. Use of methylene blue in sepsis: a systematic review. Journal of Intensive Care Medicine. 2006;21(6):359-363.
Alderton W, Cooper C, Knowles G. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001;357:593-615.
Hibbs J, Taintor R, Vavrin Z. Macrophage cytotoxicity: role for l-arginine deiminase and imino nitrogen oxidation to nitrite. Science J. 1987;235:473-476.
Marletta MA. Nitric oxide synthase structure and mechanism. J Biol Chem. 1993;268(17):12231-12234.
Tatsumi R, Wuollet A, Tabata K, Nishimura S, Tabata S, Mizunoya W, et al. A role for calcium-calmodulin in regulating nitric oxide production during skeletal muscle satellite cell activation. Am J Physiol Cell Physiol. 2009;296:922-929.
Förstermann U, Closs EI, Pollock J, Nakane M, Schwarz, Gath I, et al. Nitric oxide synthase isozymes, characterization, purification, molecular cloning, and functions. Hypertension. 1994;(6 pt 2):1121-1131.
Oz M, Lorke D, Hasan M, Petroianu. Cellular and molecular actions of methylene blue in the nervous system. Med Res Rev. 2011;31(1):93-117.
Venema RC, Sayegh HS, Arnal JF, Harrison DG. Role of the enzime calmodulin-binding domain in membrane association and phospholipid inhibition of endothelial nitric oxide syntase. J Biol Chem. 1995;270:14705-14711.
Jang D, Nelson L, Hoffman R. Methylene blue for distributive shock: a potential new use of an old antidote. J Med Toxicolo. 2013;9:242-249.
Del Duca D, Sheth SS, Clarke AE, Lachapelle KJ, Ergina PL. Use of methylene blue for catecholamine-refractory vasoplegia from protamine and aprotinin. Ann Thorac Surg. 2009;87(2):640-642.
Farina J, Celotto A, Silva M, Evora P. Guanylatecyclase inhibition by methylene blue as an option in the treatment of vasoplegia after a severe burn. A medical hypothesis. Med Sci Monit. 2012;12(5):13-17.
Viaro F, Dalio M, Evora P. Catastrophic cardiovascular adverse reactions to protamine are nitric oxide/cyclic guanosine monophosphate dependent and endothelium mediated: should methylene blue be the treatment of choice. Chest. 2002;122(3):1061-1066.
Evora P, Ribeiro P, Vicente W, Reis C, Rodrigues A, Menardi A, et al. Methylene blue for vasoplegic syndrome treatment in heart surgery. Fifteen years of questions, answers, doubts and certainties. Rev Bras Cardiovasc. 2009; 24(3):279-288.
Fisher J, Taori G, Braitberg, Graudins A. Methylene blue used in the treatment of refractory shock resulting from drug poisoning. Clin Toxicol (Phila). 2014;52(1):63-65.
Brown G, Frankl D, Terry P. Continuous infusion of methylene blue for septic shock. Postgrad Med J. 1996;72(852):612-624.
Park BK, Shim TS, Lim CM, Lee SD, Kim WS, Kim DS, et al. The effects of methylene blue on hemodynamics parameters and cytokine levels in refractory septic shock. Korean J Intern Med. 2005;20(2):123-128.
Boomern JS, To K, Chang KC, Takasu O, Osborne DF, Walton A, et al. Immunosupression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594-2605.
Munford R, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med. 2001;163(2):316-321.
Ramamoorthy S, Patel S, Bradburn E, Kadry Z, Uemura T, Janicki P. Use of methylene blue for treatment of severe sepsis in an immunosuppressed patient after liver transplantation. Case Rep Transplant. 2013;1:1-4.
Jang D, Nelson L, Hoffman R. Response to methylene blue does not have to be considered only as rescue therapy for distributive shock. J Med Toxicol. 2013;9(4):247.
Barbosa P. Methylene blue does not have to be considered only as rescue therapy for distributive shock. J Med Toxicol. 2013;9(4):246-426.
Kirov M, Evgenov O, Evgenov N, Egorina E, Sovershaev M, Sveinbjornsson B, et al. Infusion of methylene blue in human septic shock: A pilot, randomized, controlled study. Crit Care Med. 2001; 29(10):1860-1867.
Bassi E, Park M, Pontes L. Therapeutic strategies for high dose vasopressor-dependent shock. Crit Care Res Pract. 2013; 2013:654708.
Levin RL, Degrange MA, Bruno GF, Mazo CD, Taborda DJ, Griotti JJ. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg. 2004;77(2):496-499.