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Case Report

Open Access

Methylene blue? Therapeutic Alternative in the Management of Septic Shock Refractory to Norepinephrine

  • Cristian Aragón-Benedí1
  • Ana Pascual-Bellosta2
  • Sonia Ortega-Lucea2
  • Luisa Lacosta-Torrijos2
  • Teresa Jiménez-Bernadó3
  • Javier Martínez-Ubieto2
  • Research group in anesthesia resuscitation and perioperative medicine of Institute for Health Research Aragón

1Department of Anesthesia, Resuscitation and Pain Therapy, Mostoles General University Hospital, Mostoles 28935, Madrid, Spain

2Department of Anesthesia, Resuscitation and Pain Therapy, Miguel Servet University Hospital, Zaragoza 50009, Spain

3Department of Health Sciences, University of Zaragoza, Zaragoza 50009, Spain

DOI: 10.22514/sv.2020.16.0063 Vol.16,Issue 2,October 2020 pp.199-202

Published: 28 October 2020

*Corresponding Author(s): Cristian Aragón-Benedí E-mail:

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Introduction: Methylene blue is receiving special interest in perioperative and intensive care of patients with distributive shock due to its ability to block the action of nitric oxide and to antagonize deep vasodilation. Objective: The objective is to illustrate the use of the methylene blue, summarizing the perioperative management of a case with secondary vasoplegic syndrome due to a norepinephrine refractory septic shock and the response to methylene blue, reviewing the latest evidence of this therapeutic alternative. In practice:We describe the case of a 60-year-old man, paraplegic, with septic shock due to a long evolution decubitus pressure ulcer. After two hours of surgery, the patient remained with hemodynamic deterioration despite high doses of vasopressin (3 IU/hour) and norepinephrine (2 µg/kg /min), therefore methylene blue was administered with two intravenous bolus doses of 50 mg without adverse effects. After half an hour hemodynamic improvement was evidenced, allowing to decrease norepinephrine infusion and normalizing blood pressure. Finally, debridement of necrotic tissue, amputation and disarticulation of left coxofemoral joint was performed with subsequent transfer to the ICU and discharge to the spinal cord injury ward twenty eight days later. Conclusions: As it has been demonstrated in our patient, methylene blue is a therapeutic alternative to manage patients with persistent hypotension despite the use of various vasopressors during the management of vasoplegic syndrome secondary to septic shock.

Key words

Septic shock, Methylene blue, Surgical intensive care, Vasoplegic syndrome

Cite And Share

Cristian Aragón-Benedí,Ana Pascual-Bellosta,Sonia Ortega-Lucea,Luisa Lacosta-Torrijos,Teresa Jiménez-Bernadó,Javier Martínez-Ubieto,Research group in anesthesia resuscitation and perioperative medicine of Institute for Health Research Aragón. Methylene blue? Therapeutic Alternative in the Management of Septic Shock Refractory to Norepinephrine. Signa Vitae. 2020. 16(2);199-202.


[1] Hosseinian L, Weiner M, Levin MA, et al. Methylene Blue: Magic Bullet for Vasoplegia?. Anesth Analg. 2016;122:194-201.

[2] Shanmugam G. Vasoplegic syndrome-the role of methylene blue. Eur J Cardiothorac Surg. 2005;28:705-710.

[3] Carrillo-Esper R, Sosa-García JO, Carrillo-Córdova JR, et al. Azul de metileno para el manejo del choque séptico refractario a vasopresores. Rev Mex Anest. 2010;33:214-219.

[4] Manghelli J, Brown L, Tadros HB,et al. A reminder of methylene blue’s effectiveness in treating vasoplegic syndrome after on-pump cardiac surgery. Tex Heart Inst J. 2015;42:491–494.

[5] Evora PR. Methylene Blue Is a Guanylate Cyclase Inhibitor That Does Not Interfere with Nitric Oxide Synthesis. Tex Heart Inst J. 2016;43:103.

[6] Huet O, Chin-Dustin J. Septic shock: desperately seeking treatment. Clin Sci. 2014;126:31–39.

[7] Bauer CS, Vadas P, Kelly KJ. Methylene blue for the treatment of refractory anaphylaxis without hypotension. Am J Emerg Med. 2013;31:264.e3-5.

[8] Lo JC, Darracq MA, Clark RF. A review of methylene blue treatment for cardiovascular collapse. J Emerg Med. 2014;46:670-79.

[9] Evora PR. Methylene Blue and Cardiovascular Collapse. J Emerg Med. 2016;50:126-127.

[10] Pasin L, Umbrello M, Greco T, et al. Methylene blue as a vasopressor: a meta-analysis of randomised trials. Crit Care Resusc. 2013;15:42–48.

[11] Stocche RM, Garcia LV, Reis MP, et al. Methylene blue to treat anaphylaxis during anesthesia: case report. Rev Bras Anestesiol. 2004;54:809-814.

[12] Mercanoglu G, Semen O. Nitric oxide mediated the effects of nebivolol in cardiorenal syndrome. Iran J Basic Med Sci. 2019;22:1314-1324.

[13] In Duk O, Eunsil S, Jong-Mi J, et al. Use of methylene blue in vasoplegic syndrome that developed during non-cardiac surgery: A case report. Anesth Pain Med. 2019;14:460-464.

[14] Schneider F, Lutun P, Hasselmann M, et al. Methylene blue increases systemic vascular resistance in human septic shock. Preliminary observa-tions. Intensive Care Med. 1992;18:309-311.

[15] Paciullo CA, Mcmahon horner D, Hatton KW, et al. Methylene blue for the treatment of septic shock. Pharmacotherapy. 2010;30:702-715.

[16] Kirov MY, Evgenov OV, Evgenov NV, et al. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Crit Care Med .2001;29:1860–1867.

[17] Memis D, Karamanlioglu B, Yuksel M, et al. The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesth Intensive Care. 2002;30:755–762.

[18] Andresen M, Dougnac A, Díaz O, et al. Use of methylene blue in patients with refractory septic shock: impact on hemodynamics and gas exchange. J Crit Care. 1998;13:164–168.

[19] Juffermans NP, Vervloet MG, Daemen-Gubbels CR, et al. A dose finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock. Nitric Oxide. 2010;22:275–280.

[20] Zhang H, Rogiers P, Preiser JC, et al. Effects of methylene blue on oxygen availability and regional blood flow during endotoxic shock. Crit Care Med. 1995;25:1711-1721.

[21] Lavigne D. Vasopressin and methylene blue: alternate therapies in vasodilatory shock. Semin Cardiothorac Vasc Anesth. 2010;14:186-189.

[22] Carrillo-Esper R, Nuñez-Monroy FN, Alvarado-Martinez C. Azul de metileno en choque séptico refractario. Rev Asoc Mex Med Crit Ter Int.1999;13:28-35.

[23] Mccartney SL, Duce L, Ghadimi K. Intraoperative vasoplegia: methylene blue to the rescue!. Curr Opin Anaesthesiol. 2018;31:43-49.

[24] Booth AT, Melmer PD, Tribble B, et al. Methylene Blue for Vasoplegic Syndrome. Heart Surg Forum. 2017;20:E234-E238.

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