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Open Access

Comments on: Methylene blue? Therapeutic alternative in the management of septic shock refractory to norepinephrine

  • Alberto Pasqualucci1,2
  • Filomena Puntillo3
  • Giustino Varrassi4

1Department of Surgical and Biomedical Science, University of Perugia, 6100 Perugia, Italy

2Rashid Hospital, Trauma and Emergency Center, Dubai Health Autority, 4545 Dubai, UAE

3Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy

4Paolo Procacci Foundation, Via Tacito 7, 00193 Roma, Italy

DOI: 10.22514/sv.2020.16.0115 Vol.17,Issue 1,January 2021 pp.219-220

Published: 08 January 2021

*Corresponding Author(s): Giustino Varrassi E-mail:

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Alberto Pasqualucci,Filomena Puntillo,Giustino Varrassi. Comments on: Methylene blue? Therapeutic alternative in the management of septic shock refractory to norepinephrine. SignaVitae. 2021. 17(1);219-220.


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[2] Angus DC, van der Poll T. Severe sepsis and septic shock. The New England Journal of Medicine. 2013; 369: 840-851.

[3] Lambden S, Creagh-Brown BC, Hunt J, Summers C, Forni LG. Definitions and pathophysiology of vasoplegic shock. Critical Care (London, England). 2019; 22: 174.

[4] Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, et al. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. The Lancet Infectious Diseases. 2017; 17: 1180-1189.

[5] SepNet Critical Care Trials Group. Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study. Intensive Care Medicine. 2016; 42: 1980-1989.

[6] De Backer D, Foulon P. Minimizing catecholamines and optimizing perfusion. Critical Care. 2019; 23: 149.

[7] Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Critical Care Medicine. 2017; 45: 486-552.

[8] Vincent J, De Backer D. Circulatory Shock. New England Journal of Medicine. 2013; 369: 1726-1734.

[9] Scheeren TWL, Bakker J, De Backer D, Annane D, Asfar P, Boerma EC, et al. Current use of vasopressors in septic shock. Annals of Intensive Care. 2019; 9: 20.

[10] Kwok ESH, Howes D. Use of methylene blue in sepsis: a systematic review. Journal of Intensive Care Medicine. 2006; 21: 359-363.

[11] Buckley MS, Barletta JF, Smithburger PL, Radosevich JJ, Kane‐Gill SL. Catecholamine vasopressor support sparing strategies in vasodilatory shock. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2019; 39: 382-398.

[12] Schneider F, Lutun P, Hasselmann M, Stoclet JC, Tempé JD. Methylene blue increases systemic vascular resistance in human septic shock. Intensive Care Medicine. 1992; 18: 309-311.

[13] Memis D, Karamanlioglu B, Yuksel M, Gemlik I, Pamukcu Z. The influence of methylene blue infusion on cytokine levels during severe sepsis. Anaesthesia and Intensive Care. 2002; 30: 755-762.

[14] Kirov MY, Evgenov OV, Evgenov NV, Egorina EM, Sovershaev MA, Sveinbjørnsson B, et al. Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study. Critical Care Medicine. 2001; 29: 1860-1867.

[15] Weingartner R, Oliveira E, Oliveira ES, Sant’Anna UL, Oliveira RP, Azambuja LA, et al. Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue. Brazilian Journal of Medical and Biological Research. 1999; 32: 1505-1513.

[16] Donati A, Conti G, Loggi S, Münch C, Coltrinari R, Pelaia P, et al. Does methylene blue administration to septic shock patients affect vascular permeability and blood volume? Critical Care Medicine. 2002; 30: 2271-2277.

[17] Tchen S, Sullivan JB. Clinical utility of midodrine and methylene blue as catecholamine-sparing agents in intensive care unit patients with shock. Journal of Critical Care. 2020; 57: 148-156.

[18] Puntillo F, Giglio M, Pasqualucci A, Brienza N, Paladini A, Varrassi G. Vasopressor-sparing action of methylene blue in severe sepsis and shock: a narrative review. Advances in Therapy. 2020; 37: 3692-3706.

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