Effect of methylene blue on hemodynamic response in the early phase of septic shock: A case series

Fabio Luis-Silva, Mayra Gonçalves Menegueti, Lucas Sato, Leandro Moreira Peres, Corina Dos Reis Sepeda, Bruno C Petroski-Moraes, Mariana Dermínio Donadel, Gabriela Bortoleto Gallo, Maria Cecília Jordani, Fabiola Mestriner, Christiane Becari, Anibal Basile-Filho, Paulo R B Evora, Olindo Assis Martins-Filho, Maria Auxiliadora-Martins, Fabio Luis-Silva, Mayra Gonçalves Menegueti, Lucas Sato, Leandro Moreira Peres, Corina Dos Reis Sepeda, Bruno C Petroski-Moraes, Mariana Dermínio Donadel, Gabriela Bortoleto Gallo, Maria Cecília Jordani, Fabiola Mestriner, Christiane Becari, Anibal Basile-Filho, Paulo R B Evora, Olindo Assis Martins-Filho, Maria Auxiliadora-Martins

Abstract

Rationale: Methylene blue (MB) has been used to increase blood pressure in septic shock, acting on the activity of guanylate cyclase and nitric oxide synthase.

Patience concerns: The aim of this study is to demonstrate the benefit of MB in early phase of septic shock.Diagnoses: We report 6 cases of patients with septic shock with up to 72 hours of evolution.

Interventions: We used MB after fluid replacement, use of norepinephrine and vasopressin. Patients received a loading dose of MB and maintenance for 48 hours.

Outcomes: All patients presented a reduction in the dose of vasopressors and lactate levels soon after the administration of the loading dose of MB, an effect that was maintained with the maintenance dose for 48 hours. Interleukin 6 and interleukin 8 were elevated at the beginning of the septic condition, with a progressive and marked reduction after the beginning of MB infusion, demonstrating a role of MB in reducing the inflammatory activity.

Lessons: This case series suggests that MB used early in the treatment of septic shock may be useful in reducing vasopressor dose and lactate levels. Further studies are still required to further validate these findings.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1.
Figure 1.
The mechanism of methylene blue action.
Figure 2.
Figure 2.
Compendium of study population and design.
Figure 3.
Figure 3.
Mean arterial pressure (MAP) values and noradrenaline doses in µg/kg/min at the 6 study times. (A) There was a reduction in the noradrenaline dose shortly after the administration of the MB loading dose with maintenance for 48 hours. MAP values and vasopressin doses in U/min at the 6 study times. (B) We observed that there was a progressive reduction in the dose of vasopressin with withdrawal within 48 hours. MAP and serum lactate (mmol/L) values at the 6 study times. (C) We observed a progressive drop in serum lactate levels demonstrating a positive effect of MB on tissue perfusion. MB = methylene blue.
Figure 4.
Figure 4.
Serum dosage of (A) IL-10, (B) TNF-α, (C) IL-6 and (D) IL-8 and (E) NO3 in the 6 study times. (A) We observed a gradual decrease in serum IL-10 levels being more pronounced in T4, but in T6 there was an increase, which may be related to the suspension of MB before this measurement. (B) There was a tendency to decrease TNF-α over time. (C and D) The IL-6 and IL-8 cytokines initially increased with progressive and marked reduction in the times after the onset of MB, demonstrating a possible role of MB in reducing the inflammatory activity of these patients. (E) Serum levels of NO3 at the 6 study times. We observed a sharp drop in serum NO3 dosage starting in the first 24 hours. IL = interleukin, MB = methylene blue, NO = nitric oxide, NO3 = serum nitrate, TNF-alfa = tumor necrosis factor.

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