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. 2022 Nov 24:77:100139.
doi: 10.1016/j.clinsp.2022.100139. eCollection 2022.

Methylene Blue to Neonatal Septic Shock treatment in neonate pigs

Walusa Assad Gonçalves-Ferri  1 , Agnes Afrodite Sumarelli Albuquerque  2 , Renata Sayuri Ansai Pereira de Castro  2 , Cristina Helena Faleiros Ferreira  2 , Luis K Oharomari Jr  2 , Diego Fernando Silva Lessa  2 , Paulo Roberto Barbosa Evora  3
Affiliations

Methylene Blue to Neonatal Septic Shock treatment in neonate pigs

Walusa Assad Gonçalves-Ferri et al. Clinics (Sao Paulo). .

Abstract

Objective: The authors design an animal model of neonatal sepsis to analyze the treatment of neonatal septic shock with Methylene Blue (MB) in a swine model.

Methods: The study design included twenty male newborn pigs divided into four groups: 1) The control group; 2) The sepsis group (induced with lipopolysaccharide); 3) The MB group, and 4) The MB-treated sepsis group. Septic shock was defined as Blood Pressure (BP) dropping 20% below the baseline value. Continuous Blood Pressure (BP), Nitric Oxide (NO) levels, cyclic Guanosine Monophosphate (cGMP), malondialdehyde acid, base excess, lactate, arterial blood gases, hematocrit, and echocardiography were analyzed.

Results: The BP of the sepsis group treated with MB showed a slight improvement in the first hour after treatment; however, a significant difference was not observed compared to the untreated sepsis group. Besides hemodynamic stability, the current study did not show symptomatic pulmonary hypertension, suggesting that MB was safe in neonates and children. An improvement in Base Excel (BE) levels after MB administration in septic animals may indicate a possible improvement in microcirculation.

Conclusion: The MB improved biomarkers related to septic shock prognosis, although an improvement in the blood levels could not be detected. MB might be a beneficial drug for hemodynamic instability in infants.

Keywords: Infants; Methylene blue; Newborn; Nitric oxide; Septic shock; Vasoplegic syndrome.

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Conflict of interest statement

Declaration of Competing Interest The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effect of septic shock treated/ or not with Methylene Blue (MB) in neonatal pigs. Mean Blood Pressure (MBP). Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett's post-test (n = 5). (*p < 0.05; **p < 0.01).
Figure 2
Figure 2
Effect of septic shock treated or not with Methylene Blue (MB) in neonatal pigs. Central Venous Pressure (CVP). Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett's post-test (n = 5).
Figure 3
Figure 3
Effect of septic shock treated/ or not with Methylene Blue (MB) in mean values of Base Excess (BE) in neonatal pigs. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett's post-test (n = 5). (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; C vs. S: *, C vs. SMB: +).
Figure 4
Figure 4
Effect of septic shock treated/ or not with Methylene Blue (MB) in mean values of blood bicarbonate (HCO3-) in neonatal pigs. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett's post-test (n = 5). (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; C vs. S: *, C vs. SMB: +).
Figure 5
Figure 5
Effect of septic shock treated or not with Methylene Blue (MB) in Malondialdehyde Acid (MDA) levels. in neonatal pigs. Data represent means ± standard error of mean and analyzed by two-way analysis of variance (ANOVA), Dunnett's post-test (n = 5). (***p < 0.001; ****p < 0.0001; C vs. S: *, C vs. MB: #; C vs. SMB: +).
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