Effect of methylene blue on hemodynamic and metabolic response in septic shock patients

Abstract

Introduction: Septic shock is a lethal disease responsible for a large proportion of deaths in the Intensive Care Unit (ICU), even with therapy centered on fluid resuscitation, use of vasopressors and empirical antibiotic therapy applied within the first hour of diagnosis. Considering the multifactorial pathophysiology of septic shock and the mechanism of action of vasopressors, some patients may not respond adequately, which can lead to the maintenance of vasodilatation, hypotension and increased morbidity, and mortality. This protocol aims to verify whether the use of methylene blue in septic patients with an early diagnosis can contribute to an earlier resolution of a shock compared to standard treatment.Methods and analysis: This is a study protocol for a single-center randomized clinical trial design in an ICU of a tertiary university hospital. In this study, we intend to include 64 patients aged between 18 and 80 years with a diagnosis of septic shock, of any etiology, with up to 72 hours of evolution after volume restoration, using norepinephrine at a dose ≥0.2 mg/kg/min and vasopressin at a dose of 0.04 IU/min. After the initial approach, we will randomize patients into two groups, standard care, and standard care plus methylene blue. The sample size was calculated in order to show 30% differences in septic shock resolution between groups. The Research Ethics Committee approved the study, and all patients included will sign an informed consent form (Clinical registration: RBR-96584w4). Abbreviations: ARDS = acute respiratory distress syndrome, CI = cardiac index, cNOS = constitutive nitric oxide synthase, CO = Cardiac Output, EFG = global ejection fraction, HR = heart rate, IAPF = pulmonary extravascular water index, ICU = Intensive Care Unit, IDFG = global end-diastolic volume index, iNOS = induced nitric oxide synth, IPVP = pulmonary vascular permeability index, IRVSi = systemic vascular resistance index, IVSi = systolic volume index, MAP = mean arterial pressure, PVC = central venous pressure, SAPS-3 = Simplified Acute Physiology Score, SVV = systolic volume variation.

Methylene blue therapy versus standard treatment for acute-phase septic shock: a pilot randomized controlled trial

“…Figure 1 summarizes the study population and study design. Eighty patients were enrolled upon signing the informed consent form by their next of kin and were randomly allocated into two groups according to the previously published protocol [13]. After withdrawing based on clinical status (n = 48), a total of 42 patients were included in the present study; 23 patients were allocated to the control group, and 19 were randomized to the MB group.…”

“…Several studies have proposed that MB can treat circulatory shock secondary to vasoplegia via nitric oxide (NO) [7,8,[10][11][12][13][14][15]. In a rat model of endotoxemia induced by lipopolysaccharide (LPS) and treated with MB, complete prevention of leukocyte rolling and adhesion to the endothelium was observed, resulting in a consistent systemic blood pressure response and a decreased need for vasoactive medications [16].…”

Endothelial Activation and Microcirculatory Disorders in Sepsis

“…Therapeutic drugs focus on endothelial vasoreactivity, inflammation, oxidative stress, and coagulation/anticoagulation balance. Table 2 (34)(35)(36)(37)(38)(39)(40) presents the major recent trials focusing on microcirculation during sepsis. Overall, while some studies showed an improvement in microcirculatory parameters, very few interventions succeeded in reducing mortality in critically ill septic patients.…”

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

“…This case series aims to report 6 cases of patients treated with standard therapy associated with MB in the first 72 hours of septic shock onset using a protocol predefined in the literature. [ 13 ]…”