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

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.

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

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 µg/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).

MMP-2 and MMP-9 levels in plasma are altered and associated with mortality in COVID-19 patients.

Respiratory symptoms are one of COVID-19 manifestations, and the metalloproteinases (MMPs) have essential roles in the lung physiology. We sought to characterize the plasmatic levels of matrix metalloproteinase-2 and 9 (MMP-2 and MMP-9) in patients with severe COVID-19 and to investigate an association between plasma MMP-2 and MMP-9 levels and clinical outcomes and mortality. MMP-2 and MMP-9 levels in plasma from patients with COVID-19 treated in the ICU (COVID-19 group) and Control patients were measured with the zymography. The study groups were matched for age, sex, hypertension, diabetes, BMI, and obesity profile. MMP-2 levels were lower and MMP-9 levels were higher in a COVID-19 group (p < 0.0001) compared to Controls. MMP-9 levels in COVID-19 patients were not affected by comorbidity such as hypertension or obesity. MMP-2 levels were affected by hypertension (p < 0.05), but unaffected by obesity status. Notably, hypertensive COVID-19 patients had higher MMP-2 levels compared to the non-hypertensive COVID-19 group, albeit still lower than Controls (p < 0.05). No association between MMP-2 and MMP-9 plasmatic levels and corticosteroid treatment or acute kidney injury was found in COVID-19 patients. The survival analysis showed that COVID-19 mortality was associated with increased MMP-2 and MMP-9 levels. Age, hypertension, BMI, and MMP-2 and MMP-9 were better predictors of mortality during hospitalization than SAPS3 and SOFA scores at hospital admission. In conclusion, a significant association between MMP-2 and MMP-9 levels and COVID-19 was found. Notably, MMP-2 and MMP-9 levels predicted the risk of in-hospital death suggesting possible pathophysiologic and prognostic roles.