Methylene Blue and Blood Transfusion in Hemorrhagic Shock Resuscitation: An Experimental Porcine Study.

INTRODUCTION: Hemorrhagic shock requires immediate treatment to prevent mortality and organ dysfunction. This study evaluates the efficacy of methylene blue (MB) with blood transfusion (BT) as a potential rescue therapy in acute severe bleeding in pigs. METHODS: Thirty animals were randomly assigned to one of six groups following the induction of fixed-pressure hemorrhagic shock, after reaching a mean arterial pressure (MAP) of 55 mmHg - Group 1 (60 BT: BT after 60 minutes), Group 2 (60 MB: MB infusion after 60 minutes), Group 3 (60 MB + BT: MB and BT after 60 minutes), Group 4 (15 MB + BT: MB and BT after 15 minutes), Group 5 (15 BT + 60 MB: BT after 15 minutes and MB infusion after 60 minutes), and Group 6 (15 MB + 60 BT: MB infusion after 15 minutes and BT after 60 minutes). Hemodynamic and blood gas parameters were meticulously recorded, reversal of the shock was considered when MAP reached 90% of the baseline MAP. RESULTS: Except for Group 2, all groups reverted from the shock. However, groups that received MB in combination with BT, specifically Groups 3 and 4, exhibited statistically significant higher ratios of maximum MAP to baseline MAP. CONCLUSION: Using MB concomitant with BT allowed the reversal of hemorrhagic shock with higher median arterial pressure levels compared to BT alone or applying MB separately from BT. This suggests that simultaneous application of MB and BT could be a more effective strategy for reversing the effects of severe acute bleeding.

Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia.

Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia

ABSTRACT Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Infective Endocarditis Surgery. Insights from 328 Patients Operated in a University Tertiary Hospital. / Cirurgia de Endocardite Infecciosa. Análise de 328 Pacientes Operados em um Hospital Universitário Terciário.

BACKGROUND: Infectious endocarditis (IE) refers to infection of the endocardial surface of the heart and usually occurs in native or prosthetic valves. OBJECTIVE: This study aimed to raise IE data reflecting the surgical therapy in a University Hospital in the interior of the State of Sao Paulo-Brazil. METHOD: Retrospective and observational approach of 328 patients with IE who underwent surgery between 1982 and 2020. RESULTS: The main data (n=121/37%), congestive heart failure (n=114/35%), valve disease (n=92/28%), diabetes mellitus (n=85/26%), chronic kidney disease (n=59/18%), and rheumatic fever (49/15%). Renal failure is one of the main and most relevant pre-surgical risk factors for a poor prognosis. CONCLUSION: For a better clinical and surgical outcome, an early syndromic and etiological diagnosis of IE is necessary, especially in patients with multiple comorbidities.

FUNDAMENTO: A endocardite infecciosa (EI) refere-se à infecção da superfície endocárdica do coração e geralmente ocorre em valvas nativas ou protéticas. OBJETIVO: Este estudo teve como objetivo levantar dados de EI refletindo a terapêutica cirúrgica, em um Hospital Universitário do interior do estado de São Paulo ­ Brasil. MÉTODO: Abordagem retrospectiva e observacional de 328 pacientes com EI operados entre 1982 e 2020. RESULTADOS: Os principais dados (n=121/37%), insuficiência cardíaca congestiva (n=114/35%), valvopatia (n=92/28%), diabetes mellitus (n=85/26%), doença renal crônica (n=59/18%) e febre reumática (49/15%). A insuficiência renal é um dos principais e mais relevantes fatores de risco pré-cirúrgicos para um mau prognóstico. CONCLUSÃO: Para um melhor resultado clínico e cirúrgico é necessário o diagnóstico sindrômico e etiológico precoce da EI, principalmente em pacientes com múltiplas comorbidades.

Cirurgia de Endocardite Infecciosa. Análise de 328 Pacientes Operados em um Hospital Universitário Terciário / Infective Endocarditis Surgery. Insights from 328 Patients Operated in a University Tertiary Hospital

Resumo Fundamento A endocardite infecciosa (EI) refere-se à infecção da superfície endocárdica do coração e geralmente ocorre em valvas nativas ou protéticas. Objetivo Este estudo teve como objetivo levantar dados de EI refletindo a terapêutica cirúrgica, em um Hospital Universitário do interior do estado de São Paulo - Brasil. Método Abordagem retrospectiva e observacional de 328 pacientes com EI operados entre 1982 e 2020 Resultados Os principais dados (n=121/37%), insuficiência cardíaca congestiva (n=114/35%), valvopatia (n=92/28%), diabetes mellitus (n=85/26%), doença renal crônica (n=59/18%) e febre reumática (49/15%). A insuficiência renal é um dos principais e mais relevantes fatores de risco pré-cirúrgicos para um mau prognóstico. Conclusão Para um melhor resultado clínico e cirúrgico é necessário o diagnóstico sindrômico e etiológico precoce da EI, principalmente em pacientes com múltiplas comorbidades.

Abstract Background Infectious endocarditis (IE) refers to infection of the endocardial surface of the heart and usually occurs in native or prosthetic valves. Objective This study aimed to raise IE data reflecting the surgical therapy in a University Hospital in the interior of the State of Sao Paulo-Brazil. Method Retrospective and observational approach of 328 patients with IE who underwent surgery between 1982 and 2020 Results The main data (n=121/37%), congestive heart failure (n=114/35%), valve disease (n=92/28%), diabetes mellitus (n=85/26%), chronic kidney disease (n=59/18%), and rheumatic fever (49/15%). Renal failure is one of the main and most relevant pre-surgical risk factors for a poor prognosis. Conclusion For a better clinical and surgical outcome, an early syndromic and etiological diagnosis of IE is necessary, especially in patients with multiple comorbidities.

Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis.

INTRODUCTION: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale. METHODS: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output. RESULTS: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites). CONCLUSION: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.

Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis

Abstract Introduction: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale. Methods: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group — saline was injected at 0 and 10 minutes; 2) IC group — IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group — C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group — C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group — IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output. Results: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites). Conclusion: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.

Intradermal methylene blue administration on the progression of burn injuries.

OBJECTIVE: A burn injury has two defined areas: central necrosis and an adjacent area of ischaemia, which may or may not progress to necrosis. The concentration of nitric oxide (NO) increases after burn injury and may originate from potent oxidising agents. Methylene blue (MB) may act as an antioxidant and is supposed to reduce burn progression. This investigation was carried out to evaluate the effects of intradermal MB on necrosis progression in burns. METHODS: Full-thickness burn injuries were performed by applying a heated metal comb on the shaved back of male Wistar rats. The animals were divided into three groups: Control (C, n=7); MB (2mg/kg) one hour after burn injury (MB1h, n=11); and MB (2mg/kg) six hours after burn injury (MB6h, n=8). After seven days the lesions were photographed for visual assessment of burn necrosis; full-thickness cuts of lesions were dyed with Masson and Giemsa for microscopic histopathology; and tissue fragments of unburned interspaces were processed for chemiluminescence with nitrite/nitrate (NOX) and malondialdehyde (MDA) as oxidative stress markers. RESULTS: No statistically significant differences between groups were observed during visual analysis and NOX dosage. However, in microscopic analysis, the MB1h and MB6h groups showed smaller areas of necrosis, less inflammatory infiltration, and a more significant extension of interspaces. Furthermore, the dosage of MDA revealed that the MB1h group showed lower values when compared with the control group (p=0.001). CONCLUSIONS: The study provided good evidence that MB intradermal injection can reduce necrosis progression in ischaemic perilesional areas and suggests an alternative to treating burns.

After Thirty Years, We Still Cannot Understand Why Methylene Blue is not a Reference to Treat Vasoplegic Syndrome in Cardiac Surgery.

Vasoplegic syndrome (VS) comprises a constellation of concurrent signs and symptoms: hypotension, high cardiac index, low systemic vascular resistance, low filling pressures, the tendency to occur diffuse bleeding, and sustained hypotension. All of these parameters may persist even despite the use of high doses of vasoconstrictor amines. VS arises from vasoplegic endothelial dysfunction with excessive release of nitric oxide by polymorphonuclear leukocytes mediated by the nitric oxide synthase's inducible form and is associated with systemic inflammatory reaction and high morbimortality. The achievements regarding the treatment of VS with methylene blue (MB) are a valuable Brazilian contribution to cardiac surgery. The present text review was designed to deliver the accumulated knowledge in the past ten years of employing MB to treat VS after cardiac surgery. Considering that we have already published two papers describing acquired experiences and concepts after 15 and 20 years, now, as we achieve the 30-year mark, we compose a trilogy.