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.

Right atrium tumor extension through the inferior vena cava. considerations about nine cases operated under cardiopulmonary bypass

Abstract Introduction: Adrenocortical and renal cell carcinomas rarely invade the right atrium (RA). These neoplasms need surgical treatment, are very aggressive and have poor prognostic and surgical outcomes. Case series: We present a retrospective cohort of nine cases of RA invasion through the inferior vena cava (four adrenocortical carcinomas and five renal cell carcinomas). Over 13 years (2002-2014), nine patients were operated in collaboration with the team of urologists. Surgery was possible in all patients with different degrees of technical difficulty. All patients were operated considering the imaging examinations with the aid of CPB. In all reported cases (renal or suprarenal), the decision to use CPB with deep hypothermic circulatory arrest (DHCA) on surgical strategy was decided by the team of urological and cardiac surgeons. Conclusion: Data retrospectively collected from patients of public hospitals reaffirm: 1) Low incidence with small published series; 2) The selected cases did not represent the whole historical casuistry of the hospital, since they were selected after the adoption of electronic documentation; 3) Demographic data and references reported in the literature were presented as tables to avoid wordiness; 4) The series highlights the propensity to invade the venous system; 5) Possible surgical treatment with the aid of CPB in collaboration with the urology team; 6) CPB with DHCA is a safe and reliable option; 7) Poor prognosis with disappointing late results, even considering the adverse effects of CPB on cancer prognosis are expected but not confirmed.

Right Atrium Tumor Extension Through the Inferior Vena Cava. Considerations About Nine Cases Operated Under Cardiopulmonary Bypass.

INTRODUCTION: Adrenocortical and renal cell carcinomas rarely invade the right atrium (RA). These neoplasms need surgical treatment, are very aggressive and have poor prognostic and surgical outcomes. CASE SERIES: We present a retrospective cohort of nine cases of RA invasion through the inferior vena cava (four adrenocortical carcinomas and five renal cell carcinomas). Over 13 years (2002-2014), nine patients were operated in collaboration with the team of urologists. Surgery was possible in all patients with different degrees of technical difficulty. All patients were operated considering the imaging examinations with the aid of CPB. In all reported cases (renal or suprarenal), the decision to use CPB with deep hypothermic circulatory arrest (DHCA) on surgical strategy was decided by the team of urological and cardiac surgeons. CONCLUSION: Data retrospectively collected from patients of public hospitals reaffirm: 1) Low incidence with small published series; 2) The selected cases did not represent the whole historical casuistry of the hospital, since they were selected after the adoption of electronic documentation; 3) Demographic data and references reported in the literature were presented as tables to avoid wordiness; 4) The series highlights the propensity to invade the venous system; 5) Possible surgical treatment with the aid of CPB in collaboration with the urology team; 6) CPB with DHCA is a safe and reliable option; 7) Poor prognosis with disappointing late results, even considering the adverse effects of CPB on cancer prognosis are expected but not confirmed.

Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised.

OBJECTIVE: This study was conducted to reassess the concepts established over the past 20 years, in particular in the last 5 years, about the use of methylene blue in the treatment of vasoplegic syndrome in cardiac surgery. METHODS: A wide literature review was carried out using the data extracted from: MEDLINE, SCOPUS and ISI WEB OF SCIENCE. RESULTS: The reassessed and reaffirmed concepts were 1) MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not cause endothelial dysfunction; 3) The MB effect appears in cases of NO up-regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same continuous infusion because plasma concentrations sharply decrease in the first 40 minutes; and 6) There is a possible "window of opportunity" for MB's effectiveness. In the last five years, major challenges were: 1) Observations about side effects; 2) The need for prophylactic and therapeutic guidelines, and; 3) The need for the establishment of the MB therapeutic window in humans. CONCLUSION: MB action to treat vasoplegic syndrome is time-dependent. Therefore, the great challenge is the need, for the establishment the MB therapeutic window in humans. This would be the first step towards a systematic guideline to be followed by possible multicenter studies.

Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised / Vinte anos de tratamento da síndrome vasoplégica em cirurgia cardíaca. Azul de metileno revisado

Objective: This study was conducted to reassess the concepts established over the past 20 years, in particular in the last 5 years, about the use of methylene blue in the treatment of vasoplegic syndrome in cardiac surgery. Methods: A wide literature review was carried out using the data extracted from: MEDLINE, SCOPUS and ISI WEB OF SCIENCE. Results: The reassessed and reaffirmed concepts were 1) MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not cause endothelial dysfunction; 3) The MB effect appears in cases of NO up-regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same continuous infusion because plasma concentrations sharply decrease in the first 40 minutes; and 6) There is a possible "window of opportunity" for MB's effectiveness. In the last five years, major challenges were: 1) Observations about side effects; 2) The need for prophylactic and therapeutic guidelines, and; 3) The need for the establishment of the MB therapeutic window in humans. Conclusion: MB action to treat vasoplegic syndrome is time-dependent. Therefore, the great challenge is the need, for the establishment the MB therapeutic window in humans. This would be the first step towards a systematic guideline to be followed by possible multicenter studies. .

Objetivo: O presente estudo foi realizado com a finalidade de reavaliar conceitos estabelecidos em 20 anos, com ênfase nos últimos 5 anos, sobre a utilização do azul de metileno no tratamento da síndrome vasoplégica em cirurgia cardíaca. Métodos: Foram considerados dados da literatura utilizando-se três bases de dados (MEDLINE, SCOPUS e ISI Web of Science). Resultados: Os conceitos reavaliados e reafirmados foram: 1) Nas doses recomendadas o AM é seguro (a dose letal é de 40 mg/kg); 2) O AM não causa disfunção endotelial; 3) O efeito do AM só aparece em caso de supra nivelamento do NO; 4) O AM não é um vasoconstritor, pelo bloqueio da via GMPc ele libera a via do AMPc, facilitando o efeito vasoconstritor da norepinefrina; 5) A dosagem mais utilizada é de 2 mg/kg, como bolus EV, seguida de infusão contínua porque as concentrações plasmáticas decaem fortemente nos primeiros 40 minutos, e; 6) Existe uma "janela de oportunidade" precoce para efetividade do AM. Nos últimos cinco anos, os principais desafios foram: 1) Observações de efeitos colaterais; 2) A necessidade de diretrizes, e; 3) A necessidade da determinação de uma janela terapêutica para o uso do AM em humanos. Conclusão: O efeito do AM no tratamento da SV é dependente do tempo, portanto, o grande desafio atual é a necessidade do estabelecimento da janela terapêutica do AM em humanos. Esse seria o primeiro passo para a sistematização de uma diretriz a ser seguida por possíveis estudos multicêntricos. .

A variant "no-patch" technique for surgery of left ventricular aneurysms.

A variant "no-patch" technique for the surgical treatment of left ventricular aneurysms is described. The entire operation is performed using a single suture tied after the 2 encircling stitch adjustments and at the final external suture. Before the second encircling pursestring stitch, scar tissue circular plication is carried out. The final closure is completed by an out-out suture that ensures hemostasis. Finally, it is emphasized that the no-patch surgical strategy has the indirect advantage of saving time because the stitches are performed in a continuous manner.

A variant technique for the surgical treatment of left ventricular aneurysms.

OBJECTIVE: To present a surgical variant technique to repair left ventricular aneurysms. METHODS: After anesthesia, cardiopulmonary bypass, and myocardial protection with hyperkalemic tepic blood cardioplegia: 1) The left ventricle is opened through the infarct and an endocardial encircling suture is placed at the transitional zone between the scarred and normal tissue; 2) Next, the scar tissue is circumferentially plicated with deep stitches using the same suture thread, taking care to eliminate the entire septal scar; 3) Then, a second encircling suture is placed, completing the occlusion of the aneurysm, and; 4) Finally, the remaining scar tissue is oversewn with an invaginating suture, to ensure hemostasis. Myocardium revascularization is performed after correction of the left ventricle aneurysm. The same surgeon performed all the operations. RESULTS: Regarding the post-surgical outcome 4 patients (40%) had surgery 8 eight years ago, 2 patients (20%) were operated on over 6 years ago, and 1 patient (10%) was operated on more than 5 years ago. Three patients (30%) were in functional class I, class II in 2 patients (20%) and 2 patients (20%) with severe comorbidities remains in class III of the NYHA. There were three deaths (at four days, 15 days and eight months) in septuagenarians with acute myocardial infarction, diabetes and pulmonary emphysema. CONCLUSION: The technique is easy to perform, safe and it can be an option for the correction of left ventricle aneurysms.

Pressure support-ventilation versus spontaneous breathing with "T-Tube" for interrupting the ventilation after cardiac operations / Pressão de suporte ventilatório versus respiração espontânea em "Tubo-T" para a interrupção da ventilação após as operações cardíacas

OBJECTIVE: To compare pressure-support ventilation with spontaneous breathing through a T-tube for interrupting invasive mechanical ventilation in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Adults of both genders were randomly allocated to 30 minutes of either pressure-support ventilation or spontaneous ventilation with "T-tube" before extubation. Manovacuometry, ventilometry and clinical evaluation were performed before the operation, immediately before and after extubation, 1h and 12h after extubation. RESULTS: Twenty-eight patients were studied. There were no deaths or pulmonary complications. The mean aortic clamping time in the pressure support ventilation group was 62 ± 35 minutes and 68 ± 36 minutes in the T-tube group (P=0.651). The mean cardiopulmonary bypass duration in the pressure-support ventilation group was 89 ± 44 minutes and 82 ± 42 minutes in the T-tube group (P=0.75). The mean Tobin index in the pressure support ventilation group was 51 ± 25 and 64.5 ± 23 in the T-tube group (P=0.153). The duration of intensive care unit stay for the pressure support ventilation group was 2.1 ± 0.36 days and 2.3 ± 0.61 days in the T-tube group (P=0.581). The atelectasis score in the T-tube group was 0.6 ± 0.8 and 0.5 ± 0.6 (P=0.979) in the pressure support ventilation group. The study groups did not differ significantly in manovacuometric and ventilometric parameters and hospital evolution. CONCLUSION: The two trial methods evaluated for interruption of mechanical ventilation did not affect the postoperative course of patients who underwent cardiac operations with cardiopulmonary bypass.

OBJETIVO: Comparar a pressão de suporte ventilatório com a respiração espontânea em "Tubo-T" para interrupção da ventilação invasiva em pacientes submetidos à operação cardíaca. MÉTODOS: Adultos de ambos os sexos foram alocados para pressão de suporte ventilatório por 30 minutos ou o mesmo período de ventilação espontânea com "Tubo-T" antes da extubação. Realizou-se manovacuometria, ventilometria e avaliação clínica antes da operação, imediatamente antes e após a extubação, 1h e 12h após extubação. RESULTADOS: Vinte e oito pacientes foram estudados. Não ocorreram mortes ou complicações respiratórias. O tempo de pinçamento da aorta no grupo suporte ventilatório foi 62 ± 35 minutos e de 68 ± 36 minutos para o "Tubo-T" (P=0,651). O tempo de CEC no grupo suporte ventilatório foi 89 ± 44 minutos e para o "Tubo-T" de 82 ± 42 minutos (P=0,75). O índice de Tobin para o grupo suporte ventilatório foi 51 ± 25 e para o grupo "Tubo-T", 64,5 ± 23 (P=0,153). O tempo na unidade de terapia intensiva para o grupo suporte ventilatório foi 2,1 ± 0,36 dias e para o grupo "Tubo-T", 2,3±0,61 dias (P=0,581). O escore de atelectasia para o grupo "Tubo-T" foi 0,6 ± 0,8 e para o suporte ventilatório foi 0,5 ± 0,6 (P=0,979). Não houve diferença significativa na evolução clínica e nos valores de gasometria, manovacuometria e ventilometria entre ambos os grupos. CONCLUSÃO: O método utilizado para testar a adequação da interrupção da ventilação mecânica invasiva não afetou a evolução pós-operatória dos pacientes submetidos a operações cardíacas com circulação extracorpórea.

Exhaled nitrite/nitrate levels as a marker of respiratory complications after heart valve surgery.

PURPOSE: The purposes of this study are to measure the nitric oxide metabolites nitrite and nitrate (NOx) in the exhaled breath condensates (EBCs) of patients submitted to heart valve surgery and to assess the correlation between NOx levels and postoperative respiratory complications. MATERIALS AND METHODS: Exhaled breath condensate and blood samples were collected from each patient during spontaneous breathing preoperatively, during invasive mechanical ventilation in the fourth hour after surgery and 12, 24, 48, and 72 hours after the operation. Nitrite and nitrate levels in the EBC and serum were measured by chemiluminescence. RESULTS: Thirty-two patients were included in the study. In patients who presented with postoperative respiratory complications, the postoperative levels of NOx were significantly higher in the EBC from the fourth postoperative hour compared with those who experienced uneventful postoperative periods (P = .027). However, the preoperative and postoperative serum levels of NOx were not significantly different in between-group analyses (P = .995). CONCLUSION: Our results suggest that the postoperative NOx level in the EBC is an early marker of respiratory complications after heart valve surgery. Additional studies using large cohorts are necessary to corroborate our results and to better define the clinical usefulness of assessing NOx in the EBC after cardiac surgery.

Pressure support-ventilation versus spontaneous breathing with "T-Tube" for interrupting the ventilation after cardiac operations.

OBJECTIVE: To compare pressure-support ventilation with spontaneous breathing through a T-tube for interrupting invasive mechanical ventilation in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Adults of both genders were randomly allocated to 30 minutes of either pressure-support ventilation or spontaneous ventilation with "T-tube" before extubation. Manovacuometry, ventilometry and clinical evaluation were performed before the operation, immediately before and after extubation, 1h and 12h after extubation. RESULTS: Twenty-eight patients were studied. There were no deaths or pulmonary complications. The mean aortic clamping time in the pressure support ventilation group was 62 ± 35 minutes and 68 ± 36 minutes in the T-tube group (P=0.651). The mean cardiopulmonary bypass duration in the pressure-support ventilation group was 89 ± 44 minutes and 82 ± 42 minutes in the T-tube group (P=0.75). The mean Tobin index in the pressure support ventilation group was 51 ± 25 and 64.5 ± 23 in the T-tube group (P=0.153). The duration of intensive care unit stay for the pressure support ventilation group was 2.1 ± 0.36 days and 2.3 ± 0.61 days in the T-tube group (P=0.581). The atelectasis score in the T-tube group was 0.6 ± 0.8 and 0.5 ± 0.6 (P=0.979) in the pressure support ventilation group. The study groups did not differ significantly in manovacuometric and ventilometric parameters and hospital evolution. CONCLUSION: The two trial methods evaluated for interruption of mechanical ventilation did not affect the postoperative course of patients who underwent cardiac operations with cardiopulmonary bypass.

Effects of elevated perfusion pressure and pulsatile flow on human saphenous veins isolated from diabetic and non-diabetic patients.

OBJECTIVE: This study was carried out to determine high pressure and pulsatile flow perfusion effects on human saphenous vein (HSV) segments obtained from diabetic and non-diabetic patients. METHODS: The veins were perfused with oxygenated Krebs solution for 3 h, with a pulsatile flow rate of 100 mL/min and pressures of 250 × 200 or 300 × 250 mmHg. After perfusion, veins were studied by light microscopy; nitric oxide synthase (NOS) isoforms, CD34 and nitrotyrosine immunohistochemistry and tissue nitrite/nitrate (NO(x)) and malondialdehyde (MDA) quantification. RESULTS: Light microscopy revealed endothelial denuding areas in all HSV segments subjected to 300 × 250 mmHg perfusion pressure, but the luminal area was similar. The percentage of luminal perimeter covered by endothelium decreased as perfusion pressures increased, and significant differences were observed between groups. The endothelial nitric oxide synthase (eNOS) isoform immunostaining decreased significantly in diabetic patients' veins independent of the perfusion pressure levels. The inducible NOS (iNOS), neuronal NOS (nNOS) and nitrotyrosine immunostaining were similar. Significant CD34 differences were observed between the diabetic 300 × 250 mmHg perfusion pressure group and the non-diabetic control group. Tissue nitrite/nitrate and MDA were not different among groups. CONCLUSIONS: Pulsatile flow and elevated pressures for 3 h caused morphological changes and decreased the eNOS expression in the diabetic patients' veins.

Reflections on the 24 years durability of an isolate tricuspid bovine pericardium IMC/Braile bioprosthesis / Reflexões sobre a durabilidade de 24 anos de uma bioprótese IMC/Braile de pericárdio bovino em posição tricúspide isolada

We were challenged by the experience of one patient reoperation for a bioprosthetic bovine pericardium degenerative stenosis, 24 years after implantation. This bioprosthesis was implanted due to tricuspid valve bacterial staphylococcal endocarditis after septic abortion.

Vivenciamos a experiência de reoperar uma paciente por estenose degenerativa de uma prótese biológica de pericárdio bovino, após 24 anos de implante. Essa prótese degenerada havia sido implantada devido à destruição da valva tricúspide por endocardite bacteriana estafilocócica após aborto séptico.

Reflections on the 24 years durability of an isolate tricuspid bovine pericardium IMC/Braile bioprosthesis.

We were challenged by the experience of one patient reoperation for a bioprosthetic bovine pericardium degenerative stenosis, 24 years after implantation. This bioprosthesis was implanted due to tricuspid valve bacterial staphylococcal endocarditis after septic abortion.

Preoperative respiratory muscle dysfunction is a predictor of prolonged invasive mechanical ventilation in cardiorespiratory complications after heart valve surgery.

OBJECTIVE: To verify whether preoperative respiratory muscle strength and ventilometric parameters, among other clinically relevant factors, are associated with the need for prolonged invasive mechanical ventilation (PIMV) due to cardiorespiratory complications following heart valve surgery. METHODS: Demographics, preoperative ventilometric and manometric data, and the hospital course of 171 patients, who had undergone heart valve surgery at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, were prospectively collected and subjected to univariate analysis for identifying the risk factors for PIMV. RESULTS: The hospital mortality was 7%. About 6% of the patients, who had undergone heart valve surgery required PIMV because of postoperative cardiorespiratory dysfunction. Their hospital mortality was 60% (vs 4%, p < 0.001). Univariate analysis revealed that preoperative respiratory muscle dysfunction, characterized by maximal inspiratory and expiratory pressure below 70% of the predicted values combined with respiratory rate above 15 rpm during ventilometry, was associated with postoperative PIMV (p = 0.030, odds ratio: 50, 95% confidence interval (CI): 1.2-18). Postoperative PIMV was also associated with: (1) body mass index (BMI)<18.5 (odds ratio: 7.2, 95% CI: 1.5-32), (2) body weight < 50 kg (odds ratio: 6.5, 95% CI: 1.6-25), (3) valve operation due to acute endocarditis (odds ratio: 5.5, 95% CI: 0.98-30), and (4) concomitant operation for mitral and tricuspid valve dysfunction (p = 0.047, odds ratio: 5.0, 95% CI: 1.1-22). CONCLUSION: Our results have demonstrated that respiratory muscle dysfunction, among other clinical factors, is associated with the need for PIMV due to cardiovascular or pulmonary dysfunction after heart valve surgery.

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties.

OBJECTIVE: There is strong evidence that methylene blue (MB), an inhibitor of guanylate cyclase, is an excellent therapeutic option for vasoplegic syndrome (VS) treatment in heart surgery. The aim of this article is to review the MB's therapeutic function in the vasoplegic syndrome treatment. METHODS: Fifteen years of literature review. RESULTS: 1) Heparin and ACE inhibitors are risk factors; 2) In the recommended doses it is safe (the lethal dose is 40 mg/kg); 3) The use of MB does not cause endothelial dysfunction; 4) The MB effect appears in cases of nitric oxide (NO) up-regulation; 5) MB is not a vasoconstrictor, by blocking of the GMPc system it releases the AMPc system, facilitating the norepinephrine vasoconstrictor effect; 6) The most used dosage is 2 mg/kg as IV bolus followed by the same continuous infusion because plasmatic concentrations strongly decays in the first 40 minutes; 7) There is a possible 'window of opportunity' for the MB's effectiveness. CONCLUSIONS: Although there are no definitive multicentric studies, the MB used to treat heart surgery VS, at the present time, is the best, safest and cheapest option, being a Brazilian contribution for the heart surgery.