Vasopressin in vasoplegic shock in surgical patients: systematic review and meta-analysis

Purpose: Vasoplegia, or vasoplegic shock, is a syndrome whose main characteristic is reducing blood pressure in the presence of a standard or high cardiac output. For the treatment, vasopressors are recommended, and the most used is norepinephrine. However, new drugs have been evaluated, and conflicting results exist in the literature. Methods: This is a systematic review of the literature with meta-analysis, written according to the recommendations of the PRISMA report. The SCOPUS, PubMed, and ScienceDirect databases were used to select the scientific articles included in the study. Searches were conducted in December 2022 using the terms "vasopressin," "norepinephrine," "vasoplegic shock," "postoperative," and "surgery." Meta-analysis was performed using Review Manager (RevMan) 5.4. The endpoint associated with the study was efficiency in treating vasoplegic shock and reduced risk of death. Results: In total, 2,090 articles were retrieved; after applying the inclusion and exclusion criteria, ten studies were selected to compose the present review. We found no significant difference when assessing the outcome mortality comparing vasopressin versus norepinephrine (odds ratio = 1.60; confidence interval 0.47-5.50), nor when comparing studies on vasopressin versus placebo. When we analyzed the length of hospital stay compared to the use of vasopressin and norepinephrine, we identified a shorter length of hospital stay in cases that used vasopressin; however, the meta-analysis did not demonstrate statistical significance. Conclusions: Considering the outcomes included in our study, it is worth noting that most studies showed that using vasopressin was safe and can be considered in managing postoperative vasoplegic shock.

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

Abstract 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.

A Retrospective Study on Unfractionated Bovine Heparin Safety in On-Pump Cardiac Surgery

Abstract Background: Heparin decreases the risks of thrombotic phenomena in extracorporeal circulation. However, it must present a robust safety profile itself, especially for bleeding. Contamination of porcine heparin demands an alternative source and consequent assessment of safety. Objective: To evaluate the safety of unfractionated bovine heparin during on-pump cardiac surgery. Methods: Descriptive, retrospective study, evaluating medical records from all patients who had on-pump cardiac surgery over four years. We observed the occurrence of bleeding, thrombocytopenia, postoperative vasoplegia, activated clotting time values and any other coagulation phenomena as safety profile parameters. Results: We evaluated 204 medical records reporting the use of unfractionated bovine heparin. 66.18% of the patients presented thrombocytopenia, 1.04% presented bleeding of more than 2000 mL in the first 24 hours of the postoperative period. One patient presented clots in the surgical field. Median activated clotting time was 137 seconds at baseline, 803 seconds after the first dose of heparin and, after protamine, it returns to similar baseline values, that is, 149.5 seconds. Conclusion: Unfractionated bovine heparin did not present unusual adverse effects and can be considered safe for on-pump cardiac surgery.

Empleo preoperatorio de azul de metileno pre-implante de dispositivos de asistencia ventricular izquierda / Preoperative utilization of methylene blue previously to implant of left ventricular assist device

Introducción. El objetivo del presente estudio fue analizar el empleo preoperatorio de azul de metileno (AM) como prevención del desarrollo de síndrome vasopléjico en pacientes bajo implante de dispositivos de asistencia ventricular izquierda (DAVI), considerando: porcentaje de pacientes que desarrollan vasoplejía, requerimiento de vasopresores, morbimortalidad postoperatoria y seguridad del empleo del fármaco. Métodos. Fueron incluidos pacientes sometidos al implante de DAVI de flujo continuo (HeartMate II o HeartWare) entre enero de 2009 y enero de 2014. Los pacientes fueron aleatorizados a AM en dosis de 1,5 mg/Kg, previamente a la circulación extracorpórea, seguido por una infusión de 0,5 mg/Kg/hora del mismo. Se definió síndrome vasopléjico en base a hipotensión arterial con presión capilar pulmonar baja, índice cardíaco normal o elevado, resistencias sistémicas descendidas y requerimiento vasopresor. Un valor de P<0,05 se consideró significativo. Resultados. En el lapso del estudio fueron incluidos 64 pacientes, 33 de los cuales recibieron AM (dosis promedio 3,5 mg/kg) y 31 pacientes representaron el grupo control. Veinte (31,1%) pacientes desarrollaron vasoplejía, 6 (18,2%) pacientes en el grupo AM frente a 14 (45,2%) del grupo control (P=0,01; OR 0,27 con IC de 0,08-0,84). El requerimiento de vasopresores resulto, asimismo, inferior en los pretratados, 23 (69,7%) pacientes versus 30 (96,8%) pacientes (P=0,004; OR 0,07; IC 0,003-0,522). La mortalidad postoperatoria resulto de 13 (20,3%) pacientes, 4 (12,1%) de ellos en el grupo AM frente a 9 (29%) del grupo control (P=0,06; OR 0,35; IC 0,106-1,117). En todos los pacientes tratados con AM se evidenció el cambio de coloración de la orina. Cinco (7,8%) pacientes presentaron hipertensión arterial, requiriendo vasodilatadores endovenosos, 3 (9,1%) pacientes en el grupo AM frente a 2 (6,4%) en el grupo control (valor de P=0,3). Conclusiones. El empleo preoperatorio de AM se asoció con la reducción del desarrollo de síndrome vasopléjico, así como del requerimiento vasopresor. Se observó una reducción de complicaciones postoperatorias y una tendencia a menor mortalidad. Un número mayor de pacientes requiere ser valorado para comprobar la utilidad de esta estrategia

Introduction. The objective of this study was to analyze preoperative utilization of methylene blue (MB) for preventing development of vasoplegic syndrome in patients underwent left ventricle assist device (LVAD) implant considering: percentage of patients developing vasoplegia, vasopresor requirement, perioperative morbidity and mortality and safety associated with MB s use. Methods. There were admitted patients underwent an implant of a LVAD of continuous flow (HeartMate II or HeartWare) from January 2009 to January 2014. Patients were randomized to MB, 1.5 mg/Kg one hour before extracorporeal circulation followed for 0.5 mg/kg/hour or placebo (control group). It was defined vasoplegia by: arterial hypotension, low capillary pulmonary pressure, normal or elevated cardiac index, descended systemic vascular resistances and vasopresor requirement. A P<0.05 was considered significant. Results. There were included 64 patients, 33 of them were randomized to MB (average dose 3.5 mg/Kg) and 31 patients represented control group. Twenty (31.1%) patients developed vasoplegia, 6 (18.2%) patients from MB s group versus 14 (45.2%) patients from control group (P=0.01, OR 0.27, IC de 0.08-0.84). Vasopressor requirement was lower in those receiving MB 23 (69.7%) patients versus 30 (96.8%) patients (P=0.004, OR 0.07, IC 0.003- 0.522). Postoperative mortality was 13 (20.3%) patients, 4 (12.1%) of them receiving MB versus 9 (29%) patients from control group (P=0.06, OR 0.35 IC 0.106-1.117). In all treated patients it was evident a change in urine s color and also five (7.8%) patients developed arterial hypertension, requiring vasodilators 3 (9.1%) patients from MB s group versus 2 (6.4%) from control (valor de P=0.3). Conclusions. The preoperative use of MB was associated with reduction of vasoplegia and a lower vasopresor requirements. It was also observed reduction of postoperative complications and a trend to reduced mortality. A superior number of patients needs to be evaluated for proving the value of this strategy

Introdução. O objetivo deste estudo foi analisar a utilização pré-operatória do azul de metileno (AM) para prevenir o desenvolvimento da síndrome vasoplégica em pacientes submetidos a implante de dispositivo de assistência ventricular esquerda (DAVE), considerando: porcentagem de pacientes em desenvolvimento de vasoplegia, necessidade de vasopresor, morbidade e mortalidade e segurança perioperatórias associado ao uso do AM. Métodos. Foram admitidos pacientes submetidos a um implante de uma DAVE de fluxo contínuo (HeartMate II ou HeartWare) de janeiro de 2009 a janeiro de 2014. Os pacientes foram randomizados para AM, 1,5 mg/kg uma hora antes da circulação extracorpórea, seguidos por 0,5 mg/kg/hora ou placebo (grupo controle). Foi definida vasoplegia por: hipotensão arterial, pressão pulmonar capilar baixa, índice cardíaco normal ou elevado, resistências vasculares sistêmicas descendentes e necessidade de vasopresor. Um P<0,05 foi considerado significativo. Resultados. Foram incluídos 64 pacientes, 33 deles foram randomizados para MB (dose média de 3,5 mg / kg) e 31 pacientes representaram o grupo controle. Vinte (31,1%) pacientes desenvolveram vasoplegia, 6 (18,2%) pacientes do grupo AM versus 14 (45,2%) pacientes do grupo controle (P=0,01; OR 0,27; IC de 0,08-0,84). A necessidade de vasopressores foi menor nos pacientes que receberam AM 23 (69,7%) versus 30 (96,8%) pacientes (P=0,004; OR 0,07; IC 0,003-0,522). A mortalidade pós-operatória foi de 13 (20,3%) pacientes, 4 (12,1%) deles recebendo AM versus 9 (29%) pacientes do grupo controle (P=0,06; OR 0,35; IC 0,106-1,117). Em todos os pacientes tratados, foi evidente uma alteração na cor da urina e também cinco (7,8%) pacientes desenvolveram hipertensão arterial, exigindo vasodilatadores 3 (9,1%) pacientes do grupo AM versus 2 (6,4%) do controle (valor de P=0,3). Conclusões. O uso pré-operatório de AM foi associado à redução da vasoplegia e menor necessidade de vasopresor. Também foi observada redução das complicações pós-operatórias e tendência à redução da mortalidade. Um número superior de pacientes precisa ser avaliado para provar o valor dessa estratégia

Key Points for Curbing Cardiopulmonary Bypass Inflammation

PURPOSE: Cardiopulmonary bypass (CPB) procedures are thought to activate systemic inflammatory reaction syndrome (SIRS). Strategies to curb systemic inflammation have been previously described. However, none of them is adequate, since "curbing" the extent of the inflammatory response requires a multimodal approach. The aim of the present mini-review is to discuss the main key points about the main principles in cardiopulmonary bypass curbing inflammation. METHODS: No systematic literature search (MEDLINE) and extracted data from the accumulated experience of the authors. The preconceived idea of an association between severe inflammation and coagulation disorders is reviewed. Also, some fundamental concepts, CPB inflammatory biomarkers, the vasoplegic syndrome and the need forindividual CPB protocols for children, diabetes and old patients, are discussed. CONCLUSION: The ways in which surgical technique (atraumatic vein harvest, biocompatibility and shear resistance of the circuit, monitoring, minimizing organ ischemia, minimal cross-clamping trauma, and blood management) are thought to curb SIRS induced by CPB and affect positively the patient outcome.Improved patient outcomes are strongly associated with these modalities of care, more than single or combinatorial drug strategies (aprotinin, tranexamic acid, pentoxifylline) or CPB modalities (minicircuits, heparin-coated circuits, retrograde autologous prime).

Cardiopulmonary bypass increases the risk of vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure / O uso da circulação extracorpórea aumenta o risco de síndrome vasoplégica em pacientes com insuficiência renal crônica hemodialítica submetidos à revascularização cirúrgica do miocárdio

AbstractObjective:Coronary artery bypass grafting is currently the best treatment for dialysis patients with multivessel coronary artery involvement. Vasoplegic syndrome of inflammatory etiology constitutes an important postoperative complication, with highly negative impact on prognosis. Considering that these patients have an intrinsic inflammatory response exacerbation, our goal was to evaluate the incidence and mortality of vasoplegic syndrome after myocardial revascularization in this group.Methods:A retrospective, single-center study of 50 consecutive and non-selected dialysis patients who underwent myocardial revascularization in a tertiary university hospital, from 2007 to 2012. The patients were divided into 2 groups, according to the use of cardiopulmonary bypass or not (off-pump coronary artery bypass). The incidence and mortality of vasoplegic syndrome were analyzed. The subgroup of vasoplegic patients was studied separately.Results:There were no preoperative demographic differences between the cardiopulmonary bypass (n=20) and off-pump coronary artery bypass (n=30) group. Intraoperative data showed a greater number of distal coronary arteries anastomosis (2.8 vs. 1.8, P<0.0001) and higher transfusion rates (65% vs. 23%, P=0.008) in the cardiopulmonary bypass group. Vasoplegia incidence was statistically higher (P=0.0124) in the cardiopulmonary bypass group (30%) compared to the off-pump coronary artery bypass group (3%). Vasoplegia mortality was 50% in the cardiopulmonary bypass group and 0% in the off-pump coronary artery bypass group. The vasoplegic subgroup analysis showed no statistically significant clinical differences.Conclusion:Cardiopulmonary bypass increased the risk for developing postoperative vasoplegic syndrome after coronary artery bypass grafting in patients with dialysis-dependent chronic renal failure.

ResumoObjetivo:O melhor tratamento atual para os pacientes dialíticos com acometimento coronariano multiarterial é a revascularização cirúrgica do miocárdio. Dentre as complicações pós-operatórias, a síndrome vasoplégica de etiopatogenia inflamatória torna-se importante pelo impacto altamente negativo no prognóstico. Considerando que esses pacientes possuem uma exacerbação intrínseca da resposta inflamatória, nosso objetivo foi avaliar a incidência e a mortalidade da síndrome vasoplégica no pós-operatório de revascularização miocárdica nesse grupo.Métodos:Estudo retrospectivo, unicêntrico, de 50 pacientes dialíticos consecutivos e não selecionados, submetidos à revascularização miocárdica, em um hospital terciário universitário, no período de 2007 a 2012. Esses pacientes foram divididos em 2 grupos, de acordo com o emprego ou não da circulação extracorpórea. A incidência e a mortalidade da vasoplegia foram analisadas nos grupos. Após a identificação dos pacientes quanto à presença de vasoplegia, este subgrupo foi estudado separadamente.Resultados:Não houve diferenças demográficas pré-operatórias entre os grupos com circulação extracorpórea (n=20) e sem circulação extracorpórea (n=30). Dados intraoperatórios demonstraram maior número de artérias coronárias revascularizadas (2,8 vs. 1,8; P<0,0001) e maior necessidade de transfusão (65% vs. 23%; P=0,008) no grupo circulação extracorpórea. A incidência de vasoplegia foi estatisticamente maior (P=0,0124) no grupo circulação extracorpórea (30%) em comparação ao grupo sem circulação extracorpórea (3%). A mortalidade dos pacientes com vasoplegia foi 50% no grupo circulação extracorpórea e 0% no grupo sem circulação extracorpórea. A análise do subgrupo vasoplégico não demonstrou diferenças clínicas estatisticamente significantes.Conclusão:O emprego da circulação extracorpórea na revascularização cirúrgica do miocárdio em pacientes com insuficiência renal crônica dialítica aumentou o risco para desenvolvimento de síndrome vasoplégica pós-operatória.

Reclassificando o espectro de pacientes septicos com o uso do lactato: sepse grave, choque criptico, choque vasoplegico e choque disoxico / Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock

Objetivo: A definição atual de sepse grave e choque séptico inclui um perfil heterogêneo de pacientes. Embora o valor prognóstico de hiperlactatemia seja bem estabelecido, ela está presente em pacientes com ou sem choque. Nosso objetivo foi comparar o prognóstico de pacientes sépticos estratificando-os segundo dois fatores: hiperlactatemia e hipotensão persistente. Métodos: Este estudo é uma análise secundária de um estudo observacional conduzido em dez hospitais no Brasil (Rede Amil - SP). Pacientes sépticos com valor inicial de lactato das primeiras 6 horas do diagnóstico foram incluídos e divididos em 4 grupos segundo hiperlactatemia (lactato >4mmol/L) e hipotensão persistente: (1) sepse grave (sem ambos os critérios); (2) choque críptico (hiperlactatemia sem hipotensão persistente); (3) choque vasoplégico (hipotensão persistente sem hiperlactatemia); e (4) choque disóxico (ambos os critérios). Resultados: Foram analisados 1.948 pacientes, e o grupo sepse grave constituiu 52% dos pacientes, seguido por 28% com choque vasoplégico, 12% choque disóxico e 8% com choque críptico. A sobrevida em 28 dias foi diferente entre os grupos (p<0,001), sendo maior para o grupo sepse grave (69%; p<0,001 versus outros), semelhante entre choque críptico e vasoplégico (53%; p=0,39) e menor para choque disóxico (38%; p<0,001 versus outros). Em análise ajustada, a sobrevida em 28 dias permaneceu diferente entre os grupos (p<0,001), sendo a maior razão de risco para o grupo choque disóxico (HR=2,99; IC95% 2,21-4,05). Conclusão: A definição de pacientes com sepse inclui quatro diferentes perfis, se considerarmos a presença de hiperlactatemia. Novos estudos são necessários para melhor caracterizar pacientes sépticos e gerar conhecimento ...

Objective: The current definition of severe sepsis and septic shock includes a heterogeneous profile of patients. Although the prognostic value of hyperlactatemia is well established, hyperlactatemia is observed in patients with and without shock. The present study aimed to compare the prognosis of septic patients by stratifying them according to two factors: hyperlactatemia and persistent hypotension. Methods: The present study is a secondary analysis of an observational study conducted in ten hospitals in Brazil (Rede Amil - SP). Septic patients with initial lactate measurements in the first 6 hours of diagnosis were included and divided into 4 groups according to hyperlactatemia (lactate >4mmol/L) and persistent hypotension: (1) severe sepsis (without both criteria); (2) cryptic shock (hyperlactatemia without persistent hypotension); (3) vasoplegic shock (persistent hypotension without hyperlactatemia); and (4) dysoxic shock (both criteria). Results: In total, 1,948 patients were analyzed, and the sepsis group represented 52% of the patients, followed by 28% with vasoplegic shock, 12% with dysoxic shock and 8% with cryptic shock. Survival at 28 days differed among the groups (p<0.001). Survival was highest among the severe sepsis group (69%, p<0.001 versus others), similar in the cryptic and vasoplegic shock groups (53%, p=0.39), and lowest in the dysoxic shock group (38%, p<0.001 versus others). In the adjusted analysis, the survival at 28 days remained different among the groups (p<0.001) and the dysoxic shock group exhibited the highest hazard ratio (HR=2.99, 95%CI 2.21-4.05). Conclusion: The definition of sepsis includes four different profiles if we consider the presence of hyperlactatemia. Further studies are needed to better characterize septic patients, to understand the etiology and to design adequate targeted treatments. .

Disfunção endotelial vasoplégica / The endothelial vasoplegic dysfunction

Embora a maioria dos estados de choque circulatório esteja associada com diminuição do débito cardíaco, uma situação distinta ocorre nos casos de choques por diminuição da capacitância vascular, na qual a situação de vasoplegia associa-se à elevação do débito cardíaco, configurando uma situação hiperdinâmica com hipotensão grave resistente a altas doses de catecolaminas. O mau prognóstico parece mais bem correlacionado com a baixa resistência vascular, levando à conclusão de que a vasoplegia é o fator prognóstico determinante. Dessa forma, o controle parácrino da capacitância vascular passa a ser um fator extremamente importante para investigações clínicas e experimentais na busca de novos conhecimentos fisiopatológicos e terapêuticos que possam contribuir para o tratamento e prognóstico da vasoplegia. Assim, a disfunção endotelial “vasoplégica” estaria presente nos estados de choque distributivo causada por ações de citocinas que estimulam liberação patológica de fatores relaxantes do endotélio, principalmente do óxido nítrico (sepse, anafilaxia, reações anafilactoides e vasoplegias relacionadas à circulação extracorpórea). Ressalte-se que a disfunção endotelial está associada a todos os tipos de estado de choque, disfunção essa abordada nessa revisão.

Although most circulatory shock conditions are associated with decreased cardiac output, a different situation occurs in cases of circulatory shock by decreasing vascular capacitance vasoplegia when the condition is associated with elevation of cardiac output by setting a hyperdynamic state with hypotension resistant to high doses of catecholamines. The poor prognosis appears better correlated with low vascular resistance, leading to the conclusion that the vasoplegia prognostic factor is decisive. Thus, the paracrine control of vascular capacitance becomes an extremely important factor for clinical and experimental investigations in research of new pathophysiological and therapeutic knowledge that may contribute to the treatment and prognosis of vasoplegia. Thus, endothelial "vasoplegic" dysfunction would be present in the distributive shock states caused by the actions of cytokines that stimulate pathological release of endothelial relaxing factors, mainly nitric oxide (sepsis, anaphylaxis, anaphylactic reactions and vasoplegias related to cardiopulmonary bypass). It is noteworthy that endothelial dysfunction is associated with all types of shocks and this impairment is discussed in this review.

Cirugía cardiaca con circulación extracorpórea: síndrome vasoplégico y vasopresina / Vasoplegic syndrome and its treatment with vasopressin during cardiac surgery with cardiopulmonary bypass

Cardiac surgery with cardiopulmonary bypass is associated with systemic inflammatory response. In some cases this clinical condition is characterized by severe hypotension due to low systemic vascular resistance during and after cardiopulmonary bypass. Afew ofthese cases do not respond to volume or catecholamines. This condition is known as vasoplegic syndrome. Its etiology is notfully understood today and carries associated morbidity and mortality In this syndrome, vasopressin levéis are reduced, as in septic and hypovolemic shock. Supplementary vasopressin improves blood pressure and might be considered as an alternative treatment. Severa! reports have shown benefits when used alone or in combination with catecholamines. However, further studies are necessary to find the most appropriate use ofthe drug for vasoplegic syndrome.

Uso do azul de metileno na reversão de vasoplegia refratária ao uso de catecolaminas após bypass aortobifemoral / Use of methylene blue in the reversal of vasoplegia refractory to the use of catecholamines after aortobifemoral bypass

Há evidências de que o óxido nítrico (NO) tem importância na vasodilatação associada a reações vasoplégicas. O objetivo deste relato de caso é documentar um caso de vasoplegia refratária ao uso de catecolaminas após bypass aortobifemoral revertida com o uso de azul de metileno. Mulher, 50 anos, submetida a bypass aortobifemoral. Sem comorbidades. Saiu de sala cirúrgica extubada, estável e com pulsos distais presentes. Duas horas após a cirurgia, evoluiu com choque circulatório. Iniciada noradrenalina e investigadas causas de choque. Manteve-se com necessidades crescentes de aminas e parâmetros estáveis. No sexto dia pós-operatório, com a hipótese de vasoplegia refratária, optou-se pelo uso do azul. Resposta imediata, com queda nos níveis de aminas, sendo desligada a noradrenalina no dia seguinte. O azul de metileno inibe a guanilato ciclase, produtora de guanosina monofosfato cíclico. Especula-se que haja um sinergismo entre essas drogas, já que a sua associação permite a atuação do sistema adenosina monofosfato.

There is evidence that the nitric oxide plays an important role in the vasodilation associated with vasoplegic reactions. The objective of this case report is to document a case of catecholamine-refractory shock after aortobifemoral bypass treated with methylene blue. A 50-year-old woman was admitted for aortobifemoral bypass graft surgery. She did not present with any comorbidities. At the end of the surgery, she was breathing spontaneously, with palpable pedal pulses. Two hours later, the patient presented shock. Noradrenaline infusion was initiated and the causes of shock were investigated. She required increasing doses of amines and her parameters were stable. On the sixth day after surgery, methylene blue was administered due to the hypothesis of refractory vasoplegia. There was immediate response, with decrease in the catecholamine infusion levels until its withdrawal on the next day. Methylene blue inhibits the enzyme guanylate cyclase that produces GMPc. There might be a synergism between these two drugs, since their association allows the action of the AMPc system.

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties / Azul de metileno no tratamento da síndrome vasoplégica em cirurgia cardíaca: quinze anos de perguntas, respostas, dúvidas e certezas

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

OBJETIVO: Existem fortes evidências de que o azul de metileno (AM), um inibidor da guanilato ciclase, é uma excelente opção terapêutica para o tratamento da síndrome vasoplégica (SV) em cirurgia cardíaca. O objetivo deste artigo é rever o papel terapêutico do AM no tratamento da SV. MÉTODOS: Revisão da literatura em período de 15 anos. RESULTADOS: 1) A heparina e inibidores da ECA são fatores de risco; 2) Nas doses preconizadas é droga segura (a dose letal é de 40 mg/kg); 3) O AM não causa disfunção endotelial; 4) O efeito do AM só aparece em caso de supra-regulação de óxido nítrico (NO); 5) O AM não é um vasoconstritor, pelo bloqueio do sistema GMPc ele "libera" o sistema AMPc, facilitando o efeito vasoconstritor da noradrenalina; 6) A dosagem mais utilizada é 2 mg/kg em bolus endovenosa, seguida de infusão contínua, pois a concentração plasmática decai acentuadamente nos primeiros 40 minutos; 7) Existe possível "janela de oportunidade" para efetividade do AM. CONCLUSÃO: Embora não existam estudos multicêntricos definitivos, a utilização do AM no tratamento da SV em cirurgia cardíaca é, na atualidade, a melhor, mais segura e barata opção, sendo contribuição brasileira