Use of Methylene Blue to Treat Vasoplegia Syndrome in Cystic Fibrosis Patients Undergoing Lung Transplantation: A Case Series

Background: Several studies have demonstrated the utility of methylene blue (MB) to treat vasoplegic syndrome (VS), but some have cautioned against its routine use in lung transplantation with only two cases described in prominent literature. Cystic fibrosis patients commonly have chronic infections which predispose them to a systemic inflammatory syndrome-like vasoplegic response during lung transplantation. We present 13 cystic fibrosis patients who underwent lung transplantation and received MB for vasoplegic syndrome while on cardiopulmonary bypass, with or without inhaled pulmonary vasodilator therapy. Methods: Single?center, retrospective, case series analysis of cystic fibrosis patients who underwent lung transplant and received MB for vasoplegia. We defined the primary outcome as 30-day mortality, and secondary outcomes as primary graft failure, 1-year mortality, postoperative complications, and hemodynamic response to MB. Results: MB was associated with a significant increase in mean arterial pressure (MAP) (P < 0.001) in all patients, and 84.6% (11/13) of the patients had either a decrease or no change in vasopressor requirement. No patients developed acute primary graft dysfunction and there was 100% 30?day and 1?year survival. One patient required Extracorporeal membrane oxygenation (ECMO) for hypoxemia and 69% (9/13) of the patients had evidence of postoperative right ventricular dysfunction, but no patients required a right ventricular assist device. Conclusion: This case series demonstrates the effectiveness of MB in treating vasoplegia in cystic fibrosis patients during lung transplantation, without evidence of primary graft dysfunction, 30?day or 1?year mortality. The safety of MB regarding hypoxemia and increased pulmonary vascular resistance requires further investigation.

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.

VASOplegia is Predicted by Preoperative Platelet?LEucocyte conGlomerate Indices in Cardiac Surgery (VASOPLEGICS): A Retrospective Single?Center Study

Background:Post?cardiotomy vasoplegia syndrome (VS) is often linked to an exaggerated inflammatory response to cardiopulmonary bypass (CPB). At the same time, the prognostic role of platelet?leucocyte indices (PLIs) and leucocyte indices (LIs), (platelet?lymphocyte ratio [PLR], systemic immune?inflammation index [SII = platelet neutrophil/lymphocyte], aggregate index of systemic inflammation [AISI = platelet monocyte neutrophil/lymphocyte], and neutrophil?lymphocyte ratio [NLR], systemic inflammation response index [SIRI = monocyte neutrophil/lymphocyte), respectively] has been recently described in diverse inflammatory settings. Methods: The retrospective study was conducted to evaluate the VS predictive performance of PLIs and LIs in 1,045 adult patients undergoing elective cardiac surgery at a tertiary care center. VS was defined by mean blood pressure <60 mmHg, low systemic vascular resistance (SVRI <1,500 dynes.s/cm 5/m2 ), a normal or high CI (>2.5 L/min/m2 ), and a normal or reduced central filling pressure despite high?dose vasopressors. Results: About 205 (19.61%) patients developed VS postoperatively. On univariate analysis, age, diabetes, dialysis?dependent renal failure, preoperative congestive heart failure (CHF), the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, ejection fraction, NLR, PLR, SII, SIRI, AISI, CPB, and aortic cross clamp (ACC) duration, packed red blood cell (PRBC) transfusion, and time?weighted average blood glucose predicted VS. Subsequent to the multivariate analysis, the predictive performance of EuroSCORE II (OR: 3.236; 95% CI: 2.345–4.468; P < 0.001), CHF (OR: 1.04; 95% CI: 1.02–1.06; P = 0.011), SII (OR: 1.09; 95% CI: 1.02–1.18; P = 0.001), AISI (OR: 1.11; 95% CI: 1.05–1.17; P < 0.001), PRBC (OR: 4.747; 95% CI: 2.443–9.223; P < 0.001), ACC time (OR: 1.003; 95% CI: 1.001–1.005; P = 0.004), and CPB time (OR: 1.016; 95% CI: 1.004–1.028; P = 0.001) remained significant. VS predictive cut?offs of SII and AISI were 1,045 1045×109 /mm3 and 137532×109 /mm3 , respectively. AISI positively correlated with the postoperative vasoactive?inotropic score (R = 0.718), lactate (R = 0.655), mechanical ventilation duration (R = 0.837), and ICU stay (R = 0.757). Conclusions: Preoperative elevated SII and AISI emerged as independent predictors of post?cardiotomy VS.

Outcomes Following the Use of Angiotensin II in Patients with Postoperative Vasoplegic Syndrome: A Case Series

Catecholamine?resistant postoperative vasoplegic syndrome (PVS) lacks effective treatment modalities. Synthetic angiotensin II was recently approved for the treatment of vasodilatory shock; however, its use in PVS is not well described. We report outcomes in six patients receiving angiotensin II for the treatment of isolated PVS. All patients achieved their MAP goal and the majority showed improvement in lactate and background catecholamine dose; however, variables of perfusion changed discordantly. Three of six patients survived to hospital discharge.

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.

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.

Síndrome vasopléjico en cirugía cardíaca / Vasoplegia syndrome in cardiac surgery / Síndrome de vasoplegia em cirurgia cardíaca

Resumen: El síndrome de respuesta inflamatoria sistémica constituye un conjunto de situaciones clínicas de diferente gravedad, que se presenta con una incidencia de hasta el 25% durante las primeras horas del posoperatorio de cirugía cardíaca. En esta revisión, se analizan sus aspectos fisiopatológicos y los factores de riesgo que favorecen su desarrollo. Se plantea un enfoque diagnóstico, con la presentación final de una propuesta terapéutica.

Summary: The systemic inflammatory response syndrome constitutes a set of clinical situations of different severity, which presents with an incidence of up to 25% during the first hours after cardiac surgery. In this review, the pathophysiological aspects and the risk factors that favor its development are analyzed. A diagnostic approach is proposed, with the final presentation of a therapeutic proposal.

Resumo: A síndrome da resposta inflamatória sistêmica constitui um conjunto de situações clínicas de gravidade diversa, que se apresenta com incidência de até 25% nas primeiras horas de pós-operatório de cirurgia cardíaca. Nesta revisão, são analisados os aspectos fisiopatológicos e os fatores de risco que favorecem o seu desenvolvimento. É proposta uma abordagem diagnóstica, com a apresentação final de uma proposta terapêutica.

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

Use of methylene blue in vasoplegic syndrome that developed during non-cardiac surgery: A case report

BACKGROUND: Vasoplegic syndrome is an increasingly recognized disease in perioperative medicine and is characterized by severe hypotension, normal or elevated cardiac output, and decreased systemic vascular resistance. It occurs commonly after cardiopulmonary bypass but may also occur after other types of surgery.CASE: Vasoplegic syndrome developed in our patient during posterior lumbar interbody fusion because of administering nicardipine after phenylephrine. However, the blood pressure did not increase as expected despite simultaneous use of norepinephrine and vasopressin to increase the reduced systemic vascular resistance.CONCLUSIONS: We present a case of vasoplegic syndrome that developed during posterior lumbar interbody fusion and was treated successfully with methylene blue.

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.

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. .

Norepinephrine infusion increases urine output in children under sedative and analgesic infusion / Infusão de noradrenalina aumenta o débito urinário de crianças recebendo drogas sedoanalgésicas

Objective: to evaluate the effects of early norepinephrine (NE) infusion in children submitted to mechanical ventilation (MV) requiring continuous sedative and analgesic infusion. Methods: double-blinded, randomized, placebo-controlled trial enrolling children (1 month to 12 years of age) admitted to a Brazilian PICU and expected to require MV and continuous sedative and analgesic drug infusions for at least five days. Children were randomized to receive either norepinephrine (NE) (0.15 mcg/kg/min) or normal saline infusion, started in the first 24 hours of MV, and maintained for 72 hours. We compared hemodynamic variables, fluid intake, renal function and urine output between groups. Results: forty children were equally allocated to the NE or placebo groups, with no differences in baseline characteristics, laboratorial findings, PRISM II score, length of MV, or mortality between groups. The average norepinephrine infusion was 0.143 mcg/kg/min. The NE group showed higher urine output (p = 0.016) and continuous increment in the mean arterial pressure compared to the baseline (p = 0.043). There were no differences in the remaining hemodynamic variables, fluid requirements, or furosemide administration. Conclusion: early norepinephrine infusion in children submitted to MV improves mean arterial pressure and increases urine output. These effects were attributed to reversion of vasoplegia induced by the sedative and analgesic drugs. .

Objetivo: avaliar os efeitos da infusão de noradrenalina (NA) em crianças submetidas a ventilação mecânica (VM) requerendo infusão contínua de sedoanalgesia. Métodos: estudo duplo cego, randomizado e placebo controlado envolvendo crianças de 1 mês a 12 anos, admitidas em uma UTI pediátrica brasileira com a expectativa de necessidade de VM e sedoanalgesia por, no mínimo, 5 dias. As crianças foram randomizadas a receber infusão de NA (0,15 mcg/kg/min) ou solução salina, iniciadas nas primeiras 24 horas de VM e mantidas por 72 horas. Comparamos as variáveis hemodinâmicas, oferta hídrica, função renal e débito urinário entre os dois grupos. Resultados: 40 crianças foram alocadas aos grupos NA e placebo, sem diferenças nas características basais, achados laboratoriais, escore PRISM II, tempo de VM ou mortalidade. A infusão média de NA foi 0,143 mcg/kg/min. O grupo NA apresentou maior débito urinário (p = 0,016) e aumento constante da pressão arterial média quando comparado aos níveis basais (p = 0,043). Não se observou diferenças nas demais variáveis hemodinâmicas, reposição hídrica ou no uso de furosemida. Conclusão: infusão precoce de NA em crianças submetidas a VM em uso sedoanalgesia promove aumento na pressão arterial média e aumento da diurese. Esses efeitos são atribuídos à reversão da vasoplegia induzida pelas drogas sedativas e analgésicas. .

Application of induced hypothermia in vasoplegia syndrome after postcardiopulmonary bypass / 中国实用护理杂志

Objective To investigate the effects of induced hypothermia in vasoplegia syndrome after post-cardiopulmonary bypass.Methods 4 individuals diagnosed as CPB-induced vasoplegia syndrome was given hypothermia by surface cooling using hypo-hyperthermia blanket based on vasopressors and adjustment of blood volume.The surface temperature,heart rate,systolic pressure,mean arterial blood pressure,central venous pressure,oxygen saturation of blood,urine volume,systemic vascular resistance (SVR),pulmonary vascular resistance (PVR) and cardiac output (CO) were recorded.Results Systemic vascular resistance gradually improved along with normalization of cardiac output,and increased mean arterial blood pressure.Conclusions The mild hypothermia can increase blood pressure,decrease dosage of vasopressors,and may play a decisive role in some cases.So mild hypothermia may be an effec-tive alternative to treat CPB-induced vasoplegia syndrome.

Effect of a single bolus of methylene blue prophylaxis on vasopressor and transfusion requirement in infective endocarditis patients undergoing cardiac surgery / 대한마취과학회지

BACKGROUND: The accentuated nitric oxide (NO) release that is induced by the systemic inflammatory response associated with infective endocarditis (IE) and cardiopulmonary bypass (CPB) may result in catecholamine refractory hypotension (vasoplegia) and increased transfusion requirement due to platelet inhibition. Methylene blue (MB) is an inhibitory drug of inducible NO. We aimed to evaluate the effect of prophylactic MB administration before CPB on vasopressor and transfusion requirements in patients with IE undergoing valvular heart surgery (VHS). METHODS: Forty-two adult patients were randomly assigned to receive 2 mg/kg of MB (MB group, n = 21) or saline (control group, n = 21) for 20 min before the initiation of CPB. The primary end points were comparisons of vasopressor requirements serially assessed after weaning from CPB and hemodynamic parameters serially recorded before and after CPB. The secondary endpoint was the comparison of transfusion requirements. RESULTS: Two patients in the control group received MB after weaning from CPB due to norepinephrine and vasopressin refractory vasoplegia and were thus excluded. There were no significant differences in vasopressor requirements and hemodynamic parameters between the two groups. The mean number of units of packed erythrocytes transfused per transfused patient was significantly less in the MB group. The numbers of patients transfused with fresh frozen plasma and platelet concentrates were less in the MB group. CONCLUSIONS: In IE patients undergoing VHS, prophylactic MB administration before CPB did not confer significant benefits in terms of vasopressor requirements and hemodynamic parameters, but it was associated with a significant reduction in transfusion requirement.

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.