Randomized experimental study of topical vasodilators in microsurgery with cost analysis / Estudo experimental randomizado de vasodilatadores tópicos em microcirurgia com análise de custo

ABSTRACT Objective: Throughout microsurgical anastomosis, many surgeons use topical vasodilators in order to reduce pathological vasospasm. It was carried out an experimental study comparing the effectiveness of topical use of Nitroglycerin, Papaverine, Magnesium sulfate over a control group in the femoral artery and vein of rats, in reducing prolonged vasospasm. Methods: Randomized comparative experimental study in 15 rats, divided into four groups. The external diameter of the vases soaked in the randomized solution was measured. For statistical analysis, it was calculated the percentual increase in the external diameter of the vessels. Results: A statistically significant increase in arterial dilation was observed after 10 minutes of topical application of 10% magnesium sulfate compared to the control group, with p = 0.044 . No other drug showed a vasodilator effect superior to the control group. Magnesium sulfate at 10% is still not used in microsurgery and costs 15 times less than papaverine, the standard drug for topical vasodilation in clinical cases at our service. Conclusion: Magnesium sulfate had better vasodilating effects over the control group after 10 minutes of arterial microanastomosis. None of the tested drugs have presented superior vasodilating effects over each other nor the control group after venous microanastomosis. Level of evidence II, Experimental study, Randomized Trial.

RESUMO Objetivo: Durante a anastomose microcirúrgica, muitos cirurgiões utilizam vasodilatadores tópicos para reduzir o vasoespasmo prolongado patológico, assim reduzindo o risco de complicações vasculares. Entretanto, ainda faltam dados experimentais para identificação da droga padrão-ouro para vasodilatadores tópicos em microcirurgia e sua avaliação de análise de custo, já que a droga geralmente utilizada para este objetivo é baseada, na maior parte dos casos, na experiência do cirurgião. Métodos: Foi realizado um estudo experimental comparativo randomizado, avaliando a eficácia do uso tópico de Nitroglicerina, Papaverina e Sulfato de Magnésio em relação a um grupo controle, na redução do vasoespasmo na artéria e veia femoral de ratos. Foram avaliados o diâmetro externo dos vasos embebidos em solução randomizada dos fármacos para vasodilatação. Após cálculo do aumento percentual no diâmetro externo dos vasos, foi realizada análise estatística. Resultados: Observou-se aumento estatisticamente significativo da dilatação arterial após 10 minutos de aplicação tópica de sulfato de magnésio a 10% em relação ao grupo controle, com p = 0,044. Nenhuma outra droga apresentou efeito vasodilatador superior ao grupo controle. O sulfato de magnésio a 10% ainda não é utilizado em microcirurgia e apresenta custo até 15 vezes menor quando comparado com a papaverina, droga padrão para vasodilatação tópica em casos clínicos em nosso serviço. Conclusão: O sulfato de magnésio apresentou melhor efeito vasodilatador quando comparado ao grupo controle, após 10 minutos da microanastomose arterial. Nenhum dos fármacos testados apresentou efeito vasodilatador superior após a microanastomose venosa. Nível de Evidência II, Estudo experimental, Ensaio Randomizado.

Loss of response to calcium channel blockers after long-term follow-up treatment in patients with idiopathic pulmonary arterial hypertension / Perda de resposta a bloqueadores dos canais de cálcio após acompanhamento prolongado em pacientes com hipertensão arterial pulmonar idiopática

ABSTRACT Idiopathic pulmonary arterial hypertension (PAH) patients with a positive response to acute vasodilator challenge and a clinical response to calcium channel blockers (CCBs) for at least one year are traditionally designated true responders. Nevertheless, little is known about a sustained response to CCBs over longer periods of time. We evaluated the loss of response to CCBs after long-term treatment in a cohort of idiopathic PAH patients previously classified as being true responders. Our data suggest that idiopathic PAH patients can lose clinical response to CCBs even after one year of clinical stability, reinforcing the need for constant multidimensional reevaluation to assess the need for targeted PAH therapies and to classify these patients correctly.

RESUMO Pacientes com hipertensão arterial pulmonar (HAP) idiopática com resposta positiva ao teste de vasorreatividade aguda e resposta clínica a bloqueadores dos canais de cálcio (BCC) durante no mínimo um ano são tradicionalmente denominados "respondedores verdadeiros". No entanto, pouco se sabe sobre a manutenção da resposta a BCC durante períodos mais longos. Avaliamos a perda de resposta a BCC após tratamento prolongado em uma coorte de pacientes com HAP idiopática previamente considerados respondedores verdadeiros. Nossos dados sugerem que pacientes com HAP idiopática podem deixar de apresentar resposta clínica a BCC mesmo depois de um ano de estabilidade clínica, reforçando a necessidade de reavaliação multidimensional constante para avaliar a necessidade de terapias específicas para HAP e classificar esses pacientes corretamente.

Insuficiencia Cardíaca Aguda / Acute Heart Failure

En el mundo actual las perspectivas de abordaje, y las estrategias terapéuticas en cuanto a pacientes que se presenten con Insuficiencia Cardiaca (IC) de reciente diagnóstico "de novo", o que presentan una descompensación de su patología, han tenido un avance claro dándonos una gran diversidad de opciones terapéuticas para el cuidado y acompañamiento de dicha patología; así como en la perspectiva de un seguimiento crónico, no solo cardiológico, sino que se ha convertido en un verdadero desafío multidisciplinario, en busca de la mejor opción terapéutica y concluir con el cuidado paliativo de nuestro paciente.

In the current world, the perspectives of approach, and the therapeutic strategies regarding patients who present with Heart Failure (HF) of recent diagnosis "de novo", or who present a decompensation of their pathology, have had a clear advance giving us a great diversity of therapeutic options for the care and accompaniment of said pathology; as well as in the perspective of chronic follow-up, not only cardiological, but it has become a true multidisciplinary challenge, looking for the best therapeutic option and concluding with the palliative care of our patient.

The Clinical Efficacy of Pulmonary Hypertension-Specific Agents in Idiopathic Pulmonary Fibrosis: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

BACKGROUND: Pulmonary hypertension (PH) is common in patients with idiopathic pulmonary fibrosis (IPF) and is associated with poor outcomes. This study was performed to determine the clinical efficacy of PH-specific therapeutic agents for IPF patients.METHODS: We performed a systematic review and meta-analysis using MEDLINE, EMBASE, and the Cochrane Central Register. We searched randomized controlled trials (RCTs) without language restriction until November 2018. The primary outcome was all-cause mortality to end of study.RESULTS: We analyzed 10 RCTs involving 2,124 patients, 1,274 of whom received PH-specific agents. In pooled estimates, the use of PH-specific agents was not significantly associated with reduced all-cause mortality to end of study compared with controls (hazard ratio, 0.99; 95% confidence interval [CI], 0.92, 1.06; P = 0.71; I² = 30%). When we performed subgroup analyses according to the type of PH-specific agent, sample size, age, forced vital capacity, diffusion lung capacity, and the extent of honeycombing, PH-specific agents also showed no significant association with a reduction in all-cause mortality. A small but significant improvement in quality of life, measured using the St. George Respiratory Questionnaire total score, was found in the PH-specific agent group (mean difference, −3.16 points; 95% CI, −5.34, −0.97; P = 0.005; I² = 0%). We found no significant changes from baseline in lung function, dyspnea, or exercise capacity. Serious adverse events were similar between the two groups.CONCLUSION: Although PH-specific agents provided small health-related quality-of-life benefits, our meta-analysis provides insufficient evidence to support their use in IPF patients.

Effect of papaverine on left internal mammary artery flow: topical spraying versus perivascular injection method

Abstract Objective: To analyze two techniques of papaverine application, topical spray on the harvested left internal mammary artery (LIMA) and perivascular injection, to find out their ability to improve LIMA flow. Methods: Forty patients were randomized into two groups. In Group 1, papaverine was sprayed on the harvested pedunculated LIMA. In Group 2, papaverine was delivered into the perivascular plane. Drug dosage was the same for both groups. LIMA flow was measured 20 minutes after applying papaverine. Blood flow was recorded for 20 seconds and flow per minute was calculated. The systemic mean pressures were maintained at 70 mmHg during blood collection. The data collected was statistically evaluated and interpreted. Results: The LIMA blood flow before papaverine application in the Group 1 was 51.9±13.40 ml/min and in Group 2 it was 55.1±15.70 ml/min. Statistically, LIMA flows were identical in both groups before papaverine application. The LIMA blood flow, post papaverine application, in Group 1 was 87.20±13.46 ml/min and in Group 2 it was 104.7±20.19 ml/min. The Group 2 flows were statistically higher than Group 1 flows. Conclusion: Papaverine delivery to LIMA by the perivascular injection method provided statistically significant higher flows when compared to the topical spray method. Hence, the perivascular delivery of papaverine is more efficient than the spray method in improving LIMA blood flow.

Curcuma Longa Abolishes Phenylephrine-Induced Contractions in Isolated Aortic Artery of Rats

Curcuma longa has biological effects. Its cardiovascular activities are yet to be scientifically studied. Objectives: To investigate the vasorelaxant effects of the aqueous extract of Curcuma longa (AECL). Methods: Aortic annuli of normotensive rats, with or without endothelium, were set up in a data storage system with nutrient solution in recipients, with scientifically recommended temperature, aeration and tension. Over contraction by Phenylephrine, the AECL (1, 3, 10, 30, 100, 300 and 1000 µg/mL) was incubated before and after incubation with atropine or L-name or indomethacin. An AECL concentration-response curve was also built over contractions caused by elevation of extracellular K+. Data were significant when p < 0.05, with GraphPad Prism 6.0 software resolutions. Results: The AECL induced 100% vasorelaxation also in the endothelium-free annuli. The part of the endothelium-dependent effect had EC50 = 4.32 ± 0.05 µg/mL. With inhibition of NO production, the EC50 increased to 126.50 ± 2.35 µg/mL; after inhibition of prostacyclin production, to 124.6 ± 0.05 µg/mL; and after muscarinic blockade, to 437.10 ± 0.2 µg/mL. Opening of K+ channels (relaxation of 56.98%) and VOCC blockade (relaxation of 31.56%) were evident. Conclusion: AECL induced significant vasorelaxation, being more significant in the presence of endothelium. The muscarinic pathway seems to be the main one involved in this effect, followed by the NO production and prostacyclin pathways. The activity in K+ channels by AECL was more significant than its VOCC blockade. The use of other models and tools to study action mechanisms will be important and elucidating

Eventos adversos durante transporte intra-hospitalar de pacientes críticos em hospital de grande porte / Adverse events during intrahospital transport of critically ill patients in a large hospital

RESUMO Objetivo: Descrever a incidência de eventos clínicos e não clínicos durante o transporte intra-hospitalar de pacientes críticos e analisar os fatores de risco associados. Métodos: Estudo de coorte, com coleta retrospectiva, no período de outubro de 2016 a outubro de 2017, tendo sido analisados todos os transportes intra-hospitalares para fins diagnósticos e terapêuticos em hospital de grande porte, que contava com seis unidades de terapia intensiva adulto, sendo avaliados os eventos adversos e os fatores de risco relacionados. Resultados: No período, foram realizados 1.559 transportes intra-hospitalares, em 1.348 pacientes, com média de idade de 66 ± 17 anos, tempo médio de transporte de 43 ± 34 minutos. Durante o transporte, 19,8% dos pacientes estavam em uso de drogas vasoativas; 13,7% em uso de sedativos e 10,6% estavam sob ventilação mecânica. Eventos clínicos ocorreram em 117 transportes (7,5%) e não clínicos em 125 transportes (8,0%). Falhas de comunicação foram prevalentes, no entanto, aplicando-se análise multivariada, uso de sedativos, noradrenalina e nitroprussiato, e o tempo de transporte maior que 36,5 minutos estiveram associados a eventos adversos clínicos. Uso de dobutamina e tempo de transporte superior a 36,5 minutos estiveram associados a eventos não clínicos. Ao final do transporte, 98,1% dos pacientes apresentaram condições clínicas inalteradas em relação ao seu estado basal. Conclusão: Transportes intra-hospitalares estão relacionados à alta incidência de eventos adversos; o tempo de transporte e a utilização de sedativos e drogas vasoativas estiveram relacionados a esses eventos.

ABSTRACT Objective: To describe the incidence of clinical and non-clinical events during intrahospital transport of critically ill patients and to analyze the associated risk factors. Methods: Cohort study with retrospective data collected from October 2016 to October 2017. All cases of intrahospital transport for diagnostic and therapeutic purposes in a large hospital with six adult intensive care units were analyzed, and the adverse events and related risk factors were evaluated. Results: During the study period, 1,559 intrahospital transports were performed with 1,348 patients, with a mean age of 66 ± 17 years and a mean transport time of 43 ± 34 minutes. During transport, 19.8% of the patients were using vasoactive drugs; 13.7% were under sedation; and 10.6% were under mechanical ventilation. Clinical events occurred in 117 transports (7.5%), and non-clinical events occurred in 125 (8.0%) transports. Communication failures were prevalent; however, the multivariate analysis showed that the use of sedatives, noradrenaline and nitroprusside and a transport time greater than 36.5 minutes were associated with adverse clinical events. The use of dobutamine and a transport time greater than 36.5 minutes were associated with non-clinical events. At the end of transport, 98.1% of the patients presented unchanged clinical conditions compared with baseline. Conclusion: Intrahospital transport is related to a high incidence of adverse events, and transport time and the use of sedatives and vasoactive drugs were related to these events.

Advances in pharmacological treatment for acute respiratory distress syndrome / 中国基层医药

Acute respiratory distress syndrome(ARDS) is a common critical syndrome with high morbidity and mortality.The treatments include respiratory support and drug therapy.In this paper, the latest clinical advances in the treatment of ARDS with glucocorticoids, statins, antioxidants, recombinant human activated protein C, sedatives and muscle relaxants, exogenous alveolar surfactants, mesenchymal stem cells, and vasodilators are reviewed.

Milrinona inhalada en hipertensión pulmonar: A propósito de un caso / Case Report: Inhaled milrinone in pulmonary hypertension

INTRODUCCIÓN: Pulmonary hypertension (PH) is a disease that is characterized for an elevated pressure in the pulmonary artery and an increased pulmonary vascular resistance (PVR). Inhaled milrinone has demonstrated acting as a selective pulmonary vasodilator, being a useful tool for the treatment of patients with PH in the perioperative. MATERIALS AND METHODS: We report a successful case of inhaled milrinone in PH in cardiovascular surgery. The patient signed the informed consent for this report. DISCUSSION: Patients with PH has increased risk of perioperative complications (mortality as far as 37-90%) The management with intravenous vasodilators is frequently limited because of secondary effects of vasodilation and hypotension affecting the myocardial perfusion pressure. Milrinone is an inodilator that acts as an inhibitor of the phosphodiesterase III. Wang et al., and posterior studies have demonstrated that administered by inhalation it acts as a selective pulmonary vasodilator and inotrope, with a minor systemic effect. CONCLUSION: Inhaled milrinone have demonstrated to be a useful drug to lower PH, PVR and to enhance inotropism without deleterious systemic effects. Wide availability, lower costs and ease of administration make you think as it could be an ideal tool for perioperative management in patients with PH. There are still more studies to define it´s potentials.

INTRODUCCIÓN: La hipertensión pulmonar (HTP) es una enfermedad caracterizada por la elevación de las presiones de arteria pulmonar (PAP) y un aumento de la resistencia vascular pulmonar (RVP). La milrinona inhalada ha demostrado actuar como un vasodilatador pulmonar selectivo siendo una herramienta útil en el manejo de los pacientes con HTP en el perioperatorio. MATERIALES Y MÉTODOS: Reportamos un caso exitoso de milrinona inhalada en HTP en cirugía cardiovascular. La paciente firmó el consentimiento informado para este reporte. DISCUSIÓN: Pacientes con HTP tienen mayor riesgo de complicaciones perioperatorias (mortalidad hasta 37-90%). Su manejo con vasodilatadores intravenosos es frecuentemente limitado por sus efectos secundarios de vasodilatación e hipotensión, perjudicando la presión de perfusión miocárdica. La milrinona es un inodilatador que actúa como inhibidor de la fosfodiesterasa III. Wang et al., y estudios posteriores, han demostrado que administrada por vía inhalatoria actúa como un vasodilatador pulmonar selectivo e inótropo, con menor efecto sistémico. CONCLUSIÓN: La milrinona inhalada ha demostrado ser una herramienta útil para la disminución de la PAP, RVP y mejoría del inotropismo, sin efectos sistémicos deletéreos. Su amplia disponibilidad, menor costo y facilidad de administración, hacen pensar que podría ser una herramienta útil para el manejo perioperatorio de los pacientes con HTP. Hacen falta más trabajos para definir sus potencialidades.

Mecanismos regulatorios del tono vascular pulmonar neonatal: una perspectiva molecular / Regulatory mechanisms of neonatal pulmonary vascular tone: a molecular perspective

La adaptación al medio extrauterino incluye un aumento considerable de la PaO2, que induce especialmente cambios estructurales y vasoactivos en la circulación pulmonar, que llevarán a una circulación previamente pobremente irrigada, a recibir ∼100% del gasto cardíaco del recién nacido, permitiendo el normal intercambio gaseoso. La regulación local de la circulación arterial pulmonar neonatal basal, es mantenida por un delicado equilibrio entre agentes vasoconstrictores y vasodilatadores. Este equilibrio, permite mantener la circulación pulmonar como un territorio de gran flujo sanguíneo y baja resistencia. La acción de los vasoconstrictores permite la formación de las interacciones entre actina y la cadena liviana de la miosina, esta es inducida en la célula muscular lisa principalmente por dos vías: a) dependiente de calcio, que consiste en aumentar el calcio intracelular, facilitando finalmente la unión de actina y miosina, y b) independiente de calcio, la cual a través de consecutivas fosforilaciones logra sensibilizar a las proteínas involucradas promoviendo la unión de actina y miosina. Estas acciones son mediadas por agonistas generados principalmente en el endotelio pulmonar, como endotelina-1 y tromboxano, o por agonistas provenientes de otros tipos celulares como la serotonina. Los agentes vasodilatadores regulan la respuesta vasoconstrictora, principalmente inhibiendo la señalización que induce la vasocontricción independiente de calcio, a través de la activación de proteínas quinasas que inhibirán la función de la ROCK quinasa, uno de los últimos efectores de la vasocontricción antes de la formación de la unión de actina y miosina. Esta revisión describe estos mecanismos de primordial importancia en las primeras horas de nuestra vida como individuos independientes.

The extrauterine-milieu adaptation includes a considerable increase in PaO2, that specifically induces structural and vasoactive changes at pulmonary circulation. Such changes transform a poor irrigated circulation into a circulation that receive ∼100% of neonatal cardiac output, supporting the normal alveolar-capillary gas exchange. Local regulation of basal neonatal pulmonary circulation is maintaining by a delicate equilibrium between vasoconstrictor and vasodilator agents. This equilibrium, allows to maintain the pulmonary circulation as an hemodynamic system with a high blood flow and a low vascular resistance. Vasocontrictors action allows actin and light-chain myosin interaction. Two main pathways induced this effect in smooth muscle cell: a) a calcium dependent pathway, that increases intracellular calcium, facilitating actin - myosin binding, and b) the independent calcium pathway, which achieves through consecutive phosphorylation reactions sensitize the proteins involved, promoting the binding of actin and light-chain myosin. These actions are mediated by agonists produced mainly in the pulmonary endothelium, such as endothelin-1 and thromboxane, or by agonists from other cell types such as serotonin. Vasodilator agents regulate the vasoconstrictor response, mainly by inhibiting signals that induce calcium-independent vasoconstriction, through activation of protein kinases, which in turn will inhibit the function of ROCK kinase, one of the last effectors of vasoconstriction before formation of the actin and light-chain myosin binding. This review will focus on describing these mechanisms of primal importance in the first hours of our lives as independent individuals.