Chemical Angioplasty with Nitroglycerin for Vasospasm after Subarachnoid Hemorrhage: Case Series and Review

Introduction Vasospasm is a common and potentially devastating complication in patients with subarachnoid hemorrhage, causing high morbidity and mortality. There is no effective and consistent way to prevent or treat cerebral vasospasm capable of altering the morbidity and mortality of this complication. Animal and human studies have attempted to show improvement in aneurysmal vasospasm. Some sought their prevention; others, the treatment of already installed vasospasm. Some achieved only angiographic improvement without clinical correlation, others achieved both, but with ephemeral duration or at the expense of very harmful associated effects. Endovascular techniques allow immediate and aggressive treatment of cerebral vasospasm and include methods such as mechanical and chemical angioplasty. These methods have risks and benefits. Objectives To analyze the results of chemical angioplasty using nitroglycerin (GTN). In addition, to performa comprehensive review and analysis of aneurysmal vasospasm. Methods We describe our series of 77 patients treated for 8 years with angioplasty for vasospasm, either mechanical (with balloon), chemical (with GTN) or both. Results Eleven patients received only balloon; 37 received only GTN; 29 received both. Forty-four patients (70.1%) evolved with delayed cerebral ischemia and 19 died (mortality of 24.7%). Two deaths were causally related to the rupture of the vessel by the balloon. The only predictors of poor outcome were the need for external ventricular drainage in the first hours of admission, and isolated mechanical angioplasty. Conclusions Balloon angioplasty has excellent results, but it is restricted to proximal vessels and is not without complications. Chemical angioplasty using nitroglycerin has reasonable but short-lived results and further research is needed about it. It is restricted to vasospasm angioplasties only in hospitals, like ours, where better and more potent vasodilator agents are not available.

Vasoespasmo cerebral relacionado a hiperglicemia en paciente con hemorragia subaracnoidea aneurismatica: caso clínico y revisión de la literatura / Cerebral vasospasm related to hyperglycemia in patient with subaracoid aneurysmatic haemorrhage: clinical case and review of literature

La hemorragia subaracnoidea aneurismática es un fenómeno muy grave asociado a altas tasas de morbimortalidad, esta depende de la severidad inicial. El control de la glucosa es uno de los cuidados que se debe tener en cuenta ya que está estrechamente relacionada con el desarrollo de las complicaciones secundarias. Se presenta el caso clínico de un paciente con antecedente de diabetes tipo 2 tratada irregularmente, que presentó una hemorragía subaracnoidea aneurismática, complicada con vasoespasmo cerebral, infarto, hidrocefalia secundaria e infecciones pulmonares en relación a hiperglicemia durante el post operatorio de difícil y refractario tratamiento. Exponemos los mecanismos fisiopatológicos que ocasionan alteraciones de los fenómenos de autorregulación vascular cerebral y en consecuencia trastornos de la perfusión cerebral que decaen sobre el estado neurológico del paciente, sobresaltando que el control de la glucemia en el transcurso de una hemorragia subaracnoidea puede ayudar a un mejor desenlace de los pacientes.

Aneurysmal subarachnoid hemorrhage is a very serious phenomenon associated with high rates of morbidity and mortality, this depends on the initial severity. The control of glucose is one of the care that must be taken into account since it is closely related to the development of secondary complications. We present the clinical case of a patient with a history of type 2 diabetes treated irregularly, who presented an aneurysmal subarachnoid hemorrhage, complicated by cerebral vasospasm, infarction, secondary hydrocephalus and pulmonary infections in relation to hyperglycemia during the post-operative period of difficult and refractory treatment. We expose the pathophysiological mechanisms that cause alterations in the cerebral vascular self-regulation phenomena and consequently cerebral perfusion disorders that decrease the neurological state of the patient, highlighting that the control of glycemia in the course of a subarachnoid hemorrhage can help a better outcome of the patients.

Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática / Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review

RESUMO Objetivo: Revisar sistematicamente a evidência atual da eficácia de milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea. Métodos: Triaram-se as bases de dados Pubmed®, Cochrane e Embase quanto a artigos publicados entre abril de 2001 e fevereiro de 2019. Dois revisores independentes realizaram uma triagem metodológica da qualidade e a extração dos dados dos estudos. Resultados: Encontraram-se 22 estudos considerados relevantes, sendo que apenas um deles era um ensaio randomizado controlado. Os estudos demonstraram acentuada heterogeneidade e debilidade de seus critérios metodológicos. A maioria dos pacientes apresentava vasoespasmo moderado a grave. O principal método para diagnóstico do vasoespasmo foi a angiografia. Em três estudos, realizou-se administração de milrinona por via intra-arterial; em nove estudos, a administração foi endovenosa, e, em seis estudos, utilizaram-se ambas as vias de administração. A via intratecal foi utilizada em dois estudos, em um estudo, a administração foi realizada via cisterna e, em um estudo, a via de administração foi a endovascular. Os efeitos colaterais de milrinona foram descritos em seis estudos. Vinte e um estudos indicaram a resolução do vasoespasmo. Conclusão: A evidência atual indica que o uso de milrinona teve um papel no tratamento do vasoespasmo após hemorragia subaracnóidea aneurismática. Contudo, só foi realizado um ensaio randomizado controlado, com baixo nível de qualidade. Nossos achados indicam a necessidade de futuros estudos randomizados controlados com desfechos centrados no paciente, com o fim de proporcionar recomendações definitivas.

ABSTRACT Objective: To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage. Methods: The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies. Results: Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm. Conclusion: The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

Effect of magnesium sulphate and milrinone on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a randomized study / Efeitos do sulfato de magnésio e da milrinona sobre o vasoespasmo cerebral após hemorragia subaracnoidea por aneurisma: estudo randômico

Abstract Background: Aneurysmal subarachnoid hemorrhage is an important cause of premature death and disability worldwide. Magnesium sulphate is shown to have a neuroprotective effect and it reverses cerebral vasospasm. Milrinone is also used in the treatment of cerebral vasospasm. The aim of the present study was to compare the effect of prophylactic magnesium sulphate and milrinone on the incidence of cerebral vasospasm after subarachnoid hemorrhage. Methods: The study included 90 patients with aneurysmal subarachnoid hemorrhage classified randomly (by simple randomization) into two groups: magnesium sulphate was given as an infusion of 500 mg.day-1 without loading dose for 21 days. Group B: milrinone was given as an infusion of 0.5 µg.kg-1.min-1 without loading dose for 21 days. The cerebral vasospasm was diagnosed by mean cerebral blood flow velocity in the involved cerebral artery (mean flow velocity ≥ 120 cm.s-1), neurological deterioration by Glasgow coma scale, or angiography (the decrease in diameter of the involved cerebral artery >25%). Results: The mean cerebral blood flow velocity decreased significantly in the magnesium group compared to milrinone group through Day 7, Day 14 and Day 21 (p < 0.001). The incidence of cerebral vasospasm decreased significantly with magnesium compared to milrinone (p = 0.007). The Glasgow coma scale significantly improved in the magnesium group compared to milrinone group through Day 7, Day 14 and Day 21 (p = 0.036, p = 0.012, p = 0.016, respectively). The incidence of hypotension was higher with milrinone than magnesium (p = 0.012). Conclusions: The incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage was significantly lower and Glasgow coma scale significantly better with magnesium when compared to milrinone. Milrinone was associated with a higher incidence of hypotension and requirement for dopamine and norepinephrine when compared to magnesium.

Resumo Justificativa: A hemorragia subaracnoidea por aneurisma é uma importante causa de morte prematura e de incapacidade em todo o mundo. O sulfato de magnésio mostra um efeito neuroprotetor e reverte o vasoespasmo cerebral. A milrinona também é usada no tratamento de vasoespasmo cerebral. O objetivo do presente estudo foi comparar o efeito profilático do sulfato de magnésio e da milrinona sobre a incidência de vasoespasmo cerebral após hemorragia subaracnoidea. Métodos: O estudo incluiu 90 pacientes com hemorragia subaracnoidea por aneurisma randomicamente distribuídos (randomização simples) em dois grupos: sulfato de magnésio foi administrado em infusão de 500 mg.dia-1 sem dose de ataque durante 21 dias. O Grupo B recebeu milrinona em infusão de 0,5 µg.kg-1·min-1 sem dose de ataque durante 21 dias. O vasoespasmo cerebral foi diagnosticado pela velocidade média do fluxo sanguíneo cerebral na artéria cerebral envolvida (velocidade média do fluxo ≥ 120 cm.s-1), a deterioração neurológica por escala de coma de Glasgow ou angiografia (diminuição do diâmetro da artéria cerebral envolvida > 25%). Resultados: A velocidade média do fluxo sanguíneo cerebral diminuiu significativamente no grupo magnésio em comparação com o grupo milrinona nos dias 7, 14 e 21 (p < 0,001). A incidência de vasoespasmo cerebral diminuiu significativamente com o magnésio em comparação com milrinona (p = 0,007). A escala de coma de Glasgow melhorou significativamente no grupo magnésio em comparação com o grupo milrinona nos dias 7, 14 e 21 (p = 0,036, p = 0,012, p = 0,016, respectivamente). A incidência de hipotensão foi maior com milrinona do que com magnésio (p = 0,012). Conclusões: A incidência de vasoespasmo cerebral após hemorragia subaracnoidea por aneurisma foi significativamente menor e a escala de coma de Glasgow significativamente melhor com magnésio em comparação com milrinona. A milrinona foi associada a uma maior incidência de hipotensão e necessidade de dopamina e norepinefrina em comparação com o magnésio.

Síndrome de vasoconstricción cerebral reversible: Presentación como hemorragia subaracnoidea de la convexidad / Reversible Cerebral Vasoconstriction: Subarachnoid Convexity Hemorrhage

Objetivo: El propósito de este estudio es describir las características clínicas, epidemiológicas e imaginológicas de 5 pacientes con diagnóstico de síndrome de vasoconstricción reversible. Métodos: Se hizo una evaluación retrospectiva de las historias clínicas de cinco pacientes con clínica e imágenes compatibles con síndrome de vasoconstricción cerebral reversible en un hospital de alta complejidad de la ciudad de Medellín. Resultados: Los cinco casos correspondían a mujeres con una edad promedio de 50 años. En un caso se identificó como posible agente causal el consumo de bebidas energizantes con alto contenido de taurina. Todos los pacientes se presentaron con hemorragia subaracnoidea en la convexidad y evolucionaron de forma favorable. Conclusión: El síndrome de vasoconstricción cerebral reversible debe ser uno de los diagnósticos diferenciales etiológicos de hemorragia subaracnoidea de la convexidad; se presenta predominantemente en mujeres entre la cuarta y sexta década de la vida y usualmente tiene un curso benigno.

Objective: The purpose of this study is to describe the clinical, epidemiological and imaging characteristics of 5 patients with a diagnosis of reversible vasoconstriction syndrome. Methods: A retrospective evaluation of the clinical records of 5 patients with clinical and imaging diagnosis of reversible cerebral vasoconstriction syndrome was carried out in a high complexity hospital in the city of Medellín. Results: The five cases were women with an average age of 50 years. In one case, the consumption of energy drinks with a high taurine content was identified as a possible causative agent. All cases presented with brain convexity subarachnoid haemorrhage. The clinical outcome was favorable. Conclusion: The reversible cerebral vasoconstriction syndrome should be included in the differential diagnosis of convexity subarachnoid haemorrhage. It occurs predominantly in women between the fourth and sixth decade of life and usually has a benign course.

Factores de riesgo para vasoespasmo cerebral en pacientes con hemorragia subaracnoidea espontánea / Risk Factors for Cerebral Vasospasm in Patients with Spontaneous Subarachnoid Hemorrhage

Objetivos: Establecer la asociación de vasoespasmo cerebral detectado por Doppler transcraneal y la condición clínica, de acuerdo con la escala de la Federación Mundial de Sociedades de Neurocirugía, y con otros factores de riesgo en pacientes con hemorragia subaracnoidea espontánea. Materiales y métodos: Estudio observacional retrospectivo de casos y controles, con 141 pacientes diagnosticados con hemorragia subaracnoidea espontánea a quienes se les realizó Doppler transcraneal de seguimiento entre el 8 de marzo de 2011 y el 15 de marzo de 2015. Del total de pacientes se escogieron 47 con vasoespasmo detectado por Doppler transcraneal y 2 controles, sin vasoespasmo, por cada caso (94 pacientes). En las historias clínicas y las imágenes de los pacientes se estableció la asociación entre la detección de vasoespasmo por Doppler transcraneal con la condición clínica neurológica en el momento del examen, y otros factores de riesgo. Para el análisis de las variables cualitativas se utilizaron frecuencias absolutas y relativas. Para variables cuantitativas se utilizó la prueba de Shapiro Wilk. Los datos con distribución normal se presentan con medias y desviaciones estándar y aquellos sin distribución normal con medianas y rangos intercuartiles. Se evaluó la homogeneidad entre los dos grupos a través de la prueba de Chi cuadrado y el test de homogeneidad de varianzas (Levene) de acuerdo con el tipo de variable. Se consideró estadísticamente significativa una p ≤ 0,05. Resultados: El análisis bivariado no demostró resultados estadísticamente significativos en la relación entre la condición clínica neurológica y el vasoespasmo, pero sí encontró que pacientes menores de 50 años de edad presentaron más vasoespasmo (OR de 3,55 [95 % IC; 1,52-7,39]), y p: 0,003 que los de mayor edad. Conclusiones: Los pacientes menores de 50 años de edad tienen más riesgo de desarrollar vasoespasmo y no existe asociación entre la condición clínica y los resultados del Doppler transcraneal.

Objectives: Establish the association between cerebral vasospasm, detected by transcranial doppler, with the clinical condition according to the scale of the World Federation of Neurosurgical Societies (WFNS) and other risk factors in patients with spontaneous subarachnoid hemorrhage. Materials and methods: This is an observational retrospective case-control study, including 141 patients with a diagnosis of spontaneous subarachnoid hemorrhage who underwent transcranial doppler monitoring in the radiology department of the University Hospital San Vicente Foundation (HUSVF) from 8 March 2011 to 15 March 2015. Of the total number of patients with subarachnoid hemorrhage, 47 cases with vasospasm, detected by transcranial Doppler, and two controls without vasospasm (94 patients) were consecutively chosen. Subsequently, we review the medical records and images stored in the hospital´s radiology department and established the association between vasospasm detection by trasncranial Doppler with clinical neurological status at the time of the study and other risk factors. For the analysis of the qualitative variables, absolute and relative frequencies were used. Quantitative variables were tested for normal distribution with a Shapiro Wilk test. Data with normal distribution were presented with means and standard deviations and those without normal distribution with medians and interquartile ranges. Homogeneity between the two groups were evaluated by Chi-square test and test for homogeneity of variances, Levene's test, according to the type of variable (qualitative and quantitative respectively). Results were considered statistically significant if p ≤ 0.05. Results: Data from 141 patients (47 cases and 94 controls) were analyzed. The bivariate analysis didn´t show statistically significant results in the relationship between vasospasm and clinical neurological condition but found that patients younger than 50 years had more vasospasm. In the adjusted model for patients with this age, the OR was 3.55 (95 % CI, 1.52-7.39) and p: 0.003 when compared with older patients. Conclusions: This study found that patients under 50 have a higher risk of developing vasospasm compared with older patients and that there is no association between clinical condition and the results of transcranial Doppler.

Vasoespasmo cerebral y déficit isquémico tardío en la hemorragia subaracnoídea aneurismática: guías para su manejo clínico / Cerebral vasospasm and delayed ischemic deficit in the aneurysmal subarachnoid hemorrhage: guidelines to its clinical management

La presente revisión del tema Vasoespasmo y Déficit Isquémico Cerebral tardío (DIT) en la Hemorragia subaracnoidea aneurismática tiene como objetivo actualizar su manejo, basado en las hipótesis mas aceptadas que se han logrado para explicar su patogénesis. Se efectúa una introducción con conceptos generales, se revisan las bases patogénicas del Vasoespasmo y se plantea su manejo, tomando en cuenta su diagnóstico, monitorización, profilaxis y manejo avanzado de acuerdo a las últimas Guías de Manejo Clínico y según medicina basada en las evidencias.

The objective of the present review on cerebral vasospasm and cerebral delayed isquemic deficit due to subarachnoid haemorrhage secondary to ruptured cerebral aneurysm, is to update their management, based on the most accepted pathophysiological hypotesis explaining their pathogenetic mechanisms. An introduction is performed presenting general concepts, review of the most recent research works explaining their pathogenesis, and the management is stated touching diagnosis, monitoring, prophylaxis, and advanced management according with the last clinical guidelines for his management using medicine based on evidences.

Ergotismo del sistema nervioso central: Reporte de dos muertes maternas asociadas a vasoespasmo cerebral por medicamentos derivados del ergot en Antioquia, Colombia, y revisión de la literatura / Ergotism of the central nervous system: Report of two maternal deaths associated with cerebral vasospasm due to ergot-derived drugs in Antioquia, Colombia, and review of the literature

Objetivo: presentar dos casos de muerte materna asociados al uso de medicamentos derivados del ergot (ergotismo agudo severo), y realizar una revisión de la literatura de la presentación de eventos adversos en el sistema nervioso central en puérperas expuestas a estos medicamentos. Materiales y métodos: se presentan dos casos de muerte materna posparto, el primero se asoció al uso de bromocriptina para supresión de lactancia y el segundo al uso metilergometrina para controlar hemorragia poscesárea. Las pacientes fueron atendidas en instituciones de tercer nivel de complejidad en la ciudad de Medellín, Colombia. Se realizó revisión de la literatura, registrada en la base de datos Medline vía PubMed. Los términos empleados para la búsqueda fueron: derivados del ergot, bromocriptina, angeítis cerebral posparto, ergotismo, enfermedad vascular cerebral posparto. Se buscaron, sin límite de tiempo, reportes de caso, reportes de series de caso y revisiones de tema. Se buscaron informes o alertas de seguridad de agencias reguladoras tales como: la Federal Drugs Administration (FDA), la European Medicines Agency (EMA) y del Instituto Nacional de Vigilancia de Medicamentos y Alimentos (Invima). Se consultaron artículos en inglés, francés y español. Resultados: se incluyeron 16 publicaciones que cumplieron con los criterios de búsqueda. Se lograron identificar 33 casos. Dos fueron fatales, uno asociado al uso de metilergonovina venosa para el alumbramiento y el otro a ergometrina oral usado como abortivo en la semana 20 de gestación. En las neuroimágenes predominan los hallazgos isquémicos (sugestivos de vasoespasmo cerebral). En tres casos se reportó hemorragia intracerebral, uno de estos fue un caso fatal. Los síntomas más frecuentes de presentación fueron la cefalea intensa, seguida de la convulsión. Solo en nueve casos se logró identificar el antecedente de hipertensión o preeclampsia, y en cuatro migraña. La indicación para el uso de bromocriptina en todos los casos fue suprimir la lactancia. En los tres casos reportados en que se usó metilergonovina fue para realizar alumbramiento. En el sistema de farmacovigilancia colombiano no se encontraron reportes de eventos adversos serios asociados a estos medicamentos. Conclusión: se debe reconocer el ergotismo del sistema nervioso central en el puerperio por el uso de medicamentos tales como la bromocriptina y la metilergonovina, como una entidad potencialmente fatal. Es importante crear una cultura de reporte de eventos adversos serios de estos medicamentos en nuestro país.

Objective: To report two cases of maternal death associated with ergot-derived drugs (acute sever ergotism), and to conduct and review of the literature on central nervous system adverse events during the postpartum period in women exposed to these medications. Materials and methods: Two cases of maternal death during the postpartum period. The first was associated with the use of bromocriptine for breast milk suppression, and the second was associated with the use of methylergometrine for the control of bleeding after Cesarean section. The patients received care at Level III institutions in the city of Medellín, Colombia. A review of the literature was conducted in the Medline database through Pubmed. The terms used for the search were: ergot derivatives, bromocriptine, postpartum cerebralangiitis, ergotism, postpartum cerebral vascular disease. The search was conducted without a time limitation and included, case reports, case series reports, and reviews. The search also included safety reports or alerts from regulatory agencies such as the FDA, the European Medicines Agency (EMA), and Invima. Articles in English, French and Spanish were reviewed. Results: Overall, 16 publications that met the search criteria were included, and 33 cases were identified. Two of the cases were fatal, one associated with the use of intravenous methylergonovine for delivery and the second one was associated with the use of oral ergometrine to induce abortion at 20 weeks of gestation. Neuroimaging studies show, predominantly, ischemic findings (suggestive of cerebral vasospasm). In three cases, intracranial haemorrhage was reported, and one of the three cases was fatal. The most frequent presenting symptoms were intense headache, followed by seizures. It was possible to identify a history of hypertension and/or preeclampsia only in nine cases, and a history of migraine in four. The vast majority of patients were otherwise healthy. In all the cases, the indication for using bromocriptine was breast milk suppression. In the three reported cases in which methylergonovine was used, the indication was to assist delivery. No reports of serious adverse events associated with these drugs were found in the Colombian pharmacovigilance system. Conclusion: Ergotism of the central nervous system due to the use of drugs such as bromocriptine and methylergonovine must be recognised during the postpartum period because it is life-threatening. It is important to create a culture of reporting of serious adverse events associated with these medications in our country.

Hemorragia subaracnóidea espontânea não aneurismática: perimesencefálica versus não perimesencefálica / Non-aneurysmal spontaneous subarachnoid hemorrhage: perimesencephalic versus non-perimesencephalic

RESUMO Objetivo: Comparar a evolução clínica da hemorragia subaracnóidea perimesencefálica com a da hemorragia subaracnóidea não perimesencefálica. Métodos: Estudo retrospectivo, que incluiu pacientes portadores de hemorragia subaracnóidea sem causa conhecida em um hospital terciário localizado na região norte de Portugal. Os dados epidemiológicos, clínicos e de imagem foram analisados estatisticamente, levando em conta a divisão dos pacientes em duas categorias: hemorragia subaracnóidea perimesencefálica e hemorragia subaracnóidea não perimesencefálica. Resultados: Cumpriram os critérios de inclusão 62 pacientes, 46,8% deles com hemorragia subaracnóidea perimesencefálica e 53,2% com hemorragia subaracnóidea não perimesencefálica. As caraterísticas demográficas, assim como os antecedentes clínicos, foram similares entre os grupos. As complicações foram observadas mais comumente no grupo com hemorragia subaracnóidea não perimesencefálica, sendo que 84,8% desses pacientes tiveram, no mínimo, uma complicação, comparados a 48,3% dos pacientes com hemorragia subaracnóidea perimesencefálica. Vasoespasmo, infecções e hidrocefalia foram as complicações mais comuns - todas observadas mais frequentemente nos pacientes com hemorragia subaracnóidea não perimesencefálica. Dois pacientes vieram a falecer, ambos com hemorragia subaracnóidea não perimesencefálica. A mediana do tempo de permanência no hospital foi maior nos pacientes com hemorragia subaracnóidea não perimesencefálica (21 dias, em comparação aos 14 dias observados nos pacientes com hemorragia subaracnóidea perimesencefálica). Não se observaram recidivas de sangramento durante o acompanhamento (tempo médio de 15 ± 10,3 meses). Conclusão: As hemorragias subaracnóideas perimesencefálica e não perimesencefálica tiveram formas diferentes de evolução clínica, principalmente no que se referiu à taxa de complicações e ao tempo mediano de permanência no hospital. Assim, a abordagem dessas duas formas de hemorragia subaracnóidea deve ser distinta, tanto em busca de melhorar o tratamento dos pacientes quanto para obter um melhor aproveitamento dos recursos de saúde.

ABSTRACT Objective: To compare the clinical evolution of perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Methods: The study was conducted retrospectively in a tertiary hospital center in the north region of Portugal. Included patients had no identifiable cause for subarachnoid hemorrhage. Several epidemiologic, clinical and imaging aspects were statistically analyzed, taking into account the differences in perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage. Results: Sixty-two patients met the inclusion criteria (46.8% - perimesencephalic subarachnoid hemorrhage; 53.2% - non-perimesencephalic subarachnoid hemorrhage). Demographic and clinical background characteristics were similar in both groups. Complications were more frequent in patients with non-perimesencephalic subarachnoid hemorrhage - 84.8% of the patients had at least one complication versus 48.3% in perimesencephalic subarachnoid hemorrhage. Vasospasm, infection and hydrocephaly were the most common complications (each was detected more frequently in the non-perimesencephalic subarachnoid hemorrhage group than in perimesencephalic subarachnoid hemorrhage group). Two patients died, both had a non-perimesencephalic subarachnoid hemorrhage. The median inpatient time was longer in the non-perimesencephalic subarachnoid hemorrhage group (21 versus 14 days). No incidents of rebleeding were reported during the follow-up period (mean time of 15 ± 10.3 months). Conclusion: Perimesencephalic subarachnoid hemorrhage and non-perimesencephalic subarachnoid hemorrhage are two different entities that have different clinical outcomes, namely in terms of complication rate and median inpatient time. The management of these patients should respect this difference to improve treatment and optimize health care resources.

Expression of Sphingosine-1-phosphate (S1P) on the cerebral vasospasm after subarachnoid hemorrhage in rabbits

PURPOSE:To demonstrate the relationship between of sphingosine-1-phosphate (S1P) expression and subarachnoid hemorrhage (SAH).METHODS:The basilar arteries from a "double-hemorrhage" rabbit model of SAH were used to investigate the relation between S1P expression and SAH. Various symptoms, including blood clots, basilar artery cross-sectional area, and S1P phosphatase expression were measured at day 3, 5, 7, 9.RESULTS: The expression of S1P was enhanced in the cerebral vasospasm after subarachnoid hemorrhage in the rabbits. And S1P expression was consistent with the basilar artery cross-sectional area changes at day 3, 5, 7, 9.CONCLUSION: Sphingosine-1-phosphate expression in the cerebral arterial may be a new indicator in the development of cerebral vasospasm after subarachnoid hemorrhage and provide a new therapeutic method for SAH.

Intervenciones de enfermería en la persona con vasoespasmo cerebral secundario a hemorragia subaracnoidea aneurismática / Nursing interventions in the person with a secondary cerebral vasospasm aneurysmal subarachnoid haemorrhage

Introducción. El vasoespasmo cerebral como complicación de la Hemorragia subaracnoidea aneurismática, es considerado como una vasoconstricción patológica de las arterias principales de la base del encéfalo; es una condición reversible, que se caracteriza con la reducción del calibre de la luz de las arterias y por lo consiguiente una disminución del flujo sanguíneo al área perfundida por el vaso comprometido. Objetivo. Desarrollar un proceso enfermero basado en la taxonomía Nanda, Noc, Nic a una persona con vasoespasmo cerebral. Metodología. Se realizó la elección de un caso clínico, con la metodología del proceso de atención de enfermería estableciendo un plan de cuidados en el área de recuperación y terapia intermedia del Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez durante el periodo postquirúrgico inmediato. Se detectaron las necesidades básicas alteradas al realizar la valoración neurológica de enfermería. Se procedió a formular los diagnósticos de enfermería reales y de riesgo y con base en estos se planearon las intervenciones de enfermería. Conclusión. El realizar las intervenciones de enfermería de forma sistematizada a partir del proceso enfermero, se establece un método científico, en donde cada intervención se fundamenta y da pauta a la aplicación de un cuidado especializado, dirigido hacia la mejora de la persona desde el punto de vista individual y con ello detectar oportunamente signos y síntomas de alarma así como posibles complicaciones.

Introduction. The cerebral vasospasm as complication of the Haemorrhage subarachnoid aneurismática, is considered to be a pathological vasoconstriction of the main arteries of the base of the brain; it is a reversible condition, which is characterized by the reduction of the caliber of the light of the arteries and for consequent a decrease of the blood flow to the area perfundida for the awkward glass. Target. To develop a process nurse based on the taxonomy Nanda, NOC, NIC to a person with vasospasm cerebral. Methodology. There was realized the election of a clinical case, with the methodology of the process of attention of infirmary establishing a care plan in the field of recovery and intermediate therapy of the National Institute of Neurology and Neurosurgery Manuel Velasco Suárez during the immediate postsurgical period. The basic needs were detected altered on having realized the neurological infirmary evaluation. One proceeded to formulate the real diagnoses of infirmary and of risk and with base in these the infirmary interventions were planned. Conclusion. Realizing the interventions of infirmary of form systematized from the process nurse, establishes a scientific method, where every intervention is based and gives rule to the application of a specializing care, directed to the progress of the person from the individual point of view and with it to detect opportunely signs and symptoms of alarm as well as possible complication.

Descripción de los cambios en la velocidad media de flujo sanguíneo cerebral en posición supino y sedente, en pacientes con hemorragia subaracnoidea aneurismática con vasoespasmo asintomático o sin vasoespasmo: Serie de casos / Changes in cerebral blood flow velocity in supine and sitting position in patients with aneurysmal subarachnoid hemorrhage

Background: Early mobilization in intensive care units (ICU) provides respiratory, neurological and cardiovascular benefits in hospitalized patients. However, the orthostatic effects of changing from a supine to a sitting position may interfere with cerebral hemodynamics of patients with aneurysmal subarachnoid hemorrhage (aSAH). Aim: To describe the changes in mean cerebral blood flow velocity (MCBFV) in supine and sitting position, in adult patients with aSAH, with asymptomatic vasospasm (AVS) or without vasospasm (VS) at a neurosurgical ICU. Material and Methods: Descriptive case series study in 21 patients with aSAH, both with and without VS. They were positioned in a supine 30° position and then seated at the edge of bed for six minutes. MCBFV was measured by transcranial Doppler (TCD), and hemodynamic variables in both positions were registered. After this basal assessment and for 21 days after the episode of SAH, patients were seated once a day and signs of VS were recorded. Results: No significant changes in MCBFV or hemodynamic variables were detected during position changes, except for an increase in heart rate in the sitting position. No patient with AVS at the onset, had symptomatic VS during the 21 days of follow up when patients were seated. Among patients with a normal MCBFV at baseline, five patients (24%) had VS at a mean of three days after the first time that they were seated on the edge of bed. Conclusions: Sitting patients at the edge of the bed is a safe mobilization alternative for patients who suffered aSAH who did not have VS or had AVS.

Erythropoietin in vasospasm. From bench to bedside? / Eritropoietina no vasoespasmo. Da bancada do laboratório para a beira do leito?

Aneurysmal subarachnoid haemorrhage is one of the most deleterious acute neurological diseases. The cerebral ischemia secondary to arterial vasospasm occurring after aneurysmal subarachnoid haemorrhage is still responsible for the considerable morbidity and mortality in these patients. Besides the knowledge of basic mechanisms of cerebral vasoespasm following aneurysmal subarachnoid haemorrhage, the prophylaxis and treatment of this pathology however still remain suboptimal. There issome evidence that acute erythropoietin treatment may reduce the severity of cerebral vasospasm and eventually improve outcome in aneurysmal subarachnoid haemorrhage patients. There are underlying mechanisms extend far beyond erythropoiesis: like enhancing neurogenesis, decreasing inflammation and apoptosis inhibition. In this review the authors describe many of the biologic effects, especially experimental studies and clinical studies that reported why the erythropoietin could be beneficial topatients with aneurysmal subarachnoid haemorrhage.

A hemorragia subaracnóidea é uma das doenças neurológicas agudas mais graves. A isquemia cerebral secundária ao vasoespasmo arterial após a hemorragia ainda é responsável por considerável morbidade e mortalidade nesses pacientes. Ao lado do conhecimento dos mecanismos básicos do vasoespasmo na hemorragia subaracnóidea, a profilaxia e o tratamento dessa entidade ainda são insuficientes. Há evidências de que o uso da eritropoietina na fase aguda pode reduzir a gravidade do vasoespasmo e,eventualmente, melhorar o prognóstico desses pacientes. Há mecanismos de ação da eritropoietina que vão além da eritropoiese como neurogênese, redução da inflamação e inibição da apoptose. Nesta revisão, os autores elucidam inúmeros efeitos biológicos, principalmente aqueles demonstrados nos estudos experimentais e clínicos que descrevem por que a eritropoietina pode ser benéfica em pacientes com hemorragia subaracnóidea.

Relevancia de la hiperglucemia para la evolución y el desenlace de la hemorragia subaracnoidea aneurismática: evidencias y mecanismos / Relevance of hyperglycemia on the course and outcome of aneurysmal subarachnoid hemorrhage: evidence and mechanisms

La hemorragia subaracnoidea aneurismática (HSAa) puede tener un desenlace mortal en unas pocas semanas debido por las complicaciones que presenta, como el vasoespasmo y el edema cerebrales junto con la hiperglucemia. La hiperglucemia podría estar relacionada con el desarrollo del vasoespasmo y el edema cerebrales. Es posible que el control de la glucemia juegue un papel central en la evolución y el desenlace de la HSAa. Se han descrito los mecanismos por los cuales puede darse esta relación, que incluyen el equilibrio de iones, la liberación de aminoácidos excitadores, la estimulación de moléculas vasoconstrictoras y la disminución en la síntesis de vasorrelajantes. Sin embargo, existen estudios que no apoyan la hipótesis sobre la participación de la hiperglucemia en esta enfermedad. En conjunto, estas evidencias sugieren que el control de los niveles de glucosa podría modificar el desenlace de los grupos de pacientes con HSAa dependiendo de las complicaciones que presenten.

Aneurysmal subarachnoid hemorrhage (aSAH) may have a fatal outcome after a few weeks from ictus, due to its complications, like cerebral vasospasm and edema along with hyperglycemia. Hyperglycemia may be involved in the development of brain vasospasm and edema. It is possible that hyperglycemia plays a central role in the outcome of aSAH. Several mechanisms may explain this relationship; they include ion balance, excitatory amino acid release, stimulation of vasoconstrictor molecules and reduced synthesis of vasorelaxants. However, some studies do not support this hypothesis regarding the role of hyperglycemia in aSAH. Taken together, the evidence suggests that the control of glucose levels may influence the aSAH outcome depending on the complications that may develop.

C-reactive protein and vasospasm after aneurysmal subarachnoid hemorrhage1

PURPOSE: To evaluate the relationship between C reactive protein levels and clinical and radiological parameters with delayed ischemic neurological deficits and outcome after aneurysmal subarachnoid hemorrhage. METHODS: One hundred adult patients with aneurismal SAH were prospectively evaluated. Besides the baseline characteristics, daily C-reactive protein levels were prospectively measured until day 10 after subarachnoid hemorrhage. The primary end point was outcome assessed by Glasgow Outcome Scale, the secondary was the occurrence of delayed ischemic neurological deficits (DINDs). RESULTS: A progressive increase in the CRP levels from the admission to 3rd postictal day was observed, followed by a slow decrease until the 9th day. Hemodynamic changes in TCD were associated with higher serum CRP levels. Patients with lower GCS scores presented with increased CRP levels. Patients with higher Hunt and Hess grades on admission developed significantly higher CRP serum levels. Patients with higher admission Fisher grades showed increased levels of CRP. A statistically significant inverse correlation was established in our series between CRP serum levels and GOS on discharge and CRP levels. CONCLUSIONS: Higher C-reactive protein serum levels are associated with worse clinical outcome and the occurrence of delayed ischemic neurological deficits. Because C-reactive protein levels were significantly elevated in the early phase, they might be a useful parameter to monitor. .

Doppler transcraneal en pre-eclampsia / Transcranial doppler in pre-eclampsia

La preeclampsia es una afección multisistémica durante el embarazo, con alta tasa de morbilidad y mortalidad en la madre y el hijo. Dentro del espectro de efectos está la alteración del flujo sanguíneo cerebral que en ocasiones se asocia con convulsiones (eclampsia). Se ha intentado encontrar un método diagnóstico para su detección temprana, iniciar la terapia oportuna y reducir los efectos negativos. El doppler transcraneal es un examen no invasivo, de bajo costo y seguro, que puede tener un valor diagnóstico. El objetivo del artículo es una revisión sobre la utilidad del doppler transcraneal y la preeclampsia. Se buscó en la base de datos PubMed con términos MeSh. Diferentes estudios revelan índices de resistencia y pulsatilidad disminuidos en el segundo trimestre del embarazo, los cuales pueden predecir la aparición de preeclampsia.

Pre-eclampsia is a multisystem disorder of pregnancy associated with significant maternal and perinatal morbidity and mortality. Among the spectrum of effects are alterations in cerebral blood flow sometimes associated with convulsions (eclampsia). There is a need for a method for diagnosis and early detection of pre-eclampsia to allow timely intervention and reduce negative effects. Transcranial Doppler is a safe, non- invasive, low-cost method which may have a diagnostic value. The objective of this article is to conduct a review on the utility of transcranial Doppler and pre-eclampsia. The PubMed data base was reviewed using MeSh terms. Different studies reveal reduced resistance and pulsatility indices in the second trimester of pregnancy, which may predict the development of pre-eclampsia.

Terapia endovascular no vasoespasmo cerebral secundário à hemorragia subaracnóidea / Endovascular therapy for the cerebral vasospasm after subarachnoid hemorrhage

O vasoespasmo cerebral é uma complicação relativamente frequente após episódios de hemorragia subaracnóidea de etiologia aneurismática. É responsável pela mortalidade de aproximadamente 30% dos pacientes e por sequelas neurológicas em 50% dos sobreviventes. Revisão de literatura realizada em julho de 2012. Foram pesquisadas as bases de dados PubMed e BVS e selecionados 37 artigos em português e inglês. A terapia do triplo H, largamente utilizada, diminui complicações isquêmicas, mas pode piorar comorbidades. A nimodipina ainda é a única droga que melhora comprovadamente o prognóstico do paciente. O tratamento endovascular pode ser baseado em angioplastia por balão, que dilata mecanicamente os vasos estreitados, ou em administração intra-arterial de agentes vasodilatadores, como a papaverina. Angioplastia profilática em determinados segmentos arteriais pode reduzir em até 10,4% as complicações isquêmicas. A angioplastia terapêutica tem melhores resultados quando realizada nas duas primeiras horas após a instalação do vasoespasmo sintomático. A papaverina induz melhora angiográfica em até 66% dos pacientes, mas pode estar relacionada à neurotoxicidade. A terapia endovascular parece ter resultados muito positivos para o tratamento do vasoespasmo cerebral. Pela falta de evidências, no entanto, deve ainda ser reservada para pacientes refratários ao tratamento clínico ou com complicações que o impeçam.

Cerebral vasospasm is a relatively frequent complication after aneurysmal subarachnoid hemorrhages. It leads to a 30% mortality rate of patients who survived the hemorrhage and the development of neurologic deficits for 50% of the remaining. This is a literature review performed in July, 2012. Two databases were surveyed: PubMed and VHL. Thirty-seven articles in English and Portuguese were selected. ?Triple-H? therapy, widely employed, reduces ischemic complications, but can deteriorate patient?s comorbidities. Nimodipine still the only certified drug for the treatment of vasospasm. Endovascular treatment can be performed through percutaneous transluminal balloon angioplasty (TBA), which enlarges vessels mechanically, or intra-arterial administration of vasodilating agents, such as papaverine. Prophylactic angioplasty in selected arterial segments can reduce ischemic complications in until 10.4%. Therapeutic angioplasty presents better outcome when performed in the first two hours after the development of symptomatic vasospasm. Papaverine induces angiographic improvement in 66% of patients, but can be related with neurotoxicity. Endovascular therapy seems to present very positive results for the treatment of cerebral vasospasm. However, due to the lack of evidences, it should be reserved for when clinical treatment fails or cannot be performed.

Effect of cervical sympathetic block on cerebral vasospasm after subarachnoid hemorrhage in rabbits

PURPOSE: Cerebral vasospasm (CVS) is a major complication after subarachnoid hemorrhage (SAH) induced by the rupture of intracranial aneurysms. The aim of the present study was to investigate the effect and mechanism of cervical sympathetic block on cerebral vasospasm of the rabbits after SAH. METHODS: After successful modeling of cervical sympathetic block, 18 healthy male white rabbits were randomly divided into three groups (n=6), ie, sham operation group (Group A), SAH group (Group B) and SAH with cervical sympathetic block group (Group C). Models of delayed CVS were established by puncturing cisterna magna twice with an injection of autologous arterial blood in Groups B and C. A sham injection of blood through cisterna magna was made in Group A. 0.5 ml saline was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 3 d in Group B (bilateral alternating). 0.5 ml of 0.25% bupivacaine was injected each time through a catheter for cervical sympathetic block after the first injection of blood three times a day for 7 d in Group B. 2 ml venous blood and cerebrospinal fluid were obtained before (T1), 30 min (T2) and 7 d (T3) after the first injection of blood, respectively, and conserved in a low temperature refrigerator. Basilar artery value at T1, T2 and T3 was measured via cerebral angiography. The degree of damage to nervous system at T1 and T3 was recorded. RESULTS: There was no significant difference in diameter of basilar artery at T1 among three groups. The diameters of basilar artery at T2 and T3 of Groups B and C were all smaller than that in Group A, which was smaller than Group C, with a significant difference. There was no significant difference in NO and NOS in plasma and cerebrospinal fluid among three groups. The NO and NOS contents at T2 and T3 of Groups B and C were all lower than Group A; Group C was higher than Group B, with a significant difference. The nerve function at T3 of Groups B and C were all lower than Group A and that of Group C higher than Group B, with a significant difference. CONCLUSION: Cervical sympathetic block can relieve cerebral vasospasm after subarachnoid hemorrhage and increase NO content and NOS activity in plasma and cerebrospinal fluid to promote neural functional recovery.

Factores predictores del desarrollo de vasoespasmo cerebral en pacientes con hemorragia subaracnoidea aneurismática atendidos en el Hospital Nacional Edgardo Rebagliati Martins durante el periodo 2010-2011 / Factors predictors of the development of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage treated at the National Hospital Edgardo Rebagliati Martins during the period 2010 - 2011

La Hemorragia Subaracnoidea (HSA) es una condición devastadora producto de la ruptura de un aneurisma cerebral. A pesar de avances en su diagnóstico y tratamiento el pronóstico continúa siendo pobre. Su principal complicación es el vasoespasmo, una condición potencialmente tratable. El presente tuvo por finalidad identificar, ¿Cuáles son los factores predictores del desarrollo de Vasoespasmo Cerebral en pacientes con HSA aneurismática atendidos en el "Hospital Nacional Edgardo Rebagliati Martins" durante el periodo 2010 - 2011? La población fue de 127 pacientes admitidos con diagnóstico definido de HSA aneurismática entre el 1ero de Junio del 2010 y el 31 de Diciembre del 2011 y seleccionados mediante criterios. Todo paciente tuvo una evaluación clínica y tomográfica inicial y seguido en su evolución mediante una ficha durante 20 días. Se les aplicó, además, la escala de valoración de riesgo de vasoespasmo e isquemia cerebral tardía (ERVI). Se realizó una TAC cerebral a las 72 horas, a los 7 días, ya los 14 días o cuando la condición clínica lo ameritaba. Concluido el seguimiento clínico y no habiendo evidencia clínico-imagenológica de vasoespasmo el paciente terminó su participación. La edad media fue 57.5 años ± DS 18.38. Del total, 63.78 por ciento tenía una edad <=50 años. La hipertensión arterial fue el antecedente más frecuente en 48.82 por ciento. Los estadios I y II de las escalas de la WFNS y Hunt and Huss (HH) fueron los predominantes en 66.93 por ciento. Contrariamente, los estadios III y IV lo fueron en la escala de Fisher en 64.56 por ciento. La incidencia de vasoespasmo cerebral/DCI fue de 47.24 por ciento, siendo solo vasoespasmo 33.07 por ciento, con una media de 7.3 días DS ± 3.37. Hubo un incremento progresivo de vasoespasmo/DCI a medida que incrementaba el grado de la ERVI, con incidencias de 22.73 por ciento, 64.44 por ciento y 100 por ciento para los grados I, II y III, respectivamente. La hidrocefalia fue la segunda complicación en...