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.

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.

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.

Three Interesting Case Reports of Intracranial Aneurysm Managed with Triple 'H' Therapy.

Anaesthesia for aneurysm surgeries is highly specialized and unique. Vasospasm is the most important determinant for morbidity and mortality in intracranial aneurysms. For prevention and management of vasospasm Triple-H therapy (Hypertension, Hypervolemia and Haemodilution) is recommended. Triple-H therapy is gold standard in neuroanaesthesia in intracranial aneurysm surgeries in order to increase cerebral blood flow in areas affected by vasospasm and avoid damage caused by ischemia. First patient was 52 years old female with Right vertebral artery posterior inferior cerebellar artery aneurysm of size 1cm, operated successfully who became unconscious 22 hours after surgery and treated with Triple-H therapy for vasospasm. Second case was 48 years old male patient of right anterior cerebral artery aneurysm of 9mm size operated successfully after intraoperative rupture of aneurysm and subsequent vasospasm. Third case was 35 years pregnant female patient of anterior communicating artery aneurysm of 5mm size treated with triple H therapy for vasospasm.

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.

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. .

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.

Serum C-reactive protein levels predict neurological outcome after aneurysmal subarachnoid hemorrhage / O nível sérico da proteína C-reativa como fator preditivo do prognóstico neurológico após hemorragia subaracnóidea aneurismática

OBJECTIVES: Our aim was to evaluate the relationship between serum C-reactive protein (CRP) levels and the neurological prognosis and development of vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Eighty-two adult patients with aSAH diagnoses were prospectively evaluated. Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, cranial CT scans, digital subtraction angiography studies and daily neurological examinations were recorded. Serial serum CRP measurements were obtained daily between admission and the tenth day. Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRS) were used to assess the prognosis. RESULTS: Serum CRP levels were related to severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and Fisher grades presented statistically significant higher serum CRP levels. Patients with higher serum CRP levels had a less favorable prognosis. CONCLUSIONS: Increased serum CRP levels were strongly associated with worse clinical prognosis in this study.

OBJETIVOS: Nosso propósito foi avaliar a relação entre os níveis séricos de proteína C-reativa (PCR), o prognóstico neurológico e o desenvolvimento de vasoespasmo em pacientes com hemorragia subaracnóidea aneurismática (HSAa). MÉTODOS: Foram avaliados prospectivamente 82 pacientes adultos com diagnóstico de HSAa. Foram anotados em prontuário: a escala de coma de Glasgow (ECG), a escala de Hunt-Hess, a escala de Fisher, TC de crânio, angiografia cerebral e o exame neurológico diário. Foi determinada diariamente a PCR sérica, da admissão ao décimo dia. Foi utilizadas a escala de resultados de Glasgow e a escala de Rankin modificada (mRS) para avaliar o prognóstico. RESULTADOS: Os níveis séricos de PCR estavam relacionados à severidade da HSAa. Pacientes com EGC baixos e altos graus pelas escalas de Hunt-Hess e Fisher tiveram níveis de PCR séricos estatisticamente elevados. Pacientes com altos níveis de PCR séricos tiveram prognóstico menos favorável. CONCLUSÕES: Aumentos dos níveis séricos da PCR foram fortemente associados com pior prognóstico clínico neste estudo.

Fisher revised scale for assessment of prognosis in patients with subarachnoid hemorrhage / Avaliação prognóstica com escala de Fisher modificada em pacientes com hemorragia subaracnóidea

The Fisher revised scale (FRS) presents an alternative for evaluating patients with subarachnoid hemorrhage (SAH). In this study, we compared the prognosis of patients with SAH and vasospasms (VSP). METHOD: This was a prospective study on patients with a diagnosis of aneurysmal SAH, 72 hours after the initial event. Sequential neurological examinations and Hunt and Hess (HaH) score were performed on the 1st, 7th and 14th days. Transcranial Doppler was used to assess vasospasms. RESULTS: Out of the 24 patients studied, ten (41.66 percent) presented a delayed neurological deficit, such as diminished consciousness, decreased HaH score or death. The single patient classified as FS-1 did not have any delayed neurological deficit, while such deficits evolved in one patient out of five with FS-2 (20 percent); two out of seven with FS-3 (28.57 percent) and seven out of 11 with FS-4 (63.63 percent). CONCLUSION: Level three of the FS and FRS seemed to be compatible with regard to predicting the likelihood of progression to severe VSP.

A escala revisada de Fisher (FRS) representa uma alternativa para avaliação de pacientes com hemorragia subaracnóidea (HSA). Neste estudo comparamos a evolução prognóstica referente ao vasoespasmo (VSP) nos pacientes com HSA. MÉTODO: Estudo prospectivo em pacientes com diagnóstico de HSA, com 72 horas após o evento inicial. Escala de Hunt e Hess (HeH) foi realizada no 1º, 7º, 14º dia. Utilizamos Doppler transcraniano para avaliação de VSP. RESULTADOS: Dos 24 pacientes estudados dez (41,66 por cento) tiveram déficit neurológico tardio (DNT), como diminuição da consciência, grau de HeH ou morte. Um paciente de cinco classificados como FS-2 (20 por cento), dois de sete pacientes com FS-3 (28,57 por cento) e sete de 11 pacientes com FS-4 (63,63 por cento) evoluíram com DNT. Para o FRS não encontramos piora neurológica precoce no paciente com FRS-0. CONCLUSÃO: O nível três da FS e FRS parecem ser comparáveis, quando se trata de predizer a probabilidade de progressão para VSP grave.

Utilidad del doppler transcraneal en la hemorragia subaracnoidea: revisión / Usefulness of transcranial doppler in subarachnoid hemorrhage: review

This review summarizes the usefulness of transcranial Doppler (TCD) for the assessment of subarachnoid hemorrhage in the setting of a stroke unit. The basic hemodynamic principles are presented. We discuss the accuracy, the advantages and limitations of the TCD and the interpretation methods.

Esta revisión resume la utilidad del Doppler transcraneal (DTC) para la evaluación de la hemorragia subaracnoidea en instalaciones de una unidad de tratamiento de accidente vascular. Se presentan los principios hemodinámicos básicos. Se discute la eficiencia, las ventajas y las limitaciones del DTC y los métodos de interpretación.

Effect of N-acetylcysteine on vasospasm in subarachnoid hemorrhage / Efeito da N-acetilcisteína sobre o vasoespasmo na hemorragia subaracnóidea

Vasospasm remains an extremely serious complication that affects patients presenting with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms. The current therapeutic armamentarium is still insufficient in many cases, and the search for new therapies is necessary. In this study, we evaluated the effect of N-acetylcysteine (NAC) on cerebral arterial vasospasm using an experimental model. Twenty-four wistar rats were divided into 4 groups: [1] Control, [2] SAH, [3] SAH+NAC and [4] SAH+Placebo. The experimental model employed double subarachnoid injections of autologous blood. The proposed dose of NAC was 250 mg/kg intraperitoneally per day. We analyzed the inner area of the basilar artery to assess the action of NAC. The experimental model proved to be very adequate, with a mortality rate of 4 percent. The inner area of the basilar artery in the SAH group showed significant difference to the control group (p=0.009). The use of NAC significantly reduced vasospasm as compared to the untreated group (p=0.048) and established no significant difference to the control group (p=0.098). There was no significant improvement with the administration of placebo (p=0.97). The model of the dual hemorrhage proved to be very useful for vasospasm simulation, with overall low mortality. The administration of NAC significantly reduced vasospasm resulting from SAH, and may represent a new therapeutic alternative.

O vasoespasmo arterial encefálico continua sendo uma complicação extremamente grave que acomete pacientes com hemorragia subaracnóidea (HSA) por ruptura de aneurismas. O arsenal terapêutico atual ainda, em muitos casos, é insuficiente e a busca de novas alternativas terapêuticas torna-se necessária. Neste estudo, avaliamos a ação da N-acetilcisteína (NAC) sobre o vasoespasmo arterial encefálico em um modelo experimental. Foram utilizados 24 ratos wistar divididos em 4 grupos: [1] Controle, [2] HSA, [3] HSA+NAC e [4] HSA+Placebo. O modelo experimental utilizado foi o da dupla injeção subaracnóidea de sangue autólogo. A dose proposta da NAC foi de 250 mg/kg/dia por via intraperitoneal. Foi analisada a área interna da artéria basilar para avaliação da ação da NAC. O modelo experimental mostrou-se excelente com mortalidade de 4 por cento. A mensuração da área interna da artéria basilar do grupo HSA demonstrou diminuição significativa em relação ao grupo controle (p=0,009). A administração da NAC reduziu significativamente o vasoespasmo em relação ao grupo não tratado (p=0,048) e estabeleceu diferença não significativa em relação ao grupo controle (p=0,098). Não houve melhora significativa com administração de placebo (P=0,97). O modelo da dupla hemorragia mostrou-se bastante útil para reprodução do vasoespasmo, com baixos índices de mortalidade. A administração da NAC diminuiu significativamente o vasoespasmo decorrente da HSA, podendo representar uma nova alternativa terapêutica.

Effects of cervical sympathectomy on vasospasm induced by meningeal haemorrhage in rabbits / Efeitos da simpatectomia cervical sobre o vasoespasmo induzido por hemorragia meníngea em coelhos

This study investigates the role of cervical sympathectomy in the prevention of acute vasospasm induced by meningeal haemorrhage in rabbits. Sixteen adult English Norfolk rabbits were divided into 2 experimental groups: bilateral cervical sympathectomy of the superior sympathetic ganglion (SSSG, n=8), and bilateral SSSG and sympathectomy of the inferior sympathetic ganglion (SISG, n=8). Other 24 animals were used as controls. Basilar artery diameter was evaluated by angiography. SSSG protected the animals against developing cerebral vasospasm; SSSG associated with SISG did not increase this effect.

Este estudo investiga o papel da simpatectomia cervical na prevenção do vasoespasmo agudo induzido por hemorragia meníngea em coelhos. Para tanto, foram utilizados 16 coelhos adultos da raça Norfolk inglesa, divididos em 2 grupos experimentais: simpatectomia cervical bilateral do gânglio simpático cervical superior (SSSG, n=8) e SSSG associada a simpatectomia cervical bilateral do gânglio simpático cervical inferior (SISG, n=8). Outros 24 animais foram usados como controles. Os diâmetros das artérias basilares foram avaliados por medições após angiografias. SSSG protegeu os animais contra o vasoespasmo; SSSG associada a SISG não aumentou este efeito.

Transcranial Doppler sonography evaluation in patients with vasospasm following subarachnoid haemorrhage.

Transcranial Doppler (TCD) sonography is emerging as a new ultrasonography technology to look at the interaction between the brain parenchyma and perfusion during cerebrovascular accident. Before TCD sonography the vasospasm following subarachnoid haemorrhage could only be diagnosed either clinically or by invasive method ie, angiography. TCD has been proved as a wonderful non-invasive, repeatable, beat-by-beat, non-expensive technique for detection and follow-up of vasospasm after subarachnoid haemorrhage. In the present series 12 patients suspected to have vasospasm after subarachnoid haemorrhage were confirmed and monitored with the help of TCD. Most of the patients were clinically presented with increasing headache and altered sensorium. It is noticed that vasospasm following subarachnoid haemorrhage has a typical course, which has increasing trend after 4th day of subarachnoid haemorrhage and declining trend after 14th day onwards. Six out of 12 patients were in moderate grade of vasospasm, 2 out of 12 were in severe grade and 4 out of 12 were mild grade of severity.

Modelos experimentais para o estudo do vasoespasmo cerebral: revisão de literatura / Experimental animal models of cerebral vasospasm: a review

O vasoespasmo cerebral é a principal complicação da hemorragia subaracnóidea, não existindo, até o momento, um tratamento específico para ele, provavelmente em razão do desconhecimento de todos os seus mecanismos fisiopatológicos. Diante da necessidade de se conhecer melhor o vasoespasmo cerebral, vários modelos experimentais foram desenvolvidos, em diversas espécies de animais. No presente artigo é apresentada revisão sobre os modelos experimentais de vasoespasmo cerebral, com base na pesquisa no Medline Medical Database, abrangendo o período de 1060 a 2002, utilizando-se as palavras-chave animal, model, experimental, vasospasm e hemorrhage. Os modelos foram classificados em três categorias, de acordo com a técnica utilizada para promover a hemorragia subaracnóidea, sendo analisadas as vantagens e desvantagens de cada categoria.