Glibenclamide in aneurysmal subarachnoid hemorrhage: a randomized controlled clinical trial.

OBJECTIVE: Glibenclamide has been shown to improve outcomes in cerebral ischemia, traumatic brain injury, and subarachnoid hemorrhage (SAH). The authors sought to evaluate glibenclamide's impact on mortality and functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: Patients with radiologically confirmed aSAH, aged 18 to 70 years, who presented to the hospital within 96 hours of ictus were randomly allocated to receive 5 mg of oral glibenclamide for 21 days or placebo, in a modified intention-to-treat analysis. Outcomes were mortality and functional status at discharge and 6 months, evaluated using the modified Rankin Scale (mRS). RESULTS: A total of 78 patients were randomized and allocated to glibenclamide (n = 38) or placebo (n = 40). Baseline characteristics were similar between groups. The mean patient age was 53.1 years, and the majority of patients were female (75.6%). The median Hunt and Hess, World Federation of Neurosurgical Societies (WFNS), and modified Fisher scale (mFS) scores were 3 (IQR 2-4), 3 (IQR 3-4), and 3 (IQR 1-4), respectively. Glibenclamide did not improve the functional outcome (mRS) after 6 months (ordinal analysis, unadjusted common OR 0.66 [95% CI 0.29-1.48], adjusted common OR 1.25 [95% CI 0.46-3.37]). Similar results were found for analyses considering the dichotomized 6-month mRS score (favorable score 0-2), as well as for the secondary outcomes of discharge mRS score (either ordinal or dichotomized), mortality, and delayed cerebral ischemia. Hypoglycemia was more frequently observed in the glibenclamide group (5.3%). CONCLUSIONS: In this study, glibenclamide was not associated with better functional outcomes after aSAH. Mortality and delayed cerebral ischemia rates were also similar compared with placebo.

Glibenclamide in aneurysmatic subarachnoid hemorrhage (GASH): study protocol for a randomized controlled trial.

BACKGROUND: Recent findings on the benefits of glibenclamide as a neuroprotective drug have started a new era for prospective studies on sulfonylureas. The effect of glibenclamide blocking the Sur1-Trpm4 channel was examined in models of subarachnoid hemorrhage and stroke, with findings of significantly reduced tight-junction abnormalities, resulting in less edema formation and considerably reduced transsynaptic apoptosis of hippocampal neurons and significantly ameliorated impairments in spatial learning. Based on these data, we plan a clinical trial to establish evidence of glibenclamide as an adjunct treatment in aneurysmal subarachnoid hemorrhage. METHODS: An estimated 80 patients meeting the inclusion criteria of radiological confirmatory evidence of an aneurysmal subarachnoid hemorrhage, age 18-70 years, and presentation of less than 96 h from the ictus will be allocated randomly into two groups, one receiving 5 mg daily oral intake of glibenclamide for 21 days and another control group receiving a placebo. The study's primary outcome is the modified Rankin scale (mRS) after 6 months, as favorable (mRS 0-2) or unfavorable (mRS 3-6). The secondary outcomes will be late cognitive status, assessed after 6 months by psychological tests (the Short Form Health Survey Questionnaire and the Montreal Cognitive Assessment), as well as death at 6 months, delayed cerebral ischemia and occurrence of serious adverse events due to study medication. DISCUSSION: There is a growing interest in the scientific community regarding glibenclamide in brain edema and traumatic brain injury, but with very little of this interest targeting spontaneous brain hemorrhage, especially aneurism rupture. Positive outcomes are expected for the treatment patients, especially in language and memory preservation, as has been shown in experimental models. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03569540 . Retrospectively registered on 26 June 2018.

A Bibliometric Analysis of the Most Cited Articles in Neurocritical Care Research.

Bibliometric analyses may indicate the most active journals, authors, countries, institutions and specialties by evaluating the most cited articles in a given research field. To the authors' knowledge, there is no bibliometric analysis regarding neurocritical care research. Thus, the aim of this study is to analyze and to provide a scope of the current scientific production in this area. The 100 most cited articles in the neurocritical care research were retrieved from the research "(neurocritical) AND (care)" in the Scopus database. The variables collected and included in this analysis were: number of citations, article title, first author's name, year and journal of publication and its impact factor (IF), specialty, affiliation and country of the corresponding author at the time of publication, and category of the article. Also, these variables were assessed for primary research only. The articles were published in 34 different journals from 1995 to 2017, with a mean citation number of 109.36, ranging from 44 to 540. Neurocritical Care (23 articles in top 100 and 2190 citations, IF = 3.163) and Critical Care Medicine (20 articles and 2896 citations in top 100, IF = 6.630) were the journals with the greatest number of articles and citations, respectively. Neurocritical Care also had the highest number of primary research papers (15 articles, accounting for 850 citations). Excepting one article from Asia (Singapore) and one from Oceania (Australia), all the other 98 papers were from North America (67) or Europe (31). United States was the country with most articles (60, 35 primary research) and citations (6115) among the top 100. Columbia University (11 articles, being 7 primary research, and 915 citations) was the institution with the highest number of articles and primary research articles in top 100, whereas University of Heidelberg (6 articles and 1220 citations) was the most cited institution. Neurology was the specialty with the greatest number of publications in top 100 and the most cited one (57 articles and 5983 citations). The first author with the greatest number of publications as well as primary research articles was A. I. Qureshi (5 articles, being 4 primary research, and 660 citations), while the most cited was K. H. Polderman (2 articles and 749 citations). Fifty-nine publications were primary and 41 secondary research. Among primary research, treatment/management was the most frequent and most cited topics (33 articles and 4172 citations). To the authors' knowledge, this is the first bibliometric analysis regarding neurocritical care research. Our findings suggest that the neurocritical care research field is more prominent in North America and Europe, more frequently published in specific critical care journals and after 1994. The most discussed topic was related to treatment and/or management within neurocritical care.

Prognostic model for patients with traumatic brain injuries and abnormal computed tomography scans.

Traumatic brain injury (TBI) is an important cause of death and disability worldwide. The prognosis evaluation is a challenge when many variables are involved. The authors aimed to develop prognostic model for assessment of survival chances after TBI based on admission characteristics, including extracranial injuries, which would allow application of the model before in-hospital therapeutic interventions. A cohort study evaluated 1275 patients with TBI and abnormal CT scans upon admission to the emergency unit of Hospital das Clinicas of University of Sao Paulo and analyzed the final outcome on mortality. A logistic regression analysis was undertaken to determine the adjusted weigh of each independent variable in the outcome. Four variables were found to be significant in the model: age (years), Glasgow Coma Scale (3-15), Marshall Scale (MS, stratified into 2,3 or 4,5,6; according to the best group positive predictive value) and anysochoria (yes/no). The following formula is in a logistic model (USP index to head injury) estimates the probability of death of patients according to characteristics that influence on mortality. We consider that our mathematical probability model (USP Index) may be applied to clinical prognosis in patients with abnormal CT scans after severe traumatic brain injury.

Epidural Hematoma: A Prospective Analysis of Morbidity and Mortality in 173 Patients / Hematoma epidural: Uma análise prospectiva de morbidade e mortalidade em 173 pacientes

Objectives A few recent studies have focused on epidural hematomas (EDHs) that are routine in emergency rooms. The study was to evaluate the latest situation of affected patients by encephalic trauma associated with EDH in our service. Methods Prospective study between September 1, 2003 and May 30, 2009. Data were computed regarding age, sex, trauma mechanism, qualification by Glasgow coma scale admission, presence of anisocoria, and evaluation by the recovery of Glasgow scale high, with all patients by computed tomography (CT) scan. Results Among the 173 analyzed patients, mortality reached 20 patients (11.5%). Mortality was higher in the subgroup of 76 patients (44%) admitted with Glasgow coma scale (GCS ≤ 8) with 17 deceased, corresponding to 85% of total deaths. Prevalence of male subjects (140 cases, 81%) with bruises located in the temporal, frontal and parietal regions; 147 (85%) patients underwent neurosurgical treatment by craniotomy. The worst prognosis was in patients with hematomas of higher-volume (50 mL), midline structures deviations greater than 1.5 mm and basal cisterns CSF closed. Conclusion The authors emphasize the correct indication of neurosurgery and the postoperative intensive care unit (ICU) as key factors for success in the treatment of patients with EDHs.

Objetivos Poucos estudos atuais tem focado os hematomas epidurais que são rotina nos serviços de emergência. O estudo teve por objetivo avaliar a situação mais recente dos doentes acometidos por traumatismo crânio ancefálico associado a hematoma epidural no nosso serviço. Métodos Estudo prospectivo entre 1 de setembro de 2003 a 30 de maio de 2009. Foram computados dados referentes a idade, sexo, mecanismo do traumatismo, qualificação pela escala de coma de Glasgow` a admissão, presença de anisocoria e avaliação pela escala de recuperação de Glasgow na alta, tendo todos os pacientes realizado tomografia de crânio. Resultados Dentre os 173 pacientes analisados encontramos mortalidade de 20 pacientes (11,5%). No subgrupo de 76 pacientes (44%) admitidos em escala de coma de Glasgow (ECGLa) ≤ 8 pontos, a mortalidade foi superior com 17 óbitos, correspondendo a 85% do total de óbitos. Prevaleceram indivíduos do sexo masculinos (140 casos, 81%) com hematomas localizados na região temporal, seguido pelas regiões frontal e parietal; 147 (85%) foram submetidos a tratamento neurocirúrgico por craniotomia. O prognóstico foi pior nos pacientes com hematomas de volume superior a 50 mL, desvios de estruturas de linha mediana maiores que 1,5 mm e cisternas liquóricas basais fechadas. Conclusões Os autores enfatizam a correta indicação da neurocirurgia e o pósoperatório na unidade de terapia intensiva como fatores chave para o bom resultado no tratamento dos doentes com hematomas epidurais.

Hematoma epidural diagnosticado por diplopia - Relato de caso / Epidural Hematoma Diagnosed by Diplopia - Case Report

Os autores relatam e discutem o mecanismo pelo qual um paciente de 33 anos, com relato de traumatismo crânio encefálico ocorrido 5 dias antes comperda de consciência no momento do traumatismo, e assintomático nos 4 dias sequentes, iniciou diplopia no quinto dia após o traumatismo, sintoma que provocou sua ida ao pronto-socorro, a realização de exame físico neurológico normal e de tomografia do crânio devido a história e mecanismo de traumatismo, que revelou hematoma epidural occipital, prontamente operado, com o sintoma de diplopia tendo desaparecido no 14o dia após a cirurgia, já com o paciente em casa.

The authors report a male of 33 years that after head trauma occurred 5 days before developed diplopia, which motivated him to go to the emergency room, where even without changes in neurological examination, brain CT scan performed revealed an epidural hematoma occipital, operated with good functional outcome.

Sepse Brasil: estudo epidemiológico da sepse em Unidades de Terapia Intensiva brasileiras / An epidemiological study of sepsis in Intensive Care Units: Sepsis Brazil study

JUSTIFICATIVA E OBJETIVOS: A sepse representa a principal causa de morte nas UTI em todo o mundo. Muitos estudos têm demonstrado um aumento da incidência ao longo do tempo e apenas uma leve redução na mortalidade. MÉTODO: Foi realizado um estudo prospectivo em 65 hospitais de todas as regiões do Brasil. Os pacientes que foram admitidos com sepse ou que desenvolveram sepse no mês de setembro de 2003 foram incluídos. O acompanhamento foi feito até o 28º dia de internação e/ou até a alta da UTI. O diagnóstico seguiu os critérios clássicos propostos na convenção de 1991. Foram avaliados dados demográficos, escore APACHE II, escore SOFA, mortalidade, fonte de infecção, microbiologia, comorbidades, tempo de internação, uso de ventilação mecânica, cateter de Swan-Ganz, vasopressores e hemotransfusão. RESULTADOS: Setenta e cinco unidades de terapia intensiva de todas as regiões do Brasil participaram do estudo. Foram identificados 3128 pacientes e 521 (16,7 por cento) foram diagnosticados como tendo o diagnóstico de sepse, sepse grave ou choque séptico. A idade média foi de 61,7 (IQR 39-79), 293 (55,7 por cento) corresponderam ao sexo masculino, e a mortalidade global em 28 dias foi de 46,6 por cento. O escore APACHE II médio foi de 20 e o escore SOFA no D1 foi de 7 (IQR 4-10). O escore SOFA no grupo dos não-sobreviventes foi maior no D1 (8, IQR 5-11), e aumentou no D3 (9, IQR 6-12). A mortalidade na sepse, sepse grave e choque séptico foi de 16,7 por cento, 34,4 por cento e 65,3 por cento, respectivamente. O tempo médio de internação foi de 15 dias (IQR 5-22). As duas principais fontes de infecção foram o trato respiratório (69 por cento) e o abdômen (23,1 por cento). Os bacilos gram-negativos foram mais prevalentes (40,1 por cento). Os cocos gram-positivos foram identificados em 32,8 por cento e as infecções fúngicas em 5 por cento. A ventilação mecânica ocorreu em 82,1 por cento dos casos, uso de cateter de Swan-Ganz em 18,8 por cento, vasopressores...

BACKGROUND AND OBJECTIVES: Sepsis represents the major cause of death in the ICUs all over the world. Many studies have shown an increasing incidence over time and only a slight reduce in mortality. Many new treatment strategies are arising and we should define the incidence and features of sepsis in Brazil. METHODS: Prospective cohort study in sixty-five hospitals all over Brazil. The patients who were admitted or who developed sepsis during the month of September, 2003 were enrolled. They were followed until the 28th day and/or until their discharge. The diagnoses were made in accordance to the criteria proposed by ACCP/SCCM. It were evaluated demographic features, APACHE II score, SOFA (Sepsis-related Organ Failure Assessment) score, mortality, sources of infections, microbiology, morbidities and length of stay (LOS). RESULTS: Seventy-five ICUs from all regions of Brazil took part in the study.3128 patients were identified and 521 (16.7 percent) filled the criteria of sepsis, severe sepsis or septic shock. Mean age was 61.7 (IQR 39-79), 293 (55.7 percent) were males, and the overall 28-day mortality rate was 46.6 percent. Average APACHE II score was 20 and SOFA score on the first day was 7 (IQR 4-10). SOFA score in the mortality group was higher on day 1 (8, IQR 5-11), and had increased on day 3 (9, IQR 6-12). The mortality rate for sepsis, severe sepsis and septic shock was 16.7 percent, 34.4 percent and 65.3 percent, respectively. The average LOS was 15 days (IQR 5-22). The two main sources of infection were the respiratory tract (69 percent) and the abdomen one (23.1 percent). Gram-negative bacilli were more prevalent (40.1 percent). Gram-positive cocci were identified in 32.8 percent and fungi infections in 5 percent. Mechanical ventilation was observed in 82.1 percent of the patients, Swan-Ganz catheter in 18.8 percent, vasopressors in 66.2 percent and hemotransfusion in 44.7 percent. CONCLUSIONS: It was observed a high mortality...

[An epidemiological study of sepsis in Intensive Care Units: Sepsis Brazil study]. / Sepse Brasil: estudo epidemiológico da sepse em Unidades de Terapia Intensiva brasileiras.

BACKGROUND AND OBJECTIVES: Sepsis represents the major cause of death in the ICUs all over the world. Many studies have shown an increasing incidence over time and only a slight reduce in mortality. Many new treatment strategies are arising and we should define the incidence and features of sepsis in Brazil. METHODS: Prospective cohort study in sixty-five hospitals all over Brazil. The patients who were admitted or who developed sepsis during the month of September, 2003 were enrolled. They were followed until the 28th day and/or until their discharge. The diagnoses were made in accordance to the criteria proposed by ACCP/SCCM. It were evaluated demographic features, APACHE II score, SOFA (Sepsis-related Organ Failure Assessment) score, mortality, sources of infections, microbiology, morbidities and length of stay (LOS). RESULTS: Seventy-five ICUs from all regions of Brazil took part in the study.3128 patients were identified and 521 (16.7%) filled the criteria of sepsis, severe sepsis or septic shock. Mean age was 61.7 (IQR 39-79), 293 (55.7%) were males, and the overall 28-day mortality rate was 46.6%. Average APACHE II score was 20 and SOFA score on the first day was 7 (IQR 4-10). SOFA score in the mortality group was higher on day 1 (8, IQR 5-11), and had increased on day 3 (9, IQR 6-12). The mortality rate for sepsis, severe sepsis and septic shock was 16.7%, 34.4% and 65.3%, respectively. The average LOS was 15 days (IQR 5-22). The two main sources of infection were the respiratory tract (69%) and the abdomen one (23.1%). Gram-negative bacilli were more prevalent (40.1%). Gram-positive cocci were identified in 32.8% and fungi infections in 5%. Mechanical ventilation was observed in 82.1% of the patients, Swan-Ganz catheter in 18.8%, vasopressors in 66.2% and hemotransfusion in 44.7%. CONCLUSIONS: It was observed a high mortality of sepsis in the ICUs in Brazil. The high frequency of septic shock demonstrated a group at high risk of death. In order to have a better use of the resources and reduce in mortality during the next 5 years, it is very important to identify our specific features related to this syndrome.