Malignant Cerebral Ischemia in A COVID-19 Infected Patient: Case Review and Histopathological Findings.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for an unprecedented worldwide pandemic that has severely impacted the United States. As the pandemic continues, a growing body of evidence suggests that infected patients may develop significant coagulopathy with resultant thromboembolic complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. However, this data is limited and comes from recent small case series and observational studies on stroke types, mechanisms, and outcomes.1-14 Furthermore, evidence on the role of therapeutic anticoagulation in SARS-CoV-2 infected patients with elevated inflammatory markers, such as D-dimer, is also limited. We report the case of a middle-aged patient who presented with a large vessel ischemic stroke likely resulting from an underlying inflammatory response in the setting of known novel coronavirus infection (COVID-19). Histopathologic analysis of the patient's ischemic brain tissue revealed hypoxic neurons, significant edema from the underlying ischemic insult, fibrin thrombi in small vessels, and fibroid necrosis of the vascular wall without any signs of vasculature inflammation. Brain biopsy was negative for the presence of SARS-CoV-2 RNA (RT-PCR assay). Along with a growing body of literature, our case suggests that cerebrovascular thromboembolic events in COVID-19 infection may be related to acquired hypercoagulability and coagulation cascade activation due to the release of inflammatory markers and cytokines, rather than virus-induced vasculitis. Further studies to investigate the mechanism of cerebrovascular thromboembolic events and their prevention is warranted.

Análisis de la calidad de los servicios académico-administrativos en una universidad colombiana / Analysis of the quality of academic-administrative services in a Colombian university / Análise da qualidade dos serviços académico-administrativos em uma universidade colombiana

Resumen Introducción. En este artículo se presentan los resultados finales de la investigación Análisis de la calidad de los servicios académico-administrativos en una universidad colombiana. Objetivo. Determinar la percepción de los estudiantes respecto a los servicios ofrecidos. Materiales y Métodos. Se utilizó el instrumento Servqualing aplicándose a una muestra de 832 estudiantes los cuales fueron seleccionados por el método sistemático. Se realizó Análisis de Factores. Resultados. El análisis arrojó tres dimensiones con 61,39 % de la varianza explicada, KMO=0,973 y un determinante de 0,01325. La confiabilidad del instrumento de medición usando Alpha de Cronbach fue de 0,949, indicando una alta fiabilidad de la escala y validez interna y externa obtenida con pruebas estadísticas significativas al 5 %. Conclusiones. Los resultados evidencian que el nivel de calidad global de los servicios académico administrativos, tienen una Buena, percepción con una calificación de 4,08 (80 %), indicando que los mejores resultados se encontraron en los ítems asociados con la dimensión 3 y con oportunidades de mejora principalmente en la dimensión 1. Estos resultados permiten orientaciones precisas para la toma de decisiones y conllevan al mejoramiento continuo de la calidad del servicio.

Abstract Introduction. This article shows the final results of the research "Analysis of the quality of academic-administrative services in a Colombian university". Objective. Determine the perception of students regarding the services offered. Materials and Methods. For the measurement, the Servqualing instrument was applied to a sample of 832 students who were selected by the systematic method. Results. A factor analysis was carried out which showed three dimensions with 61.39% of the variance explained, KMO = 0.973 and a determinant of 0.01325. The reliability of the measuring instrument using Cronbach's Alpha was 0.949, indicating a high reliability of the scale, and internal and external validity was obtained with significant statistical tests at 5%. Conclusions. The results show that the overall quality level of academic administrative services has a good perception with a score of4.08 (80%), indicating that the best results were found in the items associated with dimension 3 and with opportunities for improvement, mainly in dimension 1. These results allow precise guidelines for decision making and lead to continuous improvement of service quality.

Resumo Introdução. Neste artigo apresenta-se os resultados finais da pesquisa Análise da qualidade dos serviços académico-administrativos em uma universidade colombiana. Objetivo. Determinar a percepção dos estudantes respeito aos serviços oferecidos. Materiais e Métodos. Utilizou-se o instrumento Servqualing aplicando-se em uma amostra de 832 estudantes os quais foram selecionados pelo método sistemático. Realizou-se Análise de Fatores. Resultados. O análise mostrou três dimensões com 61,39 % da variância explicada, KMO=0,973 e um determinante de 0,01325. A confiabilidade do instrumento de medição usando Alpha de Cronbach foi de 0,949, indicando uma alta fiabilidade da escala e validez interna e externa obtida com provas estatísticas significativas ao 5 %. Conclusões. Os resultados evidenciam que o nível de qualidade global dos serviços académico-administrativos, tem uma Boa, percepção com uma qualificação de 4,08 (80%), indicando que os melhores resultados se encontraram nos itens associados com a dimensão 3 e com oportunidades de melhora principalmente na dimensão 1. Estes resultados permitem orientações precisas para a toma de decisões e acarreiam ao melhoramento contínuo da qualidade do serviço.

The incidence and risk factors of associated acute myocardial infarction (AMI) in acute cerebral ischemic (ACI) events in the United States.

OBJECTIVES: To determine the association between myocardial infarction (AMI) and clinical outcome in patients with primary admissions diagnosis of acute cerebral ischemia (ACI) in the US. METHODS: Data from Nationwide Inpatient Sample (NIS) was queried from 2002-2011 for inpatient admissions of patients with a primary diagnosis of ACI with and without AMI using International Classification of Diseases, Ninth Revision, Clinical Modification coding (ICD-9). A multivariate stepwise regression analysis was performed to assess the correlation between identifiable risk factors and clinical outcomes. RESULTS: During 10 years the NIS recorded 886,094 ACI admissions with 17,526 diagnoses of AMI (1.98%). The overall cumulative mortality of cohort was 5.65%. In-hospital mortality was associated with AMI (aOR 3.68; 95% CI 3.49-3.88, p≤0.0001), rTPA administration (aOR 2.39 CI, 2.11-2.71, p<0.0001), older age (aOR 1.03, 95% CI, 1.03-1.03, P<0.0001) and women (aOR 1.06, 95% CI 1.03-1.08, P<0.0001). Overall, mortality risk declined over the course of study; from 20.46% in 2002 to 11.8% in 2011 (OR 0.96, 95% CI 0.95-0.96, P<0.0001). Survival analysis demonstrated divergence between the AMI and non-AMI sub-groups over the course of study (log-rank p<0.0001). CONCLUSION: Our study demonstrates that although the prevalence of AMI in patients hospitalized with primary diagnosis of ACI is low, it negatively impacts survival. Considering the high clinical burden of AMI on mortality of ACI patients, a high quality monitoring in the event of cardiac events should be maintained in this patient cohort. Whether prompt diagnosis and treatment of associated cardiovascular diseases may improve outcome, deserves further study.

Left ventricular dysfunction and cerebral infarction from vasospasm after subarachnoid hemorrhage.

BACKGROUND: Although neurogenic stunned myocardium (NSM) after aneurysmal subarachnoid hemorrhage (SAH) is well described, its clinical significance remains poorly defined. We investigated the influence of left ventricular (LV) dysfunction and cerebral vasospasm on cerebral infarction, serious cardiovascular events, and functional outcome after SAH. METHODS: Of the 481 patients enrolled in the University Columbia SAH Outcomes Project between 10/96 and 05/02, we analyzed a subset of 119 patients with at least one echocardiogram, serial transcranial Doppler (TCD) data, and with no prior history of cardiac disease. LV dysfunction was defined as an ejection fraction <40% on echocardiography. Infarction from vasospasm was adjudicated by the study team after comprehensive review of all clinical and imaging data. Functional outcome was assessed at 15 and 90 days with the modified Rankin Scale (mRS). RESULTS: Eleven percent of patients had LV dysfunction (N = 13). Younger age, hydrocephalus, and complete filling of the quadrigeminal and fourth ventricles were associated with LV dysfunction (all P < 0.05). Despite a similar frequency of pre-existing hypertension, 0% of patients with LV dysfunction reported taking antihypertensive medication, compared to 35% of those without (P = 0.009). There was a significant association between LV dysfunction and infarction from vasospasm after adjusting for clinical grade, age, and peak TCD flow velocity (P = 0.03). Patients with LV dysfunction also had higher rates of hypotension requiring vasopressors (P = 0.001) and pulmonary edema (P = 0.002). However, there was no association between LV dysfunction and outcome at 14 days after adjustment for established prognostic variables. CONCLUSIONS: LV dysfunction after SAH increases the risk of cerebral infarction from vasospasm, hypotension, and pulmonary edema, but with aggressive ICU support does not affect short-term survival or functional outcome. Antihypertensive medication may confer cardioprotection and reduce the risk of catecholamine-mediated injury after SAH.

Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke. Laboratory investigation.

OBJECT: Individually, the cytokines erythropoietin (EPO) and insulin-like growth factor-I (IGF-I) have both been shown to reduce neuronal damage significantly in rodent models of cerebral ischemia. The authors have previously shown that EPO and IGF-I, when administered together, provide acute and prolonged neuroprotection in cerebrocortical cultures against N-methyl-D-aspartate-induced apoptosis. The aim of this study was to determine whether intranasally applied EPO plus IGF-I can provide acute neuroprotection in an animal stroke model and to show that intranasal administration is more efficient at delivering EPO plus IGF-I to the brain when compared with intravenous, subcutaneous, or intraperitoneal administration. METHODS: The EPO and IGF-I were administered intranasally to mice that underwent transient middle cerebral artery occlusion (MCAO). Stroke volumes were measured after 1 hour of MCAO and 24 hours of reperfusion. To evaluate the long-term effects of this treatment, behavioral outcomes were assessed at 3, 30, 60, and 90 days following MCAO. Radiography and liquid scintillation were used to visualize and quantify the uptake of radiolabeled 125I-EPO and 125I-IGF-I into the mouse brain after intranasal, intravenous, subcutaneous, or intraperitoneal administration. RESULTS: Intranasal administration of EPO plus IGF-I reduced stroke volumes within 24 hours and improved neurological function in mice up to 90 days after MCAO. The 125I-EPO and 125I-IGF-I were found in the brain within 20 minutes after intranasal administration and accumulated within the injured areas of the brain. In addition, intranasal administration delivered significantly higher levels of the applied 125I-EPO and 125I-IGF-I to the brain compared with intravenous, subcutaneous, or intraperitoneal administration. CONCLUSIONS: The data demonstrate that intranasal EPO plus IGF-I penetrates into the brain more efficiently than other drug delivery methods and could potentially provide a fast and efficient treatment to prevent chronic effects of stroke.

Frequency and clinical impact of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage.

OBJECT: The authors sought to determine frequency, risk factors, and impact on outcome of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage (SAH). METHODS: The authors prospectively studied 580 patients with SAH admitted to their center between July 1996 and May 2002. Delayed cerebral ischemia (DCI) from vasospasm was defined as 1) a new focal neurological deficit or decrease in level of consciousness, 2) a new infarct revealed by follow-up CT imaging, or both, after excluding causes other than vasospasm. Outcome at 3 months was assessed using the modified Rankin Scale. RESULTS: Delayed cerebral ischemia occurred in 121 (21%) of 580 patients. Of those with DCI, 36% (44 patients) experienced neurological deterioration without a corresponding infarct, 42% (51 patients) developed an infarct in conjunction with neurological deterioration, and 21% (26 patients) had a new infarct on CT without concurrent neurological deterioration. In a multivariate analysis, risk factors for asymptomatic DCI included coma on admission, placement of an external ventricular drain, and smaller volumes of SAH (all p < or = 0.03). Patients with asymptomatic DCI were less likely to be treated with vasopressor agents than those with symptomatic DCI (64 vs 86%, p = 0.01). After adjusting for clinical grade, age, and aneurysm size, the authors found that there was a higher frequency of death or moderate-to-severe disability at 3 months (modified Rankin Scale Score 4-6) in patients with asymptomatic DCI than in patients with symptomatic DCI (73 vs 40%, adjusted odds ratio 3.9, 95% confidence interval 1.3-12.0, p = 0.017). CONCLUSIONS: Approximately 20% of episodes of DCI after SAH are characterized by cerebral infarction in the absence of clinical symptoms. Asymptomatic DCI is particularly common in comatose patients and is associated with poor outcome. Strategies directed at diagnosing and preventing asymptomatic infarction from vasospasm in patients with poor-grade SAH are needed.

Cardiac arrhythmias after subarachnoid hemorrhage: risk factors and impact on outcome.

OBJECTIVE: Serious cardiac arrhythmias have been described in approximately 5% of patients after subarachnoid hemorrhage (SAH). The aim of this study was to identify the frequency, risk factors and clinical impact of cardiac arrhythmia after SAH. METHODS: We prospectively studied 580 spontaneous SAH patients and identified risk factors and complications associated with the development of clinically significant arrhythmia. Multiple logistic regression analysis was used to calculate adjusted odds ratios for the effect of arrhythmia on hospital complications and 3-month outcome, as measured by the modified Rankin Scale, after controlling for age, neurological grade, APACHE-2 physiologic subscore, brain herniation and aneurysm size. RESULTS: Arrhythmia occurred in 4.3% (n = 25) of patients. Atrial fibrillation and flutter were the most common arrhythmias, occurring in 76% (n = 19) of these patients. Admission predictors of cardiac arrhythmia included older age, history of arrhythmia and abnormal admission electrocardiogram (all p < 0.05). After adjusting for length of stay, hospital complications associated with arrhythmia included myocardial ischemia, hyperglycemia, and herniation (all p < 0.05). Arrhythmia was associated with an excess ICU stay of 5 days (p = 0.002). After adjusting for other predictors of outcome, arrhythmia was associated with an increased risk of death (adjusted OR 8.0, 95% confidence interval 1.9-34.0, p = 0.005), and death or severe disability (adjusted OR 6.9, 95% confidence interval 1.5-32.0, p = 0.014). CONCLUSIONS: Clinically important arrhythmias, most often atrial fibrillation or flutter, occurred in 4% of SAH patients. Arrhythmias are associated with an increased risk of cardiovascular comorbidity, prolonged hospital stay and poor outcome or death after SAH, after adjusting for other predictors of poor outcome.

Impact of nosocomial infectious complications after subarachnoid hemorrhage.

OBJECTIVE: Critically ill neurological patients are susceptible to infections that may be distinct from other intensive care patients. The aim of this study is to quantify the prevalence, risk factors, and effect on the outcome of nosocomial infectious complications in patients with subarachnoid hemorrhage (SAH). METHODS: We studied 573 consecutive patients with SAH, identified the most prevalent infectious complications, and performed univariate analyses to determine risk factors for each complication. Multiple logistic regression models were constructed to calculate adjusted odds ratios for associated risk factors and to assess the impact of infectious complications on 3-month outcome as evaluated with the modified Rankin Scale. RESULTS: The most prevalent nosocomial infections were pneumonia (n = 114, 20%), urinary tract infection (n = 77, 13%), bloodstream infection (BSI) (n = 48, 8%), and meningitis/ventriculitis (n = 28, 5%). Significant independent associations with pneumonia included older age, poor Hunt and Hess grade, intubation/mechanical ventilation, and loss of consciousness at ictus. Urinary tract infection was associated with female sex and central line use. BSI was also associated with central line use, and meningitis/ventriculitis was associated with the presence of intraventricular hemorrhage and external ventricular drainage (all P < 0.05). After adjustment for Hunt and Hess grade, aneurysm size, and age, pneumonia (adjusted odds ratio, 2.04; 95% confidence interval, 1.12-3.71; P = 0.020) and BSI (adjusted odds ratio, 2.51; 95% confidence interval, 1.14-5.56; P = 0.023) independently predicted death or severe disability at 3 months. Prolonged length of stay was significantly associated with all infection types (P < 0.001). CONCLUSION: Pneumonia and BSI are common infectious complications of SAH and independently predict poor outcome. The implementation of infection-control measures may be needed to improve outcome after SAH.

Higher hemoglobin is associated with improved outcome after subarachnoid hemorrhage.

OBJECTIVE: There are few data regarding anemia and transfusion after subarachnoid hemorrhage (SAH). We addressed the hypothesis that higher hemoglobin (HGB) levels are associated with less death and disability after SAH. DESIGN: Prospective registry with automated data retrieval. PATIENTS: Six hundred eleven patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. SETTING: Neurologic intensive care unit. INTERVENTIONS: Patients were treated according to standard management protocols. MEASUREMENTS AND MAIN RESULTS: We electronically retrieved all HGB readings during the acute hospital stay for 611 consecutively admitted SAH patients. Outcomes were measured with the modified Rankin Scale at 14 days or discharge, and at 3 months. Patients who were independent (modified Rankin Scale, 0-3) at discharge or 14 days had higher mean (11.7 +/- 1.5 vs. 10.9 +/- 1.2, p < .001) and nadir (9.9 +/- 2.1 vs. 8.6 +/- 1.8, p < .001) HGB, and had higher HGB values every day in the hospital. There were similar results when patients were stratified by mortality. Higher HGB was associated with reduced risk of poor outcome (modified Rankin Scale, 4-6) at 14 days/discharge and 3 months after correcting for Hunt and Hess grade, age, history of diabetes, and cerebral infarction. Length of stay and HGB interacted such that lower HGB has a more pronounced effect with length of stay > 14 days. CONCLUSIONS: Higher HGB values are associated with improved outcomes after SAH at 14 days/discharge and 3 months. In contrast to general critical care patients, SAH patients may benefit from higher HGB. Determination of the optimal goal HGB after SAH will require separate prospective research.

Predictors and clinical implications of shivering during therapeutic normothermia.

BACKGROUND: Shivering during induced normothermia (IN) remains a therapeutic limitation. We investigated potential risk factors and clinical implications of shivering during IN. METHODS: Post hoc analysis was performed on 24 patients enrolled in a clinical trial of an automated surface cooling system to achieve IN. Hyponatremia was defined as serum levels <136 mmol/L and hypomagnesaemia as levels <1.5 mg/dL. Continuous heat energy transfer (kcal/h) was averaged hourly. Glasgow Coma Scale (GCS) scores were recorded every 2 h. Shivering status was documented hourly. Mixed effects modeling was used to determine clinical measures associated with shivering. Generalized estimating equation (GEE) models were used to compare baseline-adjusted repeated-measures GCS scores. RESULTS: About of 24 (39%) patients demonstrated shivering. Shivering was associated with men (67% vs. 21%, P = 0.03), hyponatremia (44% vs. 7%, P = 0.03), and hypomagnesaemia (56% vs. 7%, P = 0.02). The average kcal/h (158 +/- 645 kcal/h vs. 493 +/- 645 kcal/h, P = 0.03) was greater in shivering patients. Shivering was positively associated with increases in heart rate (P < 0.001), respiratory rate (P < 0.001), and kcal/h (P < 0.001). Non-shivering patients showed a greater increase from baseline GCS (GEE, P = 0.02) at 24 h. No differences in sedative doses or fever burden were noted between shiverers and non-shiverers. CONCLUSIONS: Men, hyponatremia, and hypomagnesaemia may predispose febrile patients treated with IN to shivering. Shivering dramatically increases the amount of heat transfer required to maintain normothermia, and may be associated with adverse effects on level of consciousness.

CT and CT-perfusion findings of reversible leukoencephalopathy during triple-H therapy for symptomatic subarachnoid hemorrhage-related vasospasm.

BACKGROUND: Reversible leukoencephalopathy syndrome (RLS) is an acute neurological syndrome associated with altered mental status and visual disturbances described in patients with sudden elevations in systemic blood pressure and other medical conditions. In this process, neuroimaging studies usually demonstrate diffuse edema involving the subcortical structures of the posterior regions of the brain. Triple H (HHH) therapy is an established treatment for symptomatic vasospasm following subarachnoid hemorrhage (SAH). RLS has not been reported in the scientific literature as a complication of HHH therapy with perfusion computed tomography (CTP) imaging documentation. CASE: A 73-year-old woman developed iatrogenic RLS during HHH therapy for SAH-related vasospasm. The computed tomography (CT) revealed bilateral parieto-occipital hypodensities. The CTP study showed increased cerebral blood volume and blood flow as well as decreased mean transit time in both parietal-occipital regions, which is compatible with vasogenic edema. CONCLUSION: The induction of hypertension as part of HHH therapy for SAH-related cerebral vasospasm may result in RLS. Therefore, it should be considered as a potentially reversible cause in the differential diagnosis of neurological deterioration in SAH patients while on HHH therapy. CTP study can offer an alternative for the assessment of this cerebrovascular syndrome.

Impact of medical complications on outcome after subarachnoid hemorrhage.

OBJECTIVE: Medical complications occur frequently after subarachnoid hemorrhage (SAH). Their impact on outcome remains poorly defined. DESIGN: Inception cohort study. PATIENTS: Five-hundred eighty patients enrolled in the Columbia University SAH Outcomes Project between July 1996 and May 2002. SETTING: Neurologic intensive care unit. INTERVENTIONS: Patients were treated according to standard management protocols. MEASUREMENTS AND MAIN RESULTS: Poor outcome was defined as death or severe disability (modified Rankin score, 4-6) at 3 months. We calculated the frequency of medical complications according to prespecified criteria and evaluated their impact on outcome, using forward stepwise multiple logistic regression after adjusting for known predictors of poor outcome. Thirty-eight% had a poor outcome; mortality was 21%. The most frequent complications were temperature>38.3 degreesC (54%), followed by anemia treated with transfusion (36%), hyperglycemia>11.1 mmol/L (30%), treated hypertension (>160 mm Hg systolic; 27%), hypernatremia>150 mmol/L (22%), pneumonia (20%), hypotension (<90 mm Hg systolic) treated with vasopressors (18%), pulmonary edema (14%), and hyponatremia<130 mmol/L (14%). Fever (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.4; p=.02), anemia (OR, 1.8; 95% CI, 1.1-2.9; p=.02), and hyperglycemia (OR, 1.8; 95% CI, 1.1-3.0; p=.02) significantly predicted poor outcome after adjustment for age, Hunt-Hess grade, aneurysm size, rebleeding, and cerebral infarction due to vasospasm. CONCLUSIONS: Fever, anemia, and hyperglycemia affect 30% to 54% of patients with SAH and are significantly associated with mortality and poor functional outcome. Critical care strategies directed at maintaining normothermia, normoglycemia, and prevention of anemia may improve outcome after SAH.

Hyperglycemia after SAH: predictors, associated complications, and impact on outcome.

BACKGROUND AND PURPOSE: Hyperglycemia is common after subarachnoid hemorrhage (SAH). The extent to which prolonged hyperglycemia contributes to in-hospital complications and poor outcome after SAH is unknown. METHODS: We studied an inception cohort of 281 SAH patients with an initial serum glucose level obtained within 3 days of SAH onset and who had at least 7 daily glucose measurements between SAH days 0 and 10. We defined mean glucose burden (GB) as the average peak daily glucose level >5.8 mmol/L (105 mg/dL). Hospital complications were recorded prospectively, and 3-month outcome was assessed with the modified Rankin scale. RESULTS: The median GB was 1.8 mmol/L (33 mg/dL). Predictors of high-GB included age > or =54 years, Hunt and Hess grade III-V, poor Acute Physiology and Chronic Health Evaluation (APACHE)-2 physiological subscores, and a history of diabetes mellitus (all P< or =0.001). In a multivariate analysis, GB was associated with increased intensive care unit length of stay (P=0.003) and the following complications: congestive heart failure, respiratory failure, pneumonia, and brain stem compression from herniation (all P<0.05). After adjusting for Hunt-Hess grade, aneurysm size, and age, GB was an independent predictor of death (odds ratio, 1.10 per mmol/L; 95% CI, 1.01 to 1.21; P=0.027) and death or severe disability (modified Rankin scale score of 4 to 6; odds ratio, 1.17 per mmol/L; 95% CI 1.07 to 1.28, P<0.001). CONCLUSIONS: Hyperglycemia after SAH is associated with serious hospital complications, increased intensive care unit length of stay, and an increased risk of death or severe disability.

Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage.

BACKGROUND: Cardiac troponin I (cTI) release occurs frequently after subarachnoid hemorrhage (SAH) and has been associated with a neurogenic form of myocardial injury. The prognostic significance and clinical impact of these elevations remain poorly defined. METHODS AND RESULTS: We studied 253 SAH patients who underwent serial cTI measurements for clinical or ECG signs of potential cardiac injury. These patients were drawn from an inception cohort of 441 subjects enrolled in the Columbia University SAH Outcomes Project between November 1998 and August 2002. Peak cTI levels were divided into quartiles or classified as undetectable. Adverse in-hospital events were prospectively recorded, and outcome at 3 months was assessed with the modified Rankin Scale. Admission predictors of cTI elevation included poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, and a composite score of physiological derangement (all P< or =0.01). Peak cTI level was associated with an increased risk of echocardiographic left ventricular dysfunction (odds ratio [OR], 1.3 per quintile; 95% CI, 1.0 to 1.7; P=0.03), pulmonary edema (OR, 2.1 per quintile; 95% CI, 1.6 to 2.7; P<0.001), hypotension requiring pressors (OR, 1.9 per quintile; 95% CI, 1.5 to 2.3; P<0.001), and delayed cerebral ischemia from vasospasm (OR, 1.3 per quintile; 95% CI, 1.07 to 1.7; P=0.01). Peak cTI levels were predictive of death or severe disability at discharge after controlling for age, clinical grade, and aneurysm size (adjusted OR, 1.4 per quintile; 95% CI, 1.1 to 1.9; P=0.02), but this association was no longer significant at 3 months. CONCLUSIONS: cTI elevation after SAH is associated with an increased risk of cardiopulmonary complications, delayed cerebral ischemia, and death or poor functional outcome at discharge.

Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage.

BACKGROUND: Aneurysm rebleeding has historically been an important cause of mortality after subarachnoid hemorrhage (SAH). OBJECTIVE: To describe the frequency and impact of rebleeding in the modern era of aneurysm care, which emphasizes early surgical or endovascular treatment. DESIGN: Inception cohort. SETTING: Tertiary care medical center. PATIENTS: A total of 574 patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. Early aneurysm repair was performed whenever feasible. MAIN OUTCOME MEASURES: Rebleeding was defined by prespecified clinical and radiographic criteria, excluding prehospital, intraprocedural, and postrepair events. Functional outcome was assessed at 3 months with the modified Rankin Scale. Multiple logistic regression was used to identify predictors of rebleeding, poor functional outcome, and mortality. RESULTS: Rebleeding occurred in 40 (6.9%) of the 574 patients; most cases (73%) occurred within 3 days of ictus. Hunt-Hess grade on admission (odds ratio [OR], 1.92 per grade; 95% confidence interval [CI], 1.33-2.75; P<.001) and maximal aneurysm diameter (OR, 1.07/mm; 95% CI, 1.01-1.13; P = .005) were independent predictors of rebleeding. After controlling for Hunt-Hess grade and aneurysm size, rebleeding was associated with a markedly reduced chance of survival with functional independence (modified Rankin Scale score,

Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study.

OBJECTIVE: Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which exhibit beneficial cerebrovascular effects by modulating inflammation and nitric oxide production, have not been evaluated in acute aneurysmal subarachnoid hemorrhage (SAH) patients. The effect of prior statin use on 14-day functional outcome and on prevention of vasospasm-induced delayed cerebral ischemia (DCI) or stroke during hospitalization was analyzed. METHODS: We conducted a 1:2 matched (age, admission Hunt and Hess grade, vascular disease/risk history) cohort study of 20 SAH patients on statins and 40 SAH controls. The primary outcome was functional outcome at 14 days (Modified Lawton Physical Self-Maintenance Scale and Barthel Index scale scores). Secondary outcomes were 14-day mortality, Modified Rankin Scale score, DCI, DCI supported by angiography/transcranial Doppler [TCD], cerebral infarctions of any type, and TCD highest mean velocity elevation. RESULTS: Statin users demonstrated a significant protective effect on 14-day Barthel Index scale and Modified Lawton Physical Self-Maintenance Scale scores (77 +/- 10 versus 39 +/- 8, P = 0.003; 12 +/- 7 versus 19 +/- 9, P = 0.03, respectively). Moreover, statin users demonstrated a significantly lower incidence of DCI and DCI supported by angiography/TCD (10% versus 43%, P = 0.02; 5% versus 35%, P = 0.01, respectively), cerebral infarctions of any type (25% versus 63%, P = 0.01), and baseline-to-final TCD highest mean velocity change of 50 cm/s or greater (18% versus 51%, P = 0.03). CONCLUSION: SAH statin users demonstrated significant improvement in 14-day functional outcome, a significantly lower incidence of DCI and cerebral infarctions of any type, as well as prevention of TCD highest mean velocity elevation. However, we did not find a significant statin impact on mortality or global outcome (Modified Rankin Scale) in this small sample. This study provides clinical evidence for the potential therapeutic benefit of statins after acute SAH.

Phenytoin exposure is associated with functional and cognitive disability after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Phenytoin (PHT) is routinely used for seizure prophylaxis after subarachnoid hemorrhage (SAH), but may adversely affect neurologic and cognitive recovery. METHODS: We studied 527 SAH patients and calculated a "PHT burden" for each by multiplying the average serum level of PHT by the time in days between the first and last measurements, up to a maximum of 14 days from ictus. Functional outcome at 14 days and 3 months was measured with the modified Rankin scale, with poor functional outcome defined as dependence or worse (modified Rankin Scale > or =4). We assessed cognitive outcomes at 14 days and 3 months with the telephone interview for cognitive status. RESULTS: PHT burden was associated with poor functional outcome at 14 days (OR, 1.5 per quartile; 95% CI, 1.3 to 1.8; P<0.001), although not at 3 months (P=0.09); the effect remained (OR, 1.6 per quartile; 95% CI, 1.2 to 2.1; P<0.001) after correction for admission Glasgow Coma Scale, fever, stroke, age, National Institutes of Health Stroke Scale > or =10, hydrocephalus, clinical vasospasm, and aneurysm rebleeding. Seizure in hospital (OR, 4.1; 95% CI, 1.5 to 11.1; P=0.002) was associated with functional disability in a univariate model only. Higher quartiles of PHT burden were associated with worse telephone interview for cognitive status scores at hospital discharge (P<0.001) and at 3 months (P=0.003). CONCLUSIONS: Among patients treated with PHT, burden of exposure to PHT predicts poor neurologic and cognitive outcome after SAH.

Dobutamine versus milrinone after subarachnoid hemorrhage.

OBJECTIVE: Neurogenic stunned myocardium is a well-recognized complication of subarachnoid hemorrhage. Dobutamine and milrinone are both used for neurogenic stunned myocardium, but there are few data comparing them after subarachnoid hemorrhage. METHODS: We compared the physiological dose response of dobutamine and milrinone in patients with subarachnoid hemorrhage requiring a pulmonary artery catheter. We located 11 patients who received either inotrope. Physiological data were fitted to a mixed model accounting for drug, dose, and between-patient variation. RESULTS: There were 11 patients who had 152 pulmonary artery catheter measurements. Two received both inotropes (but not within 4 h of each other), 2 only milrinone, and 7 only dobutamine. The groups had similar clinical and physiological characteristics. After adjustment for vasopressin, milrinone was significantly more potent in increasing cardiac output (P <0.0001) and stroke volume (P=0.03), while decreasing vascular resistance (P <0.0001) and systolic blood pressure (P=0.008), than dobutamine. CONCLUSION: These data suggest that milrinone and dobutamine should be used in different clinical situations. Milrinone may be more effective in patients with severely depressed systolic function but who have at least normal vascular resistance and blood pressure and in whom raising cardiac output is the primary goal. Dobutamine may be superior when vascular resistance or blood pressure is low.

Clinical trial of a novel surface cooling system for fever control in neurocritical care patients.

OBJECTIVE: To compare the efficacy of a novel water-circulating surface cooling system with conventional measures for treating fever in neuro-intensive care unit patients. DESIGN: Prospective, unblinded, randomized controlled trial. SETTING: Neurologic intensive care unit in an urban teaching hospital. PATIENTS: Forty-seven patients, the majority of whom were mechanically ventilated and sedated, with fever > or =38.3 degrees C for >2 consecutive hours after receiving 650 mg of acetaminophen. INTERVENTIONS: Subjects were randomly assigned to 24 hrs of treatment with a conventional water-circulating cooling blanket placed over the patient (Cincinnati SubZero, Cincinnati OH) or the Arctic Sun Temperature Management System (Medivance, Louisville CO), which employs hydrogel-coated water-circulating energy transfer pads applied directly to the trunk and thighs. MEASUREMENTS AND MAIN RESULTS: Diagnoses included subarachnoid hemorrhage (60%), cerebral infarction (23%), intracerebral hemorrhage (11%), and traumatic brain injury (4%). The groups were matched in terms of baseline variables, although mean temperature was slightly higher at baseline in the Arctic Sun group (38.8 vs. 38.3 degrees C, p = .046). Compared with patients treated with the SubZero blanket (n = 24), Arctic Sun-treated patients (n = 23) experienced a 75% reduction in fever burden (median 4.1 vs. 16.1 C degrees -hrs, p = .001). Arctic Sun-treated patients also spent less percent time febrile (T > or =38.3 degrees C, 8% vs. 42%, p < .001), spent more percent time normothermic (T < or =37.2 degrees C, 59% vs. 3%, p < .001), and attained normothermia faster than the SubZero group median (2.4 vs. 8.9 hrs, p = .008). Shivering occurred more frequently in the Arctic Sun group (39% vs. 8%, p = .013). CONCLUSION: The Arctic Sun Temperature Management System is superior to conventional cooling-blanket therapy for controlling fever in critically ill neurologic patients.