RESUMO
BACKGROUND AND PURPOSE: Clinical trials for prevention of vasospasm after aneurysmal subarachnoid hemorrhage (SAH) seldom have improved overall outcome; one reason may be inadequate sample size. We used data from the tirilizad trials and the Columbia University subarachnoid hemorrhage outcomes project to estimate sample sizes for clinical trials for reduction of vasospasm after SAH, assuming trials must show effect on 90-day patient-centered outcome. METHODS: Sample size calculations were based on different definitions of vasospasm, enrichment strategies, sensitivity of short- and long-term outcome instruments for reflecting vasospasm-related morbidity, different event rates of vasospasm, calculation of effect size of vasospasm on outcome instruments, and different treatment effect sizes. Sensitivity analysis was performed for variable event rates of vasospasm for a given treatment effect size. Sample size tables were constructed for different rates of vasospasm and outcome instruments for a given treatment effect size. RESULTS: Vasospasm occurred in 12% to 30% of patients. Symptomatic deterioration and infarction from vasospasm exhibited the strongest relationship to mortality and morbidity after SAH. Enriching for vasospasm by selection of patients with thick SAH slightly decreased sample sizes. Assuming beta=0.80, alpha=0.05 (2-tailed) and treatment effect size of 50%, total sample size exceeds 5000 patients to demonstrate efficacy on 3-month patient-centered outcome (modified Rankin Scale). CONCLUSIONS: Clinical trials targeting vasospasm and using traditional patient-centered outcome require very high sample sizes and will therefore be costly, time-consuming, and impractical. This will hinder development of new treatment strategies.
Assuntos
Ensaios Clínicos como Assunto/métodos , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/prevenção & controle , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Pregnatrienos/uso terapêutico , Tamanho da Amostra , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Doenças Cardiovasculares/epidemiologia , Hemorragia Subaracnóidea/fisiopatologia , Troponina I/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Estudos de Coortes , Eletrocardiografia , Feminino , Testes de Função Cardíaca , Humanos , Síndrome do QT Longo/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: While efforts have been made to document short-term outcomes following poor grade aneurysmal subarachnoid hemorrhage (aSAH), no data exist concerning the degree of delayed improvement in neurological function. Here we assess cognitive function, level of independence, and quality of life (QoL) over 12 months following poor grade aSAH. METHODS: Data on definitively treated poor grade patients (Hunt and Hess grade IV or V) surviving 12 months post-aSAH were obtained through a prospectively maintained SAH database. Demographic information, medical history, and clinical course were analyzed. Health outcomes assessments completed by surviving patients at discharge (DC), three months (3 M) and 12 months (12 M) follow-up, including the Telephone Interview for Cognitive Status (TICS), Barthel Index (BI), and Sickness Impact Profile (SIP), were used to evaluate cognitive function, level of independence, and QoL. FINDINGS: Fifty-six poor grade patients underwent aneurysm-securing intervention and survived at least 12 months post-aSAH. Thirty-five (63%) surviving patients underwent health outcomes assessments at DC, 3 M and 12 M post-aSAH. A majority of patients had improved scores on the TICS (DC to 3 M: 91%; 3 M to 12 M: 82%), BI (DC to 3 M: 96%; 3 M to 12 M: 92%), and SIP (3 M to 12 M: 80%) following aSAH. Using paired-sample analyses, significant improvement on each test was observed. CONCLUSION: A substantial portion of patients experience cognitive recovery, increased independence, and improved QoL following poor grade aSAH. Delayed follow-up assessments are necessary when evaluating functional recovery in this population. These findings have the potential to impact poor grade aSAH management and prognosis.
Assuntos
Hemorragia Subaracnóidea/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cognição/fisiologia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Qualidade de Vida , Perfil de Impacto da Doença , Hemorragia Subaracnóidea/psicologia , Telefone , Tomografia Computadorizada por Raios XRESUMO
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.
Assuntos
Transtornos Cognitivos/induzido quimicamente , Fenitoína/efeitos adversos , Fenitoína/uso terapêutico , Hemorragia Subaracnóidea/tratamento farmacológico , Transtornos Cognitivos/fisiopatologia , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenitoína/farmacocinética , Convulsões/etiologia , Convulsões/prevenção & controle , Fatores de Tempo , Resultado do TratamentoRESUMO
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, =4; OR, 0.08; 95% CI, 0.02-0.34) at 3 months. CONCLUSIONS: Despite an aggressive management strategy, rebleeding still occurred in 6.9% of patients and was associated with a dismal outcome. Poor Hunt-Hess grade and larger aneurysm size are related to rebleeding. Pharmacologic therapy to reduce the risk of rebleeding before aneurysm repair, particularly in patients with poor grade neurologic status and large aneurysms, deserves renewed attention.
Assuntos
Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/prevenção & controle , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/prevenção & controle , Idoso , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Prevenção Secundária , Hemorragia Subaracnóidea/diagnóstico , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Cigarette smoking is a risk factor for the formation and rupture of intracranial aneurysms. Few studies have examined predictors of resumption of cigarette smoking after a first episode of subarachnoid hemorrhage (SAH). METHODS: Of 620 SAH patients treated between July 1996 and November 2002, we prospectively evaluated continued cigarette use in 152 smokers alive at 3 months. Univariate and multivariate logistic regression analyses were used to identify potential demographic, social, and clinical predictors of continued cigarette use, defined as smoking > or =1 cigarette per week in the month before follow-up. RESULTS: Thirty-seven percent (56 of 152) resumed smoking after their SAH. Patients who continued smoking were younger, were more often black, had begun smoking at an earlier age, and had a higher frequency of prior alcohol or cocaine use and self-reported depression or anxiety than those who quit (all P<0.05). Smoking at < or =16 years of age (odds ratio [OR], 5.88; 95% confidence interval [CI], 2.33 to 14.29), self-reported depression (OR, 5.29; 95% CI, 2.10 to 13.35), and prior alcohol use (OR, 4.51; 95% CI, 1.45 to 14.05) independently predicted continued cigarette use. Smokers had a functional outcome similar to that of nonsmokers at 3 months but were more likely to resume alcohol consumption (OR, 3.88; 95% CI, 1.91 to 7.88). CONCLUSIONS: More than one third of prior smokers continue to use nicotine after SAH. Young age at smoking onset and a history of depression or alcohol use are risk factors for continued cigarette use. Targeted smoking cessation programs are needed to reduce the high rate of smoking resumption after SAH.
Assuntos
Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/epidemiologia , Hemorragia Subaracnóidea/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Comorbidade , Depressão/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Razão de Chances , Grupos Raciais , Recidiva , Fatores de RiscoRESUMO
BACKGROUND: Cognitive dysfunction is a common and disabling sequela of subarachnoid hemorrhage (SAH). Although several clinical and radiographic findings have been implicated in the pathogenesis of cognitive dysfunction after SAH, few prospective studies have comprehensively and simultaneously evaluated these risk factors. METHODS: Between July 1996 and March 2000, we prospectively evaluated 113 of 248 consecutively admitted nontraumatic SAH patients alive at 3 months with a comprehensive neuropsychological evaluation. Summary scores for 8 cognitive domains were calculated to express test performance relative to the entire study population. Clinical and radiographic variables associated with domain-specific cognitive dysfunction were identified with forward stepwise multiple regression, with control for the influence of demographic factors. RESULTS: The study participants were younger (P=0.005), less often white (P=0.006), and had better 3-month modified Rankin scores (P=0.001) than those who did not undergo neuropsychological testing. The proportion of subjects who scored in the impaired range (>2 SD below the normative mean) on each neuropsychological test ranged from 10% to 50%. Predictors of cognitive dysfunction in 2 or more domains in the multivariate analysis included global cerebral edema (4 domains), left-sided infarction (3 domains), and lack of a posterior circulation aneurysm (2 domains). Other variables consistently associated with cognitive dysfunction in the univariate analysis included admission Hunt-Hess grade >2 and thick SAH in the anterior interhemispheric and sylvian fissures. CONCLUSIONS: Global cerebral edema and left-sided infarction are important risk factors for cognitive dysfunction after SAH. Treatment strategies aimed at reducing neurological injury related to generalized brain swelling, infarction, and clot-related hemotoxicity hold the best promise for improving cognitive outcomes after SAH.
Assuntos
Transtornos Cognitivos/etiologia , Hemorragia Subaracnóidea/complicações , Doença Aguda , Adulto , Idoso , Edema Encefálico/complicações , Infarto Encefálico/complicações , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/diagnóstico por imagem , Demografia , Feminino , Seguimentos , Previsões , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Estudos Prospectivos , Radiografia , Fatores de Risco , Hemorragia Subaracnóidea/diagnóstico por imagemRESUMO
BACKGROUND AND PURPOSE: Cerebral edema visualized by CT is often seen after subarachnoid hemorrhage (SAH). Inflammatory or circulatory mechanisms have been postulated to explain this radiographic observation after SAH. We sought to determine the frequency, causes, and impact on outcome of early and delayed global cerebral edema after SAH. METHODS: We evaluated the presence of global edema on admission and follow-up CT scans in 374 SAH patients admitted within 5 days of onset to our Neurological Intensive Care Unit between July 1996 and February 2001. Using multivariate analysis, we identified predictors of global cerebral edema and evaluated the impact of global edema on outcome 3 months after onset with the modified Rankin Scale. RESULTS: Global edema was present on admission CT scans in 8% (n=29) and developed secondarily in 12% (n=44) of the patients. Global edema on admission was predicted by loss of consciousness at ictus and increasing Hunt-Hess grade. Delayed global edema was predicted by aneurysm size >10 mm, loss of consciousness at ictus, use of vasopressors, and increased SAH sum scores. Thirty-seven percent (n=137) of the patients were dead or severely disabled (modified Rankin Scale 4 to 6) at 3 months. Death or severe disability was predicted by any global edema, aneurysm size >10 mm, loss of consciousness at ictus, increased National Institutes of Health Stroke Scale scores, and older age. CONCLUSIONS: Global edema is an independent risk factor for mortality and poor outcome after SAH. Loss of consciousness, which may reflect ictal cerebral circulatory arrest, is a risk factor for admission global edema, and vasopressor-induced hypertension is associated with the development of delayed global edema. Critical care management strategies that minimize edema formation after SAH may improve outcome.
Assuntos
Edema Encefálico/epidemiologia , Hemorragia Subaracnóidea/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Edema Encefálico/diagnóstico , Edema Encefálico/mortalidade , Infarto Cerebral/diagnóstico , Infarto Cerebral/epidemiologia , Comorbidade , Demografia , Progressão da Doença , Drenagem , Feminino , Escala de Coma de Glasgow , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/mortalidade , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: Delayed cerebral ischemia (DCI) due to vasospasm is often undetected by clinical exam in patients with poor-grade subarachnoid hemorrhage (SAH). The purpose of this study was to identify quantitative EEG (qEEG) parameters that are most sensitive and specific for the detection of DCI in stuporous or comatose SAH patients. METHODS: Of 78 consecutive Hunt-Hess grade 4 or 5 SAH patients admitted to our Neuro-ICU over a 2-year period, 48 were eligible for participation and 34 were enrolled. Continuous EEG monitoring was performed from post-operative day 2 to post-SAH day 14. In each patient, 20 artifact-free, 1 min EEG-clips following an alerting stimulus were analyzed: 10 clips were obtained on monitoring day 1 (baseline), and 10 on days 4-6 (follow-up). In DCI patients, follow-up clips were obtained after the onset of deterioration and before infarction had occurred. Twelve qEEG parameters were calculated using fast Fourier transformation; generalized estimating equations were used to compare ratios of change in qEEG parameters in patients with and without DCI. RESULTS: Nine of 34 patients (26%) developed DCI. The alpha/delta ratio (alpha power/delta power; ADR) demonstrated the strongest association with DCI. The median decrease of ADR for patients with DCI was 24%, compared to an increase of 3% for patients without DCI (Z=4.0, P<0.0001). Clinically useful cut-offs included 6 consecutive recordings with a >10% decrease in ADR from baseline (sensitivity 100%, specificity 76%) and any single measurement with a >50% decrease (sensitivity 89%, specificity 84%). CONCLUSIONS: A decrease in the ADR may be a sensitive method of detecting DCI, with reasonable specificity. This post-stimulation qEEG parameter may supplement the clinical exam in poor-grade SAH patients and may prove useful for the detection of DCI. SIGNIFICANCE: Following ADRs may allow earlier detection of DCI and initiation of interventions at a reversible stage, thus preventing infarction and neurological morbidity.
Assuntos
Isquemia Encefálica/diagnóstico , Eletroencefalografia/métodos , Monitorização Fisiológica/métodos , Hemorragia Subaracnóidea/diagnóstico , Adulto , Idoso , Isquemia Encefálica/etiologia , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Hemorragia Subaracnóidea/complicações , Tomografia Computadorizada por Raios X , Transporte de PacientesRESUMO
OBJECTIVE: Proximal posteroinferior cerebellar artery (PICA) aneurysms are challenging to treat surgically, with high reported perioperative complication rates. We describe the perioperative course and long-term clinical outcomes obtained via a far lateral suboccipital approach in 20 consecutive proximal PICA aneurysms. METHODS: Data were collected prospectively on the first 20 proximal PICA aneurysms treated surgically by a single surgeon (ESC) between December 1997 and April 2003. All aneurysms were clipped via a far lateral approach. Patients with unruptured aneurysms were assessed at 3 and 12 months after surgery. For all subarachnoid hemorrhage patients, a battery of outcome tests was performed at 3- and 12-month intervals. Outcomes were then compared with those of a contemporaneously managed population of ruptured right-sided posterior communicating artery aneurysms. RESULTS: The far lateral suboccipital approach achieved adequate exposure in all cases. There were no intraoperative complications or intraoperative aneurysm ruptures. All patients with unruptured aneurysms were fully functional at long-term follow-up. At 3 months of follow-up, 93% of the subarachnoid hemorrhage patients achieved a Glasgow Outcome Scale score of 1 to 2. At 12 months of follow-up, 92% achieved a Glasgow Outcome Scale score of 1 to 2. Compared with the patients with a ruptured right-sided posterior communicating artery aneurysm, no difference could be found in quality of life or activities of daily living at either time point. CONCLUSION: The favorable outcomes and low postoperative morbidity in this subset of patients argues that clipping via this approach be considered a first-line therapeutic option. When performed in this manner, PICA aneurysm surgery seems to have no greater morbidity than right-sided posterior communicating artery aneurysm surgery.
Assuntos
Cerebelo/irrigação sanguínea , Cerebelo/cirurgia , Craniotomia/métodos , Aneurisma Intracraniano/cirurgia , Osso Occipital/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Artérias/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECT: Although upregulated adhesion molecule expression has been demonstrated in experimental models of subarachnoid hemorrhage (SAH) and in the cerebrospinal fluid of patients with aneurysmal SAH, the clinical significance of these proinflammatory findings remains unclear. The authors hypothesize that 1) serum levels of soluble intercellular adhesion molecule-l (ICAM-1) are increased in all patients with aneurysmal SAH shortly after the hemorrhagic event, and 2) elevated soluble ICAM-1 values are associated with poor patient outcome, even when controlling for the severity of the initial hemorrhagic insult. METHODS: One hundred one patients were prospectively enrolled and stratified according to their admission Hunt and Hess grade and functional status at discharge (modified Rankin Scale [mRS] score). Soluble ICAM-1 levels were determined every other day for 12 days post-SAH by using the enzyme-linked immunosorbent assay. Early soluble ICAM-1 levels (post-SAH Days 2-4) were increased compared with levels in control patients without SAH (p < 0.05). Patients with aneurysmal SAH who had a poor outcome (mRS Grades 4-6) had significantly higher soluble ICAM-1 levels over the first 2 weeks post-SAH compared with patients who had a good outcome (mRS Grades 0-3, p < 0.01). This association with outcome was predicted by late increases (Day 6, p = 0.07; Days 8-12, p < 0.05) rather than early increases (p = not significant) and was best seen in patients with Hunt and Hess Grades I and II. in whom only those with poor outcomes demonstrated delayed ICAM-1 elevations (p < 0.05). CONCLUSIONS: These data demonstrate a correlation between soluble ICAM-1 levels and functional outcome following aneurysmal SAH that appears to be, at least in part, independent of the initial hemorrhage.
Assuntos
Aneurisma Roto/diagnóstico , Molécula 1 de Adesão Intercelular/sangue , Aneurisma Intracraniano/diagnóstico , Hemorragia Subaracnóidea/diagnóstico , Vasoespasmo Intracraniano/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/sangue , Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Avaliação da Deficiência , Feminino , Humanos , Aneurisma Intracraniano/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Hemorragia Subaracnóidea/sangue , Vasoespasmo Intracraniano/sangueRESUMO
OBJECT: Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule-1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1-2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm. METHODS: Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, < 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade-matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade-matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001). CONCLUSIONS: These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.
Assuntos
Molécula 1 de Adesão Intercelular/sangue , Hemorragia Subaracnóidea/sangue , Vasoespasmo Intracraniano/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Cerebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Solubilidade , Hemorragia Subaracnóidea/diagnóstico , Regulação para Cima , Vasoespasmo Intracraniano/diagnósticoRESUMO
CONTEXT: Mortality and morbidity can be reduced if aneurysmal subarachnoid hemorrhage (SAH) is treated urgently. OBJECTIVE: To determine the association of initial misdiagnosis and outcome after SAH. DESIGN, SETTING, AND PARTICIPANTS: Inception cohort of 482 SAH patients admitted to a tertiary care urban hospital between August 1996 and August 2001. MAIN OUTCOME MEASURES: Misdiagnosis was defined as failure to correctly diagnose SAH at a patient's initial contact with a medical professional. Functional outcome was assessed at 3 and 12 months with the modified Rankin Scale; quality of life (QOL), with the Sickness Impact Profile. RESULTS: Fifty-six patients (12%) were initially misdiagnosed, including 42 of 221 (19%) of those with normal mental status at first contact. Migraine or tension headache (36%) was the most common incorrect diagnosis, and failure to obtain a computed tomography (CT) scan was the most common diagnostic error (73%). Neurologic complications occurred in 22 patients (39%) before they were correctly diagnosed, including 12 patients (21%) who experienced rebleeding. Normal mental status, small SAH volume, and right-sided aneurysm location were independently associated with misdiagnosis. Among patients with normal mental status at first contact, misdiagnosis was associated with worse QOL at 3 months and an increased risk of death or severe disability at 12 months. CONCLUSIONS: In this study, misdiagnosis of SAH occurred in 12% of patients and was associated with a smaller hemorrhage and normal mental status. Among individuals who initially present in good condition, misdiagnosis is associated with increased mortality and morbidity. A low threshold for CT scanning of patients with mild symptoms that are suggestive of SAH may reduce the frequency of misdiagnosis.
Assuntos
Erros de Diagnóstico , Hemorragia Subaracnóidea/diagnóstico , Erros de Diagnóstico/estatística & dados numéricos , Humanos , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Fatores de Risco , Perfil de Impacto da Doença , Hemorragia Subaracnóidea/terapiaRESUMO
BACKGROUND: Cognitive impairment is widely considered the main cause of disability and handicap after subarachnoid hemorrhage (SAH). The impact of depression on recovery after SAH remains poorly defined. We sought to determine the frequency of post-SAH depression, identify risk factors for its development, and evaluate the impact of depression on quality of life (QOL) during the first year of recovery. METHODS: We prospectively studied 216 of 534 SAH patients treated between July 1996 and December 2001 with complete one-year follow-up data. Depression was evaluated with the Center for Epidemiological Studies Depression (CES-D) scale, cognitive status with the Telephone Interview for Cognitive Status (TICS), and QOL with the Sickness Impact Profile (SIP) 3 and 12 months after SAH. RESULTS: Depressed mood occurred in 47% of patients during the first year of recovery; 26% were depressed at both 3 and 12 months. Non-white ethnicity predicted early (3 month) and late (12 month) depressions; early depression was also predicted by previously-diagnosed depression, cigarette smoking, and cerebral infarction, whereas late depression was predicted by prior social isolation and lack of medical insurance. Depression was associated with inferior QOL in all domains of the SIP, and changes in depression status were associated with striking parallel changes in QOL, disability, and cognitive function during the first year of recovery. CES-D scores accounted for over 60% of the explained variance in SIP total scores, whereas TICS performance accounted for no more than 6%. CONCLUSION: Depression affects nearly half of SAH patients during the first year of recovery, and is associated with poor QOL. Systematic screening and early treatment for depression are promising strategies for improving outcome after SAH.
Assuntos
Depressão/etiologia , Qualidade de Vida , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/psicologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Perfil de Impacto da Doença , Hemorragia Subaracnóidea/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: Decompressive hemicraniectomy has been proposed as a potential treatment strategy in patients with poor-grade aneurysmal subarachnoid hemorrhage presenting with focal intracerebral hemorrhage causing significant mass effect. Although hemicraniectomy improves overall survival rates, the long-term quality of life (QoL) for survivors in this patient population has not been reported. METHODS: Using adjudicated outcome assessments, we compare long-term clinical outcomes and QoL between a group of patients with poor-grade aneurysmal subarachnoid hemorrhage receiving decompressive hemicraniectomy (n=12) and a control group of similar patients managed more conservatively (n=10). RESULTS: Patients receiving decompressive hemicraniectomy experienced a statistically insignificant decrease in short-term mortality compared with controls (25 versus 42%); however, long-term QoL in hemicraniectomy survivors was generally poor. Furthermore, hemicraniectomy patients did not experience an increase in mean quality-adjusted life years over control patients (2.31 versus 2.22 yr). CONCLUSION: Decompressive hemicraniectomy prolongs short-term survival in patients with poor-grade aneurysmal subarachnoid hemorrhage with associated intracerebral hemorrhage; however, this trend is not statistically significant, and the overall QoL experienced by survivors is poor. Decompressive hemicraniectomy may be indicated if performed early in a select subset of patients. On the basis of our preliminary data, large prospective studies to investigate this issue further may not be warranted.
Assuntos
Hemorragia Cerebral/complicações , Hemorragia Cerebral/cirurgia , Descompressão Cirúrgica , Qualidade de Vida , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Dobutamina/uso terapêutico , Milrinona/uso terapêutico , Miocárdio Atordoado/tratamento farmacológico , Miocárdio Atordoado/etiologia , Inibidores de Fosfodiesterase/uso terapêutico , Hemorragia Subaracnóidea/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Aneurisma Roto/complicações , Isquemia Encefálica/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Aneurisma Intracraniano/complicações , Hemorragia Subaracnóidea/complicações , Vasoespasmo Intracraniano/etiologia , Adulto , Idoso , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Angiografia Cerebral , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Infarto Cerebral/prevenção & controle , Estudos de Coortes , Comorbidade , Avaliação de Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Vasoespasmo Intracraniano/diagnóstico por imagemRESUMO
OBJECTIVE: To determine the effect that acute physiologic derangements have on outcome after subarachnoid hemorrhage (SAH) and to design a composite score summarizing these abnormalities. DESIGN: Prospective observational study. SETTING: Neuroscience intensive care unit in a tertiary care academic center. PATIENTS: Consecutive cohort of 413 patients with SAH admitted within 3 days of SAH onset with 3-month modified Rankin Scale scores. INTERVENTIONS: None. RESULTS: Among 20 physiologic variables assessed within 24 hrs of admission, four were independently associated with death or severe disability (modified Rankin Scale score, 4-6) at 3 months in a multivariate analysis: arterio-alveolar gradient of >125 mm Hg (odds ratio [OR], 4.5; 95% confidence interval [CI], 2.7-7.6), serum bicarbonate of <20 mmol/L (OR, 2.9; 95% CI, 1.6-5.6), serum glucose of >180 mg/dL (OR, 2.8; 95% CI, 1.6-4.8), and mean arterial pressure of <70 or >130 mm Hg (OR, 1.7; 95% CI, 1.0-2.9). Based on their proportional contribution to outcome, we constructed the SAH Physiologic Derangement Score (SAH-PDS; range, 0-8) by assigning the following weights for abnormal findings: arterio-alveolar gradient, 3 points; bicarbonate, 2 points; glucose, 2 points; and mean arterial pressure, 1 point. After controlling for known predictors of death or severe disability (age, admission neurologic status, loss of consciousness, aneurysm size, intraventricular hemorrhage, and rebleeding), the SAH Physiologic Derangement Score was independently associated with poor outcome (OR, 1.3 for each point increase; 95% CI, 1.1-1.6). By contrast, the systemic inflammatory response syndrome score and the Acute Physiology and Chronic Health Evaluation II physiologic subscore did not add predictive value to the model. CONCLUSION: Acute interventions specifically targeting hypoxemia, metabolic acidosis, hyperglycemia, and cardiovascular instability may improve the outcome of SAH patients. The SAH Physiologic Derangement Score may prove useful for rapidly quantifying the severity of important physiologic derangements in acute SAH.
Assuntos
Indicadores Básicos de Saúde , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/fisiopatologia , APACHE , Análise de Variância , Aneurisma Roto/complicações , Feminino , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Observação , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Análise de Regressão , Hemorragia Subaracnóidea/etiologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Resultado do TratamentoRESUMO
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.