Avaliação da performance da escala VASOGRADE como preditora de isquemia cerebral tardia e desfechos clínicos em pacientes com Hemorragia Subaracnoidea Aneurismática
Arquivos
Data
2022-11-25
Autores
Souza, Natália Vasconcellos de Oliveira [UNIFESP]
Orientadores
Silva, Gisele Sampaio [UNIFESP]
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução. A Hemorragia subaracnóidea (HSA) aneurismática ainda é uma doença com significativa mortalidade e na sua fase subaguda a isquemia cerebral tardia (ICT) é um dos principais preditores de mal prognóstico. A ICT é também o principal motivo da permanência prolongada dos pacientes em ambiente de terapia intensiva, o que adiciona custo e morbidade à patologia. O VASOGRADE é uma escala clínica preditora de ICT que combina a escala modificada de Fisher com a escala WFNS (World Federation of Neursurgeons Society), já validado externamente em uma população de 746 pacientes. Entretanto, apesar de uso fácil e de simples visualização por cores, desde a publicação original, a escala não foi avaliada em outra coorte de pacientes, em especial em um país em desenvolvimento. Objetivos. Avaliar a performance do VASOGRADE como ferramenta prognóstica para infarto por ICT e para desfecho clínico na alta hospitalar nos pacientes admitidos com HSA em um hospital quaternário público brasileiro. Foram objetivos secundários: descrever a frequência de vasoespasmo e infarto por ICT e correlacionar as escalas prognósticas tomográficas (Fisher e Fisher modificado) e clínicas (Hunt-Hess, WFNS, VASOGRADE) com a frequência de infarto por ICT e com o desfecho clínico na alta hospitalar, descrever e comparar as características clínicas e epidemiológicas da população com HSA com e sem infarto por ICT, descrever a frequência das outras complicações neurológicas e clínicas na população do estudo, correlacionar o tempo para a admissão hospitalar e o tempo para o tratamento definitivo (clipagem ou embolização) com o grau de incapacidade na alta (Rankin modificado). Métodos. Trata-se de uma coorte multiétnica retrospectiva, que incluiu pacientes consecutivamente admitidos com HSA no hospital São Paulo, de janeiro de 2016 a janeiro de 2019. Através da análise de prontuário médico foram coletados dados clínicos e epidemiológicos dos pacientes (idade, sexo, etnia, fatores de risco) e dados referentes
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à HSA (localização do aneurisma roto, tratamento cirúrgico ou endovascular, data do ictus, número de dias ictus – admissão hospitalar, número de dias ictus – tratamento e número de dias admissão - tratamento). Os pacientes foram classificados conforme a gravidade clínica à admissão (Hunt-hess, WFNS), a quantidade de sangue na tomografia inicial (escala de Fisher modificada) e o VASOGRADE (verde, amarelo e vermelho). Foram também coletados dados referentes a complicações neurológicas (hidrocefalia, necessidade de uso de DVE, conversão definitiva do shunt para DVP, infarto por ICT, ocorrência de meningite ou ventriculite, presença de crises epilépticas, desenvolvimento de hipertensão intracraniana e necessidade de craniectomia descompressiva) e sistêmicas (pneumonia, infecção de corrente sanguínea, infecção do trato urinário ou infecção de foco indeterminado, hiponatremia e hipernatremia, complicações cardíacas e pulmonares), além de tempo de permanência em UTI, tempo de permanência hospitalar e desfecho clínico na alta hospitalar (ERm). O desfecho primário do nosso estudo foi infarto por ICT, que foi definido como novas lesões isquêmicas espontâneas em pelo menos uma tomografia de acompanhamento. Apenas infartos espontâneos (ou seja, não relacionados à clipagem ou embolização do aneurisma roto) dentro de 28 dias após a HSA foram incluídos. A imagem revisada, em consonância com a literatura, foi em 6 semanas após o ictus, ou então a última antes do óbito do paciente. As imagens foram laudadas por neurorradiologistas certificados que desconheciam o quadro clínico da paciente. A correlação entre imagem e quadro clínico do paciente foi feita pela investigadora principal. O desfecho clínico foi avaliado usando a escala modificada de Rankin na alta (ERm) através da revisão de prontuário (0-2 foi considerada um desfecho favorável, enquanto ERm de 3-6 foi considerada um desfecho desfavorável). As variáveis categóricas foram apresentadas por meio de frequências relativas e absolutas e comparadas por meio do teste qui-quadrado ou exato de Fisher, conforme o caso. As distribuições das variáveis contínuas foram avaliadas quanto à normalidade por “skewness and kurtosis” e por métodos gráficos. Aqueles com distribuição normal são apresentados como média e desvio padrão e comparados pelo teste T de Student para amostras independentes. Caso contrário, foram apresentadas por medianas e quartis e comparados pelo teste não paramétrico de Mann-Whitney. A análise de regressão logística multivariada foi empregada para verificar a independência da associação entre
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a escala VASOGRADE e infarto por isquemia cerebral tardia (ICT). As variáveis significativas ao nível de 0,10 na análise univariada foram consideradas para inclusão no modelo multivariável. Todos os testes foram bilaterais e os valores finais de P abaixo de 0,05 foram considerados estatisticamente significativos. Todas as análises foram realizadas com o software SPSS (IBM Corp. SPSS Statistics para Windows, versão 24.0. Armonk, NY). Resultados. Duzentos e doze (212) pacientes preencheram os critérios de inclusão (71,7% do sexo feminino, idade média 52,7±12,8), 69 pacientes foram classificados como VASOGRADE-verde (32,5%), 98 pacientes como VASOGRADE- amarelo (46,9%) e 45 pacientes como VASOGRADE-vermelho (20,6%). Pacientes que desenvolveram ou não infarto por ICT foram semelhantes quanto as características epidemiológicas, presença de comorbidades, localização do aneurisma, tempo do ictus à admissão e tempo para o tratamento, assim como quanto ao método de tratamento adotado. Ao todo, 18,9% (39 pacientes) apresentaram infarto por ICT e a proporção de pacientes no VASOGRADE-verde, -amarelo e -vermelho com infarto por ICT foi de 7,7%, 29% e 28%, respetivamente. A principal complicação neurológica em nossa série que não infarto por ICT foi hidrocefalia (34,9%), seguida por hipertensão intracraniana (32,5%), necessidade de DVE (26,3%), ventriculite / meningite (13,9%), presença de crises epilépticas (12%) e necessidade de craniectomia (8,1%). A hidrocefalia, a necessidade de DVE, a hipertensão intracraniana e a craniectomia foram significativamente mais frequentes em pacientes com ICT. A principal complicação clínica em nossa série foi infecção de foco indeterminado (20,6%), seguida de hipernatremia (20,1%), hiponatremia (19,6%), pneumonia (18,2%), injúria renal aguda (15,8%), infecção de corrente sanguínea (14,4%), complicações cardíacas (4,8%) e pulmonares (3,8%). Na análise univariada, pneumonia, infecção de corrente sanguínea, hipernatremia e injúria renal aguda foram significativamente mais frequentes em pacientes com infarto por ICT. Juntas, as complicações neurológicas e sistêmicas explicaram 12% da variação no desfecho funcional na alta hospitalar. A mediana de dias do ictus à admissão e do ictus ao tratamento foi respectivamente 5 (2-14) e 9 (5-19) dias. Na análise univariada, tanto o tempo do ictus à admissão quanto o tempo do ictus – tratamento foram significativamente associados à pior desfecho clínico na alta hospitalar (ERm). Após análise multivariada incluindo VASOGRADE, idade, sexo e localização do
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aneurisma, tanto o VASOGRADE-amarelo quanto o VASOGRADE-vermelho foram independentemente associados a infarto por ICT (OR 7 e 8,07, respectivamente) e desfecho desfavorável (OR 4.156, IC 95% 1.326 – 13.026; p = 0.015; OR 25.574, IC 95% 24.446 – 147.093; p < 0.0001, respectivamente). A discriminação do VASOGRADE para infarto por ICT (AUC-ROC) foi de 0,67 ± 0,04 (IC 95% 0,58–0,75; p = 0,001). O VASOGRADE-vermelho teve 97,5% de especificidade para prever ERm desfavorável na alta (IC 95% 92,8 – 99,5%), enquanto o VASOGRADE-verde teve 90,43% de especificidade para prever resultado favorável na alta (ERm 0-2, IC 95% 82,6 – 95,5 %). Conclusão. Em conclusão, em uma coorte multiétnica de pacientes com HSA aneurismática, o VASOGRADE-verde foi um bom preditor de ausência de infarto por ICT, além de ter alta especificidade para um resultado clínico favorável na alta hospitalar (ERm 0-2). Assim, pacientes nesta categoria podem ser selecionados para alta precoce da UTI, minimizando custos e complicações médicas associada ao tempo prolongado de internação. Por outro lado, os pacientes classificados como VASOGRADE-amarelo e - vermelho apresentaram maior risco para infarto por ICT. Devem, portanto, ser selecionados para atendimento em centros de HSA com alto volume, além de serem cuidadosamente monitorados para ICT em UTI. Tais métodos de estratificação são fundamentais, especialmente em países com poucos recursos financeiros e alta demanda de serviços de saúde.
Introduction. Delayed cerebral ischemia (DCI) is one of the main predictors of poor prognosis in the subacute phase of aneurysmal subarachnoid hemorrhage (SAH). The VASOGRADE is a simple aneurysmal subarachnoid hemorrhage (aSAH) grading scale, which combines the modified Fisher score (mFs) and the World Federation of Neurological Societies (WFNS), allowing the stratification of delayed cerebral ischemia (DCI) risk. It was already externally validated in a population of 746 patients, however, despite being an easy-to-use color scale, since the original publication it has not been evaluated in another cohort of patients, especially in a developing country. Besides, the VASOGRADE accuracy to predict functional outcomes is still to be determined. Objectives. To evaluate the performance of VASOGRADE as a prognostic scale for DCI- related cerebral infarction and for clinical outcome at hospital discharge in patients admitted with SAH in a public Brazilian hospital. Secondary objectives were: to describe the frequency of vasospasm and infarction by DCI-related cerebral infarction and to correlate the tomographic (Fisher and Fisher modified) and clinical (Hunt-Hess, WFNS, VASOGRADE) prognostic scales with the frequency of DCI-related cerebral infarction and with the clinical outcome at discharge. To describe and compare the clinical and epidemiological characteristics of the population with SAH with and without DCI-related infarction, to describe the frequency of other neurological and clinical complications in the study population, to correlate the time to hospital admission and the time to definitive treatment (surgical or endovascular) with the degree of disability at discharge (modified Rankin scale - mRs). Methods. This is a retrospective multiethnic cohort, which included patients consecutively admitted with SAH at the São Paulo hospital, from January 2016 to January 2019. Through the analysis of medical records, clinical and epidemiological data were collected from patients (age, sex, ethnicity, risk factors) and SAH data (location xxiii of the ruptured aneurysm, surgical or endovascular treatment, number of days from stroke onset to hospital admission, number of days from stroke onset to treatment, number of days from hospital admission to treatment). Patients were classified according to clinical severity at admission (Hunt-hess, WFNS), amount of blood at baseline (modified Fisher scale), and VASOGRADE (green, yellow, and red). The following neurological and clinical complications were evaluated: DCI-related infarction, hydrocephalus, need for external ventricular drain (EVD) and/or ventricular peritoneal shunt (VPS), meningitis or ventriculitis, seizures, intracranial hypertension (ICH) and decompressive craniectomy, infections (pneumonia, bloodstream infection, urinary tract infection), sodium disturbances (hyponatremia and hypernatremia); acute kidney injury (AKI), cardiac complications (arrhythmias and acute myocardial infarction) and pulmonary complications (pulmonary thromboembolism, acute respiratory distress syndrome, acute pulmonary edema). In addition, length of ICU and hospital stay, and clinical outcome at hospital discharge (ERm) were evaluated. The primary outcome of our study was DCI- related infarction, which was defined as new spontaneous ischemic lesions on at least one follow-up CT scan. Only spontaneous infarctions (ie, not related to clipping or embolization of the ruptured aneurysm) within 28 days after SAH were included.The revised image, in line with the literature, was 6 weeks after the ictus, or the last one before the patient's death. The images were reviewed by certified neuroradiologists who were unaware of the patient's clinical condition. The correlation between the image and the patient's clinical condition was performed by the principal investigator. Clinical outcome was assessed using the mRs at discharge (0-2 was considered a favorable outcome, while mRs of 3-6 was considered an unfavorable outcome). Categorical variables were presented using relative and absolute frequencies and compared using the chi-square test or Fisher's exact test, as appropriate. The distributions of continuous variables were evaluated for normality by “skewness and kurtosis” and by graphical methods. Those with normal distribution are presented as mean and standard deviation and compared by Student's T test for independent samples. Otherwise, they were presented by medians and quartiles and compared using the non-parametric Mann-Whitney test. Multivariate logistic regression analysis was used to verify the independence of the association between the VASOGRADE scale and delayed cerebral ischemia infarction (CTI). xxiv Significant variables at the 0.10 level in the univariate analysis were considered for inclusion in the multivariate model. All tests were bilateral and final P values below 0.05 were considered statistically significant. All analyzes were performed using SPSS software (IBM Corp. SPSS Statistics for Windows, version 24.0. Armonk, NY). Results. 212 patients met the inclusion criteria (71.7% female, mean age 52.7±12.8), 69 patients were classified as VASOGRADE-green (32.5%), 98 patients as VASOGRADE-yellow (46.9%) and 45 patients as VASOGRADE-red (20.6%). Patients who did or did not develop infarction from ICT were similar in terms of epidemiological characteristics, presence of comorbidities, location of the aneurysm, mean time of stroke onset-hospital admission and mean time of stroke onset - treatment, as well as the method of treatment adopted. Altogether, 19% (39 patients) had ICT infarction and the proportion of patients in the VASOGRADE-green, -yellow, and -red with ICT infarction was 7.7%, 29%, and 28%, respectively. The main neurological complication in our series other than ICT infarction was hydrocephalus (34.9%), followed by intracranial hypertension (32.5%), need for EVD (26.3%), ventriculitis/meningitis (13.9%), presence of epileptic seizures (12%) and need for craniectomy (8.1%). Hydrocephalus, need for EVD, intracranial hypertension, and craniectomy were significantly more frequent in patients with DCI. The main clinical complication in our series was infection of undetermined focus (20.6%), followed by hypernatremia (20.1%), hyponatremia (19.6%), pneumonia (18.2%), acute kidney injury (15.8%), bloodstream infection (14.4%), cardiac (4.8%) and pulmonary (3.8%) complications. In the univariate analysis, pneumonia, bloodstream infection, hypernatremia and acute kidney injury were significantly more frequent in patients with DCI-related infarction. Together, neurological and systemic complications explained 12% of the variation in functional outcome at hospital discharge. The median days from stroke onset to admission and from stroke onset to treatment were 5 (2-14) and 9 (5-19) days, respectively. In the univariate analysis, both the time from stroke onset to admission and the time from stroke onset to treatment were significantly associated with worse clinical outcome at hospital discharge (mRs). After multivariate analysis including VASOGRADE, age, sex, and aneurysm location, both VASOGRADE-yellow and VASOGRADE-red were independently associated with TCI infarction (OR 7 and 8.07, respectively) and unfavorable outcome (OR 4,156, CI 95 % 1,326 - 13,026; p = 0.015; OR 25,574, 95% CI xxv 24,446 - 147,093; p < 0.0001, respectively). The VASOGRADE discrimination for DCI- related infarction (AUC-ROC) was 0.67 ± 0.04 (95% CI 0.58–0.75; p = 0.001). VASOGRADE-red had 97.5% specificity for predicting unfavorable at discharge (95% CI 92.8 – 99.5%), while VASOGRADE-green had 90.43% specificity for predicting favorable outcome at discharge (mRs 0-2, 95% CI 82.6 - 95.5%). Conclusion. In conclusion, in a multiethnic cohort of patients with aneurysmal SAH, VASOGRADE-green predicted the absence of DCI and good clinical outcome at discharge with very high specificity, and patients in this category might be selected for early ICU discharge, minimizing costs and medical complications associated with prolonged hospital length. On the other hand, patients categorized as VASOGRADE-yellow and – red were at the highest risk for DCI. They should, therefore, be selected for care in high-volume aSAH centers, being aggressively monitored for DCI at the ICU. Such stratification methods are crucial, especially in countries with low financial resources and high health care services demand.
Introduction. Delayed cerebral ischemia (DCI) is one of the main predictors of poor prognosis in the subacute phase of aneurysmal subarachnoid hemorrhage (SAH). The VASOGRADE is a simple aneurysmal subarachnoid hemorrhage (aSAH) grading scale, which combines the modified Fisher score (mFs) and the World Federation of Neurological Societies (WFNS), allowing the stratification of delayed cerebral ischemia (DCI) risk. It was already externally validated in a population of 746 patients, however, despite being an easy-to-use color scale, since the original publication it has not been evaluated in another cohort of patients, especially in a developing country. Besides, the VASOGRADE accuracy to predict functional outcomes is still to be determined. Objectives. To evaluate the performance of VASOGRADE as a prognostic scale for DCI- related cerebral infarction and for clinical outcome at hospital discharge in patients admitted with SAH in a public Brazilian hospital. Secondary objectives were: to describe the frequency of vasospasm and infarction by DCI-related cerebral infarction and to correlate the tomographic (Fisher and Fisher modified) and clinical (Hunt-Hess, WFNS, VASOGRADE) prognostic scales with the frequency of DCI-related cerebral infarction and with the clinical outcome at discharge. To describe and compare the clinical and epidemiological characteristics of the population with SAH with and without DCI-related infarction, to describe the frequency of other neurological and clinical complications in the study population, to correlate the time to hospital admission and the time to definitive treatment (surgical or endovascular) with the degree of disability at discharge (modified Rankin scale - mRs). Methods. This is a retrospective multiethnic cohort, which included patients consecutively admitted with SAH at the São Paulo hospital, from January 2016 to January 2019. Through the analysis of medical records, clinical and epidemiological data were collected from patients (age, sex, ethnicity, risk factors) and SAH data (location xxiii of the ruptured aneurysm, surgical or endovascular treatment, number of days from stroke onset to hospital admission, number of days from stroke onset to treatment, number of days from hospital admission to treatment). Patients were classified according to clinical severity at admission (Hunt-hess, WFNS), amount of blood at baseline (modified Fisher scale), and VASOGRADE (green, yellow, and red). The following neurological and clinical complications were evaluated: DCI-related infarction, hydrocephalus, need for external ventricular drain (EVD) and/or ventricular peritoneal shunt (VPS), meningitis or ventriculitis, seizures, intracranial hypertension (ICH) and decompressive craniectomy, infections (pneumonia, bloodstream infection, urinary tract infection), sodium disturbances (hyponatremia and hypernatremia); acute kidney injury (AKI), cardiac complications (arrhythmias and acute myocardial infarction) and pulmonary complications (pulmonary thromboembolism, acute respiratory distress syndrome, acute pulmonary edema). In addition, length of ICU and hospital stay, and clinical outcome at hospital discharge (ERm) were evaluated. The primary outcome of our study was DCI- related infarction, which was defined as new spontaneous ischemic lesions on at least one follow-up CT scan. Only spontaneous infarctions (ie, not related to clipping or embolization of the ruptured aneurysm) within 28 days after SAH were included.The revised image, in line with the literature, was 6 weeks after the ictus, or the last one before the patient's death. The images were reviewed by certified neuroradiologists who were unaware of the patient's clinical condition. The correlation between the image and the patient's clinical condition was performed by the principal investigator. Clinical outcome was assessed using the mRs at discharge (0-2 was considered a favorable outcome, while mRs of 3-6 was considered an unfavorable outcome). Categorical variables were presented using relative and absolute frequencies and compared using the chi-square test or Fisher's exact test, as appropriate. The distributions of continuous variables were evaluated for normality by “skewness and kurtosis” and by graphical methods. Those with normal distribution are presented as mean and standard deviation and compared by Student's T test for independent samples. Otherwise, they were presented by medians and quartiles and compared using the non-parametric Mann-Whitney test. Multivariate logistic regression analysis was used to verify the independence of the association between the VASOGRADE scale and delayed cerebral ischemia infarction (CTI). xxiv Significant variables at the 0.10 level in the univariate analysis were considered for inclusion in the multivariate model. All tests were bilateral and final P values below 0.05 were considered statistically significant. All analyzes were performed using SPSS software (IBM Corp. SPSS Statistics for Windows, version 24.0. Armonk, NY). Results. 212 patients met the inclusion criteria (71.7% female, mean age 52.7±12.8), 69 patients were classified as VASOGRADE-green (32.5%), 98 patients as VASOGRADE-yellow (46.9%) and 45 patients as VASOGRADE-red (20.6%). Patients who did or did not develop infarction from ICT were similar in terms of epidemiological characteristics, presence of comorbidities, location of the aneurysm, mean time of stroke onset-hospital admission and mean time of stroke onset - treatment, as well as the method of treatment adopted. Altogether, 19% (39 patients) had ICT infarction and the proportion of patients in the VASOGRADE-green, -yellow, and -red with ICT infarction was 7.7%, 29%, and 28%, respectively. The main neurological complication in our series other than ICT infarction was hydrocephalus (34.9%), followed by intracranial hypertension (32.5%), need for EVD (26.3%), ventriculitis/meningitis (13.9%), presence of epileptic seizures (12%) and need for craniectomy (8.1%). Hydrocephalus, need for EVD, intracranial hypertension, and craniectomy were significantly more frequent in patients with DCI. The main clinical complication in our series was infection of undetermined focus (20.6%), followed by hypernatremia (20.1%), hyponatremia (19.6%), pneumonia (18.2%), acute kidney injury (15.8%), bloodstream infection (14.4%), cardiac (4.8%) and pulmonary (3.8%) complications. In the univariate analysis, pneumonia, bloodstream infection, hypernatremia and acute kidney injury were significantly more frequent in patients with DCI-related infarction. Together, neurological and systemic complications explained 12% of the variation in functional outcome at hospital discharge. The median days from stroke onset to admission and from stroke onset to treatment were 5 (2-14) and 9 (5-19) days, respectively. In the univariate analysis, both the time from stroke onset to admission and the time from stroke onset to treatment were significantly associated with worse clinical outcome at hospital discharge (mRs). After multivariate analysis including VASOGRADE, age, sex, and aneurysm location, both VASOGRADE-yellow and VASOGRADE-red were independently associated with TCI infarction (OR 7 and 8.07, respectively) and unfavorable outcome (OR 4,156, CI 95 % 1,326 - 13,026; p = 0.015; OR 25,574, 95% CI xxv 24,446 - 147,093; p < 0.0001, respectively). The VASOGRADE discrimination for DCI- related infarction (AUC-ROC) was 0.67 ± 0.04 (95% CI 0.58–0.75; p = 0.001). VASOGRADE-red had 97.5% specificity for predicting unfavorable at discharge (95% CI 92.8 – 99.5%), while VASOGRADE-green had 90.43% specificity for predicting favorable outcome at discharge (mRs 0-2, 95% CI 82.6 - 95.5%). Conclusion. In conclusion, in a multiethnic cohort of patients with aneurysmal SAH, VASOGRADE-green predicted the absence of DCI and good clinical outcome at discharge with very high specificity, and patients in this category might be selected for early ICU discharge, minimizing costs and medical complications associated with prolonged hospital length. On the other hand, patients categorized as VASOGRADE-yellow and – red were at the highest risk for DCI. They should, therefore, be selected for care in high-volume aSAH centers, being aggressively monitored for DCI at the ICU. Such stratification methods are crucial, especially in countries with low financial resources and high health care services demand.