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BACKGROUND AND PURPOSE: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). METHODS: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130-140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2-6), major disability (mRS 3-5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1-24 h. RESULTS: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2-6 or 3-5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85-1.19 [p = 0.958] and OR 0.95, 95% CI 0.80-1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95-1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23-1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18-2.12; p = 0.002). CONCLUSIONS: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups.
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Anti-Hipertensivos/uso terapêutico , Povo Asiático , Pressão Sanguínea/efeitos dos fármacos , Fibrinolíticos/administração & dosagem , Disparidades em Assistência à Saúde/etnologia , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/efeitos adversos , Ásia/epidemiologia , Austrália/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Fibrinolíticos/efeitos adversos , Estado Funcional , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/etnologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/etnologia , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , América do Sul/epidemiologia , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
Ischemic stroke (IS) is one of the most impacting diseases in the world. In the last decades, new therapies have been introduced to improve outcomes after IS, most of them aiming for recanalization of the occluded vessel. However, despite this advance, there are still a large number of patients that remain disabled. One interesting possible therapeutic approach would be interventions guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). Supportive hemodynamic therapies aiming to optimize perfusion in the ischemic area could protect the brain and may even extend the therapeutic window for reperfusion therapies. However, the knowledge of how to implement these therapies in the complex pathophysiology of brain ischemia is challenging and still not fully understood. This comprehensive review will focus on the state of the art in this promising area with emphasis on the following aspects: (1) pathophysiology of CA in the ischemic process; (2) methodology used to evaluate CA in IS; (3) CA studies in IS patients; (4) potential non-reperfusion therapies for IS patients based on the CA concept; and (5) the impact of common IS-associated comorbidities and phenotype on CA status. The review also points to the gaps existing in the current research to be further explored in future trials.
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OBJECTIVE: Access to acute stroke unit (ASU) care is known to vary worldwide. We aimed to quantify regional variations in the various components of ASU care. METHOD: Secondary analysis of the Head Positioning in acute Stroke Trial (HeadPoST), an international, multicentre, cluster crossover trial of head-up versus head-down positioning in 11,093 acute stroke patients at 114 hospitals in 9 countries. Patients characteristics and 11 standard components of processes of care were described according to ASU admission within and across four economically-defined regional groups (Australia/UK, China [includes Taiwan], India/Sri Lanka, and South America [Brazil/Chile/Colombia]). Variations in process of ASU care estimates were obtained in hierarchical mixed models, with adjustment for study design and potential patient- and hospital-level confounders. RESULTS: Of 11,086 patients included in analyses, 59.7% (n = 6620) had an ASU admission. In China, India/Sri Lanka and South America, ASU patients were older, had greater neurological severity and more premorbid conditions than non-ASU patients. ASU patients were more likely to receive reperfusion therapy and multidisciplinary care within regions, but the components of care varied across regions. With Australia/UK as reference, patients in other regions had a lower probability of receiving reperfusion therapy, especially in India/Sri Lanka (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.12-0.63) and multidisciplinary care (mainly in formal dysphagia assessment, physiotherapy and occupational therapy). CONCLUSION: There is significant variation in the components of stroke care across economically-defined regions of the world. Ongoing efforts are required to reduce disparities and optimise health outcomes, especially in resource poor areas. CLINICAL TRIAL REGISTRATION: HeadPoST is registered at ClinicalTrials.gov (NCT02162017).
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Acidente Vascular Cerebral , Austrália , Brasil , Chile , China , Colômbia , Humanos , Índia , Qualidade da Assistência à Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , TaiwanRESUMO
We hypothesized that knowledge of cerebral autoregulation (CA) status during recanalization therapies could guide further studies aimed at neuroprotection targeting penumbral tissue, especially in patients that do not respond to therapy. Thus, we assessed CA status of patients with acute ischemic stroke (AIS) during intravenous r-tPA therapy and associated CA with response to therapy. AIS patients eligible for intravenous r-tPA therapy were recruited. Cerebral blood flow velocities (transcranial Doppler) from middle cerebral artery and blood pressure (Finometer) were recorded to calculate the autoregulation index (ARI, as surrogate for CA). National Institute of Health Stroke Score was assessed and used to define responders to therapy (improvement of ≥ 4 points on NIHSS measured 24-48 h after therapy). CA was considered impaired if ARI < 4. In 38 patients studied, compared to responders, non-responders had significantly lower ARI values (affected hemisphere: 5.0 vs. 3.6; unaffected hemisphere: 5.4 vs. 4.4, p = 0.03) and more likely to have impaired CA (32% vs. 62%, p = 0.02) during thrombolysis. In conclusion, CA during thrombolysis was impaired in patients who did not respond to therapy. This variable should be investigated as a predictor of the response to therapy and to subsequent neurological outcome.
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Circulação Cerebrovascular/efeitos dos fármacos , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica/métodos , Administração Intravenosa/métodos , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular/fisiologia , Feminino , Fibrinólise , Homeostase/fisiologia , Humanos , Infarto da Artéria Cerebral Média/tratamento farmacológico , AVC Isquêmico/metabolismo , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiopatologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana/métodosRESUMO
BACKGROUND: Although the Head Positioning in acute Stroke Trial (HeadPoST) showed no effect of the flat head position (FP; vs sitting up head position (SUP)) on functional outcome, we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke (AIS) of at least moderate severity. METHODS: Subgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale (NIHSS) scores ≥7, ≥10 and ≥14, randomised to FP or SUP <4.5 hours of AIS onset on functional outcomes defined by a shift in scores on the modified Rankin scale (mRS) and death/disability (mRS scores 3-6), and any cardiovascular serious adverse event. Logistic regression analyses were undertaken adjusted for study design and baseline risk factors. RESULTS: There was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores: adjusted OR and 95% CI for ordinal shift and binary (3-6) mRS scores: for NIHSS ≥7 (n=867) 0.92 (0.67 to 1.25) and 0.74 (0.52 to 1.04); NIHSS ≥ 10 (n=606) 0.80 (0.58 to 1.10) and 0.77 (0.49 to 1.19); NIHSS ≥14 (n=378) 0.82 (0.54 to 1.24) and 1.22 (0.69 to 2.14). CONCLUSIONS: Early FP had no significant effect in patients with moderate-severe AIS. TRIAL REGISTRATION NUMBER: NCT02162017.
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AVC Isquêmico/terapia , Posicionamento do Paciente , Postura Sentada , Decúbito Dorsal , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Feminino , Estado Funcional , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Intracerebral haemorrhage is relatively common and has devastating consequences. Furthermore, non-invasive and invasive strategies to manage raised intracranial pressure remain limited and associated with high morbidity and mortality. We report a case of a 72-year-old male with intracerebral haemorrhage with ventricular extension, hydrocephalus and intracranial hypertension, who was evaluated by transcranial Doppler ultrasound and optic nerve sheath diameter. This case demonstrates that beyond pharmacological and surgical interventions, simple manipulation of arterial carbon dioxide has the propensity to improve cerebral haemodynamic parameters. Our results demonstrate the negative effects of hypercapnia on cerebral autoregulation and the benefits of having transcranial Doppler ultrasound available in the intensive care unit point of care.
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BACKGROUND: The intra-aortic balloon pump (IABP) is often used in high-risk patients undergoing cardiac surgery to improve coronary perfusion and decrease afterload. The effects of the IABP on cerebral hemodynamics are unknown. We therefore assessed the effect of the IABP on cerebral hemodynamics and on neurological complications in patients undergoing cardiac surgery who were randomized to receive or not receive preoperative IABP in the 'Intra-aortic Balloon Counterpulsation in Patients Undergoing Cardiac Surgery' (IABCS) trial. METHODS: This is a prospectively planned analysis of the previously published IABCS trial. Patients undergoing elective coronary artery bypass surgery with ventricular ejection fraction ≤ 40% or EuroSCORE ≥ 6 received preoperative IABP (n = 90) or no IABP (n = 91). Cerebral blood flow velocity (CBFV) of the middle cerebral artery through transcranial Doppler and blood pressure through Finometer or intra-arterial line were recorded preoperatively (T1) and 24 h (T2) and 7 days after surgery (T3) in patients with preoperative IABP (n = 34) and without IABP (n = 33). Cerebral autoregulation was assessed by the autoregulation index that was estimated from the CBFV response to a step change in blood pressure derived by transfer function analysis. Delirium, stroke and cognitive decline 6 months after surgery were recorded. RESULTS: There were no differences between the IABP and control patients in the autoregulation index (T1: 5.5 ± 1.9 vs. 5.7 ± 1.7; T2: 4.0 ± 1.9 vs. 4.1 ± 1.6; T3: 5.7 ± 2.0 vs. 5.7 ± 1.6, p = 0.97) or CBFV (T1: 57.3 ± 19.4 vs. 59.3 ± 11.8; T2: 74.0 ± 21.6 vs. 74.7 ± 17.5; T3: 71.1 ± 21.3 vs. 68.1 ± 15.1 cm/s; p = 0.952) at all time points. Groups were not different regarding postoperative rates of delirium (26.5% vs. 24.2%, p = 0.83), stroke (3.0% vs. 2.9%, p = 1.00) or cognitive decline through analysis of the Mini-Mental State Examination (16.7% vs. 40.7%; p = 0.07) and Montreal Cognitive Assessment (79.16% vs. 81.5%; p = 1.00). CONCLUSIONS: The preoperative use of the IABP in high-risk patients undergoing cardiac surgery did not affect cerebral hemodynamics and was not associated with a higher incidence of neurological complications. Trial registration http://www.clinicaltrials.gov (NCT02143544).
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Background The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke ( AIS ) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results Use of 8 AIS processes of care were considered: reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or "defect-free" care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI , 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI , 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions Use of evidence-based care is associated with improved clinical outcome in AIS . Strategies are required to address regional variation in the use of proven AIS treatments. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique Identifier: NCT02162017.
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Isquemia Encefálica/terapia , Medicina Baseada em Evidências , Avaliação de Processos e Resultados em Cuidados de Saúde , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Austrália , Isquemia Encefálica/fisiopatologia , China , Transtornos de Deglutição/diagnóstico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Índia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multinível , Posicionamento do Paciente , Modalidades de Fisioterapia/estatística & dados numéricos , Inibidores da Agregação Plaquetária/uso terapêutico , América do Sul , Sri Lanka , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Taiwan , Trombectomia/estatística & dados numéricos , Terapia Trombolítica/estatística & dados numéricos , Reino UnidoRESUMO
PURPOSE: Carbon dioxide (CO2) is a potent cerebral vasomotor agent. Despite reduction in CO2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO2 values in acute stroke. The aim of the study was to systematically assess CO2 levels in acute stroke. MATERIAL AND METHODS: Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO2 (PaCO2) and end-tidal CO2 (EtCO2) in acute stroke. RESULTS: After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO2 levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients. CONCLUSION: The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO2 assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings.
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Circulação Cerebrovascular/fisiologia , Hipocapnia/complicações , Hipocapnia/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Dióxido de Carbono/sangue , HumanosRESUMO
BACKGROUND: Systolic blood pressure of more than 185 mm Hg is a contraindication to thrombolytic treatment with intravenous alteplase in patients with acute ischaemic stroke, but the target systolic blood pressure for optimal outcome is uncertain. We assessed intensive blood pressure lowering compared with guideline-recommended blood pressure lowering in patients treated with alteplase for acute ischaemic stroke. METHODS: We did an international, partial-factorial, open-label, blinded-endpoint trial of thrombolysis-eligible patients (age ≥18 years) with acute ischaemic stroke and systolic blood pressure 150 mm Hg or more, who were screened at 110 sites in 15 countries. Eligible patients were randomly assigned (1:1, by means of a central, web-based program) within 6 h of stroke onset to receive intensive (target systolic blood pressure 130-140 mm Hg within 1 h) or guideline (target systolic blood pressure <180 mm Hg) blood pressure lowering treatment over 72 h. The primary outcome was functional status at 90 days measured by shift in modified Rankin scale scores, analysed with unadjusted ordinal logistic regression. The key safety outcome was any intracranial haemorrhage. Primary and safety outcome assessments were done in a blinded manner. Analyses were done on intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01422616. FINDINGS: Between March 3, 2012, and April 30, 2018, 2227 patients were randomly allocated to treatment groups. After exclusion of 31 patients because of missing consent or mistaken or duplicate randomisation, 2196 alteplase-eligible patients with acute ischaemic stroke were included: 1081 in the intensive group and 1115 in the guideline group, with 1466 (67·4%) administered a standard dose among the 2175 actually given intravenous alteplase. Median time from stroke onset to randomisation was 3·3 h (IQR 2·6-4·1). Mean systolic blood pressure over 24 h was 144·3 mm Hg (SD 10·2) in the intensive group and 149·8 mm Hg (12·0) in the guideline group (p<0·0001). Primary outcome data were available for 1072 patients in the intensive group and 1108 in the guideline group. Functional status (mRS score distribution) at 90 days did not differ between groups (unadjusted odds ratio [OR] 1·01, 95% CI 0·87-1·17, p=0·8702). Fewer patients in the intensive group (160 [14·8%] of 1081) than in the guideline group (209 [18·7%] of 1115) had any intracranial haemorrhage (OR 0·75, 0·60-0·94, p=0·0137). The number of patients with any serious adverse event did not differ significantly between the intensive group (210 [19·4%] of 1081) and the guideline group (245 [22·0%] of 1115; OR 0·86, 0·70-1·05, p=0·1412). There was no evidence of an interaction of intensive blood pressure lowering with dose (low vs standard) of alteplase with regard to the primary outcome. INTERPRETATION: Although intensive blood pressure lowering is safe, the observed reduction in intracranial haemorrhage did not lead to improved clinical outcome compared with guideline treatment. These results might not support a major shift towards this treatment being applied in those receiving alteplase for mild-to-moderate acute ischaemic stroke. Further research is required to define the underlying mechanisms of benefit and harm resulting from early intensive blood pressure lowering in this patient group. FUNDING: National Health and Medical Research Council of Australia; UK Stroke Association; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.
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Pressão Sanguínea/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Austrália/epidemiologia , Pressão Sanguínea/fisiologia , Isquemia Encefálica/patologia , Brasil/epidemiologia , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Prospectivos , República da Coreia/epidemiologia , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
We aimed to assess cerebral autoregulation (CA) and neurovascular coupling (NVC) in stroke patients of differing severity comparing responses to healthy controls and explore the association between CA and NVC with functional outcome. Patients admitted with middle cerebral artery (MCA) stroke and healthy controls were recruited. Stroke severity was defined by the National Institutes of Health Stroke Scale (NIHSS) scores: ≤4 mild, 5-15 moderate and ≥16 severe. Transcranial Doppler ultrasound and Finometer recorded MCA cerebral blood flow velocity (CBFv) and blood pressure, respectively, over 5 min baseline and 1 min passive movement of the elbow to calculate the autoregulation index (ARI) and CBFv amplitude responses to movement. All participants were followed up for three months. A total of 87 participants enrolled in the study, including 15 mild, 27 moderate and 13 severe stroke patients, and 32 control subjects. ARI was lower in the affected hemisphere (AH) of moderate and severe stroke groups. Decreased NVC was seen bilaterally in all stroke groups. CA and NVC correlated with stroke severity and functional outcome. CBFv regulation is significantly impaired in acute stroke, and further compromised with increasing stroke severity. Preserved CA and NVC in the acute period were associated with improved three-month functional outcome.
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Isquemia Encefálica/fisiopatologia , Homeostase/fisiologia , Infarto da Artéria Cerebral Média/fisiopatologia , Acoplamento Neurovascular/fisiologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Estudos de Casos e Controles , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Though genetic and environmental determinants of systemic haemodynamic have been reported, surprisingly little is known about their influences on cerebral haemodynamics. We assessed the potential geographical effect on cerebral haemodynamics by comparing the individual differences in cerebral blood flow velocity (CBFv), vasomotor tone (critical closing pressure- CrCP), vascular bed resistance (resistance-area product- RAP) and cerebral autoregulation (CA) mechanism on healthy subjects and acute ischaemic stroke (AIS) patients from two countries. METHODS: Participants were pooled from databases in Leicester, United Kingdom (LEI) and São Paulo, Brazil (SP) research centres. Stroke patients admitted within 48 h of ischaemic stroke onset, as well as age- and sex-matched controls were enrolled. Beat-to-beat blood pressure (BP) and bilateral mean CBFv were recorded during 5 min baseline. CrCP and RAP were calculated. CA was quantified using transfer function analysis (TFA) of spontaneous oscillations in arterial BP and mean CBFv, and the derived autoregulatory index (ARI). RESULTS: A total of 100 participants (50 LEI and 50 SP) were recruited. No geographical differences were found. Both LEI and SP AIS participants showed lower values of CA compared to controls. Moreover, the affected hemisphere presented lower resting CBFv and higher RAP compared to the unaffected hemisphere in both populations. CONCLUSIONS: Impairments of cerebral haemodynamics, demonstrated by several key parameters, was observed following AIS compared to controls irrespective of geographical region. These initial results should encourage further research on cerebral haemodynamic research with larger cohorts combining different populations.
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Circulação Cerebrovascular/fisiologia , Hemodinâmica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Brasil , Estudos de Casos e Controles , Feminino , Homeostase/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido , Resistência Vascular/fisiologiaRESUMO
BACKGROUND: Acute ischaemic stroke (AIS) patients often show impaired cerebral autoregulation (CA). We tested the hypothesis that CA impairment and other alterations in cerebral haemodynamics are associated with stroke subtype and severity. METHODS: AIS patients (n = 143) were amalgamated from similar studies. Data from baseline (< 48 h stroke onset) physiological recordings (beat-to-beat blood pressure [BP], cerebral blood flow velocity (CBFV) from bilateral insonation of the middle cerebral arteries) were calculated for mean values and autoregulation index (ARI). Differences were assessed between stroke subtype (Oxfordshire Community Stroke Project [OCSP] classification) and severity (National Institutes of Health Stroke Scale [NIHSS] score < 5 and 5-25). Correlation coefficients assessed associations between NIHSS and physiological measurements. RESULTS: Thirty-two percent of AIS patients had impaired CA (ARI < 4) in affected hemisphere (AH) that was similar between stroke subtypes and severity. CBFV in AH was comparable between stroke subtype and severity. In unaffected hemisphere (UH), differences existed in mean CBFV between lacunar and total anterior circulation OCSP subtypes (42 vs. 56 cmâ¢s-1, p < 0.01), and mild and moderate-to-severe stroke severity (45 vs. 51 cmâ¢s-1, p = 0.04). NIHSS was associated with peripheral (diastolic and mean arterial BP) and cerebral haemodynamic parameters (CBFV and ARI) in the UH. CONCLUSIONS: AIS patients with different OCSP subtypes and severity have homogeneity in CA capability. Cerebral haemodynamic measurements in the UH were distinguishable between stroke subtype and severity, including the association between deteriorating ARI in UH with stroke severity. More studies are needed to determine their clinical significance and to understand the determinants of CA impairment in AIS patients.
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Isquemia Encefálica/fisiopatologia , Circulação Cerebrovascular , Hemodinâmica , Artéria Cerebral Média/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Pressão Arterial , Velocidade do Fluxo Sanguíneo , Isquemia Encefálica/classificação , Isquemia Encefálica/diagnóstico por imagem , Brasil , Avaliação da Deficiência , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Prognóstico , Índice de Gravidade de Doença , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico por imagem , Ultrassonografia Doppler TranscranianaRESUMO
OBJECTIVE: To devise an appropriate measure of the quality of a magnetic resonance imaging (MRI) signal for the assessment of dynamic cerebral autoregulation, and propose simple strategies to improve its quality. MATERIALS AND METHODS: Magnetic resonance images of 11 healthy subjects were scanned during a transient decrease in arterial blood pressure (BP). Mean signals were extracted from non-overlapping brain regions for each image. An ad-hoc contrast-to-noise ratio (CNR) was used to evaluate the quality of these regional signals. Global mean signals were obtained by averaging the set of regional signals resulting after applying a Hampel filter and discarding a proportion of the lower quality component signals. RESULTS: Significant improvements in CNR values of global mean signals were obtained, whilst maintaining significant correlation with the original ones. A Hampel filter with a small moving window and a low rejection threshold combined with a selection of the 50% component signals seems a recommendable option. CONCLUSIONS: This work has demonstrated the possibility of improving the quality of MRI signals acquired during transient drops in BP. This approach needs validation at a voxel level, which could help to consolidate MRI as a technological alternative to the standard techniques for the study of cerebral autoregulation.
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Pressão Arterial/fisiologia , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Homeostase/fisiologia , Imageamento por Ressonância Magnética/métodos , Voluntários Saudáveis , Humanos , Razão Sinal-RuídoRESUMO
Cardiopulmonary bypass surgery is associated with a high incidence of neurological complications, including stroke, delirium and cognitive impairment. The development of strategies to reduce the incidence of such neurological events has been hampered by the lack of a clear understanding of their pathophysiology. Cerebral autoregulation (CA), which describes the ability of the brain to maintain a stable cerebral blood flow over a wide range of cerebral perfusion pressures despite changes in blood pressure, is known to be impaired in various neurological disorders. Therefore, we aimed to systematically review studies reporting indices of CA in cardiopulmonary bypass surgery. Databases such as MEDLINE, Web of Science, Cochrane Database of Systematic Reviews and EMBASE were searched for relevant articles. Titles, abstracts and full texts of articles were scrutinized according to predefined selection criteria. Two independent reviewers undertook the methodological quality screening and data extraction of the included studies. Twenty of 2566 identified studies were relevant. Studies showed marked heterogeneity and weaknesses in key methodological criteria (e.g. population size and discussion of limitations). All but 3 of the 20 studies described impairments of CA with cardiac surgery. Eleven studies investigated clinical outcomes, and 9 of these found a significant relationship between these and impaired CA. There is a general agreement that cardiac surgery is associated with changes in CA and that clinical outcomes appear to be significantly related to impaired CA. Further studies are now needed to determine prognostic significance and to inform future therapeutic strategies.
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Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Circulação Cerebrovascular/fisiologia , Homeostase/fisiologia , Pressão Sanguínea , Humanos , Avaliação de Resultados em Cuidados de SaúdeRESUMO
BACKGROUND: Few studies have assessed regional variation in the organisation of stroke services, particularly health care resourcing, presence of protocols and discharge planning. Our aim was to compare stroke care organisation within middle- (MIC) and high-income country (HIC) hospitals participating in the Head Position in Stroke Trial (HeadPoST). METHODS: HeadPoST is an on-going international multicenter crossover cluster-randomized trial of 'sitting-up' versus 'lying-flat' head positioning in acute stroke. As part of the start-up phase, one stroke care organisation questionnaire was completed at each hospital. The World Bank gross national income per capita criteria were used for classification. RESULTS: 94 hospitals from 9 countries completed the questionnaire, 51 corresponding to MIC and 43 to HIC. Most participating hospitals had a dedicated stroke care unit/ward, with access to diagnostic services and expert stroke physicians, and offering intravenous thrombolysis. There was no difference for the presence of a dedicated multidisciplinary stroke team, although greater access to a broad spectrum of rehabilitation therapists in HIC compared to MIC hospitals was observed. Significantly more patients arrived within a 4-h window of symptoms onset in HIC hospitals (41 vs. 13%; P<0.001), and a significantly higher proportion of acute ischemic stroke patients received intravenous thrombolysis (10 vs. 5%; P=0.002) compared to MIC hospitals. CONCLUSIONS: Although all hospitals provided advanced care for people with stroke, differences were found in stroke care organisation and treatment. Future multilevel analyses aims to determine the influence of specific organisational factors on patient outcomes.
Assuntos
Hospitais , Acidente Vascular Cerebral/terapia , Isquemia Encefálica/economia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Protocolos Clínicos , Estudos Cross-Over , Mão de Obra em Saúde/economia , Número de Leitos em Hospital/economia , Humanos , Alta do Paciente/economia , Posicionamento do Paciente , Garantia da Qualidade dos Cuidados de Saúde/economia , Fatores Socioeconômicos , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/epidemiologia , Inquéritos e Questionários , Terapia Trombolítica/economiaRESUMO
BACKGROUND: The present review investigated which findings in vascular imaging techniques can be used to predict clinical outcome and the risk of symptomatic intracerebral hemorrhage (sICH) in patients who underwent intravenous thrombolytic treatment. METHODS: Publications were searched, and the inclusion criteria were as follows: (1) published manuscripts, (2) patients with acute ischemic stroke managed with intravenous recombinant tissue plasminogen activator (rtPA), and (3) availability of imaging assessment to determine vessel patency or the regulation of cerebral blood flow prior to, during, and/or after thrombolytic treatment. Clinical outcomes were divided into neurological outcome [National Institutes of Health Stroke Scale (NIHSS) within 7 days] and functional outcome (modified Rankin score in 2-3 months). sICH was defined as rtPA-related intracerebral bleeding associated with any worsening of NIHSS. RESULTS: Thirty-nine articles were selected. Recanalization was associated with improved neurological and functional outcomes (OR = 7.83; 95% CI, 3.71-16.53; p < 0.001 and OR = 11.12; 95% CI, 5.85-21.14; p < 0.001, respectively). Both tandem internal carotid artery/middle cerebral artery (ICA/MCA) occlusions and isolated ICA occlusion had worse functional outcome than isolated MCA occlusion (OR = 0.26, 95% CI, 0.12-0.52; p < 0.001 and OR = 0.24, 95% CI, 0.07-0.77; p = 0.016, respectively). Reocclusion was associated with neurological deterioration (OR = 6.48, 95% CI, 3.64-11.56; p < 0.001), and early recanalization was associated with lower odds of sICH (OR = 0.36, 95% CI, 0.18-0.70; p = 0.003). CONCLUSION: Brain circulation data before, during, and after thrombolysis may be useful for predicting the clinical outcome. Cerebral arterial recanalization, presence and site of occlusion, and reocclusion are all important in predicting the clinical outcome.
RESUMO
BACKGROUND: Indication and timing of pharmacological venous thromboembolism prophylaxis in intracerebral hemorrhage patients is controversial. AIMS: To determine whether use of subcutaneous heparin during the first 7 days after spontaneous intracerebral hemorrhage increases risks of death and disability. METHODS: Data are from the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) study. Patients with acute intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure were included; patients received subcutaneous heparin following local best practice standards of care. Multivariable logistic regression and propensity score matched analysis were used to determine associations of heparin use on death and disability (modified Rankin scale) at 90 days. RESULTS: In 2525 patients with available data, there were 465 (22.5%) who received subcutaneous heparin. They had higher death or major disability at 90 days in crude (odds ratio 2.29, 95% confidence interval 1.85-2.84; p < 0.001), adjusted (odds ratio 1.62, 95% confidence interval 1.26-2.09; p < 0.001) and propensity score matched (odds ratio 2.06, 95% confidence interval 1.53-2.77; p < 0.001) analyses. In propensity score matched analysis, heparin-treated patients had significant lower mortality (odds ratio 0.55, 95% CI 0.35-0.87; p = 0.01) but greater major disability (odds ratio 1.68, 95% confidence interval 1.25-2.28; p < 0.001) at 90 days. However, no mortality difference was found in analysis restricted to 48-hour survivors. CONCLUSIONS: Use of subcutaneous heparin is associated with poor outcome in acute intracerebral hemorrhage, driven by increased residual disability. Despite the limitations of this study, and no clear relation of heparin with bleeding risk, we recommend careful consideration of the need for venous thromboembolism prophylaxis with heparin in intracerebral hemorrhage patients. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00716079.
Assuntos
Hemorragia Cerebral/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Heparina/administração & dosagem , Idoso , Pressão Sanguínea/efeitos dos fármacos , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/fisiopatologia , Avaliação da Deficiência , Esquema de Medicação , Feminino , Fibrinolíticos/efeitos adversos , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pontuação de Propensão , Método Simples-Cego , Absorção Subcutânea , Fatores de Tempo , Falha de TratamentoRESUMO
BACKGROUND: Positioning a patient lying-flat in the acute phase of ischaemic stroke may improve recovery and reduce disability, but such a possibility has not been formally tested in a randomised trial. We therefore initiated the Head Position in Stroke Trial (HeadPoST) to determine the effects of lying-flat (0°) compared with sitting-up (≥ 30°) head positioning in the first 24 hours of hospital admission for patients with acute stroke. METHODS/DESIGN: We plan to conduct an international, cluster randomised, crossover, open, blinded outcome-assessed clinical trial involving 140 study hospitals (clusters) with established acute stroke care programs. Each hospital will be randomly assigned to sequential policies of lying-flat (0°) or sitting-up (≥ 30°) head position as a 'business as usual' stroke care policy during the first 24 hours of admittance. Each hospital is required to recruit 60 consecutive patients with acute ischaemic stroke (AIS), and all patients with acute intracerebral haemorrhage (ICH) (an estimated average of 10), in the first randomised head position policy before crossing over to the second head position policy with a similar recruitment target. After collection of in-hospital clinical and management data and 7-day outcomes, central trained blinded assessors will conduct a telephone disability assessment with the modified Rankin Scale at 90 days. The primary outcome for analysis is a shift (defined as improvement) in death or disability on this scale. For a cluster size of 60 patients with AIS per intervention and with various assumptions including an intracluster correlation coefficient of 0.03, a sample size of 16,800 patients at 140 centres will provide 90 % power (α 0.05) to detect at least a 16 % relative improvement (shift) in an ordinal logistic regression analysis of the primary outcome. The treatment effect will also be assessed in all patients with ICH who are recruited during each treatment study period. DISCUSSION: HeadPoST is a large international clinical trial in which we will rigorously evaluate the effects of different head positioning in patients with acute stroke. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02162017 (date of registration: 27 April 2014); ANZCTR identifier: ACTRN12614000483651 (date of registration: 9 May 2014). Protocol version and date: version 2.2, 19 June 2014.