Blood pressure control in acute cerebrovascular disease

Acute cerebrovascular diseases (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) affect 780,000 Americans each year. Physicians who care for patients with these conditions must be able to recognize when acute hypertension requires treatment and should understand the principles of cerebral autoregulation and perfusion. Physicians should also be familiar with the various pharmacologic agents used in the treatment of cerebrovascular emergencies. Acute ischemic stroke frequently presents with hypertension, but the systemic blood pressure should not be treated unless the systolic pressure exceeds 220 mm Hg or the diastolic pressure exceeds 120 mm Hg. Overly aggressive treatment of hypertension can compromise collateral perfusion of the ischemic penumbra. Hypertension associated with intracerebral hemorrhage can be treated more aggressively to minimize hematoma expansion during the first 3 to 6 hours of illness. Subarachnoid hemorrhage is usually due to aneurysmal rupture; systolic blood pressure should be kept <150 mm Hg to prevent re-rupture of the aneurysm. Nicardipine and labetalol are recommended for rapidly treating hypertension during cerebrovascular emergencies. Sodium nitroprusside is not recommended due to its adverse effects on cerebral autoregulation and intracranial pressure. Hypoperfusion of the injured brain should be avoided at all costs.     

Cerebral autoregulation and acute ischemic stroke

Cerebral autoregulation tightly controls blood flow to the brain by coupling cerebral metabolic demand to cerebral perfusion. In the setting of acute brain injury, such as that caused by ischemic stroke, the continued precise control of cerebral blood flow (CBF) is vital to prevent further injury. Chronic as well as acute elevations in blood pressure are frequently associated with stroke, therefore, understanding the physiological response of the brain to the treatment of hypertension is clinically important. Physiological data obtained in patients with acute ischemic stroke provide no clear evidence that there are alterations in the intrinsic autoregulatory capacity of cerebral blood vessels, except perhaps in infarcted tissue. While it is likely safe to modestly reduce blood pressure by 10-15 mm Hg in most patients with acute ischemic stroke, to date, there are no controlled trial data to indicate that reducing blood pressure is beneficial. There may be subgroups, such as those with persistent large vessel occlusion, large infarcts with edema causing increased intracranial pressure or local mass effect, or chronic hypertension, in which blood pressure reduction may lead to impaired cerebral perfusion in noninfarcted tissue.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.53.     

Brain ischemia as a potential target of gene therapy

Brain infarction is one of the most important age-associated medical conditions, and the age-related neuronal vulnerability to brain ischemia is suggested to play an important role. Recent advancements in gene transfer techniques have provided promising approaches to the treatment of brain ischemia. In experimental studies, the ischemic penumbra area can be targeted by gene transfer even after ischemic insult, and post-ischemic gene therapy seems effective in attenuation of ischemic damage in both global and focal brain ischemia. Perivascular approaches of gene transfer to the cerebral blood vessels through the subarachnoid space may lead to prevention of brain ischemia caused by vasospasm after subarachnoid hemorrhage. Gene transfer to cerebral blood vessels and ischemic brain tissue may offer future therapeutic approaches to stroke.     

Magnetic resonance imaging: Implication in acute ischemic stroke management

Multimodality magnetic resonance imaging (MRI) techniques, including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), fluid-attenuated inversion recovery (FLAIR), T2 susceptibility imaging, and magnetic resonance angiography (MRA), quickly provide accurate information about ischemic penumbra (DWI/PWI mismatch), tissue perfusion, and vascular localization in acute stroke setting. These techniques help physicians to select the proper candidates for thrombolysis and/or neuroprotective treatment to salvage tissue at risk (mismatch) and monitor acute stroke patients after treatment. Recent and ongoing trials demonstrate the benefit of treating acute stroke patients depending on tissue at risk of infarction rather than timing of onset. These techniques will extend timing to salvage ischemic brain tissue beyond the 3-hour window. MRI is a powerful tool for managing acute stroke patients and helps elucidate the pathophysiology of cerebral ischemia in a given patient.     

New treatment options for hypertension during acute ischemic or hemorrhagic stroke

Opinion statement Widespread reluctance to treat hypertension during acute stroke is based on historical accounts of unfavorable outcomes of treatment that were badly done: therapies that cannot be controlled, such as sublingual nifedipine, oral or intramuscular antihypertensive drugs may drop blood pressure precipitously, leading to worsening of ischemia. Case fatality in stroke obeys a U-shaped relationship: blood pressures that are either too low or too high are associated with worse outcomes both in ischemic stroke and in intracerebral hemorrhage. Very high blood pressures should be lowered in acute stroke, and there are some circumstances in which high blood pressure must be treated despite the presence of stroke. To avoid worsening of ischemia by reduction in cerebral blood flow, it is necessary to treat high blood pressure in acute stroke with drugs that can be controlled; this usually means giving drugs by intravenous infusion; however, there is recent evidence that transdermal administration of nitrates, which can be removed if pressure is too low, is a convenient alternative that does not reduce cerebral blood flow in acute stroke.     

CT灌注成像在缺血性脑血管病中的临床应用

CT灌注成像(CTperfusion,cIP)为缺血性脑血管病的诊断提供了一种新的方法,评价指标包括脑血流量、脑血容量、达峰时间和平均通过时间等.这些用于评价脑血流灌注的半定量指标对于指导选择最佳治疗方案和观察疗效具有非常重要的意义.CIP在缺血性脑血管病中的主要应用范围包括急性缺血性卒中半睛带和梗死灶的判定,以及与其他手段结合预测出血性转化和选择溶栓候选病例.此外,CIP还用于慢性脑缺血患者脑血管储备功能的评价和蛛网膜下腔出血患者脑血管痉挛的诊断和疗效评价等.     

小覆盖范围CT灌注成像对急性大脑中动脉供血区脑卒中的评价

目的探讨用较小扫描范围的CT灌注成像检查对急性大脑中动脉供血区脑卒中的诊断效能。方法回顾性分析急诊接治的22例连续脑卒中患者,均在发病1～24 h行CT平扫和CT灌注成像检查。应用Z轴80 mm范围灌注参数,得出脑梗死核心区、半暗带的体积。计算半暗带/(半暗带+梗死核心区)比值。根据Z轴长度80 mm的CT灌注结果的治疗方案为基线,将较小覆盖范围获得的结果制定的治疗方案,计算较小范围灌注评价治疗的敏感性与特异性。结果当半暗带/(半暗带+梗死核心区)比值>0.2时,较小覆盖范围应用40 mm范围的CT灌注检查,可以准确评价梗死核心区与半暗带。结论大脑中动脉供血区脑卒中患者,当半暗带/(半暗带+梗死核心区)>0.2时,40 mm的Z轴覆盖范围CT灌注成像能够对病灶的范围与性质做出诊断。     

CT灌注成像在缺血性脑血管病中的临床应用

CT灌注成像(CTperfusion,cIP)为缺血性脑血管病的诊断提供了一种新的方法,评价指标包括脑血流量、脑血容量、达峰时间和平均通过时间等.这些用于评价脑血流灌注的半定量指标对于指导选择最佳治疗方案和观察疗效具有非常重要的意义.CIP在缺血性脑血管病中的主要应用范围包括急性缺血性卒中半睛带和梗死灶的判定,以及与其他手段结合预测出血性转化和选择溶栓候选病例.此外,CIP还用于慢性脑缺血患者脑血管储备功能的评价和蛛网膜下腔出血患者脑血管痉挛的诊断和疗效评价等.     

CT灌注和CT血管成像在缺血性卒中早期诊断中的作用

目的探讨CT灌注和CT血管成像对缺血性卒中患者早期诊断缺血半暗带和缺血部位的作用。方法回顾20例缺血性卒中患者,于发病24h之内均行CT灌注检查,8例行CT血管成像,获取梗死侧与正常侧脑血流量(CBF)、脑血容量(CBV)和平均通过时间(MTT)参数图和脑血管影像,将上述结果进行统计学分析。结果本组急性脑梗死16例,4例TIA患者,经CT灌注检查梗死侧缺血中心区的CBV、CBF为(2.1±0.6)ml/100g、(22.8±26.2)ml.100g-1.min-1,较正常侧明显减少,MTT为(7.6±3.2)s,与正常对照区相比差异有显著性(P<0.01)。15例可见缺血半暗带存在,CT血管成像8例,与CT灌注判断的梗塞血管基本相符。结论CT灌注成像能快速、准确反映缺血半暗带的部位、范围,结合CT血管成像,可以准确判断栓塞血管部位,对早期诊断缺血性卒中和抓住动脉溶栓时机有较好的指导作用。     

成纤维细胞生长因子与卒中后血管发生

增加缺血半暗带脑血流有利于促进神经功能恢复.成纤维细胞生长因子与卒中后血管发生密切相关,可使缺血半暗带脑血流得到改善,从而促进神经功能恢复.其应用将成为治疗缺血性卒中的一种新方法.     

尼莫地平对脑出血后缺血性脑损害保护作用的研究

目的探讨脑出血后继发性缺血性脑损害机制以及尼莫地平对脑出血后继发性缺血性脑损害的保护作用。方法60例脑出血患者随机分为尼莫地平组(30例)与常规治疗组(30例),在治疗前后用单光子发射型计算机断层显像(SPECT)观察原发灶缺血体积,血肿周围及脑部其他区域的局部脑血流量(rCBF)变化。结果尼莫地平组和常规治疗组治疗后原发灶缺血的体积明显缩小,原发灶缺血体积减少值尼莫地平组明显高于常规治疗组(P<0.01)。治疗后原发灶及远隔部位缺血灶rCBF增加值尼莫地平组明显高于常规治疗组(P<0.01)。结论脑出血后血肿周围及远隔区域可出现广泛的rCBF下降,血肿周围可能存在缺血半暗带。尼莫地平治疗脑出血有确切疗效,可改善局部脑缺血。     

Blutdruck und Gehirn

During acute cerebral infarction, autoregulation is abolished. Brain perfusion therefore directly depends on perfusion pressure and cardiac output. For this reason, in the early state of stroke, elevated blood pressure improves cerebral blood flow and only values of 210 mmHg systolic or above should be lowered. With the development of a vasogenic brain edema or a dysfunctional blood-brain barrier (usually on day 2 to 4 after infarction), blood pressure must be normalized in order to avoid hemorrhage and to minimize edema. In the presence of space occupying edema or intracranial hemorrhage, only those antihypertensive substances may be used which do not cause a dilatation of brain vessels. Direct vasodilators and calcium antagonists are not suitable in this situation. Furthermore, antihypertensive medication which causes bradycardia (e.g. beta blockers) should be avoided, because in acute stroke, brain perfusion also depends on the cardiac output.For primary and secondary stroke prevention normalization of blood pressure is essential. Efficacy is basically independent of the kind of antihypertensive medication used. Effective normalization of blood pressure probably helps to prevent vascular dementias of all kinds. Convincing studies however are still lacking for most sorts of antihypertensive medication.     

Impact of Hypertension on Stroke

Hypertension is the single most important risk factor for all types of stroke: ischemic stroke, intracerebral hemorrhage, and aneurysmal subarachnoid hemorrhage. Epidemiologic studies over the past 30 years have demonstrated a dramatic reduction in the incidence and mortality of all stroke types with good control of hypertension, and it appears that all effective antihypertensive agents have similar efficacy in their ability to reduce stroke risk. In addition, it appears that acute treatment of hypertension in the setting of intracerebral hemorrhage and subarachnoid hemorrhage is beneficial, but it is still uncertain in the setting of ischemic stroke what level of blood pressure will result in the best possible outcome.     

急性脑梗死患者影像学缺血半暗带的临床评价策略

缺血性卒中再灌注治疗近年来取得了重大进展,治疗前快速精准评估缺血半暗带是临床诊治的紧迫需求。目前,影像学是显示缺血半暗带最直观、有效的方法,该方法通过利用组织窗筛选出能够从再灌注治疗中获益的患者,并预估风险和预后。作者介绍了急性脑梗死影像学缺血半暗带的临床评估模式,并对不同发病时间、拟进行再灌注治疗患者的缺血半暗带评价策略进行了分层优先推荐。     

The Management of Hypertension for an Acute Stroke: What Is the Blood Pressure Goal?

Stroke is the 4th leading cause of death in the US and a leading cause of disability among adults. Stroke is broadly classified into ischemic and hemorrhagic subtypes. Although the pathogenesis may differ between ischemic and hemorrhagic stroke subtypes, a unifying feature is that hypertension is a major risk factor for most ischemic and hemorrhagic strokes. Prevention of first and recurrent stroke is substantially dependent on blood pressure control. There is controversy about blood pressure management in acute stroke. In this review we discuss controversies about and guidelines for management of blood pressure in acute stroke. We subdivide our discussion to address important questions about acute blood pressure management in ischemic stroke, intraparenchymal hemorrhage, and subarachnoid hemorrhage. In addition, we address BP control recommendations when tissue plasminogen activator administration is being contemplated for treatment of acute ischemic stroke.     

Hypertension and the brain. The National High Blood Pressure Education Program.

Neurogenic mechanisms are important in the maintenance of most forms of hypertension, yet the brain is highly vulnerable to the deleterious effects of elevated blood pressure. Hypertensive encephalopathy results from a sudden, sustained rise in blood pressure sufficient to exceed the upper limit of cerebral blood flow autoregulation. The cerebral circulation adapts to chronic less severe hypertension but at the expense of changes that predispose to stroke due to arterial occlusion or rupture. Stroke is a generic term for a clinical syndrome that includes focal infarction or hemorrhage in the brain, or subarachnoid hemorrhage. Atherothromboembolism and thrombotic occlusion of lipohyalinotic small-diameter end arteries are the principal causes of cerebral infarction. Microaneurysm rupture is the usual cause of hypertension-associated intracerebral hemorrhage. Rupture of aneurysms on the circle of Willis is the most common cause of nontraumatic subarachnoid hemorrhage. Stroke is a major cause of morbidity and mortality, particularly among persons aged 65 years or older. Treatment of diastolic hypertension reduces the incidence of stroke by about 40%. Treatment of isolated systolic hypertension in persons aged 60 years and older reduces the incidence of stroke by more than one third. Blood pressure management in the setting of acute stroke and the role of antihypertensive therapy in the prevention of multi-infarct dementia require further study.     

Acute cerebral ischemia in a critical care unit. A review of diagnosis and management

With an increasing understanding of the pathophysiology of human brain ischemia, it appears that time is of critical essence in the diagnosis and management of the acute stroke victim. A review of the acute ischemic stroke patient in an intensive care setting is described. Recent knowledge of clinical stroke assessment is summarized, with further emphasis on in-hospital strokes. Acute stroke units are described with a focus on the general clinical approach to patients with acute cerebral ischemia: investigations, recent treatment advances, and rehabilitation. Unless patients with acute brain ischemia are given the opportunity for aggressive management, care, and enrollment into promising therapeutic protocols, ideally within an acute stroke unit setting, the tremendous burden of stroke will not be lifted.     

Blood pressures immediately following ischemic strokes are associated with cerebral perfusion and neurologic function

The optimal range of blood pressure levels in the early phase of ischemic stroke with hypertension is still controversial. Based on our stroke registry database, we explored the relationship between blood pressure levels and cerebral perfusion in the early phase of ischemic stroke with hypertension and neurofunctional recovery at 3 months after stroke. Total 732 stroke patients with hypertension were finally analyzed. Patients were divided into quintiles according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) to perform multivariable logistic regression to analyze their relation with neurofunctional recovery, respectively. The cerebral perfusion levels displayed a reverse “U” shape curve with the change of blood pressure levels. Sufficient estimated cerebral blood flow (ECBF) in the early phase of ischemic stroke was associated with good neurofunctional recovery at 3 months after stroke. The best neurofunctional recovery was observed in the middle quintiles with SBP at 161 to 177 mm Hg and DBP at 103 to 114 mm Hg, respectively. So maintaining appropriate blood pressure levels in the early phase of ischemic stroke might be beneficial to cerebral perfusion and neurofunctional recovery.     

Early treatment of hypertension in acute ischemic and intracerebral hemorrhagic stroke: Progress achieved,challenges, and perspectives

Hypertension is the leading risk factor for ischemic and intracerebral hemorrhagic subtypes of stroke. Additionally, high blood pressure (BP) in the acute cerebrovascular event is associated with poor outcome, and a high percentage of stroke survivors have inadequate control of hypertension. The present is a systematic review of prospective, randomized, and controlled trials carried out on safety and efficacy of antihypertensive treatment of both subtypes of acute stroke. Six trials involving 7512 patients were included, which revealed controversies on the speed and the goals of treatment. These controversies could be due at least in part, from the fact that some studies analyzed the results of antihypertensive treatment in ischemic and intracerebral hemorrhagic subtypes of acute stroke together, and from a different prevalence of past-stroke in the randomized groups. Further research is necessary to establish whether standard antihypertensive treatment provides greater benefit than simple observation in patients with ischemic acute stroke and Stage 2 hypertension of JNC 7, albeit they were not candidates for acute reperfusion. In that case, the target reduction in BP could be 10% to 15% within 24 hours. The recently published INTERACT 2 has provided evidence that patients with hemorrhagic stroke may receive intensive antihypertensive treatment safely with the goal of reducing systolic BP to levels no lower than 130 mm Hg. It is important to take into account that marked BP lowering in acute stroke increases the risk of poor outcome by worsening cerebral ischemia from deterioration of cerebral blood flow autoregulation.     

Systemic inflammation, blood pressure, and stroke outcome

Hypertension is the most important modifiable risk factor for ischemic stroke, and antihypertensive treatment is of paramount importance to reduce the incidence of stroke mortality and morbidity. The significance and best management of hypertension during the first hours after stroke onset, however, are still matters of debate. Cerebral ischemia results in a complex inflammatory cascade; inflammatory mechanisms are also important participants in the pathophysiology of hypertension. There has been a convergence of evidence that is important to consider in managing systemic blood pressure after stroke to ensure an optimal outcome. The identification of useful markers will allow progress in our ability to treat blood pressure in the acute phase of a stroke. The determination of levels of C-reactive protein, an acute-phase inflammation marker, may help to guide our approach in the management of blood pressure in acute ischemic stroke. Whether this target will be useful in the development of risk prediction strategies or therapies for the treatment of stroke in humans is far from clear.