Article, Cardiology

Diagnosis and management of labile blood pressure during acute cerebrovascular accidents and other hypertensive crises


Diagnosis and management of labile blood pressure during acute Cerebrovascular accidents and

other Hypertensive crises

Joseph Varon MD*

The University of Texas Health Science Center at Houston, USA

The University of Texas Medical Branch, St. Luke’s Episcopal Hospital, Houston, Texas, USA

Received 29 December 2006; revised 8 February 2007; accepted 16 February 2007

Abstract It is estimated that with more than 40 million adults in the United States having uncontrolled hypertension, the risk of developing ischemic or hemorrhagic stroke in this population is significant. In addition, roughly 1 of 100 patients with essential hypertension will experience a Hypertensive crisis during their lifetime, and these accelerated hypertensive emergencies and urgencies complicate more than 27% of all acute medical problems in patients presenting to emergency departments (EDs) in the United States. Arterial hypertension, a prominent feature of acute stroke syndrome, usually declines spontaneously within a few days, but its presence at hospital admission or its acute development during hospitalization is often associated with worsening stroke outcome and early mortality. Control of hypertension in patients with subarachnoid and intracerebral hemorrhage, both forms of acute stroke, is directed at maintaining adequate cerebral blood flow to minimize ischemic damage and control intracerebral pressure while reducing the risk of rebleeding and developing cerebrovasospasm. Inappropriate lowering of the blood pressure in acute stroke may increase neurologic damage. However, adequate blood flow around the central area of the acute ischemic stroke or penumbra may result in ischemic cells being salvaged. Clinicians must be mindful that accelerated hypertension is associated with other types of patients seen in the ED, such as perioperative patients and patients with traumatic head injuries.

D 2007


Acute Blood pressure elevations occur as the cause or consequence of acute stroke and require rapid assessment and management [1-4]. The goals of the management of acute BP elevations in stroke are to minimize brain damage

* Corresponding author. Tel.: +1 713 669 1670; fax: +1 713 839 1467.

E-mail address: [email protected].

and protect the brain from the impact of additional vascular ischemic damage [5]. Intracerebral hemorrhage (ICH), caused by an aneurysm or vascular malformation, is often associated with a sudden increase in systemic BP. blood pressure management is an essential element of early treatment. Complicating the management of acute changes in BP are many Systemic conditions (eg, renovascular disease or endocrine abnormalities) that may cause hyper- tension. Other conditions (eg, surgery or head injury) affect

0735-6757/$ – see front matter D 2007 doi:10.1016/j.ajem.2007.02.032

BP so routinely that, for these conditions, BP monitoring is a fundamental part of patient management [6].

With acute ischemic stroke , an abrupt elevation of BP occurs as the vascular system of the brain compensates for increased resistance in intracranial vessels. Reflex mechanisms respond to blood vessel obstruction by increasing systemic BP. With ischemic stroke, the elevation of BP is typically self-limiting. Early elevation in arterial BP may stabilize in hours or days and return to a normal level within 2 days of stroke onset [7,8]. Even if BP elevations persist for longer, the poststroke hypertension is likely to remit spontaneously [9]. Treatment of acute elevations in BP associated with hemorrhagic stroke presumes that the risk of recurrent stroke or repeated hemorrhage is reduced by BP control [10-12].

It is generally agreed that for patients with subarachnoid hemorrhage , BP should be reduced from elevated levels until the aneurysm or other vascular malformation has been effectively treated [13]. Unfortunately, because of cerebrovasospasm, a complication of stroke, reflex constric- tion of cerebral arteries may occur [14]. Whereas vasospasm impedes cerebral blood flow (CBF), treatment may neces- sitate artificially elevating BP or expanding the intravascular volume to minimize ischemic damage [14,15].

Underlying the controversy about whether to treat elevated BP caused by stroke is the theory that elevation of BP is likely to be neuroprotective. With adequate blood flow around the central area of the stroke or penumbra, cells may be salvaged [5]. Upward or downward deviation of normal BP readings that persist for more than 2 days after a stroke may cause early mortality. It is unknown if elevated BP increases mortality or if it is a marker for more severe ischemic brain damage [10,16,17].


A National Library of Medicine literature search was conducted through the Publication years 2000 to 2007 for articles concerned with the management of hypertension in acute stroke and other hypertensive crises. original research using animal and human models investigating antihyperten- sive agents useful in acute stroke was considered. Pivotal articles published before the year 2000 were added as primary references. The bibliography has been annotated to identify the review articles and therapeutic guidelines in this area. For the original research articles provided in the reference list, the levels of evidence and strength of recommendation have been identified based on those adopted by the Stroke Council of the American Heart Association [17-20].


Stroke data

There are more than 700,000 new or recurrent strokes each year in the United States, resulting in more than

160,000 deaths [1,21,22]. The mortality rate within 1 month of stroke onset was found in 1 review of worldwide population-based studies to vary between 17% (Japan) and 33% (Italy) [21]. In the United States, there are more than

4.8 million stroke survivors, and after stroke onset, 20% of these needed institutional care for more than 3 months, with 15% to 30% of survivors remaining permanently disabled [1,22].

Race, sex, and age, as well as numerous risk factors including chronic hypertension, diabetes mellitus, and cigarette smoking, contribute to the risk of ischemic stroke. African Americans are at higher risk than Hispanic Americans; however, both groups are at higher risk than Americans of central and northern European descent [1,22].

Hypertension data

High BP contributes substantially to the risk of devel- oping ischemic or hemorrhagic stroke [1,4]. Because more than 60 million Americans have chronic hypertension (essential or idiopathic), the risk of stroke is significant [4,23,24].

Health statistics show that over 25% of noninstitution- alized Americans (z20 years of age) were diagnosed with hypertension between the years 1999 and 2002 [25]. It is estimated that more than 40 million adults in the United States have uncontrolled hypertension [26]. In addition, roughly 1 of 100 patients with essential hypertension will experience a hypertensive crisis during their lifetime [27,28]. It has also been estimated that by the year 2025, one third of the global population will be having hyperten- sion [29].

Classification of hypertension and stroke

Stroke is a Vascular injury to the brain or spinal cord formally known as a cerebrovascular accident. Stroke is characterized by irreversible damage to nerve cells in the central nervous system (CNS) [30,31]. Interruption of critical blood flow to part of the brain causes ischemia (Table 1) [30-32]. Bleeding into or around the brain is referred to as ICH or SAH and is the most common presentation of a ruptured Intracranial aneurysm [33,34]. Hemorrhagic strokes may produce Ischemic injury by direct

Table 1 Distribution of ischemic stroke subtypes



Percent (N = 1805)

















Adapted with permission from Foulkes et al [32].

Table 2 Classification of hypertension in adults aged z18 years [4]

BP classification

SBP (mm Hg)

DBP (mm Hg)







Stage 1 HTN



Stage 2 HTN



HTN indicates hypertension.

pressure of a blood clot on vessels feeding the neural tissues; by interrupting the supply of blood to tissues upstream from the bleeding site; or by inducing vasospasm in blood vessels exposed to the irritative effects of subarachnoid blood [30].

Cerebral ischemia results from inadequate blood flow, which prevents delivery of metabolic substrates and oxygen essential for survival of CNS tissue [30]. In addition, cerebral metabolic demands vary from region to region and from time to time; therefore, vulnerability and extent of damage to a specific part of the brain or even the spinal cord (eg, in the watershed area of the thoracic cord) vary. Once a central core of damage has occurred, toxic materials released by necrotic cells (ie, calcium ions and reactive free oxygen radicals) permeate the surrounding tissues, increasing cell vulnerability, although ischemia in outlying regions (penumbra) may not be as severe as in the original area of infarction [30,35].

Ischemic strokes may occur from atherosclerotic plaque occlusion of a major blood vessel or with clot or thrombus formation set free in the bloodstream (embolic stroke). Endothelial changes that develop in arterioles from chronic hypertension may lead to complete obstruc- tion of blood flow, resulting in relatively small or lacunar injuries in the neural tissues [36]. These distinctions may be self-evident, but they are helpful in determining a BP Management strategy.

Chronic hypertension is characterized by the severity of the elevation in systolic BP (SBP) and Diastolic BP (DBP) (Table 2) [4,37]. Blood pressures of less than 120 mm Hg (systolic) and less than 80 mm Hg (diastolic) are normal, unless the individual is symptomatic (eg, syncope or easy fatigability) [4]. Systolic levels of 120 to 139 mm Hg and diastolic levels of 80 to 89 mm Hg are considered prehypertensive [4]. Stage 1 hypertension is characterized by systolic elevation between 140 and 159 mm Hg or diastolic elevation between 90 and 99 mm Hg [4]. Stage 2 hypertension is elevated with SBP 160 mm Hg or higher or DBP 100 mm Hg or higher [4]. Hypertensive crises and emergencies are defined by acute elevation of BP and clinical end-organ dysfunction (involving CNS, heart, or kidneys) [4,28]. Hypertensive urgencies show markedly elevated BP but may be without severe symptoms or progressive end-organ damage. [38] The differentiation between hypertensive emergencies and urgencies can be ambiguous [38].

Etiology of hypertensive crises

Hypertensive emergencies and urgencies complicate more than 27% of all acute medical problems presenting to emergency departments (EDs) [39]. The common denominator of hypertensive crises is peripheral vasocon- striction that may be associated with vasculitis, withdrawal of vasodilating Antihypertensive medications, hormonal disturbances occurring with pregnancy or head trauma, or adverse reactions to medication (Table 3) [27,40].

The most common cause of hypertensive crisis is noncompliance with prescribed antihypertensive medica- tions [27,41]. In other cases, patients are compliant, but outpatient treatment of elevated SBP is inadequate. Poor therapeutic response to effective BP medications targeting chronic elevations of SBP and medication noncompliance are independent risk factors for hypertensive crises [41,42].

Hypertensive crises are also seen in renal disease (ie, renovascular hypertension) [27], and some medications may induce hypertension (eg, amphetamines, tricyclic antide- pressants [nortriptyline, amitriptyline], corticosteroids, and sympathomimetics [cocaine, pseudoephedrine]) [27,43-45]. Hypertension may also occur with head injuries. In this setting, an expanding intracranial mass may produce a paradoxical slowing of the pulse in association with a progressive elevation of SBP (Cushing effect) [46]. Post- traumatic hypertension also occurs independently of intra- cranial bleeding or hematoma formation. In addition, vasculitides (ie, lupus erythematosus) may produce hyper- tensive crises as an element of disease [27].

An international stroke study showed that with persistent elevations of BP after a stroke, there is an increased risk of recurrent stroke within 14 days of an initial ictus, as well as an increased risk of severe neurologic impairment or an increase in mortality [47].

Other forms of hypertension seen in the ED

      1. Postoperative hypertension

Between 3% and 75% of patients undergoing surgical procedures will exhibit significant elevations of BP (eg, DBP z100 mm Hg and SBP z190 mm Hg on 2 consecutive

Table 3 Causes of hypertensive crises

  • Abrupt increase in BP in patients with chronic hypertension
  • Renovascular hypertension/renal disease
  • Withdrawal from Antihypertensive drugs
  • Drug-induced hypertension (eg, amphetamines, diet pills, triCyclic antidepressants, street drugs [eg, cocaine]), drug withdrawal, pheochromocytoma
  • Preeclampsia/eclampsia
  • Head injury of any kind
  • Vasculitis
  • Scleroderma and other collagen-vascular diseases

Adapted with permission from Calhoun and Oparil [27].

hypertensive encephalopathy“>postoperative readings 2-3 hours apart) [28,48,49]. Postop- erative hypertension is often adequately managed with intravenous antihypertensives [48,50,51], and many differ- ent agents have been used for this purpose, including calcium channel blockers (eg, nicardipine) [50], nitrates, and sodium nitroprusside [48,50], However, considering the potential for severe toxicity, nitroprusside should be used only when other intravenous antihypertensive agents are not available [28]. The specific agent is chosen based upon the type of surgery performed and the patient’s medical and medication histories.

      1. Gestational hypertension

Pregnancy is associated with hypertensive disorders ranging from mild to life-threatening, and pharmacological treatment is complicated by concern for fetal and maternal safety [28,52,53]. The Maternal mortality rate (z20 weeks’ gestation) from complications of preeclampsia and eclamp- sia have been shown in one 14-year study (N = 790) to be 19.6% [54]. Before delivery, DBP should be maintained at greater than 90 mm Hg to allow for adequate uteroplacental perfusion [28]. In patients with preeclampsia, intravenous drug therapy is reserved for those with a persistently elevated SBP of greater than 180 mm Hg or DBP of greater than 110 mm Hg [28].

Hypertensive encephalopathy

Because focal neurologic signs may occur with hyper- tensive encephalopathy, the distinction between AIS and the latter syndrome may be difficult. Hypertensive encephalop- athy is relatively rare, subacutely progressive, and associ- ated with generalized signs and symptoms of brain dysfunction (eg, headache, lethargy, or seizures) [10]. Hypertensive encephalopathy will routinely be associated with papilledema and uremia, whereas AIS is likely to be associated with changes in fundi [55,56].

Signs and symptoms of hypertensive emergencies

Diverse clinical signs and symptoms prompt patients with hypertensive crises to seek or be brought in for medical attention [4]. The cardiovascular characteristics of hyper- tensive crises include angina or acute myocardial infarction. In addition, cardiac decompensation may lead to shortness of breath, Postural hypotension, or pulmonary edema [28]. The complaint of severe, catastrophic midline pain of the chest, back, or abdominal region is likely associated with aortic dissection [57]. Headache, Altered consciousness, advanced retinopathy, and papilledema are often seen in patients with hypertensive encephalopathy; however, the patient may display only cognitive or other nonfocal neurological signs [28]. If serum creatinine is acutely elevated and urinary output is diminished, the patient may be developing acute renal failure.

Traditionally, accelerated hypertension has been defined as increased BP accompanied by acute encephalopathy or nephropathy [6,28,58]. The clinical characteristics associat- ed with malignant hypertension include DBP greater than

140 mm Hg accompanied by various combinations of funduscopic findings (eg, hemorrhages, exudates, papille- dema); neurologic findings (eg, headache, confusion, somnolence, stupor, focal deficits, seizures, coma); renal findings (eg, oliguria, azotemia); and gastrointestinal find- ings (eg, nausea, vomiting) [38].

Pathogenesis and pathophysiology

Humoral vascular constrictors are most likely the basis for the abrupt and self-propagating increase in systemic vascular resistance that leads to hypertensive crises [28,59,60]. Severe elevations of BP may result in endothe- lial injury and fibrinoid necrosis of the arterioles [28,59,60]. In most cases, vascular injury leads to platelet and fibrin endothelial deposition, breakdown of normal autoregula- tion, and, with ischemia, the release of toxic vasoactive substances [28,59,60]. Many individuals presenting to the hospital with chronic hypertension and an elevated BP are thought to exhibit a rightward shift of the pressure/flow autoregulation curve with no acute end-organ damage

Table 4 Renin levels in hypertensive emergencies High Renin States

Malignant hypertension

Medium to high renin states Unilateral renovascular hypertension Renal vasculitis

Renal trauma

Renin secreting tumors Pheochromocytoma Cocaine abuse

Clonidine or methyl DOPA withdrawal Probable medium to high renin states Hypertensive encephalopathy Hypertension with cerebral hemorrhage Hypertension with (impending) stroke Hypertension with pulmonary edema

Hypertension with acute myocardial infarction or unstable angina

Dissecting aortic aneurysm Perioperative hypertension

Low renin states: sodium-volume overload Acute tubular necrosis

Acute glomerulonephritis Urinary tract obstruction Primary aldosteronism

Low renin essential hypertension Preeclampsia/eclampsia

DOPA indicates 3,4-dihydroxyphenylalanine. Reproduced from Blumenfeld and Laragh [64].

[28,61,62]. After a study of hypercapnic dogs, a study in baboons confirmed that autoregulation remained intact until BP reached approximately 40% above baseline values [63]. The Renin-angiotensin-aldosterone system plays a key role in the regulation of BP homeostasis [39,64]. Clinical syndromes associated with hypertensive crises are some- times classified according to the serum renin level (Table 4) [64]. Excessive renin production by the kidney stimulates production of Angiotensin II, a vasoconstrictor, which raises peripheral vascular resistance, thus increasing systemic BP [64]. Hypertensive crises appear to develop when the renin- angiotensin-aldosterone system spins out of control and progressively drives systemic BP higher [39,64].

The mechanism of hypertensive crises is thought by some to be associated with oxidative stress, endothelial dysfunction, and platelet aggregation. Reactive oxygen species can lead to vasoconstriction, presumably by decreasing intravascular nitric oxide production, which

disturbs endothelial function. With decreased nitric oxide production, small-vessel dilatation may be impeded [65-67].

Hypertension in AIS

As previously mentioned, the acute elevation of BP seen with AIS may be a reflex adjustment to disturbed or impaired blood flow in the brain (Fig. 1) [6,10,68,69]. It is of constant concern that the mechanisms producing ische- mic damage may result in expansion of the central core of ischemia if arterial BP is reduced precipitously [10,70]. Fine adjustments are constantly being made by an intrinsic system that regulates regional brain perfusion. This autor- egulatory system is disrupted to varying extents after an AIS [10], and the most severe disturbances are likely in and about the ischemic core. One consequence of this focal disruption of autoregulation is that tissues needing addi- tional blood flow may end up with reduced perfusion.

Fig. 1 A, Changes in vascular caliber that can be associated with Cerebral autoregulation failure. Altered intracranial autoregulation due to an intracranial lesion and/or edema results from vasodilation in an effort to increase CBF. However, beyond the lower limit of autoregulation, vessels passively collapse, and ischemia results. Beyond the upper limit of autoregulation or the bbreakthrough zone,Q increased intravascular volume and pressure results in vasogenic edema. Adapted with permission from Rose and Mayer [69]. B, Cerebral autoregulation in a healthy subject, a patient with chronic hypertension, and a patient with acute cerebral ischemia. Cerebrovascular autoregulation is a mechanism that maintains constant CBF (50 mL/100 g per minute) in spite of large changes in cerebral perfusion pressure (50-150 mm Hg). Cerebral perfusion pressure is a calculation of mean arterial pressure minus ICP or central venous pressure, whichever is greater. In healthy individuals, ICP and central venous pressure are minimal (ie, 5 mm Hg), and cerebral perfusion pressure is approximately equivalent to mean arterial pressure. Beyond the upper and lower limits of autoregulation, CBF passively and linearly follows changes in cerebral perfusion pressure. In patients with chronic hypertension, the autoregulation plateau and the upper and lower curves are shifted to the right. In patients with acute neurologic disorders (eg, traumatic brain injury, ICH, and SAH with vasospasm), CBF becomes pressure passive in areas of cerebral ischemic injury. Adapted with permission from Powers [10].

One recent study of 40 subjects with minor Middle cerebral artery stroke assessed dynamic cerebral autoregu- lation with arterial BP and Doppler-measured CBF [71]. The findings, which bdid not indicate a relevant impairment of dynamic autoregulation early after minor ischemic stroke,Q draw attention to the relationship between AIS and the disruption of autoregulation as seen in the subacute setting [71].

Diagnostic and laboratory evaluations in hypertensive crises

The key to the successful management of the patient with severely elevated BP are rapid identification of treatable causes and early introduction of intravenous antihypertensive agents where appropriate. It is important to differentiate hypertensive crises from hypertensive urgen- cies [6,28,72-74]. The targeted medical history must focus on possible causes of acute elevation of the BP. A thorough physical examination must be supplemented by appropriate laboratory evaluations, which include a complete blood count, electrolyte studies, blood urea nitrogen, and measure- ment of Creatinine levels [6,28]. women of childbearing age should have a pregnancy test. A urinalysis is essential, and a peripheral blood smear is also necessary to rule out micro- angiopathic hemolytic anemia as the basis for a hypertensive crisis [6,28].

The clinician should also inquire about prior hypertensive crises and antihypertensive medication use [6,28,75], and the fundi should be examined in all cases to detect papilledema as soon as possible. The patient should be asked specifically about the use of monoamine oxidase inhibitors, as well as the use of any recreational drugs such as cocaine or amphet- amines [6,28]. Blood pressure should be checked in each limb; obese patients require use of the appropriately sized BP cuffs. Every patient should have a chest x-ray and electrocardiogram (especially in patients with shortness of breath, chest pain, or neurological signs) [57]. For patients with neurologic signs, computed tomography (CT) or magnetic resonance imaging (MRI) scan of the head is also necessary. Much of this evaluation may be performed at the same time that Antihypertensive therapy is started [6,28,73].

Imaging modalities

computed tomography scans and MRI studies have become routine and essential in the assessment of AIS. Because of its general availability, CT is the mainstay for diagnosis of most emergent neurological situations, and its main purpose is excluding hemorrhagic etiology [76,77]. Within 6 hours of the initial ictus, noncontrast, enhanced CT provides important clues to the ischemic nature of the deficit, which may include slight hypodensity, minimal mass effect, and loss of distinction between gray and white matter densities [76,77].

Magnetic resonance imaging provides high-resolution contrast, anatomic definition, multiplanar capabilities, and is especially suited to the evaluation of cerebral ischemia due to tissue swelling, which causes enlargement or distortion of brain structures [76,78,79]. Generally, routine spin-echo (SE) MRI is more sensitive than CT for imaging patho- physiologic changes occurring during a cerebral artery ischemic event. Although subtle signal intensity changes are seen within 6 hours post-ictus on T1-weighted SE images, conspicuous changes may not be seen for 1 to 3 days [76]. Signal changes on T2-weighted images are readily seen within 8 to 24 hours post-ictus; however, fluid- attenuated inversion recovery pulse sequences have even more sensitivity for detecting early cortical Ischemic changes compared with routine SE imaging [76].

diffusion-weighted imaging (DWI) is the most sensitive imaging technique for detecting acute ischemic changes [76,80-82]. This imaging technique identifies water diffu- sion as a 3-dimensional process. The apparent diffusion coefficient is calculated by using multiple gradient duration and amplitude values for data acquisition, resulting in an apparent diffusion coefficient map. After AIS, metabolic and cellular membrane breakdown causes the trapping of intracellular water in infarcted tissues. These areas of cytotoxic edema are visualized on DWI as areas of increased signal intensity [76,83].

Another MRI technique, perfusion-weighted imaging, uses contrast media (gadolinium) to determine mean transit times, time-to-peak arrival of contrast, and regional blood flow maps to identify cerebral microcirculation [76,84]. During dynamic signal acquisition, normal vascular perfu- sion reveals a transient signal drop as gadolinium passes through. Ischemic areas show delayed signal changes because contrast is not perfused in the normal acquisition phase. As a result, areas of contrast hypoperfusion are shown as bright signal intensity on the time-to-peak perfusion map [76].

Combining data from DWI and perfusion-weighted imaging scans provides an estimate of the cerebral ischemic penumbra. Areas of decreased or reduced contrast perfusion indicate ischemic tissue–information that may be helpful when considering therapeutic choices [76,85,86].

Differential diagnosis

Many thrombotic strokes are preceded by transient ischemic attacks, which are indicative of vascular disease. Transient ischemic attacks are occasionally confused with Seizure activity, syncope, panic attacks, neurologic mi- graine, or attacks of labyrinthine vertigo. Evidence of bleeding on head CT scan and presence of blood in the cerebrospinal fluid characterize a hemorrhagic lesion [36]. Traumatic head injuries are likely candidates for accelerat- ed-malignant hypertension and are an entity that should be ruled out. During patient examination, the bCushing responseQ (decreased pulse and increased BP) should be

emergent management of hypertension”>searched for. The patient’s medical history of chronic hypertension and/or use of antihypertensive medications compel a clinician to carefully monitor BP.

Table 5 Recommended antihypertensive agents for hyper-

tensive crises


acute pulmonary edema

acute myocardial ischemia

Hypertensive encephalopathy

Acute aortic dissection


Acute renal failure/ microangiopathic anemia

Sympathetic crisis/cocaine overdose

PreferrED treatments

Fenoldopam or a combination of nitroglycerin (up to

60 lg/min) and a Loop diuretic Nicardipine is a reasonable alternative

Labetalol or esmolol in combination with nitroglycerin (up to 60 lg/min)

Labetalol, nicardipine, or fenoldopam

Labetalol or combination of nicardipine or fenoldopam and esmolol or combination

of nitroprusside with either esmolol or intravenous metoprolol

Labetalol or nicardipine; hydralazine may be used in a non-ICU setting

Fenoldopam or nicardipine

Verapamil, diltiazem, or

nicardipine in combination with a benzodiazepine

ICU indicates intensive care unit.

Reproduced with permission from Varon and Marik [6].

Emergent management of hypertension

In the ED, Intravenous nicardipine or labetalol may be first-line measures. Nicardipine is known for stability in regulating BP within a narrow range [87]. Labetalol easily controls BP reduction with use of mini boluses; however, it is contraindicated in cocaine use, asthma, and congestive heart failure (CHF) [88]. Nitroprusside has been used in the past, but it has the disadvantage of increasing intracranial pressure [51,69,89]. Other agents used successfully in hypertensive crises in the past include clonidine (oral formulation); diazoxide (rapid-acting as intravenous formu- lation); enalaprilat (angiotensin-converting enzyme inhibi- tor, intravenous formulation); esmolol (b-adrenergic blocking agent); fenoldopam (dopamine-1 agonist); trime- thaphan camsylate (nondepolarizing ganglionic blocking agent with many side effects); and phentolamine (a– adrenergic blocking agent that is helpful in catecholamine- induced hypertensive crises [eg, pheochromocytoma]) [28].

The patient in hypertensive crisis

The immediate goal of intravenous antihypertensive therapy is to reduce the DBP by 10% to 15% or to roughly 110 mm Hg. Which agent is used to accomplish this will largely be determined by clinical status of the hypertensive crisis (Table 5) [15,28]. If the patient is believed to have an aortic dissection, the reduction in DBP is accomplished over the course of 5 to 10 minutes [28]. In patients with a Hypertensive emergency but no evidence of aortic dissec- tion, the rate of reduction of the elevated BP can be more protracted. Dropping the DBP to roughly 110 mm Hg over the course of 30 to 60 minutes is desirable; however, precautions must be taken not to drop the BP any further in this short period because cerebral ischemic injury may occur. If the patient has a hypertensive urgency rather than a hypertensive emergency, BP is lowered over a more protracted period, which is often accomplished with Oral medications (eg, clonidine) over 24 to 48 hours [6,28,69].

If a rapid adjustment in BP is warranted, Intravenous medications such as labetalol, nicardipine, or sodium nitroprusside are used. Labetalol is a combined blocker of a– and b-adrenergic receptors with a hypotensive effect that begins within 2 to 5 minutes after intravenous dosing and reaches a peak in 5 to 15 minutes. The hypotensive effect persists with labetalol for about 2 to 4 hours. Maintenance of cardiac output and reduction of peripheral vascular resistance (without reducing peripheral, cerebral, renal, or Coronary blood flow) are seen with labetalol [4,28,89].

Intravenous nicardipine has been shown to be as clinically effective as sodium nitroprusside in lowering BP in hypertensive crises, generally requires fewer dose adjust-

ments, and produces fewer side effects [90]. Sodium nitroprusside is the most widely used parenteral agent for treating hypertensive crisis; however, cyanide toxicity, in some cases leading to end-organ damage, and increased ICP are associated side effects [89]. In addition, sodium nitro- prusside infusion may result in increased renal blood flow, which is likely to cause rebound hypertension. Nicardipine, however, has a predictable onset of effect in 5 to 10 minutes with intravenous administration and fewer dosage adjust- ments [6,89].

Of the pharmacological agents currently under investi- gation in phase III trials, clevidipine shows the most promising results. Clevidipine is an ultrashort-acting dihy- dropiridine calcium channel blocker whose use is not yet approved in the United States [91].

When administering any antihypertensive intravenous agent, the recommended dosage must be strictly adhered to, and the patient must be closely monitored for adverse reactions (eg, abrupt changes in the heart rate or BP level or evidence of rash, fever, or seizure activity) (Table 6) [28]. Adverse reactions must be considered in the decision to continue or advance medication dosing [28,89].

The patient with AIS

After AIS, cerebral autoregulation is impaired, and perfusion of the ischemic penumbra becomes directly

Table 7 Approach to elevated BP in AIS Clinical situation Recommendation

SBP b220 mm Hg; Observe BP unless there is other DBP b120 mm Hg end-organ involvement, such as

aortic dissection,

renal failure, or acute myocardial infarction

SBP N220 mm Hg or Labetalol 10-20 mg, IV, over DBP 121-140 mm Hg 1-2 min, repeated or doubled every

10 min to a maximum

dose of 300 mg or nicardipine 5 mg/h, IV, infusion as initial dose, titrated by

increasing by 2.5 mg/h every

5 min to maximum infusion rate thrombolytic agents“>of 15 mg/h to achieve

a 10%-15% reduction

DBP N140 mm Hg Sodium nitroprusside

0.5 lg kg–1 min–1, IV, with continuous BP monitoring to achieve a 10%-15% reduction

Adapted with permission from Adams et al [17].

pressure dependent [6,28,92,93]. The sympathetic nervous system may be involved as part of a global metabolic response (known as sympathetic crisis) to cerebral infarc- tion, cerebral hemorrhage, or associated intracranial edema [6,28]. Defective autoregulation may persist for days to weeks, during which there is overproduction of vasocon- strictive and vasodilatory substances [92-94]. With hyper- tensive encephalopathy, labetalol, nicardipine, or fenoldopam are the antihypertensive agents of choice [6]. If the clinical status is suggestive of a sympathetic crisis, verapamil may be just as effective in safely lowering BP as nicardipine or fenoldopam [6].

Table 6 Dosages of intravenous antihypertensive medica- tions for hypertensive emergencies

Drugs Dosage

Enalapril 1.25 mg, IV, over 5 min every 6 h, titrated by increments of 1.25 mg at 12- to 24-h intervals to a maximum of 5 mg every 6 h

Esmolol Loading dose of 0.5 1 mg/kg over 1 min, followed by infusion at 50 lg kg–1 min–1 and increasing to a maximum of 300 lg kg–1 min–1, as necessary

Fenoldopam Initial dose of 0.1 lg kg–1 min–1 titrated by increments of 0.05-0.1 lg kg–1 min–1 to a maximum of 1.6 lg kg–1 min–1

Labetalol 20 mg, IV, bolus followed by boluses of

20-80 mg at 10-minute intervals or infusion starting at 1-2 mg/min uptitrated until hypotensive effect is achieved

Nicardipine 5 mg/h, IV, infusion, titrated if necessary by increasing by 2.5 mg/h every 5 min to a maximum rate of 30 mg/h

Nitroprusside 0.5 lg kg–1 min–1, IV, titrated if necessary not to exceed 2 lg kg–1 min–1

Phentolamine 1 to 5 mg boluses to a maximum dose of 15 mg

Reproduced with permission from Varon and Marik [28].

The Stroke Council for the American Stroke Associ- ation recommends considering Antihypertensive treatment in individuals with ischemic strokes and DBPs of greater than 120 mm Hg or SBPs of greater than 220 mm Hg (Tables 7 and 8) [15,17,95]. There is general agreement that DBP should be reduced by 15% to 20% over the first

24 hours after a stroke if the DBP is 120 mm Hg or higher [6,15,28], and this can usually be achieved with labetalol or nicardipine [15]. If the DBP is greater than

140 mm Hg, a sodium nitroprusside infusion may be necessary [15]. If the patient is eligible for thrombolytic therapy, the BP must be maintained at desired levels (SBP V185 and DBP V110) [17].

Pharmaceutical agents that dramatically improve the outcome in stroke victims with hypertension are lacking, but there is preliminary evidence that candesartan cilexetil reduces cardiovascular morbidity and mortality in the stroke patient when given over the course of 7 days post-

ictus [96]. In the absence of unambiguous evidence supporting Alternative medications, the consensus guide- lines recommend the use of intravenous nicardipine for hypertensive episodes (DBP, 121-140 mm Hg) associated with AIS [18], as well as labetalol or nitroprusside in cases where the DBP is greater than 140 mm Hg [15]. However, patient management is substantially more complex if, after AIS, the patient received a thrombolytic agent such as recombinant tissue-type plasminogen acti- vator (rtPA) [15].

Candidates for thrombolytic agents

To be a candidate for thrombolytic agents (ie, rtPA), the patient with an ischemic stroke must have a BP that is

Table 8 Levels of evidence

Level of evidence

Level I

Level II Level III Level IV

Level V

Data from randomized trials with low

false-positive and low false-negative errors Data from randomized trials with high false-positive or high false-negative errors Data from nonrandomized concurrent cohort studies

Data from nonrandomized cohort studies using historical controls

Data from anecdotal case series

Strength of recommendation

Grade A

Grade B Grade C

Supported by level I evidence

Supported by level II evidence Supported by level III, IV, or V evidence

Reproduced with permission (pending) from Adams et al [17].

185/110 mm Hg or less or respond to antihypertensive agents sufficiently to lower the BP to 185/110 mm Hg or less. Blood pressure adjustment to below 185/110 mm Hg may be achieved with labetalol 10 to 20 mg, IV, over 1 to

2 minutes or nitropaste (1-2 in). If 2 administrations of labetalol do not lower the BP to the target range, rtPA will usually not be administered [17].

After the thrombolytic agent has been administered, BP should be checked every 15 minutes for 2 hours, every 30 minutes for the subsequent 6 hours, and every hour for the after 16 hours [17,95]. If the DBP rises above 140 mm Hg, sodium nitroprusside at 0.5 lg kg–1 min–1, IV, bolus followed by a titrated infusion may suffice to hold the BP in the desired range. With an SBP of greater than 230 mm Hg or a DBP of 121 to 140 mm Hg, nicardipine 5 mg/h, IV, initially, increasing to a maximum of 15 mg/h, if needed to drop the BP, is an option. The dose is increased every 5 minutes by an amount sufficient to increase the hourly dose by 2.5 mg if no response to the nicardipine is evident [17,95]. If this regimen fails, labetalol 10 mg, IV, may be infused over 1 to 2 minutes. The labetalol dose may be repeated or doubled every 10 minutes to a maximum Cumulative dose of 300 mg. Alternatively, labetalol drip at 2 to 8 mg/min may be appropriate with systolic levels of 180 to 230 mm Hg or diastolic levels of 105 to 120 mm Hg after rtPA administration. If BP remains elevated despite nicardipine and labetalol administration, a nitroprusside drip may be warranted [17].


The debated issues of BP management remain an integral part of Stroke prevention and poststroke care. It is well known that inappropriately lowering BP in the setting of an AIS may increase the neurologic damage associated with that stroke. More aggressive BP management is usually necessary with hemorrhagic strokes, especially if the source is an aneurysmal bleed. There is a consensus, however, that Severe hypertension associated with ischemic stroke does warrant treatment [17,18]. The drugs of choice for acute hypertension associated with stroke are nicardipine and labetalol [95].

Management of a hypertensive crisis in the context of stroke or otherwise must be rapid, and observation in an intensive care setting is generally necessary. After an acute stroke, untreated hypertension appears to increase the risk of recurrent stroke and increases the probability of ICH or extension of ICH already associated with stroke within the first 24 hours post-ictus. The intrave- nous agents most likely to prove useful in the management of hypertensive emergencies associated with CNS disease include sodium nitroprusside (with a potential for increasing ICP or causing cerebral steal), labetalol, and nicardipine.


*+[1] Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council. Stroke 2006;37:1583 – 633.

*+[2] Goldstein LB, Adams R, Becker K, et al. Primary prevention of ischemic stroke: a statement for healthcare professionals from the stroke council of the American Heart Association. Stroke 2001;32:280 – 99.

(IV, C)[3] MacMahon S, Peto R, Cutler J, et al. Epidemiology blood pressure, stroke, and coronary heart disease. Lancet 1990;335: 765 – 74.

+[4] Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure: the JNC 7 report. JAMA 2003;289:2560 – 72.

[5] Brott T, Bogousslavsky J. Treatment of acute ischemic stroke. N Engl J Med 2000;343:710 – 22.

*:[6] Varon J, Marik PE. Clinical review: the management of hypertensive crises. Crit Care 2003;7:374 – 84.

(IV, C)[7] Wallace JD, Levy LL. Blood pressure after stroke. JAMA 1981;246:2177 – 80.

(III, C)[8] Britton M, Carlsson A, De Faire U. Blood pressure course in patients with acute stroke and matched controls. Stroke 1986;17:861 – 4.

+[9] Broderick JP, Adams HP, Barsan W, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: a statement for healthcare professionals from a Special Writing Group of the Stroke Council. American Heart Association. Stroke 1999;30:905 – 15.

[10] Powers WJ. Acute hypertension after stroke: the scientific basis for Treatment decisions. Neurology 1993;43:461 – 7.

(IV, C)[11] Ohwaki K, Yano E, Hagashima H, et al. Blood pressure management in acute intracerebral hemorrhage: relationship between Elevated blood pressure and hematoma enlargement. Stroke 2004;35:1364 – 7.

[12] Chalmers J. Trials on blood pressure-lowering and secondary stroke prevention. Am J Cardiol 2003;91(10A):3G- 8G.

*:[13] Suarez JI, Tarr RW, Selman WR. Anuerysmal subarachnoid hemorrhage. N Engl J Med 2006;354:387 – 96.

[14] Talbert RL. The challenge of blood pressure management in neurologic emergencies. Pharmacotherapy 2006;26(8 pt 2): 123S- 30S.

[15] Goldstein LB. Blood pressure management in patients with acute ischemic stroke. Hypertension 2004;43:137 – 41.

(IV, C)[16] Oliveira-Filho J, Silva SCS, Trabuco CC, et al. Detrimental effect of Blood pressure reduction in the first 24 hours of acute stroke onset. Neurology 2003;61:1047 – 51.

*+[17] Adams HP, Adams RJ, Brott T, et al. Guidelines for the early management of patients with ischemic stroke. A scientific statement from the Stroke Council of the American Stroke Association. Stroke 2003;34:1056 – 83.

*:[18] Adams H, Adams R, Del Zoppo G, et al. Guidelines for the early management of patients with ischemic stroke, 2005 guidelines update. A scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke 2005;36:916 – 21.

*Highly recommended.

+Therapeutic guidelines.

:Review article.

I-V = Levels of Evidence (see Table 8) [17].

A-C = Strength of Recommendation (see Table 8) [17].

[19] Cook DJ, Guyatt GH, Laupacis A, et al. Clinical recom- mendations using levels of evidence from antithrombotic agents. Chest 1995;108:227 – 30.

[20] Oxford-Centre for Evidence-Based Medicine. Levels of evidence and grades of recommendations. Available at: [Accessed 30

January 2007].

+[21] Feigin VL, Lawes CMM, Bennett DA, et al. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neural 2003;2:43 – 53.

+[22] Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics–2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2006;113:85 – 151.

  1. Brown DJ, Metiko EB. Prevalence of hypertension in a sample of black American adults using JNC 7 classifications. J Natl Black Nurses Assoc 2005;16:1 – 5.
  2. Cooper RS, Liao Y, Rotimi C. Is hypertension more severe among U.S. blacks, or is severe hypertension more common? Ann Epidemiol 1996;6:173 – 80.
  3. National Center for Health Statistics C. Health, United States, 2005 with chartbook on the trends of the health of Americans. Centers for Disease Control Web site. Available at: http:// [Accessed 5 Sep- tember 2006].
  4. Wang TJ, Vasan RS. Epidemiology of uncontrolled hyperten- sion in the United States. Circulation 2005;112:1651 – 62.
  5. Calhoun DA, Oparil S. Treatment of hypertensive crisis. N Engl J Med 1990;323:1177 – 83.

*[28] Varon J, Marik PE. The diagnosis and management of hypertensive crises. Chest 2000;118:214 – 27.

  1. Kearney PM, Whelton M, Reynolds K, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365: 217 – 23.
  2. Sharp FR, Swanson RA, Honkaniemi J, et al. Neurochemistry and molecular biology. In: Barnett HJM, Mohr JP, Stein BM, et al editors. Stroke pathophysiology, diagnosis, and manage- ment. 3rd ed. New York, NY7 Churchill Livingstone; 1998.

p. 51 – 83.

  1. Siesjo BK, Katsura K, Zhao Q, et al. Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. J Neurotrauma 1995;12:943 – 56.

(V, C)[32] Foulkes MA, Wolf PA, Price TR, et al. The Stroke Data Bank: design, methods, and baseline characteristics. Stroke 1988;1: 547 – 54.

+(IV, C)[33] Brisman JL, Song JK, Newell DW. cerebral aneurysms.

N Engl J Med 2006;355:928 – 39.

  1. Greenberg MS. SAH and aneurysms. In: Greenberg MS, editor. Handbook of neurosurgery. 5th ed. New York (NY)7 Thieme Medical; 2000. p. 754 – 803.
  2. Mergenthaler P, Dirnagl U, Meisel A. Pathophysiology of stroke: lessons from animal models. Metab Brain Dis 2004;19:151 – 67.
  3. Ropper AH, Brown RH. Cerebrovascular disease. In: Victor M, Ropper AH, editors. Adams and Victor’s principles of neurology, 8th ed. New York (NY)7 The McGraw-Hill Companies, Inc; 2005. p. 660 – 746.
  4. Whitworth JA, World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hy- pertension (ISH) statement on management of hyperten- sion. J Hypertens 2003;21:1983 – 92.
  5. Kaplan NM. Hypertensive crises. In: Kaplan NM, editor. Kaplan’s clinical hypertension, 9th ed. Philadelphia (PA)7 Lippincott Williams & Wilkins; 2006. p. 311 – 24.
  6. Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies. J Am Soc Nephrol 1998;9:133 – 42.
  7. Oparil S, Aronson S, Deeb GM, et al. Fenoldopam: a new parenteral antihypertensive-consensus roundtable on the management of perioperative hypertension and hypertensive crises. Am J Hypertens 1999;12:653 – 64.

(III, C)[41] Tisdale JE, Huang MB, Borzak S. Risk factors for hypertensive crisis: importance of out-patient blood pressure control. Fam Pract 2004;21:420 – 4.

[42] Shea S, Misra D, Ehrlich MH, et al. Predisposing factors for severe, uncontrolled hypertension in an inner-city minority population. N Engl J Med 1992;327:776 – 81.

(IV, C)[43] Savvidou MD, Hingorani AD, Tsikas D, et al. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 2003;361:1511 – 7.

(III, C)[44] Chodera A, Konkiewicz B, Nowadowska E, et al. The effect of tricyclic antidepressants (TA) on the circulatory system in primary arterial hypertension. Int J Clin Pharmacol Biopharm 1979;17:299 – 302.

[45] Schimmer BP, Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 10th ed. New York (NY)7 McGraw-Hill; 2001. p. 1649 – 77.

[46] Shiozaki T. Hypertension and head injury. Curr Hypertens Rep 2005;7:450 – 3.

*(I, A)[47] Leonardi-Bee J, Bath PMW, Phillips SJ, et al. Blood pressure and clinical stroke outcomes in the International Stroke Trial. Stroke 2002;33:1315 – 20.

*(I, A)[48] Halpern NA, Coldbery M, Neely C, et al. Postoperative hypertension: a multicenter, prospective, randomized com- parison between intravenous nicardipine and sodium nitro- prusside. Crit Care Med 1992;20:1637 – 43.

(IV, C)[49] Gal TJ, Cooperman LH. Hypertension in the immediate postoperative period. Br J Anaesth 1975;47:70 – 4.

  1. Levy JH. Treatment of perioperative hypertension. Anesthe- siol Clin North Am 1999;17:567 – 79.
  2. Curran MP, Robinson DM, Keating GM. Intravenous nicardipine its use in the short-term treatment of hypertension and various other indications. Drugs 2006;66:1755 – 82.
  3. Duley L, Meher S, Abalos E. Management of pre-eclampsia. BMJ 2006;332:463 – 8.

(III, C)[53] Carbonne B, Jannet D, Touboul C, et al. Nicardipine treatment of hypertension in pregnancy. Obstet Gynecol 1993;81:908 – 14.

(IV, C)[54] Mackay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol 2001;97: 533 – 8.

[55] Dinsdale HB. Hypertensive encephalopathy. Neurol Clin 1983;1:3 – 16.

(IV, C)[56] Chester EM, Agamanolis DP, Banker BQ, Victor M. Hypertensive encephalopathy: a clinicopathologic study of 20 cases. Neurology 1978;28(9 pt 1):928 – 39.

  1. Khan IA, Nair CK. Clinical, diagnostic, and management perspectives of aortic dissection. Chest 2002;122:311 – 28.
  2. Hickler RB. bHypertensive emergencyQ: a useful diagnostic category. Am J Publ Health 1988;78:623 – 4.
  3. Ault MJ, Ellrodt AG. Pathophysiological events leading to the end-organ effects of acute hypertension. Am J Emerg Med 1985;3(6 Suppl):10 – 5.

(IV, C)[60] Wallach R, Karp RB, Reves JG, et al. Pathogenesis of paroxysmal hypertension developing during and after coro- nary bypass surgery: a study of hemodynamic and humoral factors. Am J Cardiol 1980;46:559 – 65.

(IV, C)[61] Strandgaard S. Autoregulation of cerebral blood flow in Hypertensive patients. Circulation 1976;53:720 – 7.

(IV, C)[62] Strandgaard S. Autoregulation of brain circulation in severe arterial hypertension. BMJ 1973;1:507 – 10.

(IV, C)[63] Harper AM, Lassen NA, MacKenzie ET, et al. Proceedings: the upper limit of bautoregulationQ of cerebral blood flow in the baboon. J Physiol 1973;234:61P- 2P.

  1. Blumenfeld JD, Laragh JH. Management of hypertensive crises: the scientific basis for treatment decisions. Am J Hypertens 2001;1:1154 – 67.
  2. Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance? Hypertension 2004;4:248 – 52.
  3. Patel HP, Mitsnefes M. Advances in the pathogenesis and management of hypertensive crisis. Curr Opin Pediatr 2005;17:210 – 4.

(III, C)[67] Lip GY, Edmunds E, Hee F, et al. A cross-sectional, diurnal, and follow-up study of platelet activation and endothelial dysfunction in malignant phase hypertension. Am J Hypertens 2001;14:823 – 8.

  1. Wahl M, Schilling L. Regulation of cerebral blood flow-a brief review. Acta Neurochir Suppl (Wien) 1993;59:3 – 10.
  2. Rose JC, Mayer SA. Optimizing blood pressure in neurolog- ical emergencies. Neurocrit Care 2004;3:287 – 300.

(III, C)[70] Chamorro A, Vila N, Ascaso C, et al. Blood pressure and func- tional recovery in acute ischemic stroke. Stroke 1998;29:1850 – 3.

(III, C)[71] Reinhard M, Roth M, Guschlbauer B, et al. Dynamic cerebral autoregulation in acute ischemic stroke assessed from sponta- neous blood pressure fluctuations. Stroke 2005;36:1684 – 9.

  1. Elliott WJ. Clinical features in the management of selective hypertensive emergencies. Prog Cardiovasc Dis 2006;48: 316 – 25.
  2. Tuncel M, Ram VC. Hypertensive emergencies. Etiology and management. Am J Cardiovasc Drugs 2003;3:21 – 31.
  3. Fenves AZ, Ram CV. Drug treatment of hypertensive urgencies and emergencies. Semin Nephrol 2005;25:272 – 80.
  4. Migneco A, Ojetti V, De Lorenzo A, et al. Hypertensive crises: diagnosis and management in the emergency room. Eur Rev Med Pharmacol Sci 2004;8:143 – 52.

*[76] Sunshine JL, Tarr RW. Neuroimaging in neuroemergencies. In: Suarez JI, editor. Critical care neurology and neurosurgery. Totowa (NJ)7 Humana Press; 2004. p. 123 – 35.

(IV, C)[77] Wall SD, Brandt-Zawadzki M, Jeffrey RB, et al. High frequency CT findings within 24 hours after cerebral infarction. AJR Am J Roentgenol 1982;138:307 – 11.

(IV, C)[78] Yuh WT, Crain MR, Loes DJ, et al. MR imaging of cerebral ischemia: findings in the first 24 hours. AJNR Am J Neuroradiol 1991;12:621 – 9.

*[79] Bryan RN, Levy LM, Whitlow WD, et al. Diagnosis of acute cerebral infarction: comparison of CTand MRI imaging. AJNR Am J Neuroradiol 1991;12:611 – 20.

[80] MR-Technology. Apparent diffusion coefficient. MR-Tech- nology Web site. Available at: serv1.php?type=db1&dbs=Apparent%20Diffusion%20Coeffi- cient [Accessed 6 September 2006].

(IV, C)[81] Hand PJ, Wardlaw JM, Rivers CS, et al. MR diffusion- weighted imaging and outcome prediction after ischemic stroke. Neurology 2006;66:1159 – 63.

  1. Schaefer PW, Copen WA, Lev MH, et al. Diffusion-weighted imaging in acute stroke. Magn Reson Imaging Clin N Am 2006;14:141 – 68.
  2. Le Bihan D, Turner R, Douek P, et al. Diffusion MR imaging: clinical applications. AJR Am J Roentgenol 1992; 159:591 – 9.
  3. Rosen BR, Belliveau JW, Vevea JM, et al. Perfusion imaging with NMR Contrast agents. Magn Reson Med 1990;14:249 – 65.
  4. Schlaug G, Benfield A, Baird AE, et al. The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology 1999;53:1528 – 37.
  5. Lovblad KO, El-Koussy M, Oswald H, et al. Magnetic resonance imaging of the ischaemic penumbra. Swiss Med Wkly 2003;133:551 – 9.
  6. Cardene IV (nicardipine hydrochloride) [package insert]. Deerfield (IL)7 Baxter Healthcare Corporation; 2006.
  7. Trandate (labetalol hydrochloride) [package insert]. San Diego (CA)7 Prometheus Laboratories; 2003.
  8. Rhoney DH, Liu-DeRyke X. Effect of vasoactive therapy on cerebral circulation. Crit Care Clin 2006;22:221 – 43.

(I, A)[90] Neutel JM, Smith DHG, Wallin D, et al. A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension. Am J Hypertens 1994;7:623 – 8.

[91] Rodriguez G, Varon J. Clevidipine: a unique agent for the critical care practitioner. Crit Care & Shock 2006;9:37 – 41.

(III, C)[92] Eames PJ, Blake MJ, Dawson SL, et al. Dynamic cerebral autoregulation and beat to beat blood pressure control are impaired in acute ischaemic stroke. J Neurol Neurosurg Psychiatry 2002;72:467 – 72.

(III, C)[93] Dawson SL, Panerai RB, Potter JF. Serial changes in static and dynamic cerebral autoregulation after acute ischaemic stroke. Cerebrovasc Dis 2003;16:69 – 75.

[94] Marshall RS. The functional relevance of cerebral hemody- namics: why blood flow matters to the injured and recovering brain. Curr Opin Neurol 2004;17:705 – 9.

*:[95] American Heart Association RS. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005;112(Suppl 1): IV1-IV211.

(I, A)[96] Schrader J, Luders S, Kulschewski A, et al. The ACCESS study evaluation of acute candesartan cilexetil therapy in stroke survivors. Stroke 2003;34:1699 – 703.

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