Crisis Hipertensivas 2006[1]

8/8/2019 Crisis Hipertensivas 2006[1]

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Hypertensive Crisis: Hypertensive Emergenciesand Urgencies

Monica Aggarwal, MD, Ijaz A. Khan, MD *Division of Cardiology, University of Maryland School of Medicine, 22 South Greene Street,

Baltimore, MD 21201, USA

Hypertension affects an estimated 50 millionpeople in the United States, and it contributed tomore than 250,000 deaths in the year 2000 becauseof end-organ damage [1]. Normal blood pressure isdened as a systolic blood pressure of less than120 mm Hg and diastolic blood pressure of lessthan 80 mm Hg. Hypertension is dened as a sys-tolic blood pressure of 140 mm Hg or higher ora diastolic blood pressure of 90 mm Hg or higher.A systolic blood pressure of 120 to 139 mm Hg ora diastolic blood pressure of 80 to 89 mm Hg isconsidered prehypertension, because people in

this range of blood pressure have higher tendencyto develop hypertension over time. There is a con-tinuous, graded relationship between hypertensionand cardiovascular risk; even a slightly elevatedblood pressure increases risk for cardiovasculardisease. The maximum blood pressure as well asthe duration of elevated pressure determines theoutcome [2,3]. Most patients who have chronicallyuncontrolled hypertension suffer end-organ dam-age over time. Patients with previously untreatedor inadequately treated high blood pressures aremost prone to acute rises in their blood pressures[4,5]. Patients with secondary causes of hyperten-sion are at higher risk of acute rises of blood pres-sure than patients who have essential hypertension[6,7]. The terms malignant hypertension, hy-pertensive emergency,and hypertensiveurgencywere instituted to describe these acute rises inblood pressure and resulting end-organ damage.

Hypertensive crisis includes hypertensive emer-gencies and urgencies. Hypertensive emergency is

dened as severe hypertension with acute end-organ damage, such as aortic dissection, heartfailure, papilledema, or stroke. Although there isno blood pressure threshold for the diagnosis of hypertensive emergency, most end-organ damageis noted with diastolic blood pressures exceeding120 to 130 mm Hg. In these patients, immediatebut monitored reduction, often accomplished withparenteral medications, is essential in preventinglong-term damage. Hypertensive urgency, on theother hand, describes signicantly elevated bloodpressure but without evidence of acute end-organ

damage. These patients also need reductions intheir blood pressures; but these reductions can beachieved over a period of days, with oral medi-cations and usually without an intensive monitor-ing setting.

Historical perspective

Physicians have noticed the effects of hyper-tension and hypertensive crises for decades. Vol-hard and Fahr [8] were the rst to notice the acutechanges in blood pressure and the differences inpathophysiology of these changes from the chron-ically elevated blood pressure. They noted thatpatients who had severe hypertension had fundo-scopic changes such as retinopathy and papille-dema along with renal insufficiency and broidnecrosis of the renal arterioles. Also, they noticedthat patients who had acute elevations in bloodpressure were more prone to papilledema and toacute changes in their kidneys. In 1914, they de-ned the term malignant hypertension as an el-evation in blood pressure with the sign of acute

end-organ damage. Subsequently, in 1921, Keithand Wagener [9] described a similar nding of

* Corresponding author.E-mail address: [email protected]

(I.A. Khan).

0733-8651/06/$ - see front matter 2005 Elsevier Inc. All rights reserved.doi:10.1016/j.ccl.2005.09.002 cardiology.theclinics.com

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papilledema and severe retinopathy in patientswho had severe hypertension but who did nothave renal insufficiency. They then realized thatthe end-organ eye andkidney damage were not mu-tually exclusive to acute hypertensive episodes andtherefore broadened the denition of malignanthypertension by stating that renal insufficiencywas not a necessary requirement for acute hyper-tensive damage. Keith and Wagener [9] also usedthe term accelerated hypertension, which theydened as a syndrome with severe elevations inblood pressure in the presence of retinal hemor-rhages and exudates but without papilledema.Later studies have shown that retinal hemorrhagesand exudates are important in malignant hyperten-sion and are associated with decreased survival.

Notably, however, the presence or absence of papilledema is not associated with decreasedsurvival [10,11] .

In 1928, Oppenheimer and Fishberg [12] werethe rst to use the term hypertensive encephalop-athy when they noted malignant hypertensionassociated with headaches, convulsions, and neu-rologic decits in a 19-year-old student. Currently,the terms malignant hypertension and acceler-ated hypertension are used infrequently andhave been replaced by terms such as hypertensivecrisis, hypertensive emergency, and hyperten-sive urgency ( Table 1 ).

Demographics

The prevalence of hypertension has increased,partially because of the stringent denition of hypertension. There are notable demographictrends in the prevalence of hypertension. Hyper-tension is more common in older age groups and ismore common in men than in women [13]. It is 1.5to two times more prevalent in black Americans.

An analysis of data from the 1999 to 2000 NationalHealth and Nutrition Examination Survey hasshown that the combined prevalence of prehyper-tension and hypertension has increased to 60% of American adults (67% of men and 50% of women),and 27% of American adults have establishedhypertension. The combined prevalence of prehy-pertension and hypertension is 40% in the 18- to39-years age group and is 88% in the greater-than-60-years age group [14]. This survey showedcertain risk predictors of hypertension. Educationlevel was a notable factor. The combined preva-lence of prehypertension and hypertension in-creased from 54% in the high-schooleducatedgroup to 65% in the nonhigh-schooleducated

group. Obesity was also an important risk predic-tor in this analysis; 75% of overweight individualswere prehypertensive or hypertensive, but only47% of the non-overweight group qualied assuch.

Patients who were noted to have prehyperten-sion were also noted to have other risk factors forstroke and cardiovascular disease, such as hyper-cholesterolemia, obesity, and diabetes. These riskfactors were less prevalent in people who hadnormal blood pressures. The percentage of peoplewho had more than one risk factor for cardiovas-cular disease was higher in the prehypertensivegroup than in patients who had normal bloodpressure [14]. This cross-sectional analysis alsoevaluated patients who, when made aware of theirhypertension, followed dietary, lifestyle, and med-ication changes. It was noted that 7% of patientsdid not adopt any lifestyle changes, and 15% of patients would not take any antihypertensive

medications. The problem was more notable inyounger patients and in Mexican-American pa-tients. Of the patients taking anti-hypertensivemedications, 54% had their hypertension con-trolled. Men and patients with higher educationwere more likely to have their blood pressureswell controlled.

Of the estimated 50 million Americans withhypertension, less than 1% will have a hyperten-sive crisis [15]. In a study by Zampaglione and as-sociates [16], hypertensive crises were found toaccount for more than 25% of all patient visitsto a medical section of an emergency department.One third of those patients were noted to havehypertensive emergencies. In the years when

Table 1Denitions

Term Denition

Prehypertension Systolic blood pressure120139 mm Hg and diastolicblood pressure 8089 mm Hg

Hypertension Systolic blood pressure O140/90 mm Hg

Hypertensivecrisis

Hypertensive urgency oremergency

Hypertensiveurgency

Acute rise in blood pressurewithout acute end-organdamage; diastolic bloodpressure usually O 120 mm Hg

Hypertensiveemergency

Acute rise in blood pressure withacute end-organ damage;diastolic blood pressure usually

O 120 mm Hg

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treatment of hypertensive crises was difficult, be-cause of inadequate monitoring and lack of paren-teral medications, survival was only 20% at 1 yearand 1% at 5 years [17]. Before antihypertensiveagents became available, thoracolumbar sympa-thectomy prolonged survival to 40% at 6.5 years.With the advent of ganglionic blocking medica-tions, the 5-year survival rates increased to 50%to 60% in 1960 [18]. During the past 2 decades,with the increased focus on blood pressure controland emphasis on compliance, the 10-year survivalrates have approached 70% [19].

Cause

Ninety-ve per cent of patients who have

hypertension have no obvious underlying cause.As such, hypertension without secondary causes isdened as essential hypertension. The remaining5% of patients have an underlying cause for theirelevated blood pressures, of which certain groupshave higher chances of presenting with a hyper-tensive crisis ( Box 1 ). Use of recreational drugs,such as cocaine, has become a frequent cause of hypertensive crisis. Cocaine amphetamines, phen-cyclidine hydrochloride, and diet pills are sympa-thomimetic and thus may cause severe acutehypertension. Patients taking monoamine oxidaseinhibitors along with tricyclic antidepressants,antihistamines, or food with tyramine are proneto hypertensive crises. Withdrawal syndromesfrom drugs such as clonidine or beta-blockersmay also precipitate hypertensive crises [20]. Pheo-chromocytoma is a rare cause of hypertensive cri-ses. Patients with spinal cord disorders, such asGuillain Barre syndrome, are also at a higher riskfor hypertensive crises. These patients are proneto autonomic overactivity syndrome manifestedby severe hypertension, bradycardia, headache,

and diaphoresis. The syndrome is triggered bystimulation of dermatomes or muscles innervatedby nerves below the spinal cord lesions.

Pathophysiology

Normal mechanisms to regulate blood pressure

Blood pressure regulation is a critical actionthat allows perfusion to vital organs of the body.This action is based on a balance between pe-ripheral vascular resistance and cardiac output andis dependent on the integrated actions of the cardiovascular, renal, neural, and endocrinesystems. This interdependence allows a back-up

system so that the body can cope with internal andexternal stresses such as thirst, fear, infection, andtrauma. Multiple intrinsic systems are activated inthe body in response to external and internalstressors [21]. The renin-angiotensin-aldosteronesystem is thought to be critically responsible forblood pressure changes. Renin is released fromthe juxtaglomerular apparatus in response to lowsodium intake, underperfusion of the kidney, andincreased sympathetic activity. Renin is responsi-ble for converting angiotensinogen to angiotensin,which is not metabolically active. The angiotensin

is subsequently converted to angiotensin II in thelungs by the angiotensin-converting enzyme. An-giotensin II is a potent vasoconstrictor, which leadsto increases in blood pressure. Besides its intrinsicvasoconstrictive effects, angiotensin II also causesaldosterone release, which further increases bloodpressure by causing salt and water retention. Stud-ies in rats support the role of the renin-angiotensin-aldosterone system in blood pressure elevation.When rats were given the Ren-2 gene, whichactivates the renin-angiotensin-aldosterone sys-tem, they developed severe hypertension [22]. Fur-ther support comes from therapeutic methods,such as using angiotensin-converting enzymeinhibitors or angiotensin receptor blockers or

Box 1. Causes of secondaryhypertension

Medications

Oral contraceptive pillsCocaine hydrochloridePhencyclidine hydrochlorideMonoamine oxidase inhibitorsSympathomimetic diet pillsNonsteroidal anti-inammatory drugsAmphetaminesCyclosporinSteroids

Acute glomerulonephritisRenal parenchymal diseaseRenal artery stenosisHyperaldosteronismCushing diseasePheochromocytomaPregnancySleep apneaCoarctation of aortaSpinal cord injuries

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surgical removal of an ischemic kidney, which canprevent blood pressure elevations [23].

The renin-angiotensin-aldosterone system isnot considered solely responsible for changes inblood pressure. Black Americans, for instance,often have low renin, angiotensin II, and aldoste-rone levels and yet have a notably higher incidenceof hypertension. Therefore, they are less responsiveto medications blocking the renin-angiotensin-aldosterone system. Theoretically, patients whohave low renin states might have noncirculatorylocal renin-angiotensin paracrine or epicrine sys-tems. These systems have been found in the kidney,arterial tree, and the heart; and are probablyresponsible for local control of blood pressure [24].

The sympathetic nervous system also affects

blood pressure, especially in times of stress andexercise. The sympathetic nervous system cancause arterial vasoconstriction and can raise car-diac output. It is thought that initially the sympa-thetic nervous system increases the cardiac outputwithout affecting peripheral vascular resistance.The raised cardiac output increases ow to thevascular bed, and as the cardiac output increases,the autoregulatory response of the vascular bed isactivated. This autoregulatory response results inconstriction of the arterioles to prevent the pres-sure from reaching the capillaries and affecting cellhemostasis [21].

In addition, endothelial function plays a centralrole in blood pressure maintenance. The endothe-lium secretes nitric oxide, prostacylin, and endo-thelin, which modulate vascular tone. Nitric oxideis released by endothelial agonists such as acetyl-choline and norepinephrine and in response toshear stress [21]. Endothelin-1 has great vasocon-strictive activities and may cause a salt-sensitiverise in blood pressure and a rise in blood pressureby triggering the renin-angiotensin-aldosterone

system [24]. Other vasoactive substances involvedin blood pressure maintenance include bradykininand natriuretic peptides. Bradykinin is a potentvasodilator that is inactivated by angiotensin-converting enzyme. Natriuretic peptides are se-creted from the heart in response to increase inblood volume and cause an increase in sodiumand water excretion.

Altered mechanisms in hypertension and hypertensive crises

The pathophysiology of hypertensive crisis isnot well understood. It is thought that an abruptrise in blood pressure, possibly secondary to

a known or unknown stimulus, may trigger theevent. During this abrupt initial rise in bloodpressure, the endothelium tries to compensate forthe change in vasoreactivity by releasing nitricoxide. When the larger arteries and arteriolessense elevated blood pressures, they respondwith vasoconstriction and subsequently with hy-pertrophy to limit pressure reaching the cellularlevel and affecting cellular activity. Prolongedsmooth muscle contraction leads to endothelialdysfunction, loss of nitric oxide production, andirreversible rise in peripheral arterial resistance.Without the continuous release of nitric oxide, thehypertensive response becomes more severe, pro-moting further endothelial damage, and a viciouscycle continues. The endothelial dysfunction is

further triggered by inammation induced bymechanical stretch. The expression of inamma-tory markers such as cytokines, endothelial adhe-sion molecules, and endothelin-1 is increased[25,26]. These molecular events probably increasethe endothelial permeability, inhibit brinolysis,and, as a result, activate coagulation. Coagulationalong with platelet adhesion and aggregation re-sults in deposition of brinoid material, increasedinammation, and the vasoconstriction of the ar-teries, resulting in further endothelial dysfunction.The role of the renin-angiotensin-aldosterone sys-tem also seems to be important in hypertensiveemergency. There seems to be an amplicationof this system that contributes to vascular injuryand tissue ischemia [27].

The blood pressure at which the acute end-organ damage starts occurring is different in eachindividual. Patients who are more chronicallyhypertensive have had more smooth muscle con-traction and subsequent arterial hypertrophy,which lessens the effect of acute rise in bloodpressure on the capillary circulation. Although

malignant hypertension is dened as a diastolicblood pressure greater than 130 mm Hg, normo-tensive patients who have not had time to establishcompensatory autoregulatory mechanisms aremore sensitive to elevations in blood pressure andmay suffer end-organ damage when diastolic bloodpressure becomes greater than 100 mm Hg.

Clinical manifestations

Hypertensive crisis shares all of the pathologicmechanisms and end-organ complications of themilder forms of hypertension [27]. In one study of the prevalence of end-organ complications in

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hypertensive crisis, central nervous system abnor-malities were the most frequent. Cerebral infarc-tions were noted in 24%, encephalopathy in16%, and intracerebral or subarachnoid hemor-rhage in 4% of patients. Central nervous systemabnormalities were followed in incidence by car-diovascular complications such as acute heart fail-ure or pulmonary edema, which were seen in 36%of patients, and acute myocardial infarction orunstable angina in 12% of patients. Aortic dissec-tion was noted in 2%, and eclampsia was noted in4.5% of patients [16]. The end-organ damage isoutlined in Box 2 .

Acute neurologic syndromes

The cerebral vasculature must maintain a con-stant cerebral perfusion despite changes in bloodpressure. Cerebral autoregulation is the inherentability of the cerebral vasculature to maintain thisconstant cerebral blood ow [28,29]. Normoten-sive people maintain a constant cerebral bloodow between mean arterial pressures of 60 mmHg and 120 mm Hg. As the mean arterial pressureincreases, there is disruption of the cerebral endo-thelium and interruption of the bloodbrain bar-rier. Fibrinoid material deposits in the cerebralvasculature and causes narrowing of the vascular

lumen. The cerebral vasculature, in turn, attemptsto vasodilate around the narrowed lumen, whichleads to cerebral edema and microhemorrhages[30]. The changes in cerebral vasculature and cere-bral perfusion seem to affect primarily the whitematter in the parieto-occipital areas of the brain[31]. The predilection toward the parieto-occipital

regions possibly results from decreased sympa-thetic innervation of the vessels in this region[32]. There are also reports of brainstem involve-ment, however [33].

Normotensive patients may develop endothe-lial dysfunction at lower mean arterial pressures,whereas chronically hypertensive patients cantolerate higher mean arterial pressures beforethey develop such a dysfunction. Chronicallyhypertensive patients have the capacity to autor-egulate and have cerebral blood ow and oxygenconsumption similar to those in normotensivepersons [34]. Changes in the structure of the arte-rial wall cause increased stiffness and higher cere-brovascular resistance, however [35]. Althougha higher threshold must be reached before they

have disruption of their autoregulation system,hypertensive patients, because of the increased ce-rebrovascular resistance, are more prone to cere-bral ischemia when ow decreases [30].

Hypertensive encephalopathy is one of theclinical manifestations of cerebral edema andmicrohemorrhages seen with dysfunction of cere-bral autoregulation. It is dened as an acuteorganic brain syndrome or delirium in the settingof severe hypertension. Symptoms include severeheadache, nausea, vomiting, visual disturbances,confusion, andfocal or generalized weakness. Signsinclude disorientation, focal neurologic defects,focal or generalized seizures, and nystagmus. If not adequately treated, hypertensive encephalopa-thy can lead to cerebral hemorrhage, coma, anddeath, but with proper treatment it is completelyreversible [36]. The diagnosis of hypertensive en-cephalopathy is a clinical diagnosis. Stroke, sub-arachnoid hemorrhage, mass lesions, seizuredisorder, and vasculitides need to be ruled out.

Cerebral infarction, caused by an imbalancebetween supply and demand, is another neurologic

sequela of severe acute rises in blood pressure [37].Intracranial and subarachnoid hemorrhages areother possible neurologic complications of hyper-tensive crisis. The risk is increased in patientswho have intracranial aneurysms and in thosetaking anticoagulant medications.

Myocardial ischemia

Hypertension affects the structure and functionof the coronary vasculature and left ventricle.Activation of the renin-angiotensin-aldosteronesystem in hypertension constricts systemic vascu-lature and, thereby, increases myocardial oxygendemand by increasing left ventricular wall tension.

Box 2. End-organ damage inhypertension

Acute neurologic syndromesHypertensive encephalopathyCerebral infarctionSubarachnoid hemorrhageIntracranial hemorrhage

Myocardial ischemia and infarctionAcute left ventricular dysfunctionAcute pulmonary edemaAortic dissectionRetinopathyRenal insufciencyEclampsia



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Increasing wall tension leads to hypertrophy of the left ventricular myocytes and to deposition of protein and collagen in the extracellular matrixof the ventricular wall. These actions increaseventricular mass, which further increases oxygendemand on the heart. A second effect of thehypertrophy is that the newly thickened ventriclecan cause coronary compression and decreasedluminal blood ow. Thirdly, hypertension canincrease the epicardial coronary wall thickness,which increases the wall-to-lumen ratio and de-creases coronary blood ow reserve. Concomitantatherosclerosis worsens the wall-to-lumen ratio,further decreases coronary ow reserve, and leadsto coronary ischemia [38]. Acute rise in bloodpressure also results in endothelial injury at the

level of the coronary capillaries.

Left ventricular failure

Another effect of hypertensive crisis on theheart is left ventricular failure and acute pulmo-nary edema. In certain cases, despite increasingwall tension, the left ventricle cannot hypertrophyenough to overcome the acute rise in systemicvascular resistance. This inability to compensateleads to left ventricular failure and a backup of ow causing pulmonary edema. Secondly, neuro-

hormonal activation of the renin-angiotensin-aldosterone system leads to increased sodiumcontent and increased total body water. In addi-tion, left ventricular hypertrophy leads to focalischemia and subsequent inadequate diastoliclling, which can result in imbalance betweenleft ventricular contraction and relaxation, leadingto pulmonary edema [5]. Clinically, patients showsigns of volume overload or signs of reduced tis-sue perfusion such as cool limbs.

Aortic dissection

Aortic dissection is the most rapidly fatalcomplication of hypertensive crises. Risk factorsfor dissection include untreated hypertension,advanced age, and diseases of the aortic wall.Dilation of the aorta caused by atherosclerosisand high blood pressures tear the intima of thevessel, allowing a surge of blood into the aorticwall. The blood driven by pulsatile pressureseparates the arterial wall into two layers [39].Clinically, patients complain of retrosternal or in-terscapular chest pain that migrates to the back. If dissection extends proximally, it can lead to aorticinsufficiency or a pericardial effusion. Dissectioncan lead to compression or occlusion of a branch

of the aorta and subsequently lead to organ ische-mia. Clinical signs that are notable with dissectioninclude discrepancies between pulses, murmur of aortic insufficiency, and neurologic decits [40].Diagnosis of aortic dissection can be conrmedwith transesophageal echocardiography, CT, orMRI [41].

Hypertensive retinopathy

Retinopathy was one of the rst signs of hypertension, noted in 1914. In the early yearsfundoscopy was considered a denitive tool indiagnosing hypertensive encephalopathy. Papille-dema was noted in patients who had hypertensiveencephalopathy but was not necessary for di-agnosis [42]. Retinal hemorrhages and exudateswere considered indicative of malignant hyperten-sion. Since 1914, multiple studies have looked atretinopathy in the setting of hypertension. Inmild to moderate hypertension, the degree of focalnarrowing of arterioles has been associated withthe level of blood pressure rise. No relationshiphas been found between retinal changes and theend-organ damages such as ventricular hypertro-phy or microalbuminuria, however [43]. Ophthal-moscopy may be useful in recognizing acutehypertensive target-organ damage such as hyper-

tensive encephalopathy, but the absence of retinalexudates, hemorrhages, or papilledema does notexclude the diagnosis [11].

Acute renal insufficiency

Acute renal insufficiency may be a cause orresult of rapidly progressive hypertension. Impor-tant causes of hypertension are parenchymaldisease, such as acute glomerulonephritis or renalartery stenosis, or cyclosporine use in kidneytransplant patients. Renal insufficiency could also

be a result of hypertension and hypertensive crisis,however. Normal renal autoregulation enables thekidney to maintain a constant renal blood ow andglomerular ltration rate for mean arterial pres-sures between 80 and 160 mm Hg. Under normalconditions, autoregulatory vasodilation is maxi-mal at a mean arterial pressure of about 80 mm Hg.In chronic hypertension, the small arteries of thekidney, including the afferent arteriole, undergopathologic changes that alter renal autoregulation,showing signs of endothelial dysfunction andimpaired vasodilation. Structural changes initiallyare probably protective of the kidney, but overtime progressive narrowing of the preglomerularvessels results in ischemic injury, tubular atrophy,

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and brosis. With the impairment of the renalautoregulatory system, the intraglomerular pres-sure begins to vary directly with systemic arterialpressure [44]. As such, the afferent vasculature be-comes a passive conduit and cannot prevent thekidney from being affected by uctuations in pres-sure and ow, leading to acute renal ischemia incases of hypertensive crisis.

Pregnancy-induced hypertension

Pre-eclampsia is characterized as a syndrome of pregnancy-induced hypertension, edema, and pro-teinuria in a pregnant woman after the twentiethweek of gestation [27]. Eclampsia is the end resultof this spectrum and is associated with acute hyper-tension, edema, proteinuria, and concomitant seiz-

ures. Although the pathophysiologic mechanismsof pre-eclampsia and eclampsia are not well under-stood, blood pressure elevation is characterized byan increased responsiveness to vasoconstrictors,especially angiotensin II. There is also decreasedsensitivity to endothelium-derived vasodilators[27]. Pregnancy-induced hypertension usually re-solves spontaneously after delivery of baby.

Postoperative hypertension

The postoperative hypertensive crisis is classi-

cally an acute rise in blood pressure within therst 2 hours after surgery and is typically short induration, with most patients requiring treatmentfor 6 hours or less [45]. Although postoperativehypertensive crises can occur with any surgery,they are more common with cardiothoracic, vas-cular, head, neck, and neurosurgical procedures[45]. In one study of patients undergoing radicalneck dissection, the frequency of hypertensivecrisis ranged from 9% to 25% [46]. A feared com-plication of postoperative hypertensive crisis isbleeding from operation site [47]. The pathophys-iology of postoperative hypertensive crisis is prob-ably related to stimulation of the sympatheticnervous system and catecholamine surge [48].

Clinical evaluation

History and detailed physical examination areimportant in all patients who present with severehypertension. A thorough history is important todetermine the time since diagnosis of hypertension,the severity, and the baseline blood pressures athome. Determining the presence of end-organdamage and other comorbidities is important,because both are crucial factors inuencing the

choice of antihypertensive drugs. Knowledge of thepatients medications and compliance with thesemedications, including over-the-counter medica-tions and recreational drugs, is essential, becauseboth could contribute to an acute rise in bloodpressure. Blood pressure should be checked in botharms and should be done in supine and standingpositions, if possible, to determine volume status.Neurologic examination is important to determinethe focal signs of an ischemic or hemorrhagicstroke. The presence of delirium, nausea, vomiting,and seizures suggests hypertensive encephalopa-thy. Fundoscopic examination could be of help,because the presence of exudates, hemorrhage, orpapilledema supports the diagnosis of hypertensiveencephalopathy. Cardiovascular examination in-

cludes listening for new murmurs of aortic in-sufficiency associated with dissection or of ischemicmitral regurgitation. A gallop or left ventricularheave could suggest heart failure. Crackles in thelung elds suggest pulmonary edema. Laboratorystudies should include serum electrolytes, bloodurea nitrogen, serum creatinine level, blood cellcount, and peripheral smear. An ECG should betaken for myocardial ischemia and left ventricularhypertrophy, and a chest radiograph should beobtained for cardiac enlargement and widenedmediastinum. Urine analysis is indicated for as-sessment of proteinuria and tubular casts. Plasmarenin and aldosterone levels could be obtained if patient is not taking diuretics or other medicationsthat could have affected these levels [22].

Treatment

Hypertensive urgency can be treated in a non-ICU setting with oral medications over 24 to 48hours. Medications such as beta-blockers, diu-retics, angiotensin-converting enzyme inhibitors,and calcium-channel blockers can be titratedinitially as an inpatient; then the patient can bedischarged with close follow-up. If there is acuteend-organ damage, however, the patient shouldbe admitted to the ICU and treated with in-travenous medications. The goal of therapy isprompt but gradual reduction in blood pressure.The most reasonable goal is to lower the meanarterial pressure by about 25% or to reduce thediastolic blood pressure to 100 to 110 mm Hg.

Medication options for treatment

There have been no large clinical trials todetermine the optimal pharmacologic therapy inhypertensive emergency patients, primarily



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because of the heterogeneity among the patientsand their end-organ damage. As such, manage-ment of hypertensive crisis should be dictated byindividual presentation and should be specic tothe end organ at risk ( Tables 2, 3 ).

Sodium nitroprusside is the drug of choice formost hypertensive emergencies because it has animmediate onset of action and can be titratedquickly and accurately. The duration of effect is1 to 2 minutes. The mechanism of action of thisagent is probably similar to that of endogenousnitric oxide. Sodium nitroprusside is an endoge-nous arteriolar and venous dilator and has noeffects on the autonomic or central nervous system[49]. The venous dilation decreases preload to theheart and subsequently decreases cardiac output,

whereas the arterial dilation inhibits the reex risein blood pressure from the drop in cardiac output.Because sodium nitroprusside is a direct vasodila-tor, one might think that it increases cerebral bloodow and intracranial pressure. The fall in systemicpressure, however, seems to inhibit the rise in cere-bral blood ow, and patients who have neurologicdamage respond well to this agent [18]. Sodium ni-troprusside must be administered as an infusionand thus requires continuous surveillance with in-tra-arterial monitoring. An end product of nitro-prusside is thiocyanate, a precursor to cyanidethat can causes nausea, vomiting, lactic acidosis,and altered mental status. Cyanide toxicity can berapidly fatal. Sodium nitroprusside is brokendown by the liver and cleared through the kidney,and thus thiocyanate levels must be followed inpatients who have hepatic or renal insufficiencyto ensure prevention of a toxic buildup [21].

Labetalol is another rst-line agent for hyper-tensive emergency. It is a combined alpha- andbeta-blocking agent; the beta-blocking activity of labetalol is ve- to tenfold that of the alphacomponent [50]. The beta effects of labetalol areonly about one fth the activity of propranolol,however [18]. Its onset of action is within 5 to10 minutes, and the duration of action is about3 to 6 hours. Labetalol can be used safely inmost patients, but caution should be exercised inpatients who have severe bradycardia, congestiveheart failure, or bronchospasm.

Fenoldopam is the rst selective dopamine-1receptor agonist approved for in-hospital shorter-term management of severe hypertension up tothe rst 48 hours of treatment [5154]. The mech-

anism of action involves activating dopamine atthe level of the kidney. Dopamine is a well-knownvasoconstrictor and is sympathomimetic at inter-mediate to high doses. At low doses, however, do-pamine lowers diastolic blood pressure and,importantly, increases renal perfusion and pro-motes diuresis. Fenoldopam is administered byparenteral continuous infusion and has 50% of its maximal effect within 15 minutes. Its durationof action is about 10 to 15 minutes; thus, it can bediscontinued swiftly if the decrease in blood pres-sure is too rapid. The efficacy of fenoldopam in re-nal perfusion is equal to or possibly better thanthat of sodium nitroprusside. There are no toxicmetabolites of fenoldopam; however, the onsetof action is slower, and the duration of effect islonger than that of sodium nitroprusside. Patientsdevelop tachyphylaxis to fenoldopam after 48hours, and headache can be a side effect.

Table 2Medications used in hypertensive emergencies

Name DosingOnset of Action

Durationof Action Preload Afterload

CardiacOutput

Renalperfusion

Sodiumnitroprusside

IV 0.2510 mg/kg/min withinseconds

12 min decreased decreased no effect decreased

Labetolol IV (20- to 80-mgbolus/10 min)

510 min 26 hr no effect decreased decreased no effect

Fenoldopam IV 0.10.6 mg/kg/min 1015 min 1015 min no effect decreased increased increasedNicardipine IV 210 mg/hr 510 min 24 hr no effect decreased increased no effectEsmolol IV 80-mg bolus over

30 seconds, followed by150 mg/kg/min infusion

610 min 20 min no effect no effect decreased no effect

Methyldopa IV (250-to 1000-mg bolus

every 6 hr)

36 hr up to 24 hr no effect decreased decreased no effect

Hydralazine IV bolus (1020 mg) 10 min 26 hr no effect decreased increased no effect

Abbreviation: IV, intravenous.

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Nicardipine is a calcium-channel blocker ad-ministered parenterally by continuous infusion forhypertensive crises. The onset of action of thisdrug is 5 to 10 minutes, and the duration of actionis 1 to 4 hours. Adverse reactions are reextachycardia and headache [55]. Nicardipine iscontraindicated in patients who have heart failure.

Esmolol is a cardioselective beta-blocker witha short duration of action. It reduces the systolicblood pressure and mean arterial pressure as wellas heart rate, cardiac output, and stroke volume.There is a notable decrease in myocardial oxygenconsumption. Peak effects are generally seen

within 6 to 10 minutes after a bolus dose. Theeffects resolve 20 minutes after discontinuation of infusion. The elimination half-life of esmolol isabout 8 minutes.

Choice of agent

The choice of pharmacologic agent to treathypertensive crisis should be tailored to eachindividual based on risks, comorbidities, and theend-organ damage. The lower limit of cerebralblood ow autoregulation is reached when bloodpressure is reduced by 25%, and the cerebralischemia can be precipitated with rapid reductionsof blood pressure of greater than 50% [35]. Hence,

the goal of therapy in hypertensive encephalopa-thy is to reduce the mean arterial pressure gradu-ally by no more than 25% or to a diastolic bloodpressure of 100 mm Hg, whichever is higher, dur-ing the rst hour. If neurologic function worsens,the therapy should be suspended, and bloodpressure should be allowed to increase [20]. In in-tracerebral or subarachnoid hemorrhage, bloodpressure reduction is necessary to stop the bleed-ing and can be facilitated by decreasing pressuresby 25%. It is important to reduce blood pressureslowly to prevent cerebral hypoperfusion to the al-ready ischemic areas [36]. Often after a strokethere is a loss of cerebral autoregulation in theinfarct/ischemic region. This loss of cerebral au-toregulation makes blood pressure reduction cau-

tionary, because the ischemic region is more proneto hypoperfusion during blood pressure reduc-tion. As such, blood pressure reduction is not rec-ommended after stroke, except in cases of extremeblood pressure elevation (diastolic blood pressureO 130 mm Hg). If neurologic function deterio-rates with reduction of blood pressure, therapyshould be suspended, and blood pressure shouldbe allowed to rise. Blood pressure usually declinesspontaneously to prestroke levels within 4 days of an acute ischemic stroke without any antihyper-tensive treatments [37]. Sodium nitroprusside isthe drug of choice for treatment of acute neuro-logic syndromes in hypertensive crisis. Labetololis a good alternative unless there is evidence of severe bradycardia associated with the cerebraledema. Clonidine and methyldopa should notbe used, because they can cause central nervoussystem depression and complicate the clinicalpicture.

Severe acute hypertension often results inmyocardial ischemia even with patent coronaryarteries. In this situation, intravenous nitroglyc-

erin is effective in reducing systemic vascularresistance and improving coronary perfusion.Nitrates should be given until symptoms subsideor until diastolic blood pressure is 100 mm Hg.Beta-blockers and calcium-channel blockers arealso potential options; both can decrease bloodpressure while improving myocardial oxygena-tion. Calcium-channel blockers should be usedwith caution in patients who have possible heartfailure. Acute pulmonary edema that is precipi-tated by hypertension is best treated with sodiumnitroprusside. The concomitant venous and arte-rial dilation improve forward ow and cardiacoutput. This agent should be used in conjunctionwith morphine, oxygen, and a loop diuretic [49].

Table 3Major side effects of medications

Name Comments Major Side Effects

Sodiumnitroprusside

Need to measurethiocyanatelevels, cautionin renalinsufficiency

Cyanide toxicity:nausea, vomiting,altered mentalstatus, lacticacidosis,death

Labetolol Alpha andbeta blocker,contraindicatedin acute heartfailure

Bradycardia,bronchospasm,nausea

Nicardipine Safe in coronarybypass patients

Reex tachycardia,ushing

Esmolol Short-actingbeta blocker,

contraindicatedin acute heartfailure

Bradycardia,bronchospasm

Methyldopa Safe in pregnancy,needs renaldosing

Drowsiness, fever, jaundice

Hydralazine Safe in pregnancy Reex tachycardia,lupus-likesyndrome



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Treatment of an aortic dissection depends onlocation of the injury [41]. Type A or proximalaortic dissections need immediate institution of antihypertensive medications and immediate sur-gery, but type B or distal aorta dissections canbe controlled medically. The medical therapy of aortic dissection is aimed at reducing the shearstress on aortic wall. This reduction is achievedby lowering diastolic blood pressure to less than100 to 110 mm Hg and by decreasing heart rate.This reduction is best achieved with a combinationof an intravenous beta-blocker and sodium nitro-prusside to decrease both the blood pressure andthe heart rate. Another option is the use of labeto-lol, which has both alpha- and beta-blockingeffects.

Renal insufficiency is a cause and a conse-quence of severe hypertension. These patientsneed reduction of systemic vascular resistancewithout compromising renal blood ow or glo-merular ltration rate. Fenoldopam is a goodchoice in these patients because of the improve-ment in renal perfusion, diuresis, and lack of production of toxic metabolites. Tolerance doesdevelop to fenoldopam after 48 hours [53]. Sodi-um nitroprusside can also be used, but there isa risk of thiocyanate toxicity, and the thiocyanatelevel needs to be closely monitored. Calcium-channel blockers are effective and well toleratedin renal transplant patients. Beta-blockers arealso useful agents in hypertension in kidney dis-ease. Calcium-channel blockers and beta-blockershave no clinically important effects on glomerularltration or renal hemodynamics [44]. Patientswho have renal insufficiency should not be treatedwith angiotensin-converting enzyme inhibitors orangiotensin receptor blockers.

In pre-eclampsia and eclampsia, blood pressurecontrol is essential. Many of the traditional anti-

hypertensive medications are contraindicated inpregnancy because of their detrimental effects onthe fetus. Angiotensin-converting enzyme inhibi-tors and angiotensin receptor blockers can ad-versely affect fetal development and increase fetalmorbidity. Calcium-channel blockers reduce bloodpressure but decrease uterine blood ow and caninhibit labor. Methyldopa is the mainstay of treatment of blood pressure in pregnant patients.It works centrally in reducing blood pressure andheart rate. Methyldopa can be administered orallyor intravenously. With renal dysfunction the dosesneed to be adjusted. The side effects are drowsi-ness, fever, and jaundice. The medication doescross into the placenta but is considered class B in

pregnancy [2]. Hydralazine is another agent that issafe in pregnancy and can be administered safelyparenterally. Hydralazine may cause reex tachy-cardia and uid retention because it activates therenin-angiotensin-aldosterone system [27]. Datashow that labetolol is probably effective in reduc-ing blood pressure in treatment of eclampsia with-out inducing fetal distress [56].

Pheochromocytoma is a rare cause of parox-ysmal or sustained blood pressure and can inducehypertensive crisis. The treatment of choice inthese patients is labetolol or phentolamine (analpha-blocking agent). It is important not to usebeta-blockers alone, because then there is anunopposed alpha activity that will worsen thevasoconstriction, resulting in a further increase in

blood pressure. A reex hypertensive crisis candevelop in patients who have abruptly stoppedtaking antihypertensives, particularly clonidine orbeta-blockers. The treatment in these cases is torestart previous medications after the initial re-duction of blood pressure with labetolol orsodium nitroprusside. Postoperative hypertensionis typically related to catecholamine surge fromactivation of the sympathetic nervous system.Therefore, the treatment of choice for postopera-tive hypertensive crisis is with a beta-blocker orlabetolol.

Summary

Hypertensive crisis is a serious condition that isassociated with end-organ damage or may resultin end-organ damage if left untreated. Causes of acute rises in blood pressure include medications,noncompliance, and poorly controlled chronichypertension. Treatment of a hypertensive crisisshould be tailored to each individual based on theextent of end-organ injury and comorbid condi-tions. Prompt and rapid reduction of bloodpressure under continuous surveillance is essentialin patients who have acute end-organ damage.

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