Hypertension Crisis in theEmergency Department

Wallace Johnson, MDa,*, My-Le Nguyen, MDb,Ronak Patel, MDb

KEYWORDS

� Hypertension crisis � Hypertensive urgency � Hypertensive emergency � Malignant hypertension� Guidelines � Management � Treatment

KEY POINTS

� An elevated blood pressure (BP) reading in the emergency department should be confirmed in morethan one anatomic location based on JNC 7 guidelines and reassessed multiple times before andduring therapy.

� Patients with severely (>180/120 mm Hg) or moderately (140–179/90–119 mm Hg) elevated BP sus-pected of having end-organ damage should undergo appropriate testing to determine if they havehypertensive urgency versus emergency. Absolute BP cutoffs are not as important as the presenceor absence of target end-organ damage.

� In general, patients with hypertensive emergency should have their mean arterial pressure (MAP)reduced by 20% to 25% in the first hour of this diagnosis. Exceptions are patients with ischemicstroke, in whom MAP should be reduced by 15% to 20%, and patients with aortic dissection thatrequires more aggressive BP reduction.

� Hypertensive patients with nausea/vomiting, headache, visual complaints, confusion, stupor, pap-illedema, or seizures may have hypertensive encephalopathy from cerebral edema. BP reductionshould be gradual, and cerebral perfusion pressure should not be decreased too rapidly.

� Patients with evidence of myocardial ischemia attributable to hypertensive emergency shouldreceive nitrates to reduce preload and improve coronary perfusion as well as b-blockers, whichcan reduce cardiac oxygen demand by lowering heart rate and afterload. b-Blockers should notbe given if there is evidence of acute heart failure or an unstable bradyarrhythmia.

� In pregnant patients with hypertensive emergencies, consider the effects of antihypertensive medi-cations on the fetus.

INTRODUCTION BP of 120 to 139 mm Hg and/or a diastolic BP of

m

Hypertension is a chronic, modifiable risk factor forcardiovascular disease; however, approximately1% to 2% of patients with hypertension willpresent with a hypertensive emergency at sometime in their lives.1 Hypertension is defined asa systolic blood pressure (BP) of 140 mm Hg orhigher and/or a diastolic BP of 90 mm Hg or higher(Box 1).2 Prehypertension is defined as a systolic

a Division of Cardiology, Hypertension Section, UniversitSt, Suite 620, Baltimore, MD 21201, USA; b Division of Ca419 W. Redwood St, Suite 620, Baltimore, MD 21201, US* Corresponding author.E-mail address: WJohnson@medicine.umaryland.edu

Cardiol Clin 30 (2012) 533–543http://dx.doi.org/10.1016/j.ccl.2012.07.0110733-8651/12/$ – see front matter � 2012 Elsevier Inc. All

80 to 89 mm Hg. This definition reflects the factthat patientswith prehypertension have a tendencyto develop full-blown hypertension over time. AsBP increases there is a continuous, graded rela-tionship between BP and cardiovascular risk, butas levels exceed 180/120 mm Hg, a hypertensivecrisis may emerge.

The terms malignant hypertension and acceler-ated hypertension were used in the past, but

y of Maryland School of Medicine, 419 W. Redwoodrdiology, University of Maryland School of Medicine,A

rights reserved. cardiology.th

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Box 1Hypertension definitions

Term Definition

Hypertensive crisisA. Hypertensiveurgency

Abrupt rise in BP withno signs of end-organdamage; diastolic BPusually >120 mm Hg

B. Hypertensiveemergency

Abrupt rise in BP withacute end-organdamage; diastolic BPusually >120 mm Hg

Prehypertension Systolic BP 120–139 mmHg and/or diastolic BP80–89 mm Hg

Hypertension Systolic BP >140 mm Hgand/or diastolicBP >90 mm Hg

Johnson et al534

now the term hypertensive crisis can refer to ei-ther a hypertensive emergency or hypertensiveurgency. In the years since the term malignanthypertension was initially coined in 1914, a largenumber of both oral and intravenous medicationshave been developed for the treatment of hyper-tensive emergencies as well as chronic essentialhypertension.3–5 Malignant hypertension was ini-tially named as such because the 1-year mortalityrate after a hypertensive emergency in 1928 was80% (similar to a malignant cancer prognosis);later, advances in medical therapy reduced the1-year mortality to 10% by 1998.6

The significant reduction in the mortality relatedto hypertensive emergencies is undeniably associ-ated with the development of both parental andoral antihypertensive agents, but increased aware-ness and published clinical guidelines have alsocontributed to better management of hypertensiveemergencies. A recent publication found thatalthough hospitalizations for hypertensive emer-gencies increased in 2007 when compared withthe year 2000, the all-cause in-hospital mortalityrate decreased.1 Deshmukh and colleagues1

believe the reduction in mortality is at least partlydue to the release of the Seventh Joint NationalCommittee2 report on the prevention, detection,evaluation, and treatment of hypertension in 2003.One of the first tasks in the emergency depart-

ment (ED) evaluation is to determine whetherthe patient’s condition represents a hypertensiveemergency or urgency. A hypertensive emergencyis defined as acute target end-organ damagetypically associated with a severely elevatedBP (systolic BP >180 mm Hg and/or diastolicBP >120 mm Hg) versus a hypertensive urgency,which is characterized by a similarly elevated BPand no target end-organ damage (see Box 1).7

The management of hypertensive emergencies inthe ED is challenging because of the lack ofevidence-based guidelines from large clinical trials.Hypertensive urgencies, in contrast to emergen-cies, can be treated with an oral regimen in anoutpatient setting. Initiating treatment for hyperten-sive urgencies in the ED remains controversialbecause there is no consensus on whether it iscost-effective and improves long-termpatient care.Causes of hypertensive emergency and urgency

are shown in Box 2.

NORMAL BLOOD PRESSURE REGULATION

In persons with normal BP regulation there is anappropriate balance between normal vital organperfusion, hypoperfusion, and hyperperfusion. BPis dependent on cardiac output and peripheralvascular resistance. The balance between cardiacoutput and peripheral vascular resistance dependson a complex set of integrated actions between thecardiovascular, neural, renal, and endocrinesystems, which is not totally understood. A multi-system approach to BP regulation allows thebody to respond to internal and external demandssuch as dehydration, thirst, infection, trauma, andrapid changes in position or volume. The renin-angiotensin-aldosterone system is one of the keysystems involved in the regulation of BP.3,4

The sympathetic nervous system also playsa major role, particularly during times of physicalstress, psychological stress, and heavy exertion.The sympathetic nervous system can increasecardiacoutput andarterial vasoconstriction. Lastly,endothelial function is also involved in BP regula-tion. The endothelium found on the vascular wallacts a regulator of BP by secreting vasodilatorsand/or vasoconstrictors in response to variousstimuli.3

ALTERED BLOOD PRESSURE REGULATIONIN HYPERTENSIVE CRISES

The mechanisms underlying both primary (essen-tial) hypertension and hypertensive crises are nottotally understood. There seem to be severalmechanisms that are found in both chronicprimary hypertension and hypertensive crises.The initial event appears to be an abrupt rise inBP from a known or unknown stimulus followedby compensatory mechanisms arising from thevascular endothelium. Initially the endotheliumreleases the vasodilator nitric oxide in an attemptto compensate for the change in vasoreactivity.The arterioles sense a rise in BP and, in turn, arte-rial smooth muscle contracts in an effort to reducethe rise in BP and to limit the effect of the BP at the

Box 2Causes of hypertensive emergency and urgency

Essential hypertension

Renovascular disease

Renal artery stenosis: atheroma or fibromuscular dysplasia

Polyarteritis nodosa

Takayasu arteritis

Renal parenchymal disease

Glomerulonephritis

Tubulointerstitial nephritis

Systemic sclerosis

Hemolytic uremic syndrome

Thrombotic thrombocytopenic purpura

Diabetes mellitus

Systemic lupus erythematosus

Renal aplasia

Renal cell carcinoma

Endocrine

Pheochromocytoma

Cushing syndrome

Primary hyperaldosteronism

Renin-secreting tumor

Drugs

Cocaine, phencyclidine, sympathomimetics, erythropoietin, cyclosporine

Antihypertensive medication withdrawal

Amphetamines

Lead intoxication

Interactions with monoamine oxidase inhibitors

Autonomic hyperreactivity

Guillain-Barre syndrome

Acute intermittent porphyria

Pregnancy related

Preeclampsia

Eclampsia

Central nervous system disorders

Head injury

Cerebral infarction

Cerebral hemorrhage

Brain tumor

Spinal cord injury

Coarctation of the aorta

Burns

Postoperative pain and/or anesthesia complications

Hypertension Crisis in the ED 535

Johnson et al536

cellular level. A vicious cycle occurs, with pro-longed arterial smooth muscle contraction leadingto more endothelial dysfunction and an inability torelease more nitric oxide, only resulting in a furtherincrease in BP.Inflammation is also a part of the pathophysi-

ology of endothelial dysfunction. The mechanicalshear forces on the vascular wall result in endothe-lial damage and dysfunction. Endothelial dysfunc-tion results in the expression of inflammatorymarkers such as endothelin-1, endothelial adhe-sion molecules, and cytokines.3,8,9 The inflamma-tory component of hypertension is believed topromote coagulation, platelet aggregation, endo-thelial layer permeability, and vasoconstriction.Thus, “hypertension begets hypertension,” andthere appears to be a complex interaction of therenin-angiotensin-aldosterone system, sympa-thetic nervous system, and endothelial dysfunctionregardless of the initial stimulus. There is alsoevidence that angiotensin II activates the expres-sion of genes for proinflammatory cytokines andactivation of transcription factor NF-kB, causinga direct toxic effect to the vessel wall.10 Anincreased level of von Willebrand factor, vonWillebrand factor prepeptide, plasmin-antiplasmincomplexes, and reduced levels of ADAMTS13 areseen in patients with hypertensive crisis, suggest-ing that thrombotic microangiopathy may playa role.11

Hypertensive crisis appears to have a similarpathophysiology to primary chronic hypertension,

Table 1Parenteral medications used for treatment of hypert

Dosing Ons

Sodiumnitroprusside

0.25–10 mg/kg/min IV infusion Witm

Nitroglycerin 5–100 mg/min IV infusion 1–5

Labetalol 20–80 mg bolus every 10 min,or 0.5–2 mg/min IV infusion

5–1

Esmolol 80 mg bolus over 30 secs then150 mg/kg/min IV infusion

1–2

Hydralazine 10–20 mg IV bolus 10–

Phentolamine 5–15 mg IV bolus 1–2

Nicardipine 2–15 mg/h IV infusion 5–1

Clevidipine 1–2 mg/h then titrate tomaximum 16 mg/h IVinfusion

1–4

Fenoldopam 0.1–0.6 mg/kg/min IV infusion 5–1

Enalaprilat 1.25–5 mg every 6 h IV bolus 15–

Abbreviation: IV, intravenous.Data from Refs.2–4

but the difference seems to be that the abruptrise in BP promotes acute target end-organdamage. The target end-organ damage may actu-ally accelerate the rise in the BP, leading to organtissue hyperperfusion and endothelial damageowing to blunted or inadequate compensatorymechanisms. This hypertensive emergency BPthreshold can occur at markedly different levelsin individual patients. Patients with chronic hyper-tension have more smooth muscle hypertrophybecause of a sustained elevation in BP, allowingtemporary and incomplete end-organ protectionat the capillary level. By contrast, normotensivepatients who undergo an abrupt increase in BPdo not have the same degree of smooth musclehypertrophy. Thus, even small abrupt rises in BPcan induce a hypertensive crisis in normotensives,partly due to the capillary damage that occurs.3 Atpresent, there is not enough evidence to supporta treatment approach based on the potentialunderlying pathophysiology of hypertensive crisis,so clinicians should achieve disease-specific BPtargets in these patients using whatever agentsnecessary, as long as there are no contraindica-tions (Tables 1 and 2).

CLINICAL MANIFESTATIONS OFHYPERTENSIVE CRISIS

The central nervous system is particularly sus-ceptible to high BP and its associated hyperperfu-sion and shear mechanical forces. In one

ensive crisis

et of Action Preload AfterloadCardiacOutput

hin seconds toinutes

Y YY No effect

min YY Y No effect

0 min No effect Y Y

min No effect No effect Y

20 min No effect Y [

min No effect Y [

0 min No effect Y [

min No effect Y [

0 min No effect Y [

30 min No effect Y [

Table 2Special indications and warnings for parenteral medications

Special Indications Warnings

Sodiumnitroprusside

Most hypertensiveemergencies

Caution with renal insufficiency; can develop cyanide toxicity,acidosis, methemoglobinemia, increased intracranialpressure, nausea, vomiting, muscle twitching, theoretical“coronary steal” (shunting of blood from diseased vesselsto well-perfused vessels may produce coronary ischemia)

Nitroglycerin Most hypertensiveemergencies,coronary ischemia

Headache; can develop tolerance, tachycardia, vomiting,methemoglobinemia, flushing

Labetalol Most hypertensiveemergencies,aortic dissection

Avoid in acute heart failure, bradycardia, andbronchoconstrictive disease

Esmolol Aortic dissection Avoid in acute heart failure, bronchoconstrictive disease, andheart block

Hydralazine Eclampsiaa Can cause reflex tachycardia, headache

Phentolamine Catecholamine excess Flushing, headache, tachycardia

Nicardipine Most hypertensiveemergencies

Avoid in acute heart failure and coronary ischemia; causesreflex tachycardia, nausea, vomiting, headache, increasedintracranial pressure

Clevidipine Most hypertensiveemergencies

Atrial fibrillation; avoid in soy allergy

Fenoldopam Most hypertensiveemergencies, acuterenal impairment,and/or hematuria

Caution with glaucoma; can cause headache, flushing,tachycardia, local phlebitis

Enalaprilat Acute left ventricularfailure

Avoid in acute myocardial ischemia

a Labetalol is safer during pregnancy.Data from Aggarwal M, Khan I. Hypertensive crisis: hypertensive emergencies and urgencies. Cardiol Clin 2006;24:135–46;

and Acelajado MC, Calhoun DA. Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evalu-ation and treatment. Cardiol Clin 2010;28:639–54.

Hypertension Crisis in the ED 537

representative study of the prevalence of end-organ complications, cerebral infarctions werenoted in 24%, intracerebral or subarachnoidhemorrhage in 4%, and hypertensive encephalop-athy in 16% of patients. Cardiovascular complica-tions in the same study included acute heart failurein 36% of patients and acute myocardial infarctionand/or unstable angina in 12%. Aortic dissectionwas noted in 2% of patients and eclampsia ofpregnancy in 4.5%.12 In the ED, clinicians needto be aware that substance abuse, medical non-compliance, and secondary hypertension aremajor causes of hypertensive crisis. Initial evalua-tion of hypertensive crisis should be focused onassessment of potential cardiovascular, cerebro-vascular, and renal damage.

CLINICAL EVALUATION OF HYPERTENSIVECRISIS IN THE ED

The usefulness of routine testing for patients withseverely elevated BP is controversial. However,

the authors believe that patients presenting tothe ED with hypertensive crisis should undergoelectrocardiography (ECG), chest radiography,computed tomography (CT) of the brain if neu-rologic symptoms are present, urinalysis, elec-trolytes/creatinine, complete blood count, andcardiac enzymes if acute coronary syndrome issuspected. This guideline is based on expertopinion and not on data from large randomizedclinical trials. As always, sound clinical judgmentshould be used in the ED setting for each individualpatient.

Neurologic Syndromes

The brain relies on a fairly constant cerebral BP tofunction properly. The cerebral vasculature musthelp maintain this steady perfusion pressuredespite changes in mean arterial pressure (MAP)through autoregulation. When this autoregulationfails in the setting of sudden and severely elevatedMAP, cerebral edema and microhemorrhages can

Johnson et al538

occur. Edema occurs when the vascular endothe-lium is disrupted owing to elevated pressurecausing leakage of plasma elements.13 Symptomscan include headache, stupor, seizures, delirium,agitation, nausea/vomiting, and visual distur-bances. Focal neurologic findings can occur, butare rare, and should raise the suspicion forischemic strokeor cerebral hemorrhage.14 Patientswith long-standing hypertension have a betterability to tolerate increases in MAP withoutincreasing cerebral perfusion. This ability is thoughtto be due to cerebral arteriolar hypertrophy, whichreduces the transmission of the elevated pressureto the capillary bed. It is essential not to lowersystemic BP too rapidly, as this can lead to a dropin cerebral perfusion pressure and cause ischemia.BP should be loweredwithin 2 to 6 hours of presen-tation to no more than 25% of the initial value.15

Myocardial Ischemia

Elevated systemic vascular resistance increasesleft ventricular (LV) myocardial wall tension andoxygen demand. In markedly elevated BP suchas in hypertensive emergencies, myocardial perfu-sion may not be able to adequately maintain theincreased myocardial oxygen demand, whichcan lead to myocardial ischemia and even infarc-tion. Patients with long-standing hypertensionmay also have LV hypertrophy, which in itselfincreases myocardial oxygen demand. Thisincreased LV mass can also cause some degreeof coronary artery compression, leading to de-creased luminal blood flow.3 Preferred agents intreating patients with hypertensive emergencieswith evidence of ischemia include nitrates thatcan lower LV preload and improve coronary bloodflow as well as b-blockers that can reduce heartrate, decrease afterload, and improve diastoliccoronary perfusion.16 Hydralazine should beavoided, as it can induce a reflex tachycardiaand increase cardiac work.

Acute Heart Failure

Acute heart failure presenting as acute pulmonaryedema in a hypertensive crisis occurs with an inci-dence of 36%,making it the secondmost commonsign of end-organ damage.3 Heart failure can occurin a hypertensive crisis but it can also be a riskfactor for the development of hypertensive crisis.17

It was initially thought that transient systolicdysfunction causes pulmonary edema in patientswith hypertensive crisis, but this theory has beenchallenged. Gandhi and colleagues18 usedtransthoracic echocardiography to evaluate LVejection fraction during acute episodes of hyper-tensive pulmonary edema and found that the left

ventricular ejection fraction was unchanged duringthe episodes as well as after treatment. However,they did observe segmental wall motion abnormal-ities after treatment. The investigators concludedthat the cause of acute heart failure in patientswith hypertensive crisis may be due to diastolicdysfunction secondary to ischemia.Sodium nitroprusside is thought to be the best

agent for acute pulmonary edema precipitated bya hypertensive crisis.3 Sodium nitroprussidedecreasesbothpreloadandafterload. It hasa rapidonset of actionandashort half-life. Cyanide toxicityis extremely rare. Thiocyanate toxicity is alsouncommon and occurs only with high doses of ni-troprusside in patients with renal insufficiency.19

Angiotensin-converting enzyme (ACE) inhibitorssuch as enalapril can be used to reduce afterloadand hence improve cardiac output.20 A newthird-generation dihydropyridine calcium-channelblocker, clevidipine, was shown in a small studyto be effective in reducing BP without adverseevents.7 In this study, 89% of patients achievedtarget BP within 30 minutes of starting clevidipine.Clevidipine selectively inhibits extracellular calciuminflux through L-type channels resulting in smoothmuscle relaxation; thus it decreases peripheralvascular resistance. An advantage of clevidipineis that it undergoes metabolism by plasma ester-ases, thus it is independent of renal or hepatic func-tion.11 Loop diuretics such as furosemide are oftenused in combination with antihypertensive therapyto induce diuresis in hypertensive pulmonaryedema. This common practice was recently chal-lenged by a prospective, randomized, double-blinded placebo-controlled study in which theeffectiveness of furosemide in lowering subjectiveperception of dyspnea was compared withplacebo. The results showed no difference in thesubjective perception of dyspnea between the 2groups. Patients in the furosemide group requiredfewer antihypertensive medications, which led toa conclusion that furosemide may have some anti-hypertensive effect via direct venodilation. Theresults of the study challenge the practice of usingloop diuretics to reduce the perception ofdyspnea.21

Aortic Dissection

Aortic dissection is a rare but potentially deadlycomplicationof a hypertensive crisis. Aortic dissec-tion can be misdiagnosed as coronary ischemia,pleurisy, heart failure, stroke, musculoskeletalpain, or an acute abdomen. One must maintaina high index of suspicion, and cardiologists mustbe particularly aware that an aortic dissection canextend into the coronary arteries and present with

Hypertension Crisis in the ED 539

both a history andECG findings identical to thoseofan acutemyocardial infarction. As far as a patient’sinitial presentation is concerned, one shouldremember the 3 Rs, namely rapid onset, ripping,and radiating pain in the chest, back, or both.Many diseases and conditions are associatedwith aortic dissection, but 75% of patients withacute aortic dissection have underlying hyperten-sion22,23 In the ED the diagnosis of aortic dissectionis made using contrast-enhanced CT, magneticresonance imaging, or transesophageal echocardi-ography (TEE), although in most settings CT ischosen because of the need for rapid diagnosis. Adisadvantageof TEE is that itmaynot give sufficientvisualization of the distal ascending aorta or theaortic arch.22

Once the diagnosis of aortic dissection is made,prompt treatment is essential because the deathrate in acute aortic dissection may be as high as1% per hour during the first 24 hours. A type-Adissection is a surgical emergency whereasa type-B dissection can often be managed medi-cally. If the vascular surgery consultant determinesthat emergency surgery is not needed, prompt BPreduction to a target systolic BP of less than 120mm Hg and reduction in heart rate to below 65beats/min should be instituted. Intravenous b-blockade with esmolol or labetalol is usuallystarted to reduce shear stress on the aorta. Otheragents such as sodium nitroprusside are oftenadded, and if the BP is refractory to multiple anti-hypertensive agents, reversible secondary causesof hypertension should be ruled out. Renal arteryhypertension or acute pain from the dissectionhas to be considered as a possible cause ofrefractory hypertension. If the aortic dissection iscomplicated by organ ischemia, limb ischemia,or refractory pain, surgical or endovasculartherapy may be necessary.22,24

Hypertensive Retinopathy

Arteriolar narrowing in patients with mild tomoderate hypertension has been described sincethe late 1800s. Vessel narrowing and arteriolarwall thickening can be early signs of poorlycontrolled BP.25 Retinopathy with bilateral flame-shaped hemorrhages and exudates (cotton-woolspots) usually indicates severe hypertension andis classified as grade III retinopathy. More ad-vanced, grade IV retinopathy includes papillede-ma, which can be seen with hypertensiveencephalopathy.26 These fundoscopic findings ofretinopathy in patients with hypertension havea low sensitivity. Also, there is a high rate of intra-observer and interobserver variability when itcomes to identifying arteriolar narrowing through

ophthalmoscopic examination. This variabilitydecreases with grade III and IV retinopathy.27

Some studies have shown an association betweenthe degree of retinopathy and signs of end-organdamage such as LV hypertrophy, microalbuminu-ria, and coronary artery disease in women.28,29

Ophthalmoscopy can be useful in recognizingacute end-organ damage in the form of papillede-ma in hypertensive encephalopathy, but the lackof arteriolar narrowing, retinal hemorrhages, exu-dates, or papilledema cannot be used to excludea diagnosis.

Acute Renal Insufficiency

Renal insufficiency can be the cause or result ofhypertensive crisis. There are changes in renalarteries in chronic hypertension, including endo-thelial dysfunction and impaired vasodilation.Thus renal autoregulation is altered, resulting inan increase of intraglomerular pressure withincreasing systemic arterial pressure. This rise inpressure can cause ischemic injury and fibrosis.3

Hypertensive emergency can occur in acuteglomerulonephritis, hemolytic uremic syndrome,renal artery stenosis, patients on hemodialysisreceiving erythropoietin with an accelerated rateof increase in hematocrit,30 and in renal transplantpatients, especially those on cyclosporin andcorticosteroids.10

Clinical presentations that suggest renal in-volvement include proteinuria, elevated serumcreatinine, hypokalemic metabolic alkalosis, andmicroangiopathic hemolytic anemia.31 Uremiawas historically the major cause of death until ofhemodialysis and improvedantihypertensivemedi-cations became available. The level of renalrecovery relates to the degree of renal impairmentat presentation and the underlying renal disorder.Minoxidil, a direct arteriolar vasodilator, is a potent,oral agent useful in malignant hypertension associ-ated with renal failure. Minoxidil may cause reflextachycardia and fluid retention.31 ACE inhibitorssuch as captopril and enalapril are the drugs ofchoice for malignant hypertension in patients whopresent with scleroderma renal crises.32 Fenoldo-pam, a selective dopamine-1 receptor agonist,which activates dopamine at the level of the kidney,is a recommended agent for patients with acuterenal insufficiency because it increases renal perfu-sion. Calcium-channel blockers and b-blockerscan also be used for lowering BP, although theyhave no effect on glomerular filtration.3

Hypertension in Pregnancy

Hypertension complicates 5% to 7% of all preg-nancies, and unfortunately is still a leading cause

Johnson et al540

of maternal and fetal morbidity and, rarely,mortality.33–36 ED physicians and obstetriciansoften have to consider preterm delivery as theonly viable option in the management of severepreeclampsia.The hypertension of pregnancy is defined as

a BP greater than 140 mm Hg systolic and/orgreater than 90 mm Hg diastolic according toNational High Blood Pressure Education Pro-gram.37 Preeclampsia is a condition that needsto be distinguished from chronic hypertension,which usually is without complications and canbe treated similarly to hypertension without preg-nancy with treatment plans that are safe for themother and fetus. Preeclampsia is primarily char-acterized by hypertension and proteinuria, butcan also involve multiple organ systems. Theproteinuria is defined by excretion of 300 mg per24 hours, a urine protein/creatinine ratio of greaterthan 0.3, or a qualitative dipstick reading of 11.38

One potentially life-threatening complication ofpreeclampsia is the HELLP syndrome, character-ized by some or all of the following signs: Hemo-lysis, abnormal Elevation of Liver enzyme levels(aspartate aminotransferase and lactate dehydro-genase), and Low Platelets (often <40,000/mL).39

There are multiple controversies related toboth the pathophysiology and management ofpreeclampsia, but there is a general consensusthat only delivery results in a true “cure”.34 Denovo hypertension alone occurring after the 20thweek of gestation in a nulliparous woman should,as a precaution, initially be treated as pre-eclampsia.7 Preeclampsia has also been found tobe a risk marker for future cardiovascular disease,so close postpartum risk-factor monitoring isstrongly recommended.Regarding treatment, there is a consensus that

antihypertensive therapy should be given to lowerthe maternal risk of central nervous systemcomplications in pregnant women with a sustainedsystolic BP greater than 160 mm Hg and/or dia-stolic BP greater than 110 mm Hg.40 At lower BPlevels between 140 and 159 mm Hg systolic and90 and 105mmHg diastolic, there is no consensuson when and how to treat these levels of bloodpressure. The antihypertensive drugs frequentlyused to treat severe hypertension in pregnancyinclude labetalol, hydralazine, nifedipine, and ni-troprusside only as a last resort.33,34 Methyldopa,a central adrenergic inhibitor, is the oral drug ofchoice.34,36 Labetalol is an adrenergic blockingagent that has an oral and parental formulationwith the extra advantage of being safe to use inbreastfeeding women. Hydralazine was onceconsidered the drug of choice in hypertensiveemergencies, but a meta-analysis of multiple

clinical trials found that compared with labetalolor nifedipine, hydralazine was associated withmore cesarean sections, more placental abrup-tion, more maternal oliguria, more adverse effectson fetal heart rate, and more maternal hypoten-sion.41 Nifedipine and magnesium sulfate haveboth been found to be effective in the treatmentof hypertension associated with pregnancy, but itis important to remember that severe reductionsin BP can occur when these agents are giventogether.

Postoperative Hypertension

Postoperative hypertension is defined as signifi-cantly elevated BP within the first 2 hours aftersurgery. The most common cause of postopera-tive hypertension is sympathetic activation andadrenergic surge. Reversible contributors to thissympathetic activation such as pain, hypoxemia,hypercarbia, hypothermia, volume overload, andanxiety should be treated first before ad-ministering antihypertensives unless end-organdamage is present.42 Urinary retention aftersurgery is also thought to cause markedly elevatedBP. Moreover, withdrawal from holding antihyper-tensives should be considered. In general,patients should not stop taking their home antihy-pertensive medications on the day of surgery,especially centrally acting agents such as cloni-dine and b-blockers. Patients with or without pre-existing hypertension can develop postoperativehypertension. Patients with poorly controlledhypertension are more likely to have postoperativehypertension.43 Treatment should be focused onthe cause of the hypertension and on whetherthe patient is able to take oral medications afterthe procedure. If possible, the patient’s homemedication can be given if there are no contraindi-cations. b-Blockers should be avoided in certaininstances such as profound bradycardia, heartblock, severe chronic obstructive pulmonarydisease, or acute heart failure.

Hyperadrenergic States

The hyperadrenergic states include pheochro-mocytoma; cocaine, amphetamine, and phency-clidine overdose; clonidine withdrawal; andmonoamine oxidase (MAO) inhibitor–tyraminereaction. In these conditions there is a surge incatecholamine levels.31 In a pheochromocytomacrisis and MAO inhibitor–tyramine reaction, phen-tolamine, phenoxybenzamine, or nitroprussidecan be used to control BP. The use of b-blockersalone is not recommended for these conditionsbecause it would result in an unopposed periph-eral a-adrenergic vasoconstriction, which further

Table 3Target blood pressure goals

Hypertensive Emergency Target Blood Pressure

Hypertensive encephalopathy MAP lowered by maximum 20% or to DBP 100–110 mm Hg withinfirst hour then gradual reduction in BP to normal range over48–72 h

Ischemic stroke MAP lowered no more than 15%–20%, DBP not less than100–110mmHg in first 24 h (thrombolytic protocols in strokemayallow slightly more aggressive management)

Ischemic stroke post-tPA SBP <185 mm Hg or DBP <110 mm Hg

Intracerebral hemorrhage MAP lowered by 20%–25%

Hypertensive retinopathy MAP lowered by 20%–25%

Left ventricular failure MAP to 60–100 mm Hg

Aortic dissection SBP 100–120 mm Hg

Acute renal insufficiency MAP lowered by 20%–25%

Pregnancy-induced hypertension SBP 130–150 mm Hg and DBP 80–100 mm Hg

Postoperative hypertension MAP lowered by 20%–25% (not based on published guidelines)

Myocardial ischemia/infarct MAP to 60–100 mm Hg

Hyperadrenergic states MAP lowered by 20%–25% (not based on published guidelines)

Abbreviations:DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure; tPA, tissue plasmin-ogen activator.

Hypertension Crisis in the ED 541

increases BP.19 Labetalol, which has both an a-and b-receptor antagonist effect, can also beused in a pheochromocytoma crisis; however,paradoxic hypertension may occur.31 In the caseof cocaine or amphetamine abuse, anxiolyticsshould be given first. Phentolamine can be addedif hypertension persists after anxiolytics have beengiven.44 Hypertension due to clonidine withdrawalshould be treated by giving clonidine first.

SUMMARY

Management of hypertensive crisis in the ED willcontinue to challenge clinicians because of thelack of randomized clinical trials. Expert opinionand sound clinical judgment will continue to guidethe management of hypertension crisis until suchtrials are completed. Hypertensive crisis persistslargely because of medication nonadherence,poorly controlled chronic hypertension, substanceabuse, and poor access to primary care. A few keyprinciples should be noted: (1) verify BP readingsbefore initiating treatment; (2) patients presentingwith a hypertensive emergency should have theirMAP reduced by 20% to 25% within the firsthour, with the exception being ischemic strokeand aortic dissection as noted in Table 3; (3)hypertensive urgencies should be treated withoral, not parental, agents; (4) appropriate testingto differentiate hypertensive urgencies versusemergencies should be done; and (5) once BP is

stabilized with parenteral therapy, the transitionto oral therapy can begin within 6 to 12 hours.

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