Management of Hypertensive Crises

Carlos Feldstein, MD*

Hypertensive emergencies are life-threatening conditions because their course is complicated withacute target organ damage. They can present with neurological, renal, cardiovascular, micro-angiopathic hemolytic anemia, and obstetric complications. After diagnosis, they require theimmediate reduction of blood pressure (in ,1 hour) with intravenous drugs such as sodiumnitroprusside, administered in an intensive care unit. These patients present with a mean arterialpressure .140 mm Hg and grade III to IV retinopathy. Only occasionally do they have hypertensiveencephalopathy, reflecting cerebral hyperperfusion, loss of autoregulation, and disruption of the blood-brain barrier. In hypertensive emergencies, blood pressure should be reduced about 10%during the first hour and another 15% gradually over the next 2 to 3 hours to prevent cerebralhypoperfusion. The exception to this management strategy is aortic dissection, for which the target issystolic blood pressure,120 mm Hg after 20 minutes. Oral antihypertensive therapy can usually beinstituted after 6 to 12 hours of parenteral therapy. Hypertensive urgencies are severe elevations of  blood pressure without evidence of acute and progressive dysfunction of target organs. Theydemand adequate control of blood pressure within 24 hours to several days with use of orallyadministered agents. The purpose of this review is to provide a rational approach to hypertensivecrisis management.

Keywords: hypertensive crisis, hypertensive emergencies, management

INTRODUCTION

The majority of cases of severe hypertension charac-terized by diastolic blood pressure (BP) .120 mm Hgor systolic BP .180 mm Hg can be controlled withdrugs given orally. However, in some patients hyper-tension is life-threatening because there is evidence of rapid failure of vital organs; these patients requireimmediate reduction of BP, usually in ,1 hour, bymeans of intravenous drugs.1–8 These conditions,called hypertensive emergencies, can occur at anyage, and their more frequent causes are listed in Table 1.Although hypertensive emergencies have becomeless common, it is estimated that about 1% of hyper-tensive patients will develop a hypertensive crisis.1,2

It has been estimated that hypertensive emergencies

account for .25% of all patients’ visits to themedical section of an emergency department, withhypertensive emergencies detected in one-third of these cases.3

Most patients presenting with hypertensive emer-gency have had previously inadequately controlledor unknown chronic hypertension, although thedisorder can present in previously normotensiveindividuals, particularly when associated with pre-eclampsia or acute glomerulonephritis.4–7 Hyperten-sive emergencies also may develop in the course of secondary hypertension, particularly that associatedwith renovascular disease, pheochromocytoma, and(less frequently) primary aldosteronism. Criticallyelevated BP without evidence of acute and progres-sive dysfunction of target organs is called hyper-tensive urgency.1–8 Such patients require adequatecontrol of BP within 24 hours to several days by meansof orally administered agents in a closely monitoredoutpatient setting.

The purpose of this review is to describe a rationalapproach toward and appropriate therapy for hyper-tensive crises.

 Hypertension Program, Hospital de Clinicas Jose de San Martın,Buenos Aires University and Instituto Universitario de Cienciasde la Salud, Buenos Aires, Argentina.*Address for correspondence: Av Rivadavia 4243, 6P, Buenos Aires(1205), Argentina. E-mail: carlfel@yahoo.com

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1075–2765 Ó 2007 Lippincott Williams & Wilkins

 

Clinical evaluation

Medical history should include previous treatments(antihypertensive agents and compliance), illicit druguse (cocaine and others), cardiovascular manifestations(heart failure, angina, aortic disection), and neurologicsymptoms (headache, blurred vision, changes in mentalstatus, nausea, vomiting, weakness, and renal symptomssuch as hematuria and oliguria). Information about othermedical conditions such as thyroid disease, Cushingsyndrome, systemic lupus, systemic sclerosis, abdominalpain, and dyspnea and the date of most recent men-struation should be ascertained. Physical examinationmust be directed toward the cardiovascular and neuro-logical systems. BP must be measured in both arms todetect any significant differences. Other tests includeperipheral pulse exploration for absence or delay (whichwould suggest aortic dissection), fundoscopy (searchingfor softexudates, hemorrhages, and papilledema), cardiacand lung auscultation (S3, rales), assessment of mental

status, and examination for focal or lateralizing neuro-logic signs that are infrequent in hypertensive encepha-lopathy and usually suggest some other cerebrovasculardisease (hemorrhage, embolism, or atherosclerotic throm- bosis). Laboratory studies and electrocardiographyshould be performed immediately after presentationand may provide crucial clues to underlying conditions.Imaging should be performed for presumptive diagnosisof the primary cause of the hypertensive crisis.

Management of hypertensive crisis

The distinctions between hypertensive emergenciesand urgencies are often ambiguous. It appears to be better to institute immediate antihypertensive treat-ment for all patients, with the agent and route of administration chosen on the basis of clinical criteriaand available resources.8

The first consideration in BP management in thesetting of a life-threatening condition is that BP level isnot the most critical factor in determining the existenceof a hypertensive emergency. Prehospital treatmentmay include furosemide when there is clear evidence of volume expansion, as in heart failure or acute nephritis.On the other hand, the use of loop diuretics mayworsen hypertension that is secondary to increasedrenin production by causing further volume contrac-tion. Nitrates and oxygen administration may be usedin conditions where they are indicated. In hypertensiveemergencies, sublingual or oral nifedipine is absolutelycontraindicated because it produces a nonpredictablereduction of BP, accompanied by heart and brain ische-mia. Clonidine is also contraindicated because it isa strong sedative and causes hypertensive reboundwhen it is withdrawn.

After hospital admission the hypertensive emer-gency should be managed with one of the parenteraldrugs listed in Table 2, according to etiology. The mainobjective is to reverse end-organ damage, which isaccomplished by reducing mean arterial pressure byup to 25% over minutes to a few hours. Once thepatient’s condition has stabilized, an oral medicationcan be substituted and the physician should discusslong-term follow-up plans.

The following are the drugs of choice in thetreatment of hypertensive emergencies.

Sodium nitroprusside is a first-choice agent for themajority of hypertensive emergencies.10,11 This agent isa potent arterial and venous vasodilator with a veryrapid onset of action (within seconds of beginning aninfusion) and a very short duration of effect; it is easilytitratable. It is administered as an intravenous infusion,with intra-arterial line BP monitoring. Nitroprussidereduces preload, afterload, and myocardial oxygen re-quirements. Because it is light-sensitive, the containers

Table 1. Causes of hypertensive emergencies.

Uncontrolled essential hypertension

Cerebrovascular conditions

Hypertensive encephalopathy

Ischemic stroke

Intracerebral hemorrhage

Eclampsia, pre-eclampsia

Renal Diseases

Acute glomerulonephritis

Renovascular hypertension

Renal crises from systemic sclerosis

Post-renal transplantation

Renal malformation

Endocrine Diseases

Pheochromocytoma

Cushing syndrome

Primary aldosteronism

Aortic dissection

Aortic coarctation

Drug-induced hypertension

Cocaine

Amphetamine

SSRI

MAOI in combination with certain foods or drugs

Rebound hypertension

Abrupt withdrawal of clonidine, ACEI, or b-blockers

Postoperative hypertension

Burns

Head injuries and CNS trauma

Autonomic hyperactivity (Guillain-Barre syndrome)

Vasculitis

SSRI, selective serotonin reuptake inhibitors; ACEI, angiotensin-

converting enzyme inhibitors; MAOI, monoamine oxidase

inhibitors; CNS, central nervous system.

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136 Feldstein 

 

and tubings must be light-resistant. Sodium nitroprus-side doses can be carefully adjusted for a controlledreduction of BP. Its main indications are hypertensivecrises complicated with hypertensive encephalopathy,heart failure, aortic dissection, and adrenergic crisis.The most important adverse effect of sodium nitro-prusside include intoxication with thiocyanate (ametabolite of nitroprusside), which can occur whenthis agent is administered for more than 48 to 72 hours,particularly in patients with renal or liver dysfunction.Thiocyanate intoxication presents with nausea, vomit-ing, tinnitus, muscle cramps, hyperreflexia, disorien-tation, and psychosis.12 Treatment of thiocyanatetoxicity includes administration of hydroxycobalaminand sodium thiosulfate infusions, and in chronic renalfailure dialysis may be indicated. Nitroprusside in highdoses may increase intracranial pressure, which couldlimit its usefulness in patients with central nervoussystem complications. Extravasation can cause localtissue necrosis.

Nitroglycerin is a powerful venodilatator that reducespreload, increases coronary blood flow through col-lateral coronary vessels dilation, suppresses coronaryvasospasm, and decreases cardiac oxygen demands.Higher doses are required to produce arteriolar vaso-dilatation. Nitroglycerin is the best agent in hyperten-sive crises that are complicated with ischemic heartdisease and after coronary bypass.10,12 Tolerance tonitroglycerine develops if it is administered continu-ously for 24 to 48 hours. Glass containers must be used because polyvinyl chloride containers and tubing mayabsorb it in an unpredictable manner. This agent iscontraindicated for cerebral hemorrhage, because itmay increase intracranial pressure, and for closed-angle glaucoma.

Nicardipine is a dihydropyridine calcium antagonistwith intermediate onset and duration of effect and aprolonged half-life, which has been used for the control

of perioperative hypertension in cardiac surgerypatients. Nicardipine also reduces cerebral ischemia.Its adverse effects include reflex tachycardia, headache,nausea, and vomiting. This agent potentiates curareeffects and has interaction with inhalant anesthetics.Nicardipine contraindications are heart block, acutemyocardial infarction, and renal failure.2,7

 Fenoldopam is a selective agonist of dopaminergic-1receptors, which produces arterial vasodilatation andincreased renal blood flow and natriuresis that is beneficial in patients with renal failure.13 This agenthas a rapid onset of action and ease of BP titration.Fenoldopam must be administered as an intravenousinfusion and not as a bolus; the increments must notexceed 0.1 mg/kg/min at 20-minute intervals, and thehighest dose should not exceed 1.7 mg/kg/min. It doesnot cause rebound hypertension, and therefore it can bewithdrawn by tapering off or stopping its administra-tion abruptly. The efficacy of fenoldopam is similar tothat of nitroprusside, but it has the advantage of notrequiring a line for intra-arterial BP monitoring.However, it is expensive and not readily available insome places. Its main indications are severe hyperten-sion with renal failure and acute heart failure.Fenoldopam is contraindicated for glaucoma. Sideeffects include headache, flushing, dizziness, tachycar-dia or bradycardia, hypokalemia, and local phlebitis.

Labetalol is a nonselective b- and a1-blocker (in theratio of 3–7:1) with a rapid onset of action, sustainedeffect, and low toxicity.12,14 It reduces peripheralvascular resistance without a reflex increase in systolicvolume. Labetalol administration does not requireintra-arterial BP monitoring. Its main indications arehypertensive encephalopathy and adrenergic crisis.This agent is contraindicated for heart failure, heart block, and chronic obstructive pulmonary disease.

Esmolol is an ultrarapid, short-acting b-1 selectiveadrenergic blocker with no intrinsic sympathomimetic

Table 2. Agents for management of hypertensive crises.

Drug Dose Onset of action Duration of action

Sodium nitroprusside 0.25–10 mg/kg/min as IV infusion;

maximal dose for 10 minutes only

Seconds to 2 minutes

after beginning of infusion

1–3 minutes

Nitroglycerin 5–100 mg/min as IV infusion 2–5 minutes 5–10 minutes

Fenoldopam 0.1–0.3 mg/kg/min as IV infusion 5–15 minutes 30 minutes to 4 hours

Nicardipine 5–15 mg/hr as IV infusion 1–5 minutes 15–120 minutes

Hydralazine 10–20 mg as IV bolus

or intramuscularly; repeat

every 4–6 hours

(maximum dose: 40 mg)

10–20 minutes 3–8 hours

IV, intravenous.

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activity; it has been approved by the U.S. Food andDrug Administration only for perioperative hyperten-sive emergencies. Esmolol administration requires aline for intra-arterial BP monitoring. Adverse reactionsinclude thrombophlebitis and extravasation of thisagent, resulting in local necrosis. It is contraindicatedfor cocaine toxicity when used alone and in heart fail-ure, chronic obstructive pulmonary disease/asthma, andatrioventricular block.

 Hydralazine is a direct arterial vasodilator. It also hasthe property of improving uterine blood flow. Theadverse effects include significant reflex sympatheticstimulation, sodium and water retention, flushing,headache, and increase of intracranial pressure. It isindicated only for pre-eclampsia and eclampsiaand is contraindicated for patients with coronaryatherosclerosis.1,2,4–9

Phentolamine is a competitive, nonselective a-blockerand is the drug of choice only for adrenergic crisis(drug-induced or secondary to pheocromocytoma).After administration of an intravenous bolus injectionof 5 to 10 mg, BP decreases within several minutes.6–8

Management of specific conditions

In general, BP should be reduced about 10% during thefirst hour and another 15% gradually over the next 2 to3 hours. The exception is aortic dissection, for whichthe target is systolic BP ,120 mm Hg after 20 minutes.In the elderly, use of lower doses of drugs is rec-ommended, and the BP should not be reduced as muchas in younger patients. Because many patients withhypertensive crisis are volume-depleted as a result of pressure-induced natriuresis, the use of loop-diureticsshould be avoided initially unless there is clearevidence of volume overload. Because of the same rea-son, potent vasodilators such as nitroprusside should be avoided because it may cause a sudden decrease inBP below a safe target level. Oral antihypertensivetherapy can usually be instituted after 6 to 12 hours of parenteral therapy.15

 Hypertensive encephalopathy

The main goal of treatment is to decrease mean arterialpressure by 20% or diastolic BP to 100 to 110 mm Hg inthe first hour. In general, the drug of choice is sodiumnitroprusside. Nevertheless, sometimes it may reducecerebral blood flow in areas with a fixed arterialnarrowing and thus lead to cerebral steal phenomenonand focal ischemia. It has been proposed that labetalol ornicardipine may be a better choice, because these drugsare less likely to decrease cerebral blood flow. Lack of improvement in neurologic symptoms suggests a stroke.Cerebral blood flow autoregulation is disrupted in thesetting of acute brain ischemia. This results when

cerebrovascular resistance fails to respond to changesin cerebral perfusion pressure. When BP is suddenlyreduced in these conditions, cerebral blood flow may bestrongly decreased and neurologic deficits may worsen.

There is consensus that BP must not be reducedin ischemic stroke patients unless they are candidatesfor thrombolytics.16 When thrombolytic treatmentis planned for ischemic stroke, the BP must be#180/105 mm Hg. If the BP is .220/120 it would be acceptable to gradually reduce the BP in 24 to48 hours. When diastolic BP is .140 mm Hg, sodiumnitroprusside should be administered in order todecrease diastolic BP 10% to 15% in 12 to 24 hours.

There is no evidence that hypertension increases therisk of intracerebral hemorrhage or of a new hemor-rhage. Vasospasm and reduction of brain perfusion arecommon in areas adjacent to an intracerebral hema-toma. Furthermore, in ischemic stroke the suddenreduction of mean arterial pressure may aggravate brain ischemia. In some cases, hypertension may bea secondary phenomenon and BP may spontaneouslydecrease in a few hours.

 Heart failure

When the patient has pulmonary edema, nitroglycerinor nitroprusside is the drug of choice, and the target isto reduce BP to normal or near-normal levels.

Coronary insufficiency

Nitroglycerin is the drug of choice and should berapidly titrated to the desired effect. One alternativeto the intravenous route is to administer 1.25 mg of isosorbide dinitrate aerosol upon arrival.17 If BP doesnot decrease with use of nitroglycerin, then nitroprus-side should be added to the regimen. Nevertheless, theadverse reactions of nitroprusside may include barore-flex activation, causing tachycardia, and coronarysteal phenomenon, with worsening of ischemia inareas with fixed coronary stenosis. Other agents thatcan be used when there is no concomitant heart failureare b-blockers.

 Aortic dissection

In this condition, systolic BP must be reduced to 100 to120 mm Hg as soon as possible, by means of acombined treatment with sodium nitroprusside anda b-blocker (esmolol appears to be more usefulthan propranolol). b-blockade must be establishedfirst, before starting the nitroprusside infusion. Analternative agent is labetalol, which may be used as theonly treatment because it has both b- and a-blockingeffects. Heart rate must be maintained between 60 and80 beats/minute.

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 Adrenergic crises

The drug of choice is phentolamine, and another optionis the combination of sodium nitroprusside and ab-blocker. It has to be taken into account that b-blockerscan exacerbate hypertension in patients with adrener-gic crisis and thus should not be used until adequatea-receptor blockade is achieved. Labetalol is relativelycontraindicated because it produces more b- thana-blocking effects, allowing a paradoxical increase inBP from the absence of opposition to the a effect of catecholamines (or cocaine, amphetamines, or tyraminein those receiving monoamine oxidase inhibitors).

Pre-eclampsia

This condition, either mild or severe, is managed bestwith a policy of delivery at or beyond 37 or 34 weeks’gestation, respectively.19 Even though no single anti-hypertensive drug has been proven to be better thananother, intravenously administered hydralazine isprobably the initial agent of choice.20 The aim is todecrease diastolic BP to 80 to 100 mm Hg. Severe pre-eclampsia should be treated with intravenous magne-sium to prevent progression to eclampsia. It must beemphasized that nitroprusside is relatively contra-indicated in pregnancy.

 Hypertensive emergencies in the perioperative setting

The drugs of choice are esmolol, nitroglycerin (aftercoronary bypass surgery), nicardipine, nitroprusside,and fenoldopam.

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