I. Problem/Condition.

Hypertensive crises encompass a spectrum of clinical situations that have in common severely elevated blood pressure (BP), usually higher than 180/110mmHg, together with progressive or impending target organ damage.

Patients with hypertensive crises may present with a range of blood pressures, varied clinical symptoms, and the presence or absence of target organ involvement. Early triage in the emergency department is critical to identifying those individuals who may require more aggressive management in the emergency room, or admission for parenteral treatment of the true hypertensive emergency.

II. Diagnostic Approach

A. What is the differential diagnosis for this problem?

Hypertensive crises encompass a spectrum of clinical situations that have in common severely elevated blood pressure (BP), usually higher than 180/110mmHg, together with progressive or impending target organ damage. Below are definitions for terminology used:

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Hypertensive urgency

Situations with markedly elevated BP but without severe symptoms or progressive target organ damage. BP should be reduced within hours with oral agents.

Hypertensive emergency

Situations that require immediate reduction in BP, usually with parental agents, because of acute or progressive target organ damage.

Accelerated-malignant hypertension

The distinction between accelerated (retinal hemorrhages and/or exudates) and malignant (papilledema) hypertension is no longer being made. Both entities reflect microvascular damage and a dire prognosis if untreated.

Hypertensive encephalopathy

Severe headache and various alterations in consciousness associated with the sudden and usually marked elevation of BP. The key to the diagnosis is that it is reversible by reduction of the BP. The algorithm shown below inTable I can help the clinician identify those patients who meet the criteria of a hypertensive emergency that requires immediate admission to an intensive care unit (ICU) for continuous monitoring of BP and initiation of parenteral antihypertensive therapy.

Table I.
Prior diagnosis, duration and treatment of hypertension
Dosing, compliance and control of hypertension
Over the counter medications
Illicit drug use e.g. cocaine use or sympathomimetic drugs
Symptoms of visual, cardiac, renal, cerebral or visual dysfunction.
Comorbid conditions
Risk factors for end-organ damage
Physical examination
Blood pressure
Cardiovascular status
Neurological status
Fluid volume status
Peripheral pulses
Complete blood count (CBC) and peripheral smear
Blood chemistry
Urine analysis
Chest X-ray (CXR), Electrocardiography (EKG)
>SpecificTesting Done if clinical picture is consistent with specific diagnosis
Neuroimaging: Acute stroke, subarcahnaoidhemorrhage
Echcocardiogram; Acute left heart failure,myocardial ischemia
CT/MRI Chest: Aortic dissection

B. Describe a diagnostic approach/method to the patient with this problem

Diagnostic evaluation

For an initial evaluation of a patient with severe hypertension, seeTable I. For end-organ damage risk factors in patients with severe hypertension, seeTable II

Table II.
Uncontrolled hypertension
Diabetes mellitus
Metabolic syndrome
Atleast three cardiovascular risk factors (Age>55 in men and >45 in women, smoking, dyslipidemia, obesity)
One or more finding of subclinical organ damage (LVH, reduced GFR or Crcl, proteinuria)
Established renal or cardiovascular disease

Patients with hypertensive crises may present with a range of blood pressures, varied clinical symptoms, and the presence or absence of target organ involvement. The clinical manifestation of hypertensive are directly related to the particular end-organ dysfunction that has occured, hence signs and symptoms usually vary. The clinical characteristics of a hypertensive emergency are listed inTable III

Table III.
Blood pressure (mm Hg) Funduscopic findings Neurologic status Cardiac findings Renal symptoms GI symptoms
Usually >220/120 Hemorrhages, exudates, papilledema Headache, confusion somnolence, stupor, visual loss,seizures, focal neurologic deficits, coma Chest pain, pulmonary edema, Prominent apical pulsation, congestive heart failure Azotemia Proteinuria oliguria Nausea vomiting

1. Historical information important in the diagnosis of this problem.

A brief but thorough history and physical examination helps determine the nature, severity and subsequent management of acute hypertensive syndromes. History should include the duration, as well as the severity of hypertension, and adequacy of control. Adherence, dosing of all current medications, including prescription and nonprescription drugs, and the use of recreational drugs, should be reviewed. Direct questioning regarding the level of adherence may help establish inadequacy of treatment or frank noncompliance.

A history of other comorbid conditions and prior cardiovascular or renal disease is essential to the initial evaluation. Historical information suggestive of neurologic, cardiovascular, and/or renal symptoms should be sought. Specific manifestations such as headache, seizures, chest pain, dyspnea, or edema should be assessed. One should also look for risk factors for endorgan damage to identify those individuals who will most benefit from aggressive long-term and short-term management.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

The intial assessment will aid in establishing the degree of involvement of affected target organs and should provide clues to the possible existence of a secondary form of hypertension, such as renovascular hypertension. If a secondary cause of hypertension is suspected, appropriate blood and urine samples should be obtained before aggressive therapy is initiated.

The physical examination should begin with an assessment of using an appropriately sized cuff in both upper extremities. Brachial, femoral, and carotid pulses should also be assessed. Ausculating lungs for evidence of pulmonary edema, neck for carotid bruit and jugular venous distention (JVD), a careful cardiovascular examination with a focus on the presence for murmurs, gallops and left ventricular heave.

The neurologic examination should be focused to asses level of consciousness, signs of meningeal irritation, visual fields, and focal signs. A careful funduscopic examination should be performed to detect the presence of hemorrhages, exudates, and/or papilledema as it is particularly useful to distinguish hypertensive emergency from urgency.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Initial laboratory studies should be limited and rapidly expedited. A urinalysis with microscopic examination of the urinary sediment, an immediate chemistry panel, and an electrocardiogram should be obtained. The urinalysis may reveal significant proteinuria, red blood cells, and/or cellular casts. Cellular casts are suggestive of renal parenchymal disease. Electrolyte abnormalities, particularly hypokalemia or hypomagnesemia, increase the risk of cardiac arrhythmias, and the chemistry panel will also provide evidence of renal or hepatic dysfunction, or both.

The electrocardiogram should identify evidence of coronary ischemia, left ventricular hypertrophy, or both, and may reveal pulse deficits, raising the question of aortic dissection. When the clinical examination suggests cerebrovascular ischemia or hemorrhage, or if the patient is comatose, a computed tomography (CT) scan of the head should be immediately obtained. If the clinical picture is consistent with acute dissection (severe chest pain, unequal pulses, widened mediastinum then CT scan of chest or MRI should be considered as part of intial evaluation.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Table IV outlines some guidelines for triage evaluation of patient with severely elevated blood pressure. Early triage in the emergency department is critical to identify those individuals who may require more aggressive management with parenteral agents for true hypertensive emergency.

Table IV.
Parameter Hypertensive urgency Hypertensive emergency
Asymptomatic Symptomatic
Blood pressure (mm Hg) >180/110 >180/120 Usually >220/140
Symptoms Headache, anxiety; often asymptomatic Severe headache, shortness of breath Shortness of breath, chest pain, nocturia, dysarthria,weakness, altered consciousness
Examination No target organ damage, no clinical cardiovascular disease Target organ damage; clinical cardiovascular disease present, stable Encephalopathy, pulmonary edema, renal insufficiency, cerebrovascular accident, cardiac ischemia
Therapy Observe 1-3 hr; initiate, resume medication; increase dosage of inadequate agent Observe 3-6 hr; lower BP with short-acting oral agent; adjust current therapy Baseline laboratory tests; intravenous line; monitor BP; may initiate parenteral therapy in emergency room
Plan Arrange follow-up within 3-7 days; if no prior evaluation,schedule appointment Arrange follow-up evaluation in less than 72 hrs Immediate admission to ICU; treat to initial goal BP;additional diagnostic studies

III. Management while the Diagnostic Process is Proceeding

A. Management of hypertensive emergencies

Initial management of blood pressure and autoregulation

The initial goal in hypertensive crises is to reduce BP, not to obtain a normal BP; BP must be lowered in a slow and controlled fashion to minimize the risk of hypoperfusion to vital organs. Under normal conditions, blood flow to cerebral coronary and renal circulatory beds remains relatively constant, despite wide BP fluctuations. In the presence of hypertensive urgency the autoregulatory curve is shifted rightwards in critical arterial beds so that higher levels of BP are tolerated, but sudden reductions in BP below the autoregulatory range of these vascular beds.

Cerebral blood flow is tightly regulated within a certain range of mean arterial pressure,with chronic hypertension, cerebral autoregulation undergoes a rightward shift Abruptly decreasing the mean arterial pressure can potentially lead to a significant drop in cerebral blood flow and, thus, cerebral ischemia may result in marked reduction in perfusion and put at risk ischemia and infarction.

For example, studies on the autoregulation of cerebral blood flow have suggested that the lower limit of autoregulation is approximately 25% below the resting mean arterial pressure in normotensive subjects and in those with uncomplicated hypertension.

Initial goal of blood pressure control

Although aggressive treatment is appropriate, the initial reduction in mean arterial pressure should not exceed 20% to 25% below the pre-treatment BP. As an alternative, mean arterial pressure can be reduced within the first 30 to 60 minutes to 110 to 115mmHg. If this level is well tolerated and the patient is clinically stable, further gradual reductions toward a normal BP can be implemented over the next 24 hours. With judicious and gradual BP lowering, hypoperfusion is rarely seen and autoregulatory mechanisms reset toward more normal levels.

Excessively rapid reductions in BP have been associated with acute deterioration in renal function, ischemic cardiac or cerebral events, and occasional retinal artery occlusion and acute blindness. There are significant exceptions to these initial recommendations and these are discussed in more detail later in the section on the treatment of select hypertensive emergencies.

Parenteral agents

Parenteral therapy may be initiated in the ED if suitable supervision and monitoring of BP can be provided. Patients with hypertensive emergency should be transferred to an ICU where continuous nursing supervision and monitoring of BP are available. For those patients with the most severe clinical manifestations or with the most labile BP, intra-arterial BP monitoring may be prudent. There are a variety of parenteral agents that are available and are effective in the immediate treatment of hypertensive emergencies. List of recommended parenteral agents are shown inTable V

Table V.
Agent Dosage Onset/duration of action (after discontinuation) Precautions
Sodium nitroprusside 0.25-10 μg/kg/min as IVinfusion Immediate/2-3 min after infusion Nausea, vomiting; prolonged use may cause thiocyanate intoxication, methemoglobinemia, acidosis, cyanide poisoning
Nitroglycerin 5-100 μg as IV infusion 2-5 min/5-10 min Headache, tachycardia, vomiting, flushing, methemoglobinemia
Nicardipine 5-15 mg/hr as IV infusion 1-5 min/15-30 min, but mayexceed 12 hr after prolonged infusion Tachycardia, nausea, vomiting, headache, increased intracranial pressure; hypotension may beprotracted after prolonged infusions
Fenoldopam mesylate 0.1-0.3 μg/kg/min as IVinfusion <5 min/30 min Headache, tachycardia,flushing, local phlebitis, dizziness
Hydralazine 5-20 mg as IV bolus or10-40 mg IM; repeat every 4-6 hr 10 min IV/>1 hr (IV);20-30 min IM/4-6 hr (IM) Tachycardia, headache,vomiting, aggravation of angina pectoris, sodium and water retention,increased intracranial pressure
Enalaprilat 0.625-1.25 mg every 6 hr asIV injection Within 30 min/12-24 hr Renal failure in patientswith bilateral renal artery stenosis, hypotension
Parenteral adrenergic inhibitors
Labetalol 20-40 mg as IV bolus every10 min; up to 2 mg/min as IV infusion 5-10 min/2-6 hr Bronchoconstriction, heartblock, orthostatic hypotension, bradycardia
Esmolol 500-μg/kg bolus injectionIV or 50-100 μg/kg/min by infusion; may repeat bolus after 5 min or increaseinfusion rate to 300 μg/kg/min 1-5 min/15-30 min First-degree heart block, congestive heart failure, asthma
Phentolamine 5-10 mg as IV bolus 1-2 min/10-30 min Tachycardia, orthostatic hypotension

The agent of choice should depend on which manifestation of end-organ damage is present as outlined further inTable VI

Table VI.
Emergency Drugs of choice Target blood pressure
Aortic dissection Nitroprusside + esmolol 110-120 SBP as soon as possible
AMI, ischemia Nitroglycerin, nitroprusside, nicardipine Secondary to ischemia relief
Pulmonary edema Nitroprusside, nitroglycerin, labetalol Improve symptoms 10%-15% in 1-2 hr
Renal emergencies Fenoldopam, nitroprusside, labetalol Target BP 20%-25% in 2-3 hr
Catecholamine excess Fenoldopam, nicardipine labetalol, phentolamine Control paroxysms 10%-15% in 1-2 hr
Hypertensive encephalopathy Nitroprusside 20%-25%in 2-3 hr
Subarachnoid hemorrhage Nitroprusside, nimodipine, nicardipine 20%-25%in 2-3 hr
Ischemicstroke Nitroprusside (controversial), nicardipine 0%-20%in 6-12 hr
Special considerations in select hypertensive emergencies

Aortic dissection

This is a special type of hypertensive emergency because of very high short-term risk and the lower recommended target systolic blood pressure. There is general agreement that at the time of diagnosis, and perhaps even when it is suspected, quickly controlling the systolic BP to lower than 120mmHg within 10 to 20 minutes supersedes the performance of any time-consuming techniques used to identify the dissection. It is important to recognize that propagation of the dissection not only on BP itself, but also on the velocity of left ventricular ejection.

A vasodilator alone is not ideal in the treatment of acute aortic dissection because it can promote reflex tachycardia, increase aortic ejection velocity, hence combination of a beta adrenergic agonist and vasodilator is the standard approach to treatment. Esmolol is the B-adrenergic antagonist of choice along with nitroprusside as the vasodilator of choice. Other effective choices or alternatives for B adrenergic are metoprolol, and for vasodilator are nicardipine and fenoldopam.

The location and the extent of the dissection will determine the need for immediate surgery versus long-term medical therapy.

Acute coronary syndrome

This situation includes patients presenting with unstable angina or myocardial infarction. Priority in this case is relief of chest pain, together with opening the coronary artery responsible in the case of a myocardial infarction. Hypertension is often affected by acute adrenergic stimulation caused by ischemic chest pain or severe anxiety. Control of BP is an important adjuvant to therapy. It is especially important if thrombolytic therapy is considered. The level of BP will determine the use of nitroglycerin or nitroprusside in this situation.

A reduction of 10% to 20% over the first 1 to 3 hours will often be sufficient to alleviate chest pain.

Acute pulmonary edema

Severe hypertension in the setting of congestive heart failure often results in pulmonary edema and a sharp reduction in effective circulating blood volume. In this setting, the agents of choice are those that reduce preload and afterload. The most effective is sodium nitroprusside or fenoldopam, although nitroglycerin can also be valuable, particularly if BP is not markedly elevated. Appropriate and timely use of a parenteral loop diuretic should also be considered.

Acute or chronic renal failure

This can be associated with severe hypertension. In particular, new or acutely worsening azotemia or the presence of dysmorphic red cells or red cell casts in the urine should prompt early and aggressive therapy. A gradual reduction in BP of 20% to 25% during the first 1 to 3 hours is particularly helpful. Nitroprusside, labetalol, and nicardipine are all effective; however, strong consideration should be given to fenoldopam as the agent of choice because of its favorable effects on renal function.

Adrenergic crises

The most commonly encountered hypertensive emergency is usually related to use of recreational drugs such as cocaine or amphetamine intoxication. Blood pressure control can be best achieved with nicardipine, fenoldapam, or verapamil in combination with bezodiazepams. If the hypertensive crisis is observed secondary to clonidine withdrawal, immediate reinstitution of clonidine is appropriate.

In all these situations, care must be taken to select antihypertensive therapies that will not result in unopposed a-adrenergic stimulation, which could worsen the hypertension. Beta-blockers are generally avoided, but if there is indication for beta-blocker use then labetalol is a useful agent with its alpha and beta blocking characteristics.

Hypertensive encephalopathy

This is a potentially lethal complication of severe hypertension and may be seen in association with a number of hypertensive emergencies. When markedly elevated BP exceeds the autoregulatory ability of the brain to maintain constant cerebral perfusion, the resultant diffuse cerebral edema can lead to progressive neurologic dysfunction. The finding of exudates, hemorrhages, and/or papilledema on funduscopic examination, together with new focal neurologic findings, altered level of consciousness, new-onset seizures, or sensory deficits, supports this diagnosis.

Although hypertensive encephalopathy typically follows a more subacute time course, it is nevertheless a diagnosis of exclusion and requires that stroke, intracranial hemorrhage, seizure disorders, or mass lesions be ruled out. Distinguishing among these potential mechanisms of injury can be clinically difficult, and has a significant impact on subsequent therapy. The best approach is to use an available imaging procedure to clarify the diagnosis.

When hypertensive encephalopathy is suspected, BP should be promptly lowered with nitroprusside or labetalol, with careful monitoring and frequent neurologic assessments. BP reduction can be associated with dramatic improvement in cerebral function. However, deterioration in neurologic function will require re-evaluation and consideration of other possible diagnoses.

Subarachnoid hemorrhage

Controlled lowering of the BP is currently recommended. There is no evidence that hypertension provokes further bleeding in patients with intracranial bleed. Agent of choice again would be sodium nitroprusside. Nicardipine has also proved effective. Another dihydropyridine calcium antagonist, nimodipine, has demonstrated antihypertensive and anti-ischemic effects that may improve long-term outcomes of subarachnoid hemorrhage but not necessarily ischemic stroke.

Ischemic stroke

This is a special situation and there is a controversy regarding the optimal management of patients suffering from an ischemic stroke in the setting of hypertension. Stroke may result from hypertension or the hypertension may be a consequence of the event itself. In the latter situation, BP elevations will often remit during the first several days of hospitalization.

The stroke may result in the creation of watershed areas of tissue that are not ischemic and remain viable as long as perfusion is maintained; they may depend on the higher perfusion pressure conferred by the systemic hypertension. Thus, acute reductions in BP may result in extension of the ischemic damage to these areas.

The American Stroke Association and the European Stroke initiative guidelines recommend withholding antihypertensive therapy for acute ischemic stroke unless there is planned thrombolysis. Recommendation is not to pursue BP reduction aggressively unless the BP following admission persists at higher than 220mmHg/120mmHg.

In these patients, the aim is to reduce the pressure by no more than 10-15% in the first 24 hours. First-line agents include nitroprusside, nicardipine, fenoldopam, and labetalol. The use of parenteral agents with short half-lives is most appropriate in this situation.