Hypertensive Crisis

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88 Hypertensive Crisis

Emergency and Urgency

Hypertension is a common problem, and its incidence may be increasing in adults.1 Population data also suggest hypertension is increasing globally; 972 million individuals worldwide now have hypertension,1 and 30% of hypertensive individuals are unaware of their diagnosis.2 Of the 59% of hypertensive individuals being treated for hypertension, only 34% have a blood pressure less than 140/90 mm Hg.2 The exact risk of hypertensive crisis is not clear, but most authors estimate the risk to be less than 1%; it may be increasing.3,4

Hypertensive emergency is defined as an elevated blood pressure associated with evidence of acute end-organ damage. With acute damage to vital organs such as the kidney, heart, and brain, there is a significant risk of morbidity in hours without therapeutic intervention. Both the absolute level of blood pressure as well as the time course of blood pressure elevation determines the development of crisis. In general, with hypertensive crisis, the diastolic blood pressure is above 120 mm Hg. However, in children, gravid females, and previously normotensive individuals, hypertensive crises may occur with relatively minor increases in blood pressure. It is very important to identify this syndrome early to prevent end-organ damage and institute appropriate therapy as soon as the diagnosis is realized. Malignant hypertension is a specific syndrome in which a markedly elevated blood pressure is associated with hypertensive neuroretinopathy.

Individuals with hypertensive urgency have an elevated blood pressure (systolic blood pressure often >180 and diastolic pressure often >115 mm Hg) without evidence of acute end-organ damage. Hypertensive urgency may be associated with chronic, stable complications such as stable angina, previous myocardial infarction, chronic congestive heart failure, chronic renal failure, previous transient ischemic attacks, or previous cerebrovascular accident with no threat of an acute insult. Hypertensive urgency may also be associated with inadequately treated blood pressure or noncompliance. Complications from hypertensive urgency are not immediate. In contrast to hypertensive crisis, a more gradual blood pressure reduction over hours is recommended.

An increased blood pressure can occur in the absence of acute or chronic target organ dysfunction. When the etiology of hypertension is not identified, the blood pressure is lowered over days to weeks. However, occasionally an elevated blood pressure may result from drug use, including over-the-counter medications such pseudoephedrine and elicit substance abuse, as for example with cocaine. In these situations, the blood pressure is lowered rapidly. The focus of this chapter is hypertensive emergencies including hypertensive crisis and hypertensive urgency.

image Pathophysiology of Hypertensive Crisis

The precise pathophysiology of hypertensive crisis is unknown. An abrupt increase in blood pressure is one of the initiating events in the transition from simple hypertension or normotension to hypertensive crisis. The product of cardiac output and peripheral vascular resistance determines blood pressure. The initial blood pressure increase is likely secondary to an increase in vascular resistance. Considerable evidence suggests that mechanical stress in the arteriolar wall leads to disruption of endothelial integrity.5 With disruption of vascular integrity, diffuse microvascular lesions develop.6,7 Fibrinoid necrosis of the arterioles is seen in vulnerable organs and is considered the histologic hallmark of hypertensive crisis.6,7 It is unclear whether hypertension alone causes the development to hypertensive crisis or whether other factors are necessary. For example, increases in peripheral vascular resistance result in part from activation of the renin-angiotensin-aldosterone system. Evidence suggests angiotensin II may directly injure the vascular wall by activation of genes for proinflammatory cytokines (interleukin 6) and also of nuclear factor κB.8,9 Other vascular-toxic influences may contribute to increased peripheral vascular resistance, including hyperviscosity, immunologic factors, and other hormones including catecholamines, vasopressin, and endothelin.1012 The end result of these changes is a significant increase in peripheral vascular resistance, with ischemia of heart, brain, and kidneys.

In considering hypertensive crisis and treatment, the impact of blood pressure on cerebrovascular physiology is important. For example, hypertensive encephalopathy is a distinct clinical syndrome that occurs when rapidly rising central perfusion pressures exceed the ability of the central nervous system (CNS) to autoregulate. Autoregulation of cerebral blood flow refers to the ability of the brain to maintain a constant cerebral blood flow as the cerebral perfusion pressure varies between 60 to 150 mm Hg. In the setting of chronic hypertension, the range of autoregulation is increased from 60 to 150 mm Hg to 80 to 160 mm Hg. Autoregulation of cerebral blood flow (CBF) is a function of cerebral perfusion pressure (CPP, derived from the mean arterial pressure [MAP] minus the venous pressure) and cerebral vascular resistance, according to the following equation:


Under normal physiologic conditions, the backflow in the cerebral venous system or venous pressure is near zero, and the arterial pressure determines the CPP. With acute brain jury, as seen with subarachnoid hemorrhage, stroke, and intracranial hemorrhage, the ability of the brain to autoregulate and maintain cerebral blood flow is impaired. Inability to autoregulate cerebral blood flow is also seen in hypertensive crisis when the MAP is greater than 140 mm Hg.

image Diagnosis of Hypertensive Emergencies

Medical History, Physical Examination, and Laboratory Evaluation

Hypertension from any cause may enter an “emergent” phase. Although hypertensive emergency usually occurs in individuals with a history of essential hypertension, it is also is seen in individuals with secondary hypertension and in individuals with no hypertensive history, as in preeclampsia, pheochromocytoma, drug withdrawal, and acute glomerulonephritis. A medication history, including over-the-counter medications and illegal drug use, should be ascertained from every patient. Malignant hypertension is a unique clinical/pathologic syndrome that is associated with hypertensive crisis. Increases in blood pressure and target-organ damage are caused by changes in the vasculature characterized by fibrinoid necrosis and a proliferative endarteritis. Risk factors associated with the development of malignant hypertension include age between 30 and 50 years,13 male gender,5 African American background,14 and smoking (increases the risk by 2.5- to 5-fold).15

Patients with hypertensive crisis present with a variety of symptoms. The most common is headache. It is either sudden in onset or represents a change from a usual headache pattern and is often worst in the morning. The location is generally occipital or anterior, with a steady quality. Other symptoms include visual complaints (scotoma, diplopia, hemianopsia, blindness), neurologic symptoms (focal deficits, stroke, transient ischemic attacks, confusion, somnolence), ischemic chest pain, renal symptoms (nocturia, polyuria, hematuria), back pain (aortic aneurysm), and gastrointestinal complaints (nausea, vomiting). Weight loss occurs as the high levels of circulating renin and angiotensin induce a diuresis.16 These patients often present with intravascular volume depletion, which has strong implications for treatment.

The blood pressure is measured in both arms and also with the patient lying and standing. In hypertensive emergency, diastolic blood pressures are usually above 120 mm Hg. Pathologic processes that cause stiffening of the vascular wall can prevent vessel compression by external compression with a blood pressure cuff. This results in an artificial increase (at times extreme) in the systolic and diastolic blood pressure, or “pseudohypertension.” Pseudohypertension can occur in atherosclerosis, Monckeberg’s medial calcification, and metastatic calcification, as experienced in end-stage renal disease. Clues to pseudohypertension include a markedly elevated blood pressure in an individual without evidence of end-organ damage. The diagnosis is suggested by a palpable radial artery after proximal compression (Osler’s maneuver).17

A dilated funduscopic examination should be performed on all individuals. Arteriolar thickening reflects chronic hypertension and is manifested by increased light reflex, vascular tortuosity, and arteriovenous nicking where the arterioles cross the venules. These funduscopic findings reflect chronic hypertension and have no prognostic significance with regard to hypertensive crisis. As hypertension increases in severity, there are additional findings caused by the breakdown of the blood-retina barrier, leading to retinal hemorrhage and leakage of lipids, causing hard exudates. Additional findings as the blood pressure continues to increase may include cotton-wool spots as a result of nerve ischemia and swelling of the optic nerve with papilledema.18

A complete cardiovascular examination should include a careful cardiac evaluation for evidence of left ventricular hypertrophy, which can occur with long-standing hypertension. Examination of the abdomen should include evaluation for a enlarged kidneys, as seen with polycystic kidney disease, as well as for evidence of aortic aneurysm. Lastly, a careful neurologic examination should be done to rule out any evidence of a cerebral vascular accident. Alterations in mental status may indicate a stroke or hypertensive encephalopathy. Symptoms of hypertensive encephalopathy include headache, visual changes, and seizures. Focal neurologic symptoms are unusual without an associated cerebral bleed. Hypertensive neuroretinopathy is usually present but may be absent in patients in whom the pressure increase has been very abrupt, such as in cases of acute glomerulonephritis or catecholamine excess states.

The initial laboratory evaluation should include a serum sodium, chloride, potassium, bicarbonate, creatinine and blood urea nitrogen, complete blood count (with a peripheral smear to identify schistocytes), prothrombin time, activated partial thromboplastin time, serum and urine toxicology screen, pregnancy test when appropriate, an electrocardiogram, and a urinalysis. Evidence of intravascular hemolysis is common and may make it difficult to differentiate hypertensive crisis from primary vasculitis with secondary hypertension.19,20 The renin-angiotensin-aldosterone axis is markedly activated, as evidenced by hypokalemia and metabolic alkalosis.3,21 The blood urea nitrogen and creatinine are often elevated. The urinalysis may show small amounts of proteinuria as well as hematuria with occasional erythrocyte casts.5 Marked increases in proteinuria suggest a primary glomerular process such as glomerulonephritis as the etiology of the elevated blood pressure.

If hypertensive encephalopathy is suspected, magnetic resonance imaging (MRI) should be performed. With hypertensive encephalopathy, edema may occur in the posterior regions of the cerebral hemispheres, particularly in the parieto-occipital regions, a finding called posterior leukoencephalopathy on MRI. However, brainstem involvement on MRI has also been reported.22,23 It is important to consider and eliminate other conditions with a similar clinical presentation (Box 88-1). Several important diagnostic considerations help exclude other causes of altered mental status: (1) symptoms of generalized brain dysfunction tend to develop over time (12-24 hours) with hypertensive encephalopathy, as compared to acutely with ischemic stroke or cerebral hemorrhage; (2) focal neurologic findings are unusual with hypertensive encephalopathy unless there is an associated bleed; (3) papilledema is almost always noted with hypertensive encephalopathy and if absent should raise suspicion of another etiology; (4) in comparison to an acute CNS bleed, mental status with hypertensive encephalopathy improves within 24 to 48 hours of treatment.

image Treatment of Hypertensive Emergency

Patients with hypertensive crisis are best treated parenterally with intensive care monitoring by arterial cannulation or automated blood pressure cuff measurement. In general, the need to lower the blood pressure and the rate at which this should occur is dictated by the clinical setting. Excessive falls in pressure should be avoided, given the potential negative impact on renal, cerebral, and coronary ischemia.

In most but not all settings, blood pressure can be reduced acutely by 20% to 25% within minutes to hours.3 After the patient is stabilized at this pressure, the blood pressure may be further decreased to 160/100-110 mm Hg over the next 2 to 6 hours.3 If the patient is clinically stable, the blood pressure may then be decreased toward a normal blood pressure over the next 24 to 48 hours.3 With these decreases in blood pressure, CNS blood flow autoregulation is usually maintained. Clinical settings where additional considerations and alternative approaches to reducing blood pressure should be considered include (1) ischemic stroke where immediate reduction of blood pressure is usually not indicated except when the blood pressure is over 220/120 or the patient requires thrombolytic therapy, (2)acute aortic dissection where a rapid blood pressure reduction in 15 to 30 minutes to a systolic blood pressure under 100 mm Hg is clinically warranted if the patient tolerates, and (3) in previously normotensive subjects with abrupt increases in BP.

More rapid reduction in blood pressure is also recommended in patients with active unstable angina or congestive heart failure with pulmonary edema. Exceptions to rapid blood pressure reduction may include older patients with carotid stenosis. Older adults are particularly susceptible to CNS hypoperfusion. In addition, recent data (discussed later) suggest that significant reduction of blood pressure in older adults in the setting of ischemic stroke may not be beneficial. Blood pressure management in patients with stroke or intracranial bleeding is controversial, since the loss of CNS blood flow autoregulation and the presence of brain edema require high systemic pressures to provide adequate cerebral perfusion.

From 40% to 50% of hypertensive crises arise in patients with preexisting hypertension without identifiable secondary causes.24,25 Essential hypertension is the underlying disorder in the majority of African American individuals.2628 In contrast, from 50% to 60% of white patients with malignant hypertension have an identifiable cause (Box 88-2). Renovascular hypertension secondary to either fibromuscular dysplasia or atherosclerosis is not uncommon. Up to 20% of cases of malignant hypertension occur in patients with underlying chronic glomerulonephritis. Other renal causes include reflex nephropathy (particularly in children) and analgesic nephropathy.3

image Specific Treatment Recommendations for Hypertensive Crisis Based on Etiology

General Comment on Medication Used to Treat Hypertensive Crisis

The classes of parenteral antihypertensive agents available to treat hypertensive crisis include direct vasodilators (sodium nitroprusside, nitroglycerin), α- and β-adrenergic blockers (labetalol), α-adrenergic blockade (phentolamine), angiotensin-converting enzyme (ACE) inhibitors (enalaprilat), calcium channel blockers (nicardipine), and dopamine agonists (fenoldopam). Some of the advantages and disadvantages of these medications are detailed in Table 88-1. There is no consensus on the most effective antihypertensive medications in the setting of a CNS insult and no large randomized trials demonstrating the superiority of a given agent. Rather, the choice of antihypertensive therapy should be individualized to the patient and clinical setting. However, most authors now caution the use of nitroprusside in the setting of increase in intracranial pressure. Vasodilators increase blood volume and therefore have the potential to increase the intracranial pressure (ICP). Animal and human studies in the setting of a normal ICP show no effect of nitroprusside on ICP.1921 However, in studies on animals and humans with preexisting increased ICP, nitroprusside increased the ICP, likely reflecting vasodilatation on the background of decreased cranial compliance.2933 When sodium nitroprusside is contraindicated, other treatment options include labetalol and nicardipine. Fenoldopam, which is an agonist of the vasodilator dopamine-1 receptor, shares with nitroprusside a rapid onset and short duration of action. In addition, fenoldopam, in contrast to nitroprusside, increases renal blood flow, induces natruresis, and produces no toxic metabolites.3438

TABLE 88-1 Treatment of Hypertensive Crisis: Intravenous Medication

Drug Name and Mechanism of Action Indications/Advantages/Dose Disadvantages/Adverse Effects/Metabolism Cautions
Sodium nitroprusside:
Nitric oxide compound; vasodilation of arteriolar and venous smooth muscle
Increases cardiac output by decreasing afterload
Useful in most hypertensive crisis
Onset of action immediate, duration of action 1-2 min
Dose: 0.25 µg/kg/min
Maximum dose: 8-10 µg/kg/min
Contraindicated in high-output cardiac failure, congenital optic atrophy. Anemia and liver disease at risk of cyanide toxicity: acidosis, tachycardia, change in mental status, almond smell on breath. Renal disease at risk of thiocyanate toxicity: psychosis, hyperreflexia, seizure, tinnitus. Cautious use with increased intracranial pressure. Do not use maximum dose for more than 10 minutes. Crosses the placenta.
Directly interacts with nitrate receptors on vascular smooth muscle
Primarily dilates venous bed
Decreases preload
Use with symptoms of cardiac ischemia, perioperative hypertension in cardiac surgery
Initial dose: 5 µg/min
Maximum dose: 100 µg/min
Contraindicated in angle-closure glaucoma, increased intracranial pressure. Blood pressure decreased secondary to decreased preload, cardiac output—avoid when cerebral or renal perfusion compromised. Caution with right ventricular infarct.
β-Adrenergic blockade and α-adrenergic blockade IV
α:β-Blocking ratio is 1 : 7
Onset of action 2-5 min
Duration 3-6 hours
Bolus 20 mg, then 20-80 mg every 10 min for maximum dose 300 mg
Infuse at 0.5-2 mg/min
Avoid in bronchospasm, bradycardia, congestive heart failure, greater than first-degree heart block, second/third trimester pregnancy. Use caution with hepatic dysfunction, inhalational anesthetics (myocardial depression). Enters breast milk.
Cardioselective β1-adrenergic blocking agent
Use with aortic dissection
Use during intubation, intraoperative, and postoperative hypertension
Onset 60 seconds, duration 10-20 min
200-500 µg/kg/min for 4 min, then infuse 50-300 µg/kg/min
See labetalol. Not dependent on renal or hepatic function for metabolism (metabolized by hydrolysis in RBC).
Postsynaptic dopamine-1 agonist; decreases peripheral vascular resistance; 10 times more potent than dopamine as vasodilator
May be advantageous in kidney disease, increases renal blood flow, increases sodium excretion, no toxic metabolites
Initial dose: 0.1 µg/kg/min, with titration every 15 min
No bolus
Contraindicated in glaucoma (may increase intraocular pressure) or allergy to sulfites; hypotension, especially with concurrent beta-blocker. Check serum potassium every 6 hours. Concurrent acetaminophen may significantly increase blood levels. Dose-related tachycardia.
Primarily dilates arteriolar vasculature
Primarily used in pregnancy/eclampsia
Dose: 10 mg every 20-130 min; maximum dose 20 mg
Decreases blood pressure in 10-20 min
Duration of action 2-4 h
Reflex tachycardia; give beta-blocker concurrently. May exacerbate angina. Half-life 3 hours, affects blood pressure for 100 hours. Depends on hepatic acetylation for inactivation.
α-Adrenergic blockade
Used primarily to treat hypertension from excessive catecholamine excess (e.g., pheochromocytoma)
Dose: 5-15 mg
Onset of action 1-2 min, duration 3-10 min
β-blockade is generally added to control tachycardia or arrhythmias. As in all catecholamine excess states, beta-blockers should never be given first, as the loss of β-adrenergically mediated vasodilatation will leave α-adrenergically mediated vasoconstriction unopposed and result in increased pressure.
Dihydropyridine calcium channel blocker; inhibits transmembrane influx of calcium ions into cardiac and smooth muscle
Onset of action 10-20 min, duration 1-4 h
Initial dose: 5 mg/h to maximum of 15 mg/h
Avoid with congestive heart failure, cardiac ischemia. Adverse effects include tachycardia, flushing, HA.
Short-acting dihydropyridine calcium channel hypertension99
Initial dose: 1 mg/h; can be increased to 21 mg/h Reduces blood pressure without affecting cardiac filling pressures or causing reflex tachycardia
Angiotensin-converting enzyme inhibitor
Onset of action 15-20 min, duration 12-24 h
Dose: 1.25-5 mg every 6 h
Response not predictable, with high renin states may see acute hypotension. Hyperkalemia in setting of reduced glomerular filtration rate. Avoid in pregnancy.
Trimethaphan:Nondepolarizing ganglionic blocking agent; competes with acetylcholine for postsynaptic receptors Used in aortic dissection
Dose: 0.5-5 mg/min
Does not increase cardiac output. No inotropic cardiac effect. Disadvantages include parasympathetic blockade, resulting in paralytic ileus and bladder atony, and development of tachyphylaxis after 24-96 hours of use.