Hypertensive crisis: Emergency and urgency

Hypertension is a common problem, and population data suggest its incidence is increasing globally. One billion individuals worldwide now have hypertension. Nearly one in three US adults has hypertension. Compared with two-thirds in the past decade, currently half of these individuals do not have their blood pressure under control. One-third of those in whom it is not controlled are unaware of their diagnosis. ^, The exact risk of hypertensive crisis is not clear, but most authors estimate it to be less than 1%. A carefully conducted descriptive analysis from the Nationwide Emergency Department (ED) Sample’s ED visits report hypertensive emergencies in fewer than 2 in 1000 adult ED visits and 6 in 1000 visits carrying any diagnosis of hypertension in 2013. These data reveal a prevalence much lower than previously thought.

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 and the time course of the elevation determine the development of an emergency. In general with hypertensive emergency, the diastolic blood pressure is above 120 mm Hg. However, in children, gravid females, and previously normotensive individuals, hypertensive emergencies 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 made. 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 [SBP] often >180 mm Hg 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. The focus of this chapter is on both types of hypertensive crises, with the emphasis on hypertensive emergency.

Pathophysiology of hypertensive emergency

The precise pathophysiology of hypertensive emergency is unknown. An abrupt increase in blood pressure is one of the initiating events in the transition from simple hypertension or normotension to hypertensive emergency. 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 vascular myogenic responses and disruption of endothelial integrity. With disruption of vascular integrity, diffuse microvascular lesions develop. ^, Fibrinoid necrosis of the arterioles and myointimal proliferation are seen in vulnerable organs and are considered the histologic hallmark of hypertensive emergency. ^, Endothelial damage also causes impaired production of nitric oxide. These maladaptive responses result in increases in peripheral resistance and set up a vicious cycle, where relative hypoperfusion from vasoconstriction causes a further increase in vasoactive hormones. For example, hypoperfusion causes activation of the renin–angiotensin–aldosterone system, and evidence suggests angiotensin II may directly injure the vascular wall by activation of genes for proinflammatory cytokines (e.g., interleukin-6) and also of nuclear factor κB. ^, Other vascular-toxic influences may contribute to increased peripheral vascular resistance, including hyperviscosity; immunologic factors; and other hormones, including catecholamines, vasopressin, and endothelin. The end result of these changes is a significant increase in peripheral vascular resistance, with ischemia of heart, brain, and kidneys.

In considering hypertensive emergencies and their 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 (CPPs) exceed the ability of the central nervous system (CNS) to autoregulate. Autoregulation of cerebral blood flow (CBF) refers to the ability of the brain to maintain a constant CBF as the CPP varies between 60 and 150 mm Hg. In the setting of chronic hypertension, the range of autoregulation is increased to a range of 80–160 mm Hg. Autoregulation of CBF is a function of CPP (derived from the mean arterial pressure [MAP] minus the venous pressure) and cerebral vascular resistance (CVR), according to the following equation:

CBF = CPP/CVR

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 injury, as seen with subarachnoid hemorrhage, stroke, and intracranial hemorrhage, the ability of the brain to autoregulate and maintain CBF is impaired. Inability to autoregulate CBF is also seen in hypertensive emergency when the MAP is greater than 140 mm Hg. Failure of autoregulation leads to transmission of elevated blood pressure resulting in endothelial damage, with blood–brain barrier disruption leading to fluid and protein transudation, vasogenic edema, and further cerebral vasoconstriction causing infarcts in the brain.

Diagnosis of hypertensive emergencies

Medical history, physical examination, and laboratory evaluation

From 40% to 50% of hypertensive emergencies arise in patients with preexisting hypertension without identifiable secondary causes. ^, Essential hypertension is the underlying disorder in the majority of Black individuals. In contrast, from 50% to 60% of white patients with malignant hypertension have an identifiable cause ( Box 78.1 ). Renovascular hypertension secondary to either fibromuscular dysplasia or atherosclerosis is not uncommon. Hypertensive emergency can occur 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 and pathologic syndrome where 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, male gender, Black background, and smoking (increases the risk by 2.5- to 5-fold).

BOX 78.1

MAO, Monoamine oxidase.

Syndromes of Hypertensive Crisis

Malignant hypertension
Nonmalignant hypertension with target-organ disorders
- Patient requiring emergency surgery with poorly controlled hypertension
- Hyperviscosity syndrome
- Postoperative patient
- Renal transplant patient: acute rejection, transplant renal artery stenosis
- Quadriplegic patient with autonomic hyperreflexia
- Severe burns
- Acute aortic dissection
- Intracranial hemorrhage, ischemic stroke, or subarachnoid hemorrhage
- Hypertensive encephalopathy
- Myocardial ischemia/acute left ventricular failure
- Preeclampsia/eclampsia
- Antiphospholipid antibody syndrome
- Acute renal failure
  - Scleroderma renal crisis
  - Chronic glomerulonephritis
  - Reflux nephropathy
  - Analgesic nephropathy
  - Acute glomerulonephritis
  - Radiation nephritis
  - Ask-Upmark kidney
  - Chronic lead intoxication
- Renovascular hypertension
  - Fibromuscular dysplasia
  - Atherosclerosis
- Endocrine hypertension
  - Congenital adrenal hyperplasia
  - Pheochromocytoma
  - Oral contraceptives
  - Aldosteronism
  - Cushing disease/syndrome
- Systemic vasculitis
- Atheroembolic renal crisis
- Drugs
  - Oral contraceptives
  - Nonsteroidal antiinflammatory agents
  - Atropine
  - Corticosteroids
  - Sympathomimetics
  - Erythropoietin
  - Lead intoxication
  - Cyclosporine
- Catecholamine excess states
  - Pheochromocytoma
  - MAO/tyramine interaction
  - Antihypertensive withdrawal
  - Cocaine intoxication, sympathomimetic overdose

The clinical presentation of hypertensive emergency may include headache that is generally located occipitally or anteriorly, with a steady quality. Other symptoms include visual complaints (scotoma, diplopia, hemianopsia, blindness), neurologic symptoms (focal deficits, stroke, transient ischemic attacks, seizures, 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. These patients often present with intravascular volume depletion, which has strong implications for treatment.

The blood pressure is measured in both arms with the patient lying and standing. Pathologic processes such as atherosclerosis, Monckeberg medial calcification, and metastatic calcification as experienced in end-stage renal disease (ESRD), cause stiffening of the vascular wall, which can prevent vessel compression by external compression with a blood pressure cuff. This results in an artificial and at times extreme increase in the systolic and diastolic blood pressures, or “pseudohypertension.” 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 despite proximal compression with a sphygmomanometer (Osler maneuver).

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 changes have no prognostic significance with regard to hypertensive emergency. However, 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 or cotton-wool spots as a result of nerve ischemia and swelling of the optic nerve with papilledema.

A complete cardiovascular examination should include a careful evaluation for evidence of left ventricular hypertrophy and heart failure and peripheral pulse examination for absence or delay suggestive of aortic dissection. Chest x-ray or point-of-care ultrasonography can be used to discriminate cardiac from noncardiac dyspnea. ^, Examination of the abdomen should include evaluation for enlarged kidneys, as seen with polycystic kidney disease, and for evidence of aortic aneurysm. Last, a careful neurologic examination should be done to rule out any evidence of a cerebrovascular accident. Alterations in mental status may indicate a stroke or hypertensive encephalopathy. 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 ( Box 78.2 ). Evidence of intravascular hemolysis is common and may make it difficult to differentiate hypertensive emergency from primary vasculitis with secondary hypertension. ^, The renin–angiotensin–aldosterone axis is markedly activated, as evidenced by hypokalemia and metabolic alkalosis. ^, The blood urea nitrogen and creatinine are often elevated. The urinalysis may show small amounts of proteinuria and hematuria with occasional erythrocyte casts. Marked increases in proteinuria suggest a primary glomerular process such as glomerulonephritis as the etiology of the elevated blood pressure.

BOX 78.2

CT, Computed tomography; ECG, electrocardiogram; MRI, magnetic resonance imaging.

Proposed Diagnostic Studies in Patients With Suspected Hypertensive Emergency

Laboratory analysis

Hemoglobin, platelet count
Serum creatinine, sodium, potassium, bicarbonate, lactic dehydrogenase (LDH), haptoglobin, prothrombin time, activated partial thromboplastin time
Serum and urine toxicology screen
Quantitative urinalysis for protein, urine sediment for erythrocytes, leukocytes, cylinders, and casts

Diagnostic examination

ECG (ischemia, arrhythmias, left ventricular hypertrophy)
Fundoscopy

On indication

Troponin-T, creatine kinase (CK) and its isoenzyme MB (CK-MB)
Pregnancy test
Peripheral blood smear (for assessment of schistocytes)
Plasma renin activity and plasma aldosterone levels, serum metanephrines
Connective tissue disorders serology
Chest x-ray (fluid overload)
Transthoracic echocardiography (cardiac structure and function) or point-of-care cardiac and lung ultrasound (cardiac pulmonary edema)
CT (or MRI) brain (intracranial hemorrhage)
CT angiography of thorax and abdomen (acute aortic disease)
Renal ultrasound (postrenal obstruction, kidney size, left-to-right difference)

If hypertensive encephalopathy is suspected, magnetic resonance imaging (MRI) of the brain should be performed. Edema seen posteriorly, particularly in the parieto-occipital regions (a finding earlier called posterior leukoencephalopathy and now the widely accepted term posterior reversible encephalopathy syndrome [PRES] ) and rarely in the brainstem, is a manifestation of hypertensive encephalopathy. ^, It is important to consider and eliminate other conditions with a similar clinical presentation ( Box 78.3 ). 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 with acutely in 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; and (4) in comparison with an acute CNS bleed, mental status with hypertensive encephalopathy improves within 24–48 hours of treatment.

BOX 78.3

Differential Diagnosis of Hypertensive Encephalopathy

Cerebral infarction
Subarachnoid hemorrhage
Intracerebral hemorrhage
Subdural or epidural hematoma
Brain tumor or other mass lesion
Seizure disorder
Central nervous system vasculitis
Encephalitis/meningitis
Drug ingestion
Drug withdrawal

Treatment of hypertensive emergency

Patients with hypertensive emergency 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 are dictated by the clinical setting. Excessive falls in pressure should be avoided, given the potential for resulting in renal, cerebral, and coronary ischemia.

In most but not all settings, blood pressure can be reduced acutely by 20%–25% within minutes to hours. Although the autoregulatory range of CBF is reset upward in chronic hypertension, the lower limit of the autoregulation remains approximately 25% below the resting MAP in patients with both normotension and chronic hypertension. When the arterial blood pressure falls below this lower limit, CBF progressively decreases and symptoms of low CBF, including nausea, yawning, hyperventilation, clamminess, and syncope, develop. To protect cerebral function, after an initial reduction of blood pressure by 20% within the first hour, blood pressure is further reduced over the next 2–6 hours to the 160/110 mm Hg range as long as the patient remains stable. Assuming continued stability, the blood pressure may then be decreased to 140/90 mm Hg over the next 24–48 hours. With these decreases in blood pressure, CBF autoregulation is usually maintained. There are several clinical settings where additional issues and alternative approaches to reducing blood pressure should be considered. In ischemic stroke, immediate reduction of blood pressure is usually not indicated except when the blood pressure is over 220/120 mm Hg or the patient requires thrombolytic therapy. Recent data indicate that acute blood pressure reduction is of no benefit (CATIS trial) or even harmful (SCAST trial). ^, In intracerebral hemorrhage (ICH), acute lowering of SBP to 140 mm Hg is recommended based on weak evidence. Results of the INTERACT2 study support this recommendation, although further lowering to 126 mm Hg did not result in any additional benefit in the ATACH2 trial. ^, In acute aortic dissection, if the patient tolerates it, a rapid blood pressure reduction in 15–30 minutes to a SBP under 100 mm Hg is clinically warranted. Finally, 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, given that these individuals are particularly susceptible to CNS hypoperfusion. Significant reduction of blood pressure in the setting of ischemic stroke may not be beneficial (discussed later). Overall, blood pressure management in patients with stroke or intracranial bleeding is controversial, because the loss of CBF autoregulation and the presence of brain edema require high systemic pressures to provide adequate cerebral perfusion.

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