Continuing Education Activity

Malignant hypertension is a term that has been used to describe patients with elevated blood pressure (BP) and multiple complications with poor prognoses. Today, the term hypertensive crisis is used to describe patients who present with severe BP elevations as follows: Systolic blood pressure and (SBP) greater than 180 mm Hg and Diastolic blood pressure (DBP) greater than 120 mm Hg). The diagnosis can be further classified as a hypertensive emergency when severe elevation in BP is associated with end-organ damage or hypertensive urgency when severe hypertension occurs without it. This activity reviews the cause of malignant hypertension, its pathophysiology and highlights the role of the interprofessional team in its management.

Objectives:

• Outline the causes of malignant hypertension.

• Describe the presentation of a patient with malignant hypertension.

• Summarize the treatment of malignant hypertension.

• Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by malignant hypertension.

Introduction

Malignant hypertension is a term that has been used to describe patients with elevated blood pressure (BP) and multiple complications (End organ damage) with a poor prognosis. Today, the term hypertensive crisis is used to describe patients who present with severe BP elevations as follow:

• Systolic blood pressure (SBP) greater than 180 mm Hg 
• Diastolic blood pressure (DBP) greater than 120 mm Hg) 

The diagnosis can be further classified as a hypertensive emergency when severe elevation in BP is associated with end-organ damage or hypertensive urgency when severe hypertension occurs without it. Prompt treatment of BP can prevent a hypertensive emergency and, consequently, serious life-threatening complications.[1][2][3][4]

To make a diagnosis of malignant hypertension, papilledema has to be present. In malignant hypertension, the key is to lower the blood pressure within a few hours.

Etiology

There are multiple causes of malignant hypertension (hypertensive crisis), including the following:

• Medication noncompliance
• Renovascular diseases, such as renal artery stenosis, polyarteritis nodosa, and Takayasu arteritis
• Renal parenchymal disease including glomerulonephritis, tubulointerstitial nephritis, systemic sclerosis, hemolytic-uremic syndrome, systemic lupus erythematosus
• Endocrine dysfunction, such as pheochromocytoma, Cushing disease, primary hyperaldosteronism, renin-secreting tumor
• Coarctation of aorta; drugs or other exposures, including cocaine, phencyclidine, sympathomimetics, erythropoietin, cyclosporine
• Antihypertensive medication withdrawal
• Amphetamines
• Central nervous system disorders, such as head injury, cerebral infarction, and cerebral hemorrhage

Epidemiology

Hypertensive emergencies are unusual, with a projected incidence of 1 to 2 cases per million per year. However, a recent investigation showed that the estimated number of visits due to this condition and the rate per million per adult emergency department (ED) visits have more than doubled from 2006 to 2013. Few examples include eclampsia (2%), cerebral infarction (39%), and acute pulmonary edema (25%).

Pathophysiology

Hypertensive emergencies occur when a relatively rapid elevation of BP develops in a short period. An increase in systemic vascular resistance by increasing vasoconstriction mechanisms through renin-angiotensin activation, pressure natriuresis, hypoperfusion, and ischemia are the most common culprits of end-organ damage. The classic vascular feature is fibrinoid necrosis of the small vessels. In addition, red cell destruction is common as they pass through these obstructed vessels leading to microangiopathic hemolytic anemia. Another feature of a hypertensive emergency is the loss of autoregulation in the brain, which can present as hypertensive encephalopathy.

History and Physical

Most patients have persistently elevated BP for years before presenting with the hypertensive emergency. Initial questioning should focus on finding indicators related to end-organ damage, including headaches, nausea or vomiting, visual disturbances, chest or back pain, dyspnea, orthopnea, or visual disturbances. Review all prescription and nonprescription medications, adherence, and time from the last dose. Ask about recreational drug use, such as amphetamines, cocaine, phencyclidine.

On physical exam, confirm BP on both arms using an appropriately-sized blood pressure cuff. Funduscopic exam findings may include hemorrhages, exudates, or papilledema. Assess for murmurs and gallops or other signs of heart failure. Look for evidence of pulmonary edema, abdominal bruits. Neurological findings can include stupor, seizures, delirium, agitation.[5][6][7]

Evaluation

The history and physical examination are really important in patients presenting with a very elevated BP or an acute rise over a previously normal baseline, even if the presenting BP is less than 180/120 mm Hg. Furthermore, the following evaluation should be performed to find the presence of end-organ damage in association with targeted clinical symptoms or signs:

• Electrocardiography
• Chest x-Ray
• Urinalysis
• Electrolytes and creatinine
• Cardiac biomarkers, when the acute coronary syndrome is suspected
• Toxicology screen
• CT/MRI of the brain, when head injury, neurologic symptoms, hypertensive retinopathy, nausea, or vomiting are present
• Contrast CT/MRI of the chest or TEE, if aortic dissection is suspected

It is often easiest to categorize hypertensive emergencies by the organ that is being damaged. The evaluation above can usually identify the at-risk target organ and direct both the target BP and the promptness with which the target is achieved.

The cardiac exam may reveal the presence of an MI, CHF, or pulmonary edema. Concentric left ventricular hypertrophy is often present, including the 4th heart sound. Always check the blood pressure in both arms to rule out aortic dissection. Patients may also have bruit in the neck and groin.

CNS exam may reveal a headache, visual changes, vomiting, confusion, and seizures. The eye exam may reveal soft exudates, flame-shaped hemorrhages, and papilledema.

The renal exam may present with oliguria, and the GI symptoms may include nausea, vomiting, and vague abdominal pain.

Treatment / Management

Adequate therapy, including the choice of the medication and the BP target, changes depending on the specific hypertensive emergency and the affected organ.[8][9][10][11]

It is not recommended to decrease the BP too fast or too much, as ischemic damage can occur in vascular territories that have become habituated with the elevated level of BP. However, for most hypertensive emergencies, mean arterial pressure (MAP) should be reduced by approximately 10 to 20% within the first hour and by another 5% to 15% over the next 24 hours. This often results in a target BP of less than 180/120 mm Hg for the first hour and less than 160/110 mm Hg for the next 24 hours, but rarely less than 130/80 mm Hg during that time frame.

Common intravenous (IV) medications and doses used to treat hypertensive emergencies include:

• Nicardipine, initial infusion rate 5 mg per hour, increasing by 2.5 mg per hour every 5 minutes to a maximum of 15 mg per hour
• Sodium nitroprusside, 0.3 to 0.5 mcg/kg/minute, increases by 0.5 mcg/kg per minute every few minutes as needed to a maximum dose of 10 mcg/kg per minute.
• Labetalol 10 to 20 mg IV followed by bolus doses of 20 to 80 mg at 10-minute intervals until a target blood pressure is reached to a maximum 300-mg cumulative dose
• Esmolol, initial loading dose 500 mcg/kg/minute over 1 minute, then 50 to 100 mcg/kg/minute to a maximum dose of 300 mcg/kg per minute.

If there is any possibility of over or underestimating BP using frequent noninvasive cuff measurements or if the end-organ damage is life-threatening, consider arterial catheterization for precise, second-to-second measurements allowing for more careful medication titration.

The major exceptions to gradual BP lowering over the first day are:

• Acute phase of an ischemic CVA: The BP is usually not treated unless it is greater than 185/110 mmHg in patients whose reperfusion therapy could be an option or greater than 220/120 mm Hg in patients who might not qualify for it. Consider labetalol or nicardipine infusion.
• Acute aortic dissection: The SBP should be lowered to 120 mm Hg within 20 minutes, and a target heart rate around 60 beats per minute to reduce aortic shearing forces. Treatment usually requires a beta-blocker and a vasodilator. Options include esmolol, nicardipine, or nitroprusside.
• An intracerebral hemorrhage: The goals of therapy are different and depend on the location and surgical approach.
• Acute myocardial ischemia: Nitroglycerin is the drug of choice; do not use if the patient has taken phosphodiesterase inhibitors, including sildenafil or tadalafil, within the past 48 hours.

After a suitable period, often 8 to 24 hours, of BP control at a target, oral medications are usually given, and the initial intravenous therapy is tapered and discontinued.

Differential Diagnosis

• Acute kidney injury
• Aortic coarctation
• Aortic dissection
• Chronic kidney disease
• Eclampsia
• Hypercalcemia
• Hyperthyroidism
• Pheochromocytoma
• Renal artery stenosis
• Subarachnoid hemorrhage

Staging

ACEP Guidelines for managing hypertension in the ED

1. In asymptomatic patients with elevated BP, routine screening for end-organ damage is not recommended.
2. In select patients (poor follow-up) screening for elevated creatinine may identify the renal injury.
3. In asymptomatic patients with elevated BP, immediate medical intervention is not necessary.
4. Selected patients with poor follow-up can be treated in the ED for elevated blood pressure.
5. All patients with asymptomatic elevated BP should be referred to a cardiology outpatient clinic.

Prognosis

The prognosis of patients with malignant hypertension is guarded. Five-year survivals of 75% to 84% have been reported with treatment; without treatment, the life expectancy is less than 24 months. Most deaths are a result of heart failure, stroke, or renal failure.

Complications

Multiple complications can arise when target organs are affected, including encephalopathy, intracerebral hemorrhage, acute myocardial infarction, acute heart failure, pulmonary edema, unstable angina, dissecting aortic aneurysm, acute kidney injury, and vision loss.

Pearls and Other Issues

Most patients with severely elevated BP have no acute end-organ damage (hypertensive urgency). Nevertheless, some patients have signs and symptoms of acute, ongoing injury, which is recognized as hypertensive emergency or formerly as malignant hypertension.

It is generally not recommended to decrease the BP too quickly or too much as ischemic damage can occur in vascular territories that have become habituated with the elevated level of BP. For most hypertensive emergencies, the MAP should be reduced gradually by approximately 10 to 20% within the first hour and by a further 5% to 15% over the next 24 hours, with a final goal of approximately 25% reduction compared with baseline. 

Many patients have poorly controlled essential or secondary hypertension. Thus, long-term management turns out to be the primacy once the hypertensive crisis has been addressed.

Enhancing Healthcare Team Outcomes

The management of malignant hypertension requires an interprofessional team that includes an internist, nephrologist, cardiologist, and neurologist. Untreated, elevated blood pressure has high morbidity and mortality, including enormous healthcare costs. Therefore, the primary care providers, including the nurse practitioner, should regularly monitor blood pressure and emphasize medication compliance.

For asymptomatic patients, admission is not recommended. However, those with symptoms need to be monitored, and the specialists consulted to determine the presence of end-organ injury.

It is not recommended to decrease the BP too fast or too low, as ischemic damage can occur in vascular territories that have become habituated with the elevated level of BP. However, for the majority of hypertensive emergencies, mean arterial pressure (MAP) should be reduced by approximately 10% to 20% within the first hour and by another 5% to 15% over the next 24 hours.

All patients with hypertension should be encouraged to follow up in the outpatient clinic with a cardiology nurse. In addition, adherence to a low salt diet is beneficial. Finally, the interprofessional team members should continually encourage patients to remain compliant with their blood pressure medications and monitor their blood pressure at home.

Outcomes

The outcome for most patients with malignant hypertension in the short term is good, but in the long term, exacerbations are common. Strokes, vision loss, kidney damage, and adverse cardiac events are known to occur in a number of patients who are not compliant with therapy.[12] [Level V]