Continuing Education Activity

Hypertensive encephalopathy is a less commonly encountered type of hypertensive emergency, highlighted by mental status changes and severely elevated blood pressure. This is a condition that is one of the manifestations of a hypertensive emergency, which requires prompt but meticulous treatment. This activity describes the evaluation, diagnosis, and management of hypertensive encephalopathy. It also reviews the role of the interprofessional team in improving care for patients with this condition, especially following treatment.

Objectives:

• Describe the etiology and epidemiology of hypertensive encephalopathy medical conditions and emergencies.

• Review the evaluation of patients with hypertensive encephalopathy.

• Outline the management options available for hypertensive encephalopathy.

• Summarize the importance of improving care coordination and communication among the interprofessional team to improve outcomes for patients with hypertensive encephalopathy

Introduction

A hypertensive emergency is a life-threatening condition where ongoing target-organ damage occurs due to markedly elevated blood pressure. Pulmonary edema, cardiac ischemic events, acute renal failure, aortic dissection, eclampsia, retinopathy, and encephalopathy may present as a result of organ injury due to hypertension.

Hypertensive encephalopathy is a less commonly encountered type of hypertensive emergency. It is characterized by signs of cerebral edema that occur after a severe episode of hypertension. This condition is usually diagnosed retrospectively after symptoms dramatically resolve by lowering the patient’s blood pressure, and other causes of the neurologic disease have been ruled out. Symptoms of hypertensive encephalopathy include the gradual onset of headache, nausea, and vomiting, followed by neurologic symptoms such as restlessness, confusion, seizures, and potentially coma. If hypertension is treated promptly, the symptoms of encephalopathy are usually reversible.[1]

Etiology

Hypertensive encephalopathy is triggered most commonly by inadequately controlled primary hypertension. Secondary causes of hypertension can also predispose patients to this condition. 

Hypertensive encephalopathy shares multiple characteristics with other syndromes causing cerebral edema, such as posterior reversible encephalopathy syndrome (PRES), hypertensive brainstem encephalopathy, and eclampsia.

Evaluation for chronic or acute renal disease, sympathomimetic ingestion (amphetamines, cocaine), side effects from drugs such as immunosuppressive agents, preeclampsia, and eclampsia should be considered if primary hypertension has not been previously diagnosed.

Epidemiology

In the United States, approximately 50% of the adult population has some degree of hypertension.[2] Hypertensive emergencies account for a small percentage (less than 2%) of hypertensive presentations in emergency departments. Hypertensive encephalopathy specifically accounts for 15% of the hypertensive emergencies seen.[3][4]

Pathophysiology

Normally, the brain sustains blood flow within a narrow perfusion pressure range without being affected by fluctuations in systemic arterial pressure. For healthy individuals, the pressure ranges are 50-150 mm Hg cerebral perfusion pressure (CPP) or 60 to 160 mm Hg mean arterial pressure (MAP).The CPP = MAP – intracranial pressure (ICP).[5]

With increased MAP, cerebral arteriolar vasoconstriction occurs, and conversely, with decreased MAP, arteriolar dilation occurs to keep the CPP constant. This adaptive process maintains brain perfusion at a constant level despite systemic blood pressure changes. However, a sudden and severe increase in arterial pressure can exceed this autoregulatory mechanism because the arterioles are limited in their ability to constrict. The then intracerebral elevated blood pressure causes a breach in the blood-brain barrier, and vascular fluid diffuses across the capillary membranes into the brain parenchyma. This leads to the development of cerebral edema, increased intracranial pressure, and neurologic deficits such as altered mentation, visual deficits, and seizures.

In patients with chronic hypertension, the cerebral vasculature undergoes adaptations, such as arteriolar hypertrophy, to allow for a higher autoregulatory range. Lowering the blood pressure too quickly in these patients can produce cerebral ischemia at a higher MAP compared to normotensive patients.

In previously normotensive patients, acute episodes of hypertension may induce hypertensive encephalopathy at diastolic blood pressures as low as 100 mm Hg. This scenario may be seen with patients that develop eclampsia or in patients receiving cytotoxic and immunosuppressive therapies.[6][7] It is hypothesized that these conditions directly elicit a toxic effect on the vascular endothelium and lead to dysfunction of the blood-brain barrier.

History and Physical

A thorough physical exam and history are primarily used to diagnose hypertensive encephalopathy in patients presenting with elevated blood pressure in addition to altered mental status, visual abnormalities, headache, or seizures. Eliciting a thorough drug history is essential for identifying any previously used antihypertensive drugs. Typically, patients who develop hypertensive encephalopathy have chronic uncontrolled hypertension and may have recently discontinued their antihypertensive medication.[8] Individuals that have rapidly developing and/or intermittent episodes of hypertension are also more at risk for developing hypertensive encephalopathy.

The majority of patients with this diagnosis have blood pressures in excess of 220/120 mm Hg.[9] These patients should be evaluated for signs of organ damage that can be found during a hypertensive emergency. In particular, thoracic auscultation may reveal signs reflective of cardiac dysfunction, such as extra heart sounds or pulmonary edema, with rales heard on lung auscultation.[10] Fundoscopy may show retinal hemorrhages and papilledema, which is a sign of severe hypertensive retinopathy. A complete neurologic exam can identify whether focal or non-focal deficits are present and may warrant other differential diagnoses for conditions that cause similar symptoms to be considered.

Evaluation

A diagnosis of hypertensive encephalopathy is made in patients with severely elevated blood pressure plus neurologic symptoms by ruling out other conditions that may cause similar symptoms. Ischemic stroke and the intracerebral hemorrhage must be excluded in these patients because these conditions are treated differently and are not managed primarily or exclusively by lowering blood pressure.  

Neuroimaging, such as computerized tomography (CT) or magnetic resonance imaging (MRI), should be performed to aid in identifying brain lesions responsible for neurologic signs or to exclude conditions such as ischemic stroke or intracerebral hemorrhage. CT may not be as sensitive as MRI in identifying regions of brain edema, but it is usually more readily available, and takes less time to perform, and is essential in ruling out some intracranial lesions. T2-weighted MRI can localize regions of cerebral edema found with hypertensive encephalopathy, which can then be characterized further as posterior reversible encephalopathy syndrome (PRES) or hypertensive brainstem encephalopathy. Bilateral white matter edema in the posterior cerebral hemispheres is characteristic of PRES.[11] The distribution of cerebral edema is localized, particularly to the parieto-occipital regions in PRES and the pontine region in cases of hypertensive brainstem encephalopathy. Although PRES can be associated with hypertensive encephalopathy, it can be found in normotensive individuals with conditions that cause vascular injuries, such as autoimmune disease, use of immunosuppressive drugs, and preeclampsia. 

Lumbar puncture is not required for the diagnosis of hypertensive encephalopathy but may be performed when a patient is being evaluated for encephalopathy to determine etiology. In PRES, there may be a modestly elevated protein level without pleocytosis, i.e., an albuminocytologic dissociation.[12]

Other end-organ injuries in a hypertensive emergency may be present in addition to hypertensive encephalopathy. Heart failure, acute kidney injury, or retinopathy can be seen with this condition. Diagnostics such as ECG, thoracic radiography, urinalysis, cardiac enzymes, and a metabolic panel with electrolytes and creatinine should be pursued to evaluate for end-organ damage and potential causes of secondary hypertension. In female patients of childbearing age, urine pregnancy testing or serum human chorionic gonadotropin level can be measured to evaluate for eclampsia-related conditions. Toxicologic screening assays can be considered if there is clinical suspicion for the ingestion of sympathomimetic agents.

Treatment / Management

While the initial diagnosis and treatment of a hypertensive emergency may occur in the emergency department, definitive treatment for this condition is usually performed in an intensive care unit. The primary treatment for this condition involves administering antihypertensive drug therapy to lower the MAP by 10% to 15% during the first hour. The MAP should not be lowered by more than 25% of the original baseline MAP within the first day of treatment. This cautious reduction of blood pressure decreases the risk of ischemic events and allows for the healing of brain vasculature. If the MAP falls below the hypertensive-adapted autoregulatory range in the brain, as would occur with overaggressive hypertensive therapy, there is an increased risk of stroke as well as ischemic complications in other organs.[13][14] Exceptions to this conservative lowering of blood pressure include ischemic stroke, intracerebral hemorrhage, and aortic dissection.

Parenteral antihypertensive agents should be used initially. Oral antihypertensive agents should be avoided in this initial treatment phase because of the inability to titrate to effect, as well as a potentially slower onset of action. Parenteral antihypertensive drugs commonly used for this condition include nicardipine (5 mg/hour to the usual maximum dose 15 mg/hour), labetalol, fenoldopam, and clevidipine. Fenoldopam, a dopamine receptor agonist, may be preferential in patients with renal impairment as it has demonstrated a renal-protective effect.[15]

Oral antihypertensives may be started as the initial intravenous therapy is tapered and discontinued after a suitable period (often 8 to 24 hours) of reaching the target blood pressure. 

In pregnant patients with eclampsia, antihypertensive therapies are chosen based on concerns for the health of the placenta and fetus. Delivery of the infant and placental tissues may be instituted. 

Antiseizure medication may be prescribed and continued until symptoms and neuroimaging findings begin to improve. The antiseizure medication can be tapered usually after one to two weeks, as continued seizure recurrence after resolution of encephalopathy is rare.[16] Drug selection for seizure treatment may depend on other comorbidities the patient has, such as pregnancy or renal function impairment. 

Patients with PRES that concurrently have hypertension are treated with antihypertensive drugs similarly as those with hypertensive encephalopathy.[9] Immunosuppressive drug dosages may be reduced or discontinued in patients that develop symptoms of PRES. If a patient is changed to a different immunosuppressive drug, it is recommended that neuroimaging be performed if symptoms of PRES recur and to avoid using prior drugs that were associated with an encephalopathic episode. It has been reported that fluid therapy overload, MAP greater than 25% of baseline, and creatinine values greater than 1.8 mg/dL are risk factors for developing this condition in patients receiving cytotoxic and immunosuppressive drugs.[17]

Differential Diagnosis

Differential diagnoses include:

• Ischemic stroke
• Intracerebral hemorrhage
• Intracranial tumor
• Occult brain trauma
• Acute toxic metabolic encephalopathy
• Central venous thrombosis

Treatment Planning

Parenteral Antihypertensives

1. Nicardipine: The initial dose is 5 mg/hour, and the usual maximum dose is 15 mg/hour.
2. Labetalol: A 20 mg bolus is given initially, followed by subsequent boluses of 20 to 80 mg intravenously every 10 minutes to a maximum total dose of 300 mg in a day. Labetalol can also be given as a continuous infusion at 0.5 to 2 mg/min. Labetalol should not be used without prior adequate alpha blockade in patients with hyperadrenergic states (e.g., cocaine-induced hypertension)
3. Fendolopam: The initial dose of infusion is 0.1 mcg/kg per min, and the dose is titrated at 15-minute intervals, depending upon the response. Especially beneficial in patients with kidney disease.
4. Clevidipine: The initial dose is 1 mg/hour, and the usual maximum dose is 21 mg/hour.
5. Sodium nitroprusside: The initial dose is 0.25 to 0.5 mcg/kg/min and the usual maximum dose is 8 to 10 mcg/kg/min. Not a first-line drug as it may cause cyanide toxicity. Use with caution in patients with kidney disease.

Prognosis

In most cases, hypertensive encephalopathy can be reversed with a prompt but conservative lowering of the blood pressure. The prognosis for this condition can vary depending on whether other comorbidities are present. Once patients are released from the hospital, continued vigilance in hypertension management is necessary. These patients are at risk for other hypertensive crises if they become noncompliant with their medications in the future.

Complications

Failure or late treatment of a hypertensive emergency can result in renal failure, retinopathy, myocardial infarction, and stroke. In particular, without prompt treatment of high blood pressure in patients with encephalopathy, brain edema can progress and lead to status epilepticus, coma, or death. Aggressive treatment of hypertension is not advised and can lead to ischemic conditions in target organs, especially in patients with an adapted autoregulatory mechanism due to chronic hypertension.

Consultations

Depending on the clinical picture, the following consultants should be involved:

• Intensivist
• Cardiologist
• Neurologist
• Radiologist

Deterrence and Patient Education

Patients should be educated about treatment compliance and advised home monitoring of blood pressure in case of uncontrolled hypertension. Moreover, a diet rich in sodium and cholesterol should be reduced. Weight loss, as well as exercise, should be encouraged as they play vital role in controlling blood pressure.

Pearls and Other Issues

• The symptoms of hypertensive encephalopathy are insidious. Headache, nausea, and vomiting gradually worsen with time and are followed by non-localizing neurologic symptoms. This is in contrast to the abrupt and focal neurologic symptoms found with ischemic stroke or intracerebral hemorrhage.
• CT is not sensitive enough to rule out brain edema but is essential in evaluating other causes of altered mental status.[9]
• Avoid an overaggressive lowering of the blood pressure during the treatment of this condition as it may result in ischemic organ damage. The blood pressure should not be lowered any more than 25% of the baseline blood pressure within the first day of treatment.
• The most commonly used first-choice antihypertensive drug for this condition is nicardipine.[9]

Enhancing Healthcare Team Outcomes

As this condition is treated in an intensive care unit setting, the patient’s medical treatment will be managed primarily by an intensivist with consultations from other specialists, such as a cardiologist, neurologist, and radiologist, as dictated by other organ involvement. 

Encouraging patients to develop a medical home with their primary care provider is important as this contributes to better patient outcomes. Once discharged from the hospital, follow-up with a primary care provider is essential to encourage continued blood pressure monitoring and hypertension management. A pharmacy consult to determine the appropriate agents and dosing is beneficial. The pharmacist, nursing staff, and primary care provider should educate the patient and their family about the importance of medication compliance and instructions on the use of antihypertensive medications. The primary care team should emphasize educating the patient on lifestyle changes such as exercise, smoking cessation, and healthy eating habits.  

Consultation with a social worker may be needed in the case of those patients that do not have primary care options. Unfortunately, a high percentage of this patient population does not remain compliant with antihypertensive medications and seeks management in the emergency room. Healthcare outcomes are improved when hypertension is managed as an outpatient with their primary care provider rather than in an emergency. When the interprofessional healthcare team functions collaboratively and not in "silos," patient outcomes will improve. [Level 5]