Cardiovascular Disorders

Hypertension is one of the most common conditions affecting patients in developed countries. As the population ages and the emergency department continues to serve populations without access to appropriate primary care, issues regarding hypertension will become more important. Emergency Physicians must be comfortable in evaluating and treating patients with conditions associated with an acute rise in blood pressure, conditions secondary to long-standing hypertension, as well as with the complications of medications used to control hypertension.

Definitions

• Essential Hypertension is a persistently elevated blood pressure measured on two separate occasions. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has classified hypertension based on the degree of elevation (Table 2A.1).
• Hypertensive Urgency is the presence of an elevated BP without signs or symptoms of end organ damage. Blood pressure should be reduced gradually over 24-48 h in hypertensive urgencies.
• Hypertensive Emergency is the presence of an elevated BP with evidence of end-organ damage. Table 2A.2 lists conditions regarded as true hypertensive emergencies. These conditions necessitate the careful reduction of blood pressure in minutes to hours.

Epidemiology/Pathophysiology

• The majority of hypertensive emergencies occur in previously hypertensive patients. In these patients, the ability of the body to autoregulate blood pressure is adjusted to accommodate for the chronic elevation of blood pressure. A hypertensive emergency occurs with an acute elevation in blood pressure over baseline.
• While the actual blood pressure is important in the evaluation and diagnosis of these conditions, it is the presence of end-organ damage and not the actual blood pressure measurement that indicates the need for emergent lowering of blood pressure.
• The rate of elevation of the blood pressure may be more important in the pathogenesis of end-organ damage than the actual blood pressure.

Diagnosis and Evaluation

History and Physical Examination

• The evaluation of the hypertensive patient involves a careful history focused on evaluating the presence of symptoms suggestive of end-organ damage, the risk of developing subsequent end-organ damage if untreated, and anypast treatment for hypertension or associated conditions.

Table JNC-VI classification of blood pressure in adults

Category	Systolic BP	Diastolic BP
Optimal	<120	<80
Normal	<130	<85
High-Normal	130-139	85-89
Hypertension
Stage 1	140-159	90-99
Stage 2	160-179	100-109
Stage 3	>180	>110

• Patients should also be questioned regarding foods, medicines, or the use of medications or illicit drugs which may contribute to blood pressure elevation.
• Physical exam begins with the proper measurement of blood pressure in multiple extremities with a proper sized blood pressure cuff.
• Examination should include a complete neurologic evaluation including fundoscopy to rule out retinal hemorrhages or papilledema, cardiovascular exam including evaluation of new murmurs, an S3 or S4, pulses in multiple extremities, pulmonary exam listening for findings indicative of pulmonary edema, and an abdominal exam to evaluate for bruits or aneurysms.

Laboratory and Studies

• The laboratory examination in severely hypertensive patients is geared towards the evaluation of any presenting emergent condition.
• Baseline studies should include a CBC to evaluate for the microangiopathic hemolytic anemia associated with malignant hypertension, evaluation of electrolytes and renal function, evaluation of cardiac specific enzymes, and urinalysis to evaluate for proteinuria and/or hematuria.
• An EKG and CXR should be obtained to evaluate cardiovascular emergencies.
• Other studies including CT scans, abdominal ultrasound, or aortography are done as needed.

Specific Hypertensive Emergencies

Certain disease processes are discussed in greater detail in other sections of this handbook. However, treatment with respect to blood pressure control is discussed here.

Table Hypertensive emergencies

Hypertensive encephalopath
Stroke (ischemic or hemorrhagic) Myocardial infarction or unstable angina
Pulmonary edema/congestive heart failure
Aortic dissection
Acute renal failure
Preeclampsia/eclampsia
Microangiopathic hemolytic anemia
Catecholamine excess

Hypertensive Encephalopathy

• When the acutely elevated blood pressure exceeds the CNS’s ability for autoregulation, uncontrolled cerebral blood flow occurs. This results in vasospasm, vascular damage and leakage, and potential cerebral hemorrhage, ischemia, and/or edema.
• Patient complaints include headache, vomiting, drowsiness, confusion, visual changes, or focal neurologic changes. Papilledema is present and severe retinopathy is often present.
• Untreated, patients will progress to coma and death.
• Treatment involves the acute lowering of blood pressure with titratable IV medications. By definition, patients with hypertensive encephalopathy lack cerebral autoregulation. Precipitous lowering of the systemic blood pressure may cause a dangerous fall in cerebral perfusion pressure, leading to further cerebral ischemia. Therefore, careful monitoring of patients is necessary to evaluate for neurologic deterioration. Systemic blood pressure reduction should be done slowly with published guidelines of approximately 15-20% reduction in diastolic pressure within 1 h or a diastolic pressure of 110 mm Hg as therapeutic goals.

Hypertensive Stroke

• Severe, uncontrolled hypertension is frequently an etiologic factor in patients with strokes. Patients with this degree of hypertension have cerebral autoregulatory set points changed to accommodate the degree of chronic hypertension. Therefore, overaggressive lowering of blood pressure may cause a dangerous lowering of cerebral perfusion pressure and extend ischemic zones of the brain.
• Patients with hemorrhagic infarctions may present with severe hypertension as a response to the bleed, as well as an etiology of the infarction. This may resolve without treatment.
• With the above considerations, there is debate in the literature regarding the appropriate management of severe hypertension in stroke. Many authors recommend lowering for diastolic pressures >120, while others recommend that blood pressure never needs acute lowering in the emergency setting.

Hypertension with Ischemic Coronary Syndromes

• Severe hypertension is an etiologic factor in atherosclerotic heart disease. Many patients presenting with acute coronary syndromes (myocardial infarction or unstable angina) have chronic hypertension which may be severe or uncontrolled. Acute elevations in blood pressure may exacerbate coronary ischemia by increasing ventricular strain and myocardial oxygen demand.
• Decreasing afterload with the use of IV nitrates decreases myocardial work. IV ß-blockers also decrease myocardial work by decreasing blood pressure and heart rate.
• The use of direct vasodilators, which may cause a reflex tachycardia, is contraindicated in the setting of ischemia.

Hypertension with Pulmonary Edema or Congestive Heart Failure

• Severe hypertension is an etiologic factor for congestive heart failure but may also be secondary to the catecholamine response to pulmonary edema.
• Treatment for these patients includes nitroglycerin and diuretics but may also require the addition of morphine sulfate and nitroprusside. The use of morphine sulfate is effective in decreasing the catecholamine response to heart failure. Both nitroglycerin and nitroprusside produce vasodilatation in the capacitance vessels thus improving cardiac hemodynamics. Nitroprusside has a more pronounced effect on arterioles, thus reducing afterload. However, a reflexive tachycardia and increased inotropy may counteract the decrease in afterload and even lead to an increase in cardiac workload.
  Nitroprusside may also cause coronary steal in patients with coronary artery disease. It is therefore not the first line drug in cardiac failure with severe hypertension.

Aortic Dissection

• The control of hypertension is essential in the emergency stabilization of a patient with an aortic dissection.
• The use of both ß-blockers and nitroprusside is recommended to both decrease the systemic blood pressure and to decrease the shearing force of the systolic pulse on the weakened aortic wall. Standard medications used are nitroprusside plus labetolol or esmolol.
• Blood pressure should be decreased to the lowest possible level without exacerbating ischemic symptoms.

Hypertension and Acute Renal Failure

• Patients with long-standing uncontrolled hypertension often develop renal failure.
  Acute elevations in blood pressure may lead to intrarenal vascular injury, glomerular ischemia, and subsequent hematuria, proteinuria and loss of renal function.
• The management of acute renal failure secondary to acute hypertension is focused on maintaining normal volume status, renal perfusion, and minimizing secondary complications.
• IV ß-blockers or calcium channel blockers are the drugs of choice. They must be used with caution, and euvolemia must be maintained in order to not decrease renal perfusion to a level which exacerbates instead of alleviating renal damage. The use of diuretics may be either beneficial, if used in hypervolemic or euvolemic patients to increase
  GFR, or problematic if used in hypovolemic patients. Nitroprusside, while effective for decreasing blood pressure, is problematic in patients with renal dysfunction because the thiocyanate metabolite of the drug may accumulate, leading to cyanide toxicity.
• Dialysis may be needed in severely symptomatic or hypertensive patients.

Preeclampsia/Eclampsia

• Preeclampsia and eclampsia represent diffuse end-organ damage secondary to pregnancy induced hypertension.
• Most patients with preeclampsia/eclampsia are vasoconstricted and hypovolemic.
• Hydralazine is the standard antihypertensive used in preeclampsia. However, IV ß-blockers or calcium channel blockers may also be used.
• Careful management of volume status is important as these patients have renal and often cerebral vascular injury and are therefore prone to develop edema with overaggressive hydration. The treatment for preeclampsia/eclampsia is delivery of the fetus and placenta and close communication with an obstetric specialist is required.

Microangiopathic Hemolytic Anemia

• The endovascular damage associated with hypertensive crises results in fibrin deposition in arterioles and ultimately fibrinoid necrosis. This fibrin deposition may lead to a hemolytic anemia which is diagnosed by the presence of schistocytes on peripheral blood smear. This anemia is rarely seen in isolation in hypertensive emergencies and management is based on end-organ damage in other organ systems.

Catecholamine Excess

• Excess catecholamines may lead to hypertensive emergencies. Causes include pheochromocytomas; ingestions of stimulant medications or drugs, such as cocaine or amphetamines; withdrawal syndromes as seen in the rebound hypertension with clonidine withdrawal; or the ingestion of tyramine rich foods while taking MAOIs. These conditions all result in an increased a-adrenergic tone.
• Treatment requires a blockade with phentolamine. B-blockade alone is contraindicated as it leads to unopposed a stimulation. In the case of stimulant drug ingestions, anxiolytics such as lorazepam or valium may be effective in lowering blood pressure as well as treating associated hyperactivity.

Medications Used to Treat Hypertensive Emergencies and Urgencies

Pharmacologic treatment of hypertensive emergencies requires medications which are rapid acting, easily titratable, and which lack significant side effects. Intravenous medications are the most appropriate for true emergencies. Patients must be closely monitored during the use of these medications for adverse reactions including hypotension or worsening of the underlying condition.

In hypertensive urgencies, the blood pressure may be reduced slowly. Oral medications may be appropriate in these situations.

Sodium Nitroprusside

• Nitroprusside is the drug of choice for most hypertensive emergencies.
• Nitroprusside decreases both afterload and preload by direct arterial and venous dilatation. The blood pressure response is dose dependent.
• It is administrated as a light-sensitive IV solution at doses beginning at 0.25 mcg/ kg/min. Onset of action is within 1-2 min. The half-life is 3-4 min which allows the pharmacologic effect to be quickly discontinued in patients with adverse reactions.
• As discussed above, nitroprusside may have multiple cardiovascular complications including an increase in cardiac work as well as coronary steal in atherosclerotic coronaries. However, in patients with congestive heart failure, nitroprusside has been shown to be effective in increasing cardiac output.
• Theoretically, nitroprusside may adversely effect cerebral perfusion. Nitroprusside’s potent vasodilatation may cause dilation in the cerebral vasculature, thus increasing cerebral blood flow and intracerebral swelling. However, the decrease in systemic blood pressure counteracts this effect, making nitroprusside the drug of choice in patients with hypertensive encephalopathy.
• Nitroprusside is metabolized into thiocyanate and may therefore lead to cyanide toxicity if administered for a prolonged time or to patients with either liver or kidney disease.

Nitroglycerin

• Nitroglycerin is a direct vasodilator that acts predominantly on the venous circulation. At higher doses it has some effect on arterial tone.
• Doses begin at 5 mcg/min. Onset is within 1-5 min.
• Nitroglycerin dilates coronary arteries and thus, it is used primarily as an anti-anginal medication in patients with acute coronary syndromes. Nitroglycerin decreases preload which improves cardiac mechanics in failing hearts.
• Nitroglycerin may cause hypotension, especially in the face of hypovolemia, as well as headache, flushing and nausea.

Labetolol

• Labetolol produces both a and ß blockade. It can be given both IV and PO. Therapeutic effect can be seen in approximately 2-5 min and peaks in approximately 10 min. Initial loading dose of 20 mg over 2 min can be repeated in 10 min intervals until a response is noted.
• IV labetolol produces orthostatic hypotension.
• It does not cause a decrease in cerebral or peripheral blood flow and is safe in patients with coronary artery disease.
• Contraindications are those for all ß-blockers as a group and include bronchospasm, CHF, or heart block. Labetolol may also cause postural hypotension.

Emergency	Medications of Choice	Contraindicated Medications
Hypertensive Encephalopathy Stroke	Nitroprusside
Ischemic coronary syndromes	Medication not indicated Nitroglycerin	Hydralazine
CHF/Pulmonary edema Aortic dissection	Nitroglycerin Nitroprusside plus ß-blocker, Esmolol	Hydralazine
Acute renal failure	Nicardipine	ß-blocker
Preeclampsia/Eclampsia	Hydralazine
Catecholamine excess	Phentolamine, Lorazepam	ß-blocker alone

Esmolol

• Esmolol is an ultra-short acting ß-blocker with a rapid onset of action and cessation of action when discontinued.
• It is used IV and is most suitable for relatively unstable patients with supraventricular dysrhythmias or aortic dissection.
• Contraindications include those previously mentioned for ß-blockers.

Nicardipine

• Nicardipine is a titratable IV calcium channel blocker which may also be given orally.
• The onset is 5-15 min with duration of action approximately 30 min. The starting dose is 5-15 mg/h.
• Nicardipine decreases afterload without reducing heart rate or cardiac output. It has a favorable effect on failing hearts by improving ejection fraction and acts as an anti-anginal by dilating coronary arteries.
• Adverse effects include hypotension, headache, and nausea.

Hydralazine

• Hydralazine produces direct vasodilatation and is the drug of choice in hypertensive emergencies associated with pregnancy.
• As with all direct arterial dilators, hydralazine causes a reflex tachycardia causing an increase in cardiac work. Hydralazine is therefore not used in patients with cardiac ischemia and severe hypertension

Phentolamine
• Phentolamine is an IV short acting a-adrenergic blocker with rapid onset.
• It is given as an initial bolus of 5-10 mg and repeated as necessary.
• Adverse effects include the development or exacerbation of coronary ischemia.
• Its use is limited to settings with catecholamine excess.

Nifedipine

• Oral nifedipine was used commonly in the treatment of hypertensive emergencies.
• It causes a potent arteriole dilatation 5-10 min after administration. Unfortunately, this reduction in blood pressure is often uncontrolled, leading to adverse effects on cerebral blood flow as well as adverse cardiac effects secondary to reflexive tachycardia.
  It is contraindicated in hypertensive emergencies because of these dangers.

Clonidine

• Clonidine is a central acting a antagonist.
• Reductions in blood pressure can be seen 30 min after oral administration with maximal effect in 2-4 h.
• While it appears to be safe, it has a slower onset than the IV drugs listed above. It is also not easily titratable and thus may be dangerous if adverse effects occur.
• Clonidine also causes drowsiness and thus difficulties in monitoring mental status.

Common Effects of Anti-Hypertensive Medications

Anti-hypertensive medications are prescribed commonly. A functional knowledge of the use and side-effect profile of these drugs is important when managing patients taking these medications.

Diuretics

• Diuretics are an excellent choice for initial therapy in hypertension. If they are not the initial medication used, they are indicated as a secondary medication as they have an additive effect on blood pressure when used in combination. They are especially effective in African Americans.
• The most common side effects of the diuretics are due to their effect on fluid and electrolyte balance. Dehydration is the most obvious side effect. Hypokalemia and hyperkalemia may both occur depending on the agent used.
• Diuretics may also cause increases in uric acid and thus precipitation of gouty arthritis.

Beta Blockers

• Beta blockers are recommended as monotherapy for hypertension. They are especially useful in patients with ischemic heart disease, tachydysrhythmias, essential tremor, or migraines.
• Beta blockade may cause exacerbation of asthma or other bronchospastic diseases. It may worsen CHF or cause heart block especially when combined with calcium channel blockers. Beta blockade may mask the symptoms of hypoglycemia in diabetics.
  Depression and sexual dysfunction may also occur.

Calcium Channel Blockers

• Calcium channel blockers are especially effective in African Americans.
• Vasodilatation by calcium channel blockade may precipitate orthostatic hypotension or peripheral edema, especially in the elderly. CHF may be worsened by the negative inotropic effect of these medications. Heart block may also occur.

ACE Inhibitors