A. Definitions

1. Severe elevation in blood pressure, with diastolic blood pressure (DBP) > 120-130 mmHg.
2. Emergency if acute or ongoing end-organ damage occurs
3. Urgency: absence of end-organ damage

B. Causes

1. Chronic essential hypertension (HTN) with acute exacerbation (most common)
2. Renovascular HTN
   1. Atheromatous
   2. Fibromuscular Dysplasia
3. Parenchymal Renal Disease
   1. Acute glomerulonephritis
   2. Renal Infarction
   3. Vasculitis
4. Endocrine
   1. Pheochromocytoma
   2. Cushing's Syndrome
   3. Renin-secreting tumors
   4. Mineralocortoic Excess (rarely causes emergency)
5. Drug Ingestion
   1. Tricyclic anti-depressants
   2. Monoamine Oxidase (MAO) Inhibitors
   3. Cocaine
   4. Amphetamines
6. Anti-hypertensive drug withdrawal or failed compliance
   1. Centrally acting anti-hypertensives (such as clonidine)
   2. Peripheral alpha blockers (such as prazosin)
   3. Beta-Blocker acute withdrawal
7. Pregnancy: Pre-eclampsia and Eclampsia
8. Autonomic Hyperactivity
   1. Guillain-Barre Syndrome
   2. Spinal Cord Injury
   3. Acute intermittant porphyria
9. Scleroderma Renal Crisis [8,10]

C. Pathophysiology

1. Imbalance between vasodilators and vasoconstrictors
   1. Endothelium is a major mediator of intrinsic vascular tone
   2. Various hormones in paracrine and endocrine fashion modify endothelial responses
   3. Vasoconstricting influences overwhelm vasodilators, leading to hypertensive crisis
2. Vasodilators
   1. Reduce blood pressure, counteract vasoconstrictors
   2. Nitric oxide (NO) released by endothelium is the major mediator
   3. NO production is stimulated by acetylcholine, norepinephrine, substance P
   4. Shear stress also stimulates NO production
   5. Prostacyclin (PGI2) is another important vasodilator
3. Vasocontrictors
   1. Activation of renin-angiotensin system is important
   2. Angiotensin II is a major vasoconstrictor
   3. Antidiuretic hormone (ADH or vasopressin) is also a vasoconstrictor
   4. Endothelin I production by endothelium is also important in vasoconstriction
   5. Vasoconstrictors often stimulated expression of endothelial cell adhesion molecules (CAM)
4. Progression of Hypertensive Crisis
   1. Likely that hypertensive urgency is precursor to emergency
   2. End-organ damage likely due to formation of platelet-fibrin clots in vasculature
   3. The clots are formed when platelets bind to CAMs on stressed endothelium
   4. Release of thromboxane A2 further stimulates platelet aggregation
   5. Fibrinogen and red blood cells are trapped in the platelet plug
   6. Thus, urgency has minimal platelet clot formation, mostly vasoconstriction
   7. Hypertensive emergency involves clot formation and end-organ ischemic damage

D. Presentation

1. Asymptomatic in some patients (that is, hypertensive urgency)
2. Headache, Visual Changes
3. Cardiac
   1. Chest Pain (myocardial infarction)
   2. Acute pulmonary edema (usually with diastolic dysfunction) [9]
4. Aortic Dissection
   1. Pain to Back - thoracic aortic dissection
   2. Abdominal Pain - abdominal aortic dissection
5. Flank Pain - renal disease
6. Cerebrovascular Symptoms
   1. Mental Status Changes
   2. Stroke
   3. Encephalopathy - due to elevated cerebral perfusion pressures and blood flow
   4. Posterior Leukoencephalopathy
7. Posterior Leukoencephalopathy (rare) [2]
   1. Reversible syndrome usually occurs in setting of hypertension
   2. Responds to reduction in blood pressure
   3. MRI changes can be quite dramatic showing white matter abnormalities

E. Treatment Overview [1]

1. Tailor to individual patient situation
2. Based on absolute value of BP as well as on organ involvement and damage
3. Hypertensive urgencies can usually be treated with oral antihypertensive agents
   1. ACE inhibitors - caution with renal disease
   2. Calcium channel antagonists
   3. ß-blockers - particularly with history of myocardial ischemia
   4. Alpha-blockers
   5. Combination therapy
4. Hypertensive Emergency
   1. Admission to intensive care unit
   2. Arterial line placed to monitor blood pressure
   3. Therapy instituted rapidly (do not wait for invasive monitoring)
   4. Over initial minutes to hours, rapidly reduce BP by no more than 20-25%
   5. Goal is diastolic blood pressure 100-110 mmHg
   6. More rapid reduction initially can worsen end-organ dysfunction
   7. Specific drug therapy is tailored to end-organ involvement

F. Specific Treatments in Hypertensive Emergency [3,4]

1. Encephalopathy: Nitroprusside, Labetolol, Diazoxide
2. Cerebral Infarction: no treatment (hemorrhage control), Nitroprusside, Labetolol
3. Myocardial Ischemia, Infarction: Nitroglycerine, Labetolol, ß-adrenergic blockers
4. Acute Pulmonary Edema: Nitroprusside (or Nitroglycerin) and Loop Diuretic
5. Aortic Dissection: Nitroprusside and ß-adrenergic blockers, Labetolol
6. Eclampsia: Hydralazine, Labetolol, Diazoxide (rapidly deliver baby)
7. Acute Renal Insufficiency: Nitroprusside, Labetolol, Ca antagonists
8. Funduscopic changes: Nitroprusside, Labetolol, Ca antagonists
9. Hemolytic Anemia, Microangiopathic: Nitroprusside, Labetolol, Ca antagonists
10. Sublingual nifedipine is unsafe and is NOT recommended for hypertensive crisis [7]

G. Specific Parenteral Anti-Hypertensive Agents [1,3]

1. Fenoldopam (Corlopam®) [5,6,11]
   1. New, parenteral peripheral dopamine (DA1) receptor agonist
   2. Vasodilatory and natriuretic effects; may be renal protective
   3. Starting dose is 0.1-0.3µg/kg/minute IV infusion; maximum 1.6µg/kg/minute IV
   4. Onset 4-5 minutes, duration 10-30 minutes
   5. Effectively lowers BP in patients with renal insufficiency and hypertensive emergency
   6. Preserves or improves renal function in these patients
   7. Useful in nearly all hypertensive emergencies; caution with glaucoma
   8. Side effects typical of vasodilation (hypotension, flushing, headache, dizziness)
2. Sodium Nitroprusside
   1. Standard rapidly acting agent effective in many cases
   2. Dose is 0.25-10µg/kg/minute as IV infusion
   3. Nitroprusside has decreased efficacy in renal failure
   4. Toxic levels of cyanide build up rapidly in patients with renal failure
   5. Nausea, vomiting, muscle twitching and sweating can occur
3. Nitroglycerin
   1. Highly effective in setting of coronary ischemia, acute coronary syndromes
   2. Dose is 5-100µg/min as IV infusion
   3. May cause headache, vomiting, methemoglobinemia
   4. Excellent for titrating blood pressure in setting of coronary ischemia
4. Enalaprilat
   1. Intravenous formulation of enalapril (ACE inhibitor)
   2. Dose is 1.25-5.0mg q6 hour IV (duration of action ~6 hours)
   3. Onset of action in 15-30 minutes
   4. Highly variable response; precipitous BP drop in high-renin states
   5. May be most useful in acute cardiogenic pulmonary edema
   6. Avoid in acute myocardial infarction
5. Hydralazine
   1. Indicated primarily for eclampsia
   2. Dose is 10-20mg IV bolus titrate to effect (onset <20 minutes, duration 3-8 hours)
   3. Can be given IM as well, 10-50mg (onset 20-30 minutes)
   4. Tachycardia, flushing, headache, vomiting, increased angina may occur
6. Nicardipidne
   1. IV formulation available though not commonly used
   2. Dose is 5-15mg/hr IV, onset 5-10 minutes, duration 1-4 hours
   3. Do not use in acute CHF or with coronary ischemia
   4. May be most useful for hypertension in setting of subarachnoid hemorrhage
7. Labetalol
   1. Mixed alpha/beta blocker, excellent for most hypertensive emergencies
   2. Dose is 20-80mg IV bolus every 10 minutes or 0.5-2mg/min infusion IV
   3. Onset <10 minutes; duration 3-6 hours
   4. Avoid in patients with heart block, severe asthma, acute CHF (anti-inotropic)
   5. First or second line for eclampsia; excellent in catecholamine surges
8. Esmololol (Breviblock®)
   1. Very short half life (2-4 minutes) non-selective ß-blockade
   2. Dose is 250-500µg/kg/min for 1 minute, then 50-100µg/kg for 4 minutes
   3. Sequence may be repeated, and continuous drip may be maintained
   4. Onset of action is 1-2 minutes; 10-20 minute duration
   5. Mainly for acute aortic dissection, perioperatively, acute coronary ischemia
   6. May be used with caution in acute MI with depressed LV to modulate heart rate
   7. Very close monitoring is required, and fluid load is large with this agent
9. Phentolamine
   1. Mainly for catecholamine surges (pure alpha-adrenergic blockade)
   2. Dose is 5-15mg IV; onset 1-2 minutes; duration 3-10 minutes
   3. Tachycardia, flushing and headache may occur
10. Diazoxide - obsolete

H. Side Effects of Treatment

1. Hypotension and Tachycardia
2. Nausea and Vomiting
3. Headache
4. Acute hypotension
5. Nitroprusside: thiocyanate and cyanide toxicity
6. ß-Adrenergic Blockers: depression of cardiac function, worsening heart failure

Resources

Mean Arterial Pressure (MAP)

References

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2. Hinchey J, Chaves C, Appignani B, et al. 1996. NEJM. 334(8):494
3. Sixth Report by JNC on Hypertension (JNC-VI). 1997. Arch Intern Med. 157(21):2413
4. Calhoun DA and Oparil S. 1990. NEJM. 323(17):1177
5. Shusterman NH, Elliott WJ, White WB. 1993. Am J Med. 95(2):161
6. Fenoldapam. 1998. Med Let. 40(1027):55
7. Grossman E, Messerli FH, Grodzicki T, Kowey P. 1996. JAMA. 276(16):1328
8. Steen VD and Medsger TA Jr. 2000. Ann Intern Med. 133(8):600
9. Gandhi SK, Powers JC, Nomeir AM, et al. 2001. NEJM. 344(1):17
10. Korn JH and Mauiyyedi S. 2001. NEJM. 345(8):596 (Case Record)
11. Murphy MB, Murray C, Shorten GD. 2001. NEJM. 345(21):1548