6.2.1. History of present illness (HPI)

• most patients have persistently elevated blood pressure for years before presenting with hypertensive emergency⁽²⁾
• ask about recent blood pressure measurements as rate of increase in blood pressure above baseline blood pressure measurements may be more important than absolute blood pressure levels⁽²⁾
• ask about neurologic symptoms, such as⁽⁶⁾
  • headache
  • nausea or vomiting
  • visual disturbances
• sudden onset of severe headache suggests subarachnoid hemorrhage⁽²⁾
• rapid onset of radiating pain in chest and/or back may suggest aortic dissection⁽⁶⁾
• ask about dyspnea, orthopnea, cough, or fatigue, which may suggest cardiac decompensation (Curr Hypertens Rep 2015 Feb;17(2):5)

6.2.2. Medication history

• review all prescription and nonprescription medications⁽²⁾
• review current antihypertensive regimen, adherence, and time from last dose⁽²⁾
• ask about use of sildenafil (Viagra) since concomitant nitrate administration can be fatal

6.2.3. Social history (SH)

• ask about recreational drug use, such as⁽²⁾
  • amphetamines
  • cocaine
  • phencyclidine

6.3.1. General physical

• confirm blood pressure on both arms using appropriately sized blood pressure cuff⁽²⁾
• physical exam to evaluate for end-organ damage and to differentiate between hypertensive urgency and hypertensive emergency⁽²⁾

6.3.2. HEENT

• funduscopic exam findings may include⁽²⁾
  • advanced retinopathy with arteriolar changes
  • hemorrhages
  • exudates
  • papilledema

6.3.3. Cardiac

• assess for murmurs and gallops⁽²⁾
• assess for signs of heart failure, which is second most common sign of end-organ damage⁽⁶⁾ (see Acute heart failure for details)

6.3.4. Lungs

• assess for evidence of pulmonary edema (wheezing, rales)⁽²⁾

6.3.5. Abdomen

• bruits suggest renal artery stenosis⁽²⁾
• abdominal aortic aneurysm
• auscultate for murmur, which may suggest aortic dissection (Curr Hypertens Rep 2015 Feb;17(2):5)

6.3.6. Extremities

• check pulses in all extremities, where unequal pulses may suggest aortic dissection⁽²⁾

6.3.7. Neuro

• assess for neurologic signs⁽⁶⁾
  • stupor
  • seizures
  • delirium
  • agitation
  • mental status exam - altered consciousness may indicate hypertensive encephalopathy⁽²⁾
• lateralizing signs are uncommon in hypertensive encephalopathy and suggest vascular event⁽²⁾

7.4.1. General principles

• blood pressure goals⁽²⁾
  • in most cases of hypertensive emergency, lower diastolic pressure by 10%-15% or to approximately 110 mm Hg over 30-60 minutes
    • Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) 2003 guidelines recommend reducing mean arterial pressure by ≤ 25% in first hour to goal of 160/100-110 mm Hg by 2-6 hours
    • European Society of Hypertension/European Society of Cardiology (ESH/ESC) 2013 guidelines recommend reducing blood pressure by < 25% during first hours followed by further cautious reduction
    • Reference - Ochsner J 2014 Winter;14(4):655 full-text
  • for aortic dissection, lower systolic pressure to < 120 mm Hg rapidly (5-10 minutes)
• consider starting lower doses or infusion rates in patients > 65 years old⁽³⁾
• transition to oral therapy as soon as possible after blood pressure stabilization⁽³⁾
•  insufficient evidence to determine whether antihypertensive drugs reduce mortality or morbidity in patients with hypertensive emergencies
  • based on Cochrane review limited by heterogeneity
  • systematic review of 15 randomized trials evaluating antihypertensive drugs in 869 patients presenting with hypertensive emergency
  • 2 trials were placebo-controlled, 14 of 15 trials were open-label
  • drug classes evaluated were nitrates (9 trials), angiotensin-converting enzyme (ACE) inhibitors (7 trials), diuretics (3 trials), calcium channel blockers (6 trials), alpha-1 adrenergic antagonists (4 trials), direct vasodilators (2 trials), and dopamine agonists (1 trial)
  • among 7 trials that reported mortality, 6 deaths occurred but allocated treatment group was not reported for 5 of the deaths
  • insufficient data on clinical outcomes for meta-analysis
  • Reference - Cochrane Database Syst Rev 2008 Jan 23;(1):CD003653 (review updated 2008 Nov 12)
• for hypertensive urgency (no evidence of end-organ damage)^(1, 2)
  • may use oral medications, with several hours of observation, to lower blood pressure gradually over 24-48 hours
  • adjust hypertensive therapy regimen
  • close follow-up should be arranged

7.4.2. Drug options by presenting condition

• acute aortic dissection^(2, 5)
  • target systolic blood pressure (SBP) is < 120 mm Hg within 5-10 minutes
  • goal of blood pressure control is reduction of shear-force (dP/dt) during systole
  • treatment usually requires beta blocker and vasodilator
  • if vasodilator used without beta blocker, reflex tachycardia may develop and aggravate dissection
  • options include
    • for beta blocker - esmolol or metoprolol⁽²⁾
    • for vasodilator - nicardipine, nitroprusside, or fenoldopam⁽²⁾
  • see Thoracic aortic dissection for additional information
• acute ischemic stroke
  • lowering blood pressure may increase ischemia in peri-infarct area and lead to increased morbidity
  • for thrombolysis candidates
    • IV therapy indicated if systolic pressure > 185 mm Hg or diastolic pressure > 110 mm Hg to achieve eligibility for IV recombinant tissue-type plasminogen activator (rt-PA) (AHA/ASA Class I, Level B)
    • options include
      • labetalol 10-20 mg IV over 1-2 minutes (may repeat once)
      • nicardipine infusion
    • blood pressure should be maintained at < 180/105 mm Hg for at least first 24 hours after thrombolysis
  • for patients who are not candidates for thrombolysis
    • antihypertensive medications should be withheld unless systolic blood pressure > 220 mm Hg or diastolic blood pressure > 120 mm Hg (AHA/ASA Class I, Level C)
    • lower blood pressure by about 15% during first 24 hours after stroke onset (AHA/ASA Class I, Level C)
  • Reference - Stroke 2013 Mar;44(3):870 full-text
  • see Blood pressure management in acute ischemic stroke for additional information

• acute hemorrhagic stroke
  • if SBP is between 150 and 220 mm Hg and patient lacks contraindication to acute BP treatment
    • SBP target of 140 mm Hg is safe (AHA/ASA Class I, Level A)
    • SBP target of 140 mm Hg may improve functional outcome (AHA/ASA Class IIa, Level B)
  • if SBP > 220 mm Hg, consider aggressive reduction of BP with continuous IV infusion and frequent BP monitoring (AHA/ASA Class IIb, Level C)
  • Reference - Stroke 2015 Jul;46(7):2032 full-text
  • 2015 guidelines do not specify which antihypertensive medications; previous 2007 guidelines suggest potential medications include (AHA/ASA Class IIb, Level C)
    • enalaprilat
    • esmolol
    • hydralazine
    • labetalol
    • nitroglycerin
    • nicardipine
    • nitroprusside (use with caution as nitroprusside can decrease cerebral blood flow while increasing intracranial pressure)
    • Reference - Stroke 2007 Jun;38(6):2001 full-text
  • see Intracerebral hemorrhage for additional information

• acute myocardial ischemia^(3, 5)
  • lower target blood pressure after acute coronary syndrome is controversial
    • low diastolic pressure may be associated with greater risk of coronary heart disease in these patients
    • increased incidence of coronary events reported in patients at high cardiovascular risk and systolic BP ≤ 120-125 mm Hg and diastolic BP ≤ 70-75 mm Hg
    • Reference - Curr Hypertens Rep 2015 Feb;17(2):5
  • nitroglycerin is drug of choice
  • do not use nitroglycerin if patient has taken phosphodiesterase inhibitors (including sildenafil, tadalafil) within past 48 hours
  • alternatives to nitroglycerin include
    • labetalol
    • esmolol
    • clevidipine
    • nicardipine
  • enalaprilat has been associated with increased mortality when given during first 24 hours of myocardial infarction
  • nitroprusside may increase mortality when infused shortly after onset of acute myocardial infarction
  • see ST-elevation myocardial infarction (STEMI) and Acute coronary syndromes for additional information
• acute postoperative hypertension^(2, 5)
  • usually starts < 2 hours after surgery
  • most patients require treatment for ≤ 6 hours
  • no consensus regarding treatment threshold except for cardiac surgery patients where treatment recommended for BP > 140/90 mm Hg or mean arterial pressure (MAP) ≥ 105 mm Hg
  • options include
    • esmolol
    • nicardipine
    • clevidipine
    • labetalol
    • nitroprusside
• acute pulmonary edema^(2, 5)
  • treatment requires both preload and afterload reduction
  • options include nitroglycerin or nitroprusside
  • loop diuretics used to reduce pulmonary congestion (such as furosemide) may also lower blood pressure
  • see Acute heart failure for additional information
• acute renal failure⁽³⁾
  • nicardipine
  • fenoldopam - may also reduce need for renal replacement therapy (RRT) and in-hospital mortality in critically ill patients with acute renal failure (level 2 [mid-level] evidence)
  • clevidipine
• hypertensive encephalopathy
  • treat promptly as delay can lead to seizures and neurologic deficits
  • blood pressure goals
    • lower mean systolic pressure by no more than 20%-25% or a diastolic blood pressure of 100 mm Hg in first 1-2 hours
    • subsequently, targets are systolic pressure of 160 mm Hg and diastolic pressure of 90-100 mm Hg
  • commonly used agents include IV labetalol or nicardipine
  • avoid nitroprusside which might increase intracranial pressure
  • Reference - Curr Hypertens Rep 2014 Jun;16(6):436

• preeclampsia/eclampsia
  • no antihypertensive medication specifically FDA approved for use in pregnant women
  • initiate antihypertensive treatment for diastolic blood pressure ≥ 105-110 mm Hg
  • maintain SBP 130-160 mm Hg and diastolic blood pressure 80-110 mm Hg
  • options include
    • labetalol
    • hydralazine
    • nifedipine
  • nitroprusside and angiotensin-converting enzyme (ACE) inhibitors contraindicated in pregnant patients
  • treatment usually also includes magnesium sulfate for seizure prevention and IV fluids
  • see Hypertensive disorders of pregnancy for details

• sympathetic crisis (such as cocaine overdose)⁽²⁾
  • avoid beta blockers which might lead to unopposed alpha stimulation and increased BP
  • options include
    • nicardipine
    • verapamil
    • diltiazem
    • phentolamine
  • consider treatment with benzodiazepine in addition to specific antihypertensive medication
  • avoid beta-adrenergic antagonists if sympathetic overstimulation present

7.4.3. Parenteral (IV) vasodilators

•  sodium nitroprusside (Nipride)^(1, 2)
  • arteriolar and venous vasodilator
  • dosing
    • initial dose of sodium nitroprusside is 0.3-0.5 mcg/kg/minute
    • increases by 0.5 mcg/kg/minute until blood pressure target reached or maximum dose 10 mcg/kg/minute
  • intraarterial blood pressure monitoring recommended
  • avoid in patients with hepatic or renal failure if possible
  • significant toxicities with higher doses or longer duration of exposure
    • cyanide/thiocyanate toxicity
      • may occur with prolonged (> 48 hours) or too rapid (> 2 mcg/kg/minute) infusion
      • discontinue nitroprusside if serum thiocyanate > 12 mg/dL (206.4 mcmol/L) or signs of intoxication (acute psychosis, disorientation, muscle spasms, hyperreflexia)
    • may cause hypoxemia in patients with chronic pulmonary disease by reversing pulmonary vasoconstriction
•  nicardipine (Cardene IV)^(1, 2, 3)
  • dihydropyridine calcium channel blocker
  • initial infusion rate 5 mg/hour, increasing by 2.5 mg/hour every 5 minutes to a maximum of 15 mg/hour
  • once target blood pressure reached, wean by 3 mg/hour as tolerated
  • may cause reflex tachycardia, headache, flushing
•  fenoldopam (Corlopam)^(1, 2, 3)
  • dopamine D1-like receptor agonist, arteriolar vasodilator, natriuretic and diuretic effects
  • unlike other parenteral antihypertensive agents, fenoldopam maintains or improves renal function
  • dosing
    • adults - usual initial dose 0.1-0.3 mcg/kg/minute, titrate dose up or down by 0.05-0.1 mcg/kg/minute every 15 minutes (maximum 1.6 mcg/kg/minute)
    • pediatric patients - usual initial dose 0.2 mcg/kg/minute, increase by up to 0.3-0.5 mcg/kg/minute every 20-30 minutes (maximum observed effect at 0.8 mcg/kg/minute)
    • maximum treatment duration ≤ 48 hours
  • side effects - hypotension, flushing, dizziness, headache, reflex tachycardia, nausea, hypokalemia, increased intraocular pressure
  • safety with beta blocker not established, may cause unanticipated degree of hypotension
  • contraindicated if allergy to sulfites
  • fenoldopam appears as effective as sodium nitroprusside in patients with acute severe hypertension (level 2 [mid-level] evidence)
    • based on randomized trial without blinding
    • 183 adults aged 21-80 years with supine diastolic blood pressure (DBP) ≥ 120 mm Hg were randomized to fenoldopam vs. sodium nitroprusside IV
      • IV treatment titrated to DBP 95-110 mm Hg or maximum reduction 40 mm Hg for very high blood pressures
      • infusions maintained for ≥ 6 hours then patients weaned off IV treatment and oral medication started
    • 30 patients (16.4%) excluded from efficacy analysis because of protocol violation
    • no significant differences in control and maintenance of DBP, adverse effects, or time to achieve target blood pressure
    • Reference - Acad Emerg Med 1995 Nov;2(11):959, editorial can be found in Acad Emerg Med 1995 Nov;2(11):947, commentary can be found in Acad Emerg Med 1996 Jun;3(6):646
  • review of fenoldopam can be found in N Engl J Med 2001 Nov 22;345(21):1548
• clevidipine (Cleviprex) FDA approved for use in lowering high blood pressure
  • nationwide recall of 15 lots of Cleviprex due to potential presence of particulate matter found to be inert stainless steel particles
    • for updated list of affected lots see Firm Press Release
    • Reference - FDA MedWatch 2010 Mar 17
  • calcium channel blocker
  • dosing
    • starting dose is 1-2 mg/hour IV
    • dose can be doubled every 90 seconds until blood pressure approaches the target, then increased more slowly every 5-10 minutes as needed up to maximum 16 mg/hour
    • limited experience with doses > 32 mg/hour or any dose ≥ 72 hours
  • may cause reflex tachycardia
  • contraindicated in patients with soy or egg allergies and patients with defective lipid metabolism
  • lipid emulsion containing 2 kcal/mL
    • 1,000 mL or 21 mg/hour is maximum lipid load recommended in 24-hour period
    • monitor triglyceride levels if prolonged administration
    • calculate kcals from lipid and adjust nutrition regimen if needed
  • References - Am J Health Syst Pharm 2009 Aug 1;66(15):1343⁽³⁾, Med Lett Drugs Ther 2008 Sep 22;50(1295):73 TOC, Prescriber's Letter 2008 Oct;15(10):56
  • efficacy
    • clevidipine appears effective for acute perioperative hypertension in patients having cardiac surgery (level 2 [mid-level] evidence)
      • based on analysis of 3 randomized trials without blinding
      • 1,512 patients having cardiac surgery with acute perioperative hypertension were randomized to clevidipine vs. nitroglycerin vs. sodium nitroprusside vs. nicardipine
      • no significant differences between groups for incidence of myocardial infarction, stroke, or renal dysfunction
      • sodium nitroprusside associated with higher mortality than clevidipine (p = 0.04), but no significant differences comparing clevidipine vs. nitroglycerin vs. nicardipine
      • clevidipine more effective than nitroglycerin and sodium nitroprusside for maintaining blood pressure within target range, clevidipine and nicardipine were equivalent
      • Reference - Anesth Analg 2008 Oct;107(4):1110
    • clevidipine reported to be effective for treating hypertensive emergencies in adults (level 3 [lacking direct] evidence)
      • based on case series
      • 126 adults ≥ 18 years old who presented to emergency department with severe hypertension (systolic blood pressure > 180 mm Hg and/or diastolic blood pressure > 115 mm Hg) were treated with clevidipine
      • clevidipine started at 2 mg/hour and titrated by doubling increments every 3 minutes to maximum 32 mg/hour over 30 minutes, then continued for 18-96 hours
      • 102 of 126 patients (81%) had end-organ injury at baseline
      • 104 of 117 (88.9%) achieved target systolic blood pressure target range within 30 minutes of starting clevidipine
      • 108 of 117 patients (92.3%) who received ≥ 18 hours of clevidipine did not require additional IV antihypertensive agents
      • 115 of 126 patients (91.3%) successfully transitioned to oral antihypertensive therapy
      • Reference - Ann Emerg Med 2009 Mar;53(3):329, editorial can be found in Ann Emerg Med 2009 Mar;53(3):339, commentary can be found in Ann Emerg Med 2009 Aug;54(2):301
•  nitroglycerin (Nitro-bid IV)^(1, 2, 3)
  • venous dilator and, to a much lesser extent, also arterial dilator
  • primarily used for treatment of hypertension accompanying myocardial ischemia or pulmonary edema
  • do not use nitroglycerin if patient has taken phosphodiesterase inhibitors (including sildenafil, tadalafil) within past 48 hours
  • dosing
    • initial dose is 5 mcg/minute
    • increase by 5 mcg/minute every 3-5 minutes to 20 mcg/minute
    • if response is inadequate at 20 mcg/minute, increase by 10 mcg/minute every 3-5 minutes
    • usual limit is 200 mcg/minute
    • increase more slowly when blood pressure starting to respond
  • side effects - headache, tachycardia, vomiting, flushing, methemoglobinemia, tolerance with prolonged use
  • requires special delivery system due to drug binding to premature ventricular complexes (PVC) tubing
•  enalaprilat (Vasotec IV)^(1, 2)
  • ACE inhibitor
  • adults
    • 1.25 mg every 6 hours in patients not taking diuretic or if converting from enalapril monotherapy
    • 0.625 mg initially in patients taking diuretic, repeat dose after 1 hour if inadequate response, may give additional doses of 1.25 mg every 6 hours as needed
    • maximum 5 mg every 6 hours
  • children and adolescents aged 1-17 years - 0.05-0.1 mg/kg per dose (maximum 1.25 mg per dose)
  • doses of enalaprilat higher than 0.625 mg appear no more effective for initial therapy (level 2 [mid-level] evidence)
    • based on small randomized trial
    • 65 patients with hypertensive urgencies (SBP > 210 mm Hg and/or DBP > 110 mm Hg) or emergencies (DBP > 100 mm Hg and angina pectoris, hypertensive encephalopathy, or heart failure) were randomized to enalaprilat 0.625 mg vs. 1.25 mg vs. 2.5 mg vs. 5 mg
    • response defined as stable reduction of SBP < 180 mm Hg, DBP < 95 mm Hg, and relief of symptoms in patients with hypertensive emergencies
    • response achieved within 45 minutes in
      • 67% with 0.625 mg dose
      • 65% with 1.25 mg dose
      • 59% with 2.5 mg dose
      • 62% with 5 mg dose
    • no severe side effects observed
    • Reference - Arch Intern Med 1995 Nov 13;155(20):2217
  • risks - renal failure in patients with bilateral renal artery stenosis, hypotension (precipitous drop in blood pressure if volume-depleted)
•  hydralazine (Apresoline)^(1, 3)
  • arterial vasodilator
  • not FDA approved for treatment of hypertensive emergencies
  • not used as initial therapy due to prolonged and unpredictable antihypertensive effects
  • dosing for hypertensive emergencies
    • adults - 10-20 mg IV bolus every 4-6 hours or 10-40 mg intramuscularly (usual dose 20-40 mg), repeat IV doses every 4-6 hours as needed
    • children and adolescents aged 1-17 years - 0.2-0.6 mg/kg IV or intramuscularly per dose, repeat IV dose every 4 hours as needed
    • in pregnancy - usual initial dose 5-10 mg, then additional 5-10 mg (range 5-20 mg) every 20-30 minutes as needed
  • hydralazine causes reflex stimulation of sympathetic nervous system and may increase pulse rate and intracranial pressure; however, this can be blunted by giving beta blocker at the same time
  • contraindication - hypertension with heart failure, cardiac ischemia, angina, aortic dissection
• diazoxide (Hyperstat, Proglycem)
  • arteriolar vasodilation
  • dosing
    • initial dose 1-3 mg/kg (maximum 150 mg) or 50-100 mg total every 5-15 minutes until desired effect
    • 300 mg dose not recommended
  • second drug of choice in hypertensive encephalopathy
  • contraindications - ischemic heart disease, intracranial hemorrhage, dissecting aneurysm, pulmonary edema
  • side effects - hypotension, tachycardia, aggravation of angina pectoris, nausea, vomiting, hyperglycemia with repeated injections, sodium retention, cardiac ischemia

7.4.4. Parenteral (IV) adrenergic inhibitors

•  labetalol (Trandate, Normodyne)^(1, 2, 3)
  • beta and alpha-1 blocker
  • adult dosing
    • loading dose of labetalol 20 mg IV followed by either
      • bolus doses of 20-80 mg at 10-minute intervals until target blood pressure reached
      • infusion of 0.5-2 mg/ minute, adjusted until target BP is achieved
    • bolus dose injections of 1-2 mg/kg may cause precipitous drops in blood pressure and should not be used
    • maximum cumulative dose 300 mg
  • for children aged 1-17 years – 0.2-1 mg/kg (maximum 40 mg per dose) or 0.25-0.3 mg/kg/hour continuous infusion
  • side effects - postural hypotension, dizziness, fatigue, nausea, bronchoconstriction, heart block
  • contraindications - bronchial asthma, bronchospasm, acute left ventricular failure, bradycardia, second- or third-degree heart block, cardiogenic shock, hypoperfusion
•  esmolol (Brevibloc)^(1, 2, 3)
  • beta-1-selective adrenergic receptor blocker
  • adult dosing
    • initial loading dose 500 mcg/kg/minute over 1 minute, then 50-100 mcg/kg/minute (for 4 minutes)
    • to increase, repeat bolus dose and increase infusion in 50 mg/kg/minute increments as needed to maximum of 300 mg/kg/minute
  • for children and adolescents aged 1-17 years - 100-500 mcg/kg/minute as continuous infusion (not FDA approved for children)
  • do not use with other beta blocker therapy or if patient has bradycardia or decompensated heart failure
•  phentolamine ⁽³⁾
  • alpha blocker
  • not FDA approved for treatment of hypertensive crises
  • use caution if known coronary artery disease
  • 5-15 mg IV bolus (maximum 15 mg)
  • used primarily in catecholamine-related hypertensive emergencies, such as cocaine intoxication, amphetamine toxicity, clonidine withdrawal, monoamine oxidase inhibitor drug interactions, pheochromocytoma
  • side effects - tachycardia, orthostatic hypotension, headache, flushing
• methyldopa ⁽²⁾
  • centrally acting alpha agonist
  • adults - usual dose 250-500 mg every 6 hours as needed (maximum 1 g every 6 hours)
  • children - usual dose 20-40 mg/kg/24 hours in divided doses every 6 hours (maximum 65 mg/kg or 3 g daily, whichever is less)
  • may cause drowsiness

7.4.5. Oral agents

• nicardipine
  • vasodilator
  • dosing 20-40 mg orally 3 times daily
  • side effects - headache, nausea, vomiting, hypotension
  • see also Nicardipine
• captopril
  • onset within 15 minutes
  • 25 mg orally 2-3 times daily
  • may cause hypotension, renal failure in bilateral renal artery stenosis
  • see also Captopril
• labetalol
  • onset 20 minutes to 2 hours
  • discontinue IV therapy and initiate oral therapy when diastolic blood pressure starts to decrease
  • initial dose 200 mg oral, then additional 200-400 mg dose after 6-12 hours as needed
  • see also Labetalol

• nifedipine (oral and sublingual forms) not recommended for treatment of hypertensive emergencies⁽²⁾