Nitro-Bid IV, NitroStat IV)/arterial and

venous vasodilator

IV infusion 5–100 mcg/minute 2–5 minutes 5–10 minutes after

D/C infusion

Nitroprusside

g

(Nipride,

Nitropress)/arterial

and venous

vasodilator

IV infusion.

a Start: 0.5 mcg/kg/minute

Usual: 2–5 mcg/kg/minute Max: 8

mcg/kg/minute

Seconds 3–5 minutes after

D/C infusion

Medication

Major Side Effects (All Can Cause

Hypotension)

Avoid or Use Cautiously in Patients

With These Conditions

Clevidipine Atrial fibrillation, nausea, vomiting,

headache, acute renal failure, reflex

tachycardia, MI

Allergy to soybeans, soy products, eggs or

egg products, severe aortic stenosis,

defective lipid metabolism, HF

Enalaprilat Hyperkalemia, acute kidney injury in those

who are volume depleted

Hyperkalemia, bilateral renal artery

stenosis, pregnancy (teratogenic)

Esmolol Nausea, thrombophlebitis, painful

extravasation

Asthma, bradycardia, decompensated HF,

advanced heart block

Fenoldopam Tachycardia, headache, nausea, flushing Glaucoma

Hydralazine Tachycardia, headache, angina Angina pectoris, MI, aortic dissection

Labetalol Abdominal pain, nausea, vomiting, diarrhea Asthma, bradycardia, decompensated HF

Nicardipine Headache, flushing, nausea, vomiting,

dizziness, tachycardia; local

thrombophlebitis change infusion site after

12 hours

Angina pectoris, decompensated HF,

increased intracranial pressure

Nitroglycerin Methemoglobinemia, headache, tachycardia,

nausea, vomiting, flushing, tolerance with

prolonged use

Pericardial tamponade, constrictive

pericarditis, or increased intracranial

pressure

Nitroprusside Nausea, vomiting, diaphoresis, weakness,

thiocyanate toxicity,

h cyanide toxicity (rare)

i

Chest pain, nausea, vomiting, dizziness,

headache, nasal congestion, arrhythmia

Renal failure (thiocyanate accumulation),

hepatic impairment (cyanide toxicity),

pregnancy, increased intracranial pressure,

acute coronary syndrome

aNot approved by the U.S. Food and Drug Administration for treatment of acute hypertension.

bApproved for intraoperative and postoperative treatment of hypertension.

cParenteral hydralazine is an intermediate treatment between oral agents and more aggressive therapies such as

nitroprusside. It can be given IV or intramuscularly, but there is no appreciable difference in onset of action (20–40

minutes) between the two routes. This slow onset minimizes hypotension.

dLabetalol is contraindicated in acute decompensated heart failure because of its β-blocking properties. Infusions

start at 2 mg/minute and are titrated until a satisfactory response or a cumulative dose of 300 mg is achieved.

e

Indicated for short-term treatment of hypertension when the oral route is not feasible or desirable.

fRequires special delivery system owing to drug binding to polyvinyl chloride tubing. Also see Chapters 12, Chronic

Stable Angina, and Chapter 13, Acute Coronary Syndromes, for further information regarding nitroglycerin.

gThe container should be wrapped with metal foil to prevent light-induced decompensation once reconstituted; the

product will be a red-brown solution. Under these conditions, the solution is stable for 4 to 24 hours. A rising BP

may indicate loss of potency. A change in color to yellow does not indicate effectiveness. The appearance of a

dark brown, green, or blue color indicates loss in activity. When changing to a new bag, the administration rate may

require adjustment.

hThiocyanate levels rise gradually in proportion to the dose and duration of administration. The half-life of

thiocyanate is 2.7 days with normal renal function and 9 days in patients with renal failure. Toxicity occurs after 7

to 14 days in patients with normal renal function and after 3 to 6 days in renal failure patients. Thiocyanate serum

levels should be measured after 3 to 4 days of therapy, and the drug should be discontinued if levels exceed 10 to

12 mg/dL. Thiocyanate toxicity causes a neurotoxic syndrome of toxic psychosis, hyperreflexia, confusion,

weakness, tinnitus, seizures, and coma.

iSigns of cyanide toxicity include lactic acidosis, hypoxemia, tachycardia, altered consciousness, seizures, and the

smell of almonds on the breath. Concurrent administration of sodium thiosulfate or hydroxocobalamin may reduce

the risk of cyanide toxicity in high-risk patients.

ACE, angiotensin-converting enzyme; BP, blood pressure; D/C, discontinued; HF, heart failure; IV, intravenous;

MI, myocardial infarction.

Table 16-3

Oral Medications Commonly Used in the Treatment of Hypertensive Urgencies

Medication

a

(Brand Name) Dose/Route

Onset of

Action

Duration of

Action

Major Side

Effects

a

Avoid or Use

Cautiously in

Patients With

These

Conditions

Captopril

b

(Capoten)

12.5-, 25-, 50-,

100-mg tablets

ACE inhibitor

6.5–50 mg PO 15 minutes 4–6 hours Hyperkalemia,

angioedema,

increased SCr if

volume

depletion, rash,

pruritus, loss of

taste

Renal artery

stenosis,

hyperkalemia,

volume

depletion, acute

kidney injury,

pregnancy

Clonidine

(Catapres)

0.1-, 0.2-, 0.3-mg

tablets

Central α2

-

agonist

0.1–0.2 mg PO

initially, then 0.1

mg/hour up to 0.8

mg total

0.5–2 hours 6–8 hours Sedation, dry

mouth,

bradycardia,

constipation

Altered mental

status, severe

carotid artery

stenosis

Labetalol

(Normodyne,

Trandate)

100-, 200-, 300-

mg tablets

α- and βadrenergic

blocker

200–400 mg PO

repeated every

2–3 hours

30 minutes–2

hours

4 hours Orthostatic

hypotension,

nausea,

vomiting

HF, asthma,

bradycardia

Minoxidil

(Loniten)

2.5-, 10-mg

tablets

Arterial and

5–20 mg PO 30–60 minutes;

maximum

response in 2–4

hours

12–16 hours Tachycardia,

fluid retention

Angina, HF

venous

vasodilator

aAll may cause hypotension, dizziness, and flushing.

bOther oral ACE inhibitors too slow in onset to be useful but should be used for maintenance therapy to improve

adherence as captopril requires multiple daily doses.

ACE, angiotensin-converting enzyme; HF, heart failure, PO, orally; SCr, serum creatinine.

p. 336

p. 337

Figure 16-1 Overview of management for a hypertensive crisis. BP, blood pressure; CNS, central nervous

system; IV, intravenous; MAP, mean arterial pressure; MI, myocardial infarction; SBP, systolic blood pressure.

Goals of Therapy

The rate of BP lowering must be individualized depending on whether the patient

presents with a hypertensive urgency or emergency. Also, ischemic damage to the

heart and brain can be provoked by a precipitous fall in BP.

26–30 As treatment is

initiated, clinicians should recognize that the elderly and patients with severely

defective autoregulatory mechanisms are at high risk for developing hypotensive

complications. The latter group includes those with autonomic dysfunction or fixed

sclerotic stenosis of cerebral or neck arteries.

31

In addition, patients who have

chronically elevated BP are less likely to tolerate abrupt reductions in their BP, and

the amount of reduction appropriate for those patients is somewhat less than for those

whose BP is acutely elevated.

For hypertensive emergencies, it is recommended that the mean arterial pressure

be reduced initially by no more than 25% (within minutes to 1 hour); then if stable,

this should be followed by further reduction toward a goal of 160/100 mm Hg within

2 to 6 hours and gradual reduction to normal during the next 8 to 24 hours.

4 A DBP of

100 to 110 mm Hg is an appropriate initial therapeutic goal.

1 Lower pressures are

typically indicated for patients with aortic dissection (Case 16-6).

Another exception to this rule applies in patients with acute cerebrovascular

accidents. Cerebral autoregulation is disrupted in this setting, and the use of

antihypertensives may cause a reduction in cerebral blood flow and increasing

morbidity.

32 Current guidelines recommend lowering BP after acute ischemic stroke

if the systolic BP is greater than 220 mm Hg or the DBP is greater than 120 mm Hg in

patients ineligible for thrombolytic therapy; a lower blood goal can be achieved, if

medically necessary, to manage a condition such as a MI or aortic dissection. The

systolic BP should be lowered to less than 185 mm Hg and DBP to less than 110 mm

Hg in candidates for thrombolytics.

33 The systolic BP should be maintained at less

than 180 mmHg and the DBP at less than 105 mmHg for the first 24 hours after

thrombolytic therapy. A lower BP in patients undergoing thrombolytic therapy

reduces the risk of intracerebral bleeding.

33 Additionally, in those with hypertensive

encephalopathy, cerebral hypoperfusion may occur if the mean BP is reduced by

more than 40%.

34 Thus, in the presence of hypertensive encephalopathy it is

suggested that within the first hour of treatment the mean pressure be lowered by no

more than 20% or to a DBP of 100 mm Hg, whichever is greater.

34,35

p. 337

p. 338

Table 16-4

Treatment Recommendations for Hypertensive Emergency

Clinical

Presentation Recommendation Rationale

Aortic dissection Nitroprusside, nicardipine,

or fenoldopam plus

esmolol or IV metoprolol;

labetalol; trimethaphan.

Avoid inotropic therapy.

Vasodilator will decrease pulsatile stress in aortic vessel to

prevent further dissection expansion. β-blockers will prevent

vasodilator-induced reflex tachycardia.

Angina, myocardial

infarction

Nitroglycerin plus esmolol

or metoprolol; labetalol.

Avoid nitroprusside.

Coronary vasodilation, decreased cardiac output, myocardial

workload, and oxygen demand. Nitroprusside may cause

coronary steal.

Acute pulmonary

edema, left

ventricular failure

Nitroprusside, or

nitroglycerin and a loop

diuretic. Alternative:

enalaprilat. Avoid

nondihydropyridines, βblockers.

Promotion of diuresis with venous dilatation to decrease

preload. Nitroprusside, enalaprilat decrease afterload.

Nicardipine may increase stroke volume.

Acute kidney injury Nicardipine or

fenoldopam. Avoid

nitroprusside, enalaprilat.

Peripheral vasodilation without affecting renal clearance.

Cocaine overdose Nicardipine, fenoldopam,

verapamil, or nitroglycerin.

Alternative: labetalol.

Avoid β-selective

blockers.

Vasodilation effects without potential unopposed αadrenergic receptor stimulation. CCBs control overdoseinduced vasospasm.

Pheochromocytoma Nicardipine, fenoldopam,

or verapamil. Alternatives:

labetalol. Avoid βselective blockers.

Vasodilation effects without potential unopposed αadrenergic receptor stimulation.

Hypertensive

encephalopathy,

intracranial

hemorrhage,

subarachnoid

hemorrhage,

ischemic stroke,

thrombotic stroke

Nicardipine, clevidipine or

labetalol. Avoid

nitroprusside, nitroglycerin,

enalaprilat, hydralazine.

Vasodilation effects without compromised CBF induced by

nitroprusside and nitroglycerin. Enalaprilat and hydralazine

may lead to unpredictable BP changes when carefully

controlled BP management is required.

BP, blood pressure; CBF, cerebral blood flow; CCB, calcium-channel blocker; IV, intravenous.

HYPERTENSIVE URGENCIES

Patient Assessment

CASE 16-1

QUESTION 1: M.M. is a 60-year-old African American man with a long history of HF with a preserved

ejection fraction (HFpEF), poorly controlled hypertension believed to be caused by nonadherence, and a history

of MI. He was referred from a community health center this morning for a thorough evaluation of his elevated

BP. He has not taken his enalapril, carvedilol, or amlodipine for the past 7 days. M.M. is completely

asymptomatic. Physical examination reveals a BP of 180/120 mm Hg and a pulse of 92 beats/minute.

Funduscopic examination is pertinent for mild arteriolar narrowing, without hemorrhages or exudates. The discs

are flat. His lungs are clear, and the cardiac examination is unremarkable. The electrocardiogram indicates

normal sinus rhythm at a rate of 90 beats/minute. The chest radiograph is interpreted as mild cardiomegaly.

Serum electrolytes, blood urea nitrogen, and serum creatinine are within normal limits. A urinalysis is significant

for 2+ proteinuria. How quickly should his BP be lowered, and what therapeutic options are available?

The absolute magnitude of BP elevation does not in itself constitute a medical

emergency requiring an acute reduction in BP. There is no evidence of

encephalopathy, cardiac decompensation, chest pain, or rapid change in renal

function. Therefore, no evidence exists to indicate a rapid deterioration in the

function of target organs. One would classify M.M.’s case as a hypertensive urgency.

As is often the case, M.M.’s lack of BP control is related to medication

nonadherence. M.M.’s clinical presentation requires that his BP be lowered during

the next 12 to 24 to 48 hours while being careful not to induce hypotension. Rapidacting oral agents can be used for this purpose; parenteral therapy is not warranted. A

number of different oral regimens using clonidine, captopril, labetalol, or minoxidil

are available. Restarting his medications in a controlled manner so as not to drop his

BP too rapidly may also be a reasonable option for treatment. Later, he can be

converted to a regimen designed to enhance adherence by selecting medications with

once-daily dosing. For example, lisinopril or another long-acting angiotensinconverting enzyme (ACE) inhibitor would be preferred for maintenance instead of

the enalapril previously prescribed. One should also determine and address barriers

to

p. 338

p. 339

medication adherence with the patient including cost of therapy, lack of

understanding of the benefits of therapy, misconceptions of the side effect profiles,

and so forth. Timely follow-up within 1 week after treatment of hypertensive urgency

is of paramount importance for the appropriate management of these patients.

Oral Drug Therapy

RAPIDLY ACTING CALCIUM-CHANNEL BLOCKERS

CASE 16-1, QUESTION 2: M.M.’s physician has ordered immediate-release nifedipine to be given 10 mg

sublingually. Is this appropriate therapy to treat his hypertensive urgency?

Captopril, clonidine, labetalol, and minoxidil have all been used to lower BP

acutely. These oral agents take several hours to adequately lower pressure and are

therefore useful in treating hypertensive urgencies but not emergencies. Oral acting

ACE inhibitors, other than captopril, are not useful for acutely lowering BP because

of a slower onset of action.

The immediate-release calcium-channel blockers, including diltiazem, verapamil,

and nicardipine, can rapidly lower BP; however, the most extensive experience is

with nifedipine. Nifedipine, when given orally or by the “bite and swallow” method,

was previously recommended as a rapid-acting alternative to parenteral therapy in

the acute management of hypertension. However, its use has been associated with

life-threatening adverse events related to ischemia, MI, and stroke.

26–30 The cavalier

use of immediate-release nifedipine to acutely lower BP is potentially dangerous and

should be discouraged.

36,37 M.M.’s BP can be managed safely using other oral

medications. Captopril, clonidine, or labetalol can be used to lower his BP, and he

can be restarted on his oral maintenance regimen with appropriate follow-up care.

CLONIDINE

CASE 16-1, QUESTION 3: A decision is made not to use nifedipine, but rather to give M.M. oral clonidine.

What is an appropriate starting and maintenance dose?

Clonidine is considered a safe, effective first-line therapy for hypertensive

urgency. It is a centrally acting, α2

-adrenergic agonist that inhibits sympathetic

outflow from the central nervous system. BP can be lowered gradually over the

course of several hours using oral clonidine. Traditional dosing regimens have

included an initial oral loading dose (0.1–0.2 mg) followed by repeated doses of 0.1

mg/hour until the desired response is achieved or until a cumulative dose of 0.8 mg is

reached.

38 Some authors, however, have cautioned against the use of sequential

loading doses, citing lack of benefit over placebo and the potential for unpredictable

adverse effects, particularly abrupt occurrences of hypotension.