Hypertensive Crisis
Hypertensive Crisis
Hypertensive Crisis
35 (2008) 475–487
Hypertensive Crises
Christopher J. Hebert, MD*, Donald G. Vidt, MD
Department of Nephrology and Hypertension, Cleveland Clinic, Suite A51,
9500 Euclid Avenue, Cleveland, OH 44195, USA
Definitions
Patients presenting with very high blood pressuredblood pressure
greater than 180/110 mm Hgdshould be triaged into one of three mutually
exclusive groups.
1. Severe hypertension is present when blood pressure exceeds 180/110 mm
Hg in the absence of symptoms beyond mild or moderate headache, and
without evidence of acute target organ damage.
2. Hypertensive urgency is present when blood pressure exceeds 180/
110 mm Hg in the presence of significant symptoms, such as severe
headache or dyspnea, but no or only minimal acute target organ
damage.
3. Hypertensive emergency is present when very high blood pressure
(often O220/140 mm Hg) is accompanied by evidence of life-threaten-
ing organ dysfunction. Box 1 lists the important causes of hypertensive
emergencies.
* Corresponding author.
E-mail address: hebertc@ccf.org (C.J. Hebert).
0095-4543/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.pop.2008.05.001 primarycare.theclinics.com
476 HEBERT & VIDT
Epidemiology
Among the 65 million Americans with hypertension, the minority have
controlled blood pressure, with estimates falling between 38% and 44%
[1,2]. Hypertensive crises, however, occur in less than 1% of individuals
with hypertension [3].
Although crises are infrequent, very elevated blood pressure is a common
clinical scenario facing the physician. In the United States, more that
250,000 emergency department visits in 2005 were attributed to the diagnosis
of hypertension (International Classification of Diseases, Ninth Revision [ICD9]
diagnoses 401.0, 401.1, 401.9), with 14% resulting in hospital admission [4].
Some have suggested that hospitalization for hypertensive emergency
reflects upon the quality of ambulatory care (ie, an ambulatory care–
sensitive condition) [5]. There are two ways in which an emergency depart-
ment evaluation might indicate poor-quality ambulatory care. First, the
treating physician may have failed to achieve good blood pressure control,
HYPERTENSIVE CRISES 477
resulting in less effective care [6]. Secondly, a patient with very elevated
blood pressure may have been referred to the emergency department
when office management was possible, making care less efficient. With
high effectiveness and high efficiency being two key aims of high quality
care [6], failure to achieve good blood pressure control and inappropriate
referral undermine efforts to streamline and improve health care. An appro-
priate assessment of patients with very elevated blood pressure will identify
the few patients requiring admission and acute reduction in blood pressure
among the many who require initiation of oral medication on an outpatient
basis and follow-up care.
Bender and colleagues [7] studied 50 patients who presented to an emer-
gency department and found that the most common reason precipitating the
crisis was running out of medication. Furthermore, the average cost was
$1543 per visit, which underscores the importance of effective primary
care. Particularly common is rebound hypertension after abrupt discontin-
uation of clonidine or a beta-blocker [8]. This rebound hypertension is
thought to be due to an acute increase in sympathetic outflow.
Assessment
A timely and focused history, physical examination, and select testing is
important in the initial assessment of the patient with very elevated blood
pressure.
History
The history should be completed in a timely manner and capture several
key pieces of information. The physician should assess the duration and
severity of hypertension. The relevant symptoms to address include head-
ache, chest pain, dyspnea, edema, acute fatigue, weakness, epistaxis, seizure,
or change in level of consciousness. Such symptoms as tachycardia, diapho-
resis, and tremor may suggest pheochromocytoma, and thinning of skin and
weight gain may suggest Cushing syndrome. Any history of comorbid
conditions or end organ damage is important, such as left ventricular hyper-
trophy, chronic kidney disease, or prior stroke or myocardial infarction.
Direct questioning regarding adherence to any prescribed antihypertensive
medications is necessary, as well as recent use of such medications as oral
contraceptives, monoamine oxidase inhibitors, nonsteroidal anti-inflamma-
tory drugs, cyclosporine, stimulant/anorectic agents, and prednisone. The
patient should be questioned for use of alcohol as well as recreational drugs,
particularly cocaine, amphetamines, and phencyclidine hydrochloride.
Physical examination
The measurement of blood pressure should be performed with proper
technique and, in the setting of diminished pedal pulses, should include
478 HEBERT & VIDT
Testing
In the emergency department setting, a limited but expeditious battery of
tests should include a chemistry panel, urinalysis with microscopic examina-
tion of the sediment, and ECG. A chest radiograph is important if there is
a suspicion of heart failure or pulmonary disease. A CT scan of the head is
indicated if history or examination suggests a central nervous system disor-
der. In the office setting or with less severe elevations of blood pressure,
clinical judgment should guide testing, but in all cases a careful history
and examination are critical.
In practice, emergency department evaluations often are lacking. For
example, Karras and colleagues [9] observed care for patients with severely
elevated blood pressure at four academic emergency departments. Serum
chemistry was performed in only 73% of cases, ECG in 53%, and urinalysis
in 43%. The goal should be a timely evaluation that includes the essential
clinical tests.
Goals of treatment
Proper triage prepares the physician to establish short- and long-term
goals for the patient with very elevated blood pressure (Table 1).
There is a distinct lack of trial evidence that patients with severe hyper-
tension (without crisis) benefit from acute lowering of blood pressure, and
it may be associated with risk. For example, short-acting nifedipine has
been associated with severe hypotension, stroke, acute myocardial infarc-
tion, and death, and is no longer a part of the management of severe hyper-
tension [10]. Although other oral medications for acute blood pressure
reduction may not have such clear documentation of harm, the evidence
of benefit is lacking, and the edict ‘‘first, do no harm’’ is advisable.
Therefore, management of severe hypertension should include brief office
observation (hours), initiation or resumption of oral antihypertensive med-
ication, and arrangement for timely follow-up care, usually within 72 hours.
For patients with hypertensive urgency, again clear evidence of benefit of
acute lowering of blood pressure is lacking, but expert opinion [11–13] favors
judicious acute treatment with an oral agent with rapid onset of action. The
short-term goal is to reduce the blood pressure within 24 to 72 hours, and
appropriate follow-up should be mandatory. For noncompliant patients,
Table 1
Triage of patients with very elevated blood pressure
Severe hypertension Hypertensive urgency Hypertensive emergency
Blood Pressure O180/110 mm Hg O180/110 mm Hg Often O220/140 mm Hg
Clinical features: symptoms May be asymptomatic; headache Severe headache, dyspnea, edema Chest pain, severe dyspnea,
altered mental status, focal
neurologic deficit
Clinical features: findings No acute target organ damage Acute target organ damage usually Life-threatening target organ
HYPERTENSIVE CRISES
absent, but may include elevated damage (eg, acute myocardial
serum creatinine infarction, stroke,
encephalopathy, acute renal
failure, heart failure)
Immediate goal Lower blood pressure within days Lower blood pressure within Immediate blood pressure
24–72 hours reduction; decrease by
15%–25% within 2 hours
Treatment setting Outpatient Usually outpatient Inpatient, intensive care unit
Medications Long-acting, oral Oral medications with rapid onset Intravenous medication
of action; occasionally
intravenously
Follow-up Within 3–7 days Within 24–72 hours As appropriate after hospital
management
479
480 HEBERT & VIDT
Pharmacotherapy
For severe hypertension, initiation or resumption of long-acting antihy-
pertensive medication is warranted.
If immediate reduction of blood pressure is indicated (urgency), medica-
tions with rapid onset of action are preferred. Oral medications that may be
appropriate include clonidine, (0.1–0.2 mg), labetalol (200–400 mg), or cap-
topril (12.5–25 mg). Use of drugs with rapid onset carries two caveats. First,
a large dose should be followed by a longer period of observation in the
office or emergency department to assess for hypotension. Secondly, the
effect of a drug with short onset of action (eg, clonidine) may decrease
shortly after discharge to home, resulting in return of very elevated blood
pressure. To avoid this occurrence, one can either continue dosing of the
same drug as an outpatient, or begin a long-acting drug (eg, amlodipine,
extended-release metoprolol, diuretic) in the office. Table 2 lists some com-
monly used oral agents in the treatment of hypertensive crises.
Parenteral agents are indicated for some cases of hypertensive urgency
and all cases of hypertensive emergency. Table 3 lists some commonly
used intravenous medications.
Table 2
Preferred medications for hypertensive urgencies
Agent Dose Onset of action Comment
Labetalol 200–400 mg po 20–120 min Bronchoconstriction, heart block,
aggravate heart failure
Clonidine 0.1–0.2 mg po 30–60 min Rebound hypertension with
abrupt withdrawal
Captopril 12.5–25 mg po 15–60 min Can precipitate acute renal
failure in setting of bilateral
renal artery stenosis
Nifedipine, 30 mg po 20 min Avoid short-acting oral or
extended sublingual nifedipine due to risk
release of stroke, acute myocardial
infarction, severe hypotension
Amlodipine 5–10 mg po 30–50 min Headache, tachycardia, flushing,
peripheral edema
Prazosin 1–2 mg po 2–4 hours Syncope (first dose), tachycardia,
postural hypotension
Table 3
Preferred medications for hypertensive emergencies
Onset/duration of action
Agent Dose (after discontinuation) Precautions
Parenteral vasodilators
Sodium nitroprusside 0.25–10.00 mg/kg/min as intravenous Immediate/2–3 min Nausea, vomiting, muscle twitching; with
infusion; maximal dose for 10 min only after infusion prolonged use, may cause thiocyanate
intoxication, methemoglobinemia acidosis,
cyanide poisoning; bags, bottles, and
delivery sets must be light-resistant
Glyceral trinitrate 5–100 mg as intravenous infusion 2–5 min/5–10 min Headache, tachycardia, vomiting, flushing,
methemoglobinemia; requires special
delivery systems due to the drug’s binding
to polyvinyl chloride tubing
HYPERTENSIVE CRISES
Nicardipine 5–15 mg/h intravenous infusion 1–5 min/15–30 min, but may Tachycardia, nausea, vomiting, headache,
exceed 12 h increased intracranial pressure, possible
after prolonged infusion protracted hypotension after prolonged infusions
Verapamil 5–10 mg intravenous; can follow with 1–5 min/30–60 min Heart block (first-, second-, and third-degree),
infusion of 3–25 mg/h especially with concomitant digitalis or
b-blockers; bradycardia
Fenoldopam 0.1–0.3 mg/kg/min intravenous infusion !5 min/30 min Headache, tachycardia, flushing, local phlebitis
Hydralazine 10–20 mg as intravenous bolus or 10–40 mg 10 min intravenous/O1 h Tachycardia, headache, vomiting, aggravation
intramuscularly; repeat every 4–6 h (intravenous); of angina pectoris
20–30 min intramuscularly/
4–6 h intramuscularly
Enalaprilat 0.625–1.250 mg intravenous every 6 h 15–60 min/12–24 h Renal failure in patients with bilateral renal
artery stenosis; hypotension
Parenteral adrenergic inhibitors
Labetalol 10–80 mg as intravenous bolus every 10 min; 2–5 min/2–4 h Bronchoconstriction, heart block, orthostatic
up to 2 mg/min as intravenous infusion hypotension
Esmolol 500 mg/kg bolus injection intravenously 1–5 min/15–30 min First-degree heart block, congestive
or 25–100 mg/kg/min by infusion; may heart failure, asthma
repeat bolus after 5 min or increase infusion
rate to 300 mg/kg/min
481
Phentolamine 5–15 mg as intravenous bolus 1–2 min/10–30 min Tachycardia, orthostatic hypotension
482 HEBERT & VIDT
Limiting its use are several potential side effects, including reflex tachy-
cardia, headache, and vomiting. The reflex tachycardia makes this drug gen-
erally undesirable for treatment of crises associated with acute coronary
syndrome or acute aortic dissection.
Phentolamine is a potent alpha-1 antagonist with a rapid onset of action
that has traditionally been used in cases of catecholamine excess, such as
pheochromocytoma crisis. Side effects can be problematic with this drug, par-
ticularly orthostatic hypotension, flushing, headache, and reflex tachycardia.
Oral clonidine is a useful drug for hypertensive urgency due to its rapid
onset of action. However, multiple doses of clonidine can be a setup for
hypotension if the patient is not observed for a sufficient amount of time.
The practice of clonidine loading has largely fallen out of favor. One small
trial of clonidine loading among patients with severe asymptomatic hyper-
tension found no benefit [17].
Renal emergencies
Measurement of serum creatinine and a urinalysis with examination of the
sediment is important for all patients with hypertensive emergency. A renal
emergency is present if new or acutely worsening renal dysfunction is pres-
ent or if the urine sediment contains red cell casts or dysmorphic red cells.
Fenoldopam is a strong choice of agent in this case due to its efficacy in
reducing blood pressure along with its action to increase renal blood flow
and urine output. Sodium nitroprusside and labetalol are also useful.
A temporary reduction in glomerular filtration rate may occur with acute re-
duction of severely elevated blood pressure, even in crises of nonrenal causes.
Short-term dialysis is sometimes necessary. Careful monitoring of renal func-
tion, electrolytes, and volume status is necessary throughout the clinical course.
Adrenergic crises
Examples of adrenergic crises include pheochromocytoma crisis, cocaine
or amphetamine intoxication, and clonidine withdrawal. Drugs to consider
HYPERTENSIVE CRISES 485
Pregnancy
Pregnancy-associated crises pose a challenge because many of the com-
monly used drugs for acute lowering of blood pressure are contraindicated
in pregnancy. The drugs of choice include hydralazine, methyldopa, and mag-
nesium sulfate. Beta-blockers or nifedipine are sometimes used in addition.
Follow-up
Studies suggest that patients treated for hypertensive crises often do not
get adequate discharge instructions. Karras and colleagues [9] found that
only 29% of such patients seen in four urban academic emergency depart-
ments received written instructions to follow up with a primary care
provider. For many such patients, the risk attributable to ongoing poor
control of blood pressure clearly outweighs the short-term risk of a transient
rise in blood pressure.
Prevention
Hypertensive crises are largely preventable. Inadequate management of
hypertension by the physician, poor adherence to therapy by the patient,
and insufficient access to care are important factors leading to crises.
Patients presenting with hypertensive crisis often have a history of poorly
controlled blood pressure. Failure to intensify the treatment regimen in
response to an elevated blood pressure in the office has been repeatedly
correlated with poor control. More aggressive and effective execution of
a treatment plan for hypertension is important in the effort to prevent crises.
Another common scenario preceding a crisis is a patient discontinuing
medications. Discontinuation of any antihypertensive medication can pre-
cipitate a crisis as the antihypertensive effect wears off. In addition, rebound
hypertension can follow abrupt discontinuation of high-dose beta-blockers
or clonidine.
Poor access to care may be considered a system-level factor that contrib-
utes to the occurrence of hypertensive crises. Often a timely office visit or
telephone call is all it takes to prevent a crisis.
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