H yperte n s i ve C r i s i s

A Review of Pathophysiology and

Treatment
Deborah A. Taylor,

PharmD

KEYWORDS
 Hypertensive urgency  Hypertensive emergency  Hypertensive crisis
KEY POINTS
 Treatment guidelines have been published by Joint National Committee (JNC) groups in
an effort to reduce hypertension.
 Patients with hypertensive urgency may only need treatment with oral medications and
can be safely discharged with close follow-up with a medical professional. Blood pressure
in these patients will still be elevated above normal.
 Patients with hypertensive emergency require admission to intensive care units and administration of intravenous medications to safely reduce blood pressure levels. Blood pressure
in these patients must be reduced over a period of time to avoid other medical crisis.
 The effects that hypertension has on vital the organs of the body has been shown to lead
to other health issues in most patients.
 It is important for medical practitioners to have a working knowledge of medications for
hypertensive crisis.

INTRODUCTION

According to the Centers for Disease Control and Prevention, approximately 70 million
American adults (29%) have hypertension and only about half (52%) have their blood
pressure (BP) under control.1,2 When uncontrolled over a time span of years, hypertension can lead to damage of vital organs, namely the cardiovascular, neurologic, and
renal systems. Many medications are on the market to treat patients with hypertension. Knowledge of these agents, their characteristics, and their proper use helps to
decrease the damage to organs that ultimately will result in an increased cost burden
to the health care system.
Guidelines for treatment of hypertension were changed in late 2013 with the publication of the 2014 evidence-based guideline for the management of high BP in adults

Disclosures: None.
Department of Pharmacy and Clinical Nutrition, Grady Health System, 80 Jesse Hill Jr Drive SE,
Atlanta, GA 30303, USA
E-mail address: dtaylor@gmh.edu
Crit Care Nurs Clin N Am - (2015) -http://dx.doi.org/10.1016/j.cnc.2015.08.003
ccnursing.theclinics.com
0899-5885/15/$ see front matter 2015 Elsevier Inc. All rights reserved.

Taylor

from the panel members appointed to the Eighth Joint National Committee (JNC8).3
Treatment modalities were now based on age, race, and the presence of diabetes
mellitus or chronic kidney disease.
Despite these recommendations and others, however, clinicians continue to see
many patients with undiagnosed and uncontrolled hypertension. Because the
choice of medical therapy is crucial, through PubMed searches this article reviews
the pathophysiology of hypertensive crisis and the treatment choices currently
available.
DEFINITIONS

Hypertensive crisis by definition is divided into 2 categories: hypertensive urgency or

hypertensive emergency.2,46 Both groups present with severely elevated BP, but the
differences lie in the presence of target organ damage (TOD) (seen only in hypertensive emergency) and the treatment options (Fig. 1).

Type
Hypertensive Emergency

Hypertensive Urgency

Blood Pressure
Severe BP elevaon without TOD

Severe BP elevaon, >180/120 with

TOD

Treatment
Gradualy reduce BP with oral/IV medicaons
Close outpaent follow-up

Admit to ICU
Administer IV anhypertensives

Fig. 1. Hypertensive crisis. BP, blood pressure; ICU, intensive care unit; IV, intravenous; TOD,
target organ damage.

CLINICAL PRESENTATION
Hypertensive Urgency

Patients will present with elevated BP greater than 180/120 mm Hg, without signs of
TOD. Presenting symptoms may include headache, shortness of breath, anxiety, and
epistaxis.7
Hypertensive Emergency

Patients will present with elevated BP greater than 180/120 mm Hg, and will show
signs of TOD (Box 1).
When a patient presents with hypertensive crisis, several things should be done as
soon as possible, including mental status checks, continuous monitoring of BP, and
an electrocardiogram to ascertain heart rate and rhythm. The physician should obtain
a medical history noting the length and extent of the presenting symptoms, and a review of all current medications (prescription and nonprescription), and ask questions
to determine medication compliance and recreational drug use.68 Close attention
should paid to those patients with comorbid disease states and effects on the neurologic, renal, and cardiovascular systems.

Hypertensive Crisis

Box 1
Signs of target organ damage seen in hypertensive emergency
Cardiac
 Aortic dissection
 Heart failure/left ventricular hypertension
 Acute pulmonary edema
 Myocardial ischemia/unstable angina
Renal
 Acute/chronic renal disease
 Hematuria
Neurologic
 Cerebral vascular accident
 Intracerebral hemorrhage
 Headache
 Confusion
 Visual loss
 Hypertensive encephalopathy
Ophthalmic
 Retinopathy
Data from Refs.7,8,15

PATHOPHYSIOLOGY

Armed with the knowledge of the many causes of hypertension and hypertensive
crisis, this article initially reviews normal autoregulation of blood flow.911
BP is the pressure or tension exerted by the blood as it circulates through the arterial
vessels, and is expressed in mm Hg (millimeters of mercury). As seen by the following
equation, BP is a product of cardiac output (CO) and total peripheral resistance (TPR).
BP 5 CO  TPR
Factors that contribute to hypertension include, but are not limited to, malfunctions
in the humoral system (ie, the renin-angiotensin-aldosterone system) and the neuronal
and autoregulatory systems.
Autoregulation is defined as the intrinsic ability of an organ to maintain a constant
blood flow despite changes in perfusion pressure (arterial minus venous pressure,
PA PV). When perfusion pressure decreases to an organ, blood flow (F) initially decreases, but returns toward normal levels over the next few minutes. This autoregulatory response occurs in the absence of neural and hormonal influences and therefore
is intrinsic to that organ. Autoregulation occurs normally in response to hypoperfusion
to the brain, heart, and kidneys.
In the equation displayed in Fig. 2, when perfusion pressure initially decreases,
blood flow F decreases because of the relationship between pressure, flow, and
resistance.12
Autoregulation helps to maintain normal blood flow to vital organs while maintaining
a homeostatic BP.

Taylor

Fig. 2. Autoregulation equation. (From Klabunde RE. Cardiovascular physiology concepts.

Available at: http://www.cvphysiology.com. Accessed July, 2015; with permission.)

Fig. 3 shows the effects of suddenly reducing perfusion pressure from 100 to 70 mm
Hg in a vascular bed without autoregulation. There is a decrease in blood flow and an
increase in vascular resistance. In organs with autoregulation, after the initial decrease
in perfusion pressure and flow, the flow will gradually increase as the vasculature dilates and resistance decreases (red lines in Fig. 3). After a few minutes, the flow will
achieve a new steady-state level very close to normal.9
Failure of this autoregulatory response is seen in hypertensive crisis. Resistance,
and BP, will continue to increase with loss of the autoregulation.
ETIOLOGY

Most patients who present with hypertensive crisis usually have a history of hypertension. The following list includes some of the commonly suggested causes of hypertensive crisis:
Pregnancy
Preeclampsia, eclampsia
Medications
Compliance
Sudden withdrawal of medications, especially b-blockers, clonidine
Therapeutic inertia: providers failure to increase therapy when treatment goals
are unmet13
Drug interactions

Fig. 3. Effects of perfusion pressure reduction without autoregulation. PRU100, peripheral

resistance units per 100 g tissue. (From Klabunde RE. Cardiovascular physiology concepts.
Available at: http://www.cvphysiology.com. Accessed July, 2015; with permission.)

Table 1
Parenteral infusions for rapid blood pressure control in hypertensive emergencies
Drug

Dosage

Onset (min)

Duration

Comments

Sodium
nitroprusside

0.5 mg/kg/min, increase 0.5 mg/kg/min

every 2060 min

<2

110 min

Black-box warning.c Max. dose

10 mg/kg/min. Caution when used
with other antihypertensives

Nitroglycerin

5 mg/min, increase by 5 mg/min every

35 min up to 20 mg/min

Immediate

35 min

Ensure adequate hydration. Use with

caution in head trauma, avoid if recent
use of Viagra (24 h) or Cialis (48 h)

Nitrates

Calcium-Channel Blockers
Clevidipine

12 mg/h initially, usual dose w46 mg/h

24

515 min

Titration-may double every 90 s to goal

BP. Every 12 mg/h increase equals w2
4 mm Hg SBP reduction

Nicardipine

5 mg/h initially, increasing by 2.5 mg/h

every 15 min to max. 15 mg/h

10

8 h

Consider reducing at rate of 3 mg/h after

response is achieved

0.10.3 mg/kg/min, increasing by

0.050.1 mg/kg/min every 15 min to
target BP

10

1h

Use for short-term reduction of BP for up

to 48 h. Use low initial dose to prevent
reflex tachycardia

Dopamine-1 Agonist
Fenoldopam

Adrenergic-Blocking Agents
Bolus 1020 mg, then infusion 2 mg/min
initially, titrating to response. Max.
6 mg/min

25

218 h (based on
single and subsequent
doses)

Do not withdraw abruptly

Esmolol

Varies by situation

210 (quickest
time if loading
dose given)

1030 min

Used also for intra- and postoperative

hypertension
(continued on next page)

Hypertensive Crisis

Labetalol

Taylor

Table 1
(continued )
Drug

Dosage

Onset (min)

Duration

Comments

Hydralazine

Preeclampsia or eclampsia: 5 mg/dose,

then 510 mg every 2030 min as
needed
Hypertension: IV, 1020 mg/dose every 4
6 h as needed. May increase to
40 mg/dose. Change to oral as soon as
possible

520

14 h, depending on
whether patient is a
fast or slow acetylatora

Use for hypertension secondary to

preeclampsia or eclampsia

Enalaprilat

IV dose is 1.25 mg 6 h over a 5-min period

1530

612 h

Slow onset, long duration, frequent

dosing (every 6 h), used when patient
cannot take oral

Phentolamine

520 mg for hypertensive crisis, 5 mg IV

12 h
Surgery due to pheochromocytoma: 5 mg
(max. dose) 12 h before procedure,
repeat as needed every 24 h until
hypertension controlled

Immediate

1530 min

Hypertension associated with

pheochromocytomab

Other Agents

Abbreviations: BP, blood pressure; IV, intravenous; max., maximum; SBP, systolic blood pressure.
a
Acetylator: an organism capable of metabolic acetylation. Those animals that differ in their inherited ability to metabolize certain drugs, for example, isoniazid and hydralazine, are termed fast or slow acetylators.
b
Pheochromocytoma: a tumor of the adrenal glands. Symptoms include headache, sweating, palpitations, and elevated BP (http://medical-dictionary.
thefreedictionary.com).
c
A cautionary label for all therapeutic agents and/or products and relevant literature that the FDA regards as being hazardous to health if incorrectly administered (http://medical-dictionary.thefreedictionary.com).
Data from Refs.5,6,11,12,15,16

Hypertensive Crisis
Box 2
Most common side effects of hypertension drugs
Nitroprusside
Acute coronary syndrome (ACS), aortic dissection, blood pressure control after bypass surgery
Adverse events (AE): headache, palpitations, bradycardia, cyanide toxicity, hypothyroidism,
methemoglobinemia
Use is limited because of the black-box warninga contains cyanide molecules that can accumulate in the body in renal and hepatic failure patients. Nitroprusside should be administered at
the same time as a longer-acting antihypertensive medication so that the duration of treatment with nitroprusside can be minimized.
Nitroglycerin
ACS, preeclampsia
AE: reflex tachycardia, headache, methemoglobinemia
Clevidipine
ACS, postoperative hypertensive emergency
AE: reflex tachycardia, nausea/vomiting, headache, hypotension
Note: formulation contains soy and egg. Watch for allergic reaction in affected patients.
Nicardipine
ACS
AE: flushing, tachycardia, palpitations, pulmonary edema, nausea/vomiting
Fenoldopam
AE: headache, electrocardiogram (ECG) changes, hypotension, tachycardia, nausea/vomiting,
xerostomia
Labetalol
Aortic dissection
AE: bradycardia, pulmonary edema, heart block
Esmolol
Aortic dissection
AE: headache, hypotension, wheezing, ECG changes, hypotension, bradycardia
Hydralazine
AE: edema, hypotension
Enalaprilat
Heart failure, hypertension when oral administration is not feasible
AE: hypotension, cough. Watch for signs of angioedema
Phentolamine
To counteract the effects of hypertension caused by catecholamine (occurs in
pheochromocytoma, monoamine oxidase inhibitor interactions, cocaine or amphetamine use)
AE: hypotension, tachycardia, arrhythmias
a
A black box warning indicates that medical studies show that the drug carries a considerable risk of serious or even life threatening adverse effects. The US Food and Drug Administration (FDA) may ask pharmaceutical companies to place a black-box warning on the labeling of
a prescription drug, or in literature describing it. It is the strongest warning that the FDA
requires.
Data from Refs.5,6,11,12,1416

Taylor

Monoamine oxidase inhibitors

Recreational drug use: increased release of catecholamines
Cocaine
Amphetamines
Head trauma
Postoperative presentation
PHARMACOLOGIC TREATMENT APPROACH
Hypertensive Urgency

For patients who present with hypertensive urgency, the goal is not to reduce BP to
normal.5,6,11,12,1417 Patients may be under observation for a few hours with medical
therapy that may include the restart or titration of home/previous medications. Patients must be monitored for signs of TOD and altered mental status.
Hypertensive Emergency

Patients are admitted to the intensive care unit for medical treatment with parenteral
antihypertensives. Close monitoring of these patients is essential, as arterial lines are
frequently used for infusion of medications (Table 1).
Regarding which drugs should be used and the potential adverse effects to watch
out for, it should be borne in mind that all agents can cause hypotension. Box 2 should
be used only as a guide.
SUMMARY

It is important to evaluate and treat patients newly diagnosed with hypertension with
proper medications and follow-up to prevent the progression of uncontrolled hypertension to hypertensive urgency or emergency. The prompt recognition of a hypertensive emergency at triage with the appropriate diagnostic tests will lead to the adequate
reduction of BP, ameliorating the incidence of negative consequences. Adequate
treatment will help to alleviate the progression of disease and improve long-term
outcomes.1
REFERENCES

1. Rodriguez MA, Kumar SK, De Caro M. Hypertensive crisis. Cardiol Rev 2010;
18(2):1027.
2. Hypertension. Available at: http://www.cdc.gov/nchs/fastats/default.htm. Accessed July, 2015.
3. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311(5):50720.
4. Nwankwo T, Yoon SS, Burt V, et al. Hypertension among adults in the US: National
Health and Nutrition Examination Survey, 2011-2012. NCHS data brief, no. 133.
Hyattsville (MD): National Center for Health Statistics, Centers for Disease Control
and Prevention, US Dept of Health and Human Services; 2013.
5. Morrison A, Vijayan A. Hypertension. In: The Washington manual of medical therapeutics. 32nd edition. Philadephia: Lippincott Williams & Wilkins; 2007.
p. 10218.
6. Tuncel M, Ram V. Hypertensive emergencies. Am J Cardiovasc Drugs 2003;3(1):
2131.

Hypertensive Crisis

7. McKinnon M, ONeill J. Hypertension in the emergency department: treat now,

later, or not at all. Emerg Med Pract 2010;12:6.
8. ClinicalAdvisor. Stat Consult: hypertensive emergency/hypertensive urgency.
2012. Available at: www.clinicaladvisor.com. Accessed July 2015.
9. Klabunde R. Cardiovascular physiology concepts. 2nd edition. 2011. Available
at: www.cvphysiology.com, www.cvpharmacology.com. Accessed July, 2015.
10. Available at: www.heart.org/Conditions/HighBloodPressure. Accessed July,
2015.
11. Dipiro J, Talbert R, Saseen JJ, et al. Pharmacotherapy. A pathological approach.
7th edition. p. 14171.
12. Available at: druginfo.com. Accessed August, 2015.
13. Okonofua EC, Simpson KN, Jesri A, et al. Therapeutic inertia is an impediment to
achieving the healthy people 2010 blood pressure control goals. Hypertension
2006;47:34551.
14. Available at: http://www.uptodate.com. Accessed August, 2015.
15. Varon J, Marik P. Management of hypertensive crises. Crit Care 2003;7(5):
37484.
16. Tulman DB, Stawicki SP, Papadimos TJ, et al. Advances in management of acute
hypertension: a concise review. Discov Med 2012;13(72):37583. Accessed July,
2015.
17. Slama M, Modeliar SS. Hypertension in the intensive care unit. Curr Opin Cardiol
2006;21:27987. Lippincott Williams & Wilkins.