REVIEW

CURRENT
OPINION Hypertensive crisis: an update on clinical approach
and management
Emrah Ipek a, Ahmet Afşin Oktay b,c, and Selim R. Krim b,c

Purpose of review
Here, we review current concepts on hypertensive crisis (HTN-C) with a focus on epidemiology, causes,
pathophysiology and prognosis. We also offer a practical approach to the management of HTN-C.
Recent findings
HTN-C is characterized by a severe and abrupt increase in blood pressure (BP) with impending or
progressive acute end-organ damage (EOD). HTN-C can be divided into hypertensive emergency (HTN-E)
and hypertensive urgency (HTN-U) based on the presence or absence of acute EOD, respectively. Recent
retrospective studies have demonstrated that emergency department (ED) referrals from an outpatient clinic
or rapid BP-lowering strategies in the ED do not lead to improved outcomes in patients with HTN-U.
Summary
HTN-C can be a de-novo manifestation or a complication of essential or secondary HTN. The presence of
acute EOD is a major poor prognostic indicator in HTN-C. The main objectives of the management of HTN-
C are distinction of HTN-E from HTN-U and appropriate risk stratification, prevention or regression of acute
EOD due to severely elevated BP, prevention of recurrence of HTN-C with an effective long-term
management plan and avoidance of rapid lowering of BP except in some special circumstances. The
majority of patients with asymptomatic HTN-U can be safely managed in the outpatient setting without
exposing them to the risks of aggressive BP lowering. However, patients with HTN-E require
hospitalization, prompt treatment and close monitoring.
Keywords
antihypertensive agents, blood pressure, emergencies, hypertension

BACKGROUND and/or a DBP at least 120 mmHg [2,5,6]. It should be

Hypertension is a growing public health problem
across the world. Unless diagnosed early and prop-
erly managed, hypertension may lead to several
devastating sequelae including renal failure, coron-
ary artery disease, heart failure, stroke and death [1].
Hypertension is usually defined as a systolic blood
pressure (SBP) at least 140 mmHg and\or a diastolic
blood pressure (DBP) at least 90 mmHg [2].
Although a standard definition still lacks, hyper-
tensive crisis (HTN-C) is usually defined by a severe
and abrupt increase in blood pressure (BP) with
impending or progressive acute end-organ damage
(EOD) [2]. HTN-C is classified into two: hypertensive
emergency (HTN-E) and hypertensive urgency
(HTN-U) based on the presence or absence of acute
EOD, respectively [2,3]. EOD usually manifests as an
acute dysfunction in the cardiovascular, cerebro-
&
vascular, pulmonary or renal systems [4 ]. The BP
threshold for defining HTN-C is still not well estab-
lished. However, according to the general consen-
sus, HTN-C is defined with a SBP at least 180 mmHg
noted that the percentage increase in BP may be
clinically more relevant than the actual BP level.
Malignant HTN is a historical term from the
preantihypertensive medication era and has
traditionally been used to define severely elevated
BP with associated complications such as encephal-
opathy, acute nephropathy and retinopathy
(including papilledema and retinal haemorrhages).
The epidemiology and natural course of HTN-C
have significantly changed with the advent and
a
Department of Cardiology, Erzurum Training and Research Hospital,
Erzurum, Turkey, bDepartment of Cardiovascular Diseases, John Ochsner
Heart and Vascular Institute and cOchsner Clinical School - The Univer-
sity of Queensland School of Medicine, New Orleans, Louisiana, USA
Correspondence to Selim R. Krim, MD, Section of Cardiomyopathy &
Heart Transplantation, John Ochsner Heart and Vascular Institute, Ochs-
ner Medical Center, 1514 Jefferson Highway, New Orleans, LA 70121,
USA. Tel: +1 504 842 3925; e-mail: selim.krim@ochsner.org
Curr Opin Cardiol 2017, 32:397–406
DOI:10.1097/HCO.0000000000000398

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Hypertension
KEY POINTS
 Despite a significant decrease in mortality and
improvement in survival, the overall incidence of HTN-C
and frequency of hospitalizations continue to rise.
 Nonadherence to antihypertensive medications is the
most important risk factor promoting HTN-C.
 Important risk factors for hypertension include excessive
salt intake, high body weight, decreased physical
activity, lower consumption of fruits, vegetables and
potassium and increased alcohol consumption.
 Illicit drug use remains a major public health problem
and an important cause of HTN-C.
 Most of the patients with asymptomatic HTN-U do not
require ED referral or hospital admission and can be
managed with oral agents as outpatient.
widespread use of antihypertensive drugs. Epide-
miological studies from the preantihypertensive
medication era reported that HTN-C would affect
nearly 7% of individuals with essential hypertension
with a 1-year mortality rate of 79% and a median
survival of nearly 10 months [5]. Despite the great
progress made in the management of hypertension,
HTN-C remains an important medical emergency
affecting 1–2% of patients with essential hyperten-
sion [7].
Here, we review the current concepts on HTN-C
with a focus on epidemiology, causes, pathophysi-
ology and prognosis. We also discuss some import-
ant caveats in the management of HTN-C.
EPIDEMIOLOGY
Owing to a strong correlation between BP and acute
stress, elevated BP is a very common finding in the
emergency department (ED). In fact, a recent epi-
demiologic study found that severely elevated BP
was present in 18% of patients admitted to the ED
[8]. Compared with the frequency of encounters for
severely elevated BP, true HTN-E remains uncom-
mon. A recent nationwide study demonstrated that
the frequency of HTN-E is 0.2% of all adult ED visits
&
in the US [9 ]. Among all patients who are seen for
the primary diagnosis of HTN-C in ED, the pro-
portion of those with HTN-U and HTN-E are 75
and 25%, respectively [10]. HTN-C usually, but
not always, affects patients with a prior diagnosis
of HTN who are treated with antihypertensive medi-
cations [11–13]. Males, blacks and elderly are the
demographic groups more predominantly affected
by HTN-C [5,11,14].
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Nonadherence to antihypertensive medications
is probably the most important risk factor for HTN-
C. Other common risk factors include obesity, coro-
nary artery disease, hypertensive heart disease, the
requirement of multiple antihypertensive drugs at
baseline and not being under the care of a primary
care physician [11,15]. Readmission with the same
diagnosis is not uncommon in patients who require
hospitalization for HTN-C. Medication nonadher-
ence, substance abuse and dialysis treatment for
end-stage renal disease (ESRD) were reported to
predict readmission with HTN-C [16].
CAUSES
HTN-C can develop de-novo or present as a compli-
cation of essential or secondary hypertension [11].
The etiologic factors that can induce HTN-C are
listed in Table 1.
Kidney disease
Because of the essential role played by the renal
system in BP regulation, any type of renal paren-
chymal or renal artery disease can lead to HTN-C [3].
Moreover, acute kidney injury (AKI) may be a con-
&
sequence of HTN-C [3,4 ]. Patients with ESRD are at
risk for having HTN-C in the setting of inadequate
dialysis and related volume overload. In kidney
transplant recipients, cyclosporine and corticoste-
roids can cause a significant increase in BP. In
patients with HTN-E complicated with AKI, the
presence of underlying renal disease at baseline
and the degree of renal impairment at admission
impact the level of renal recovery after control of BP
[3].
Rebound hypertension
Medication nonadherence, inappropriate dosing
intervals of antihypertensive medications and inter-
ruption of antihypertensive treatment (for a stress
test, procedures, etc.) are common causes of uncon-
trolled BP [13,17,18]. Withdrawal of certain BP
medications, specifically drugs acting on the sym-
pathetic nervous system, can cause an abrupt
increase in BP, which is referred as rebound hyper-
tension.
Clonidine is a centrally acting alpha-adrenocep-
tor agonist with rapid onset of action and it is
usually preferred in the setting of resistant hyper-
tension or intolerance to other antihypertensives.
The abrupt cessation of high doses of clonidine
can induce pheochromocytoma-like symptoms
and rebound hypertension with a BP above the
&
pretreatment levels [19,20 ]. Abrupt cessation of
Volume 32  Number 4  July 2017
 Clinical approach to hypertensive crisis Ipek et al.

Table 1. Causes of hypertensive crisis

Essential hypertension
Renal Glomerulonephritis, tubulointerstitial nephritis, end-stage renal disease, renal artery stenosis, haemolytic
uremic syndrome, renal vein thrombosis, polyarthritis nodosa, renal cell carcinoma
Drug or substance withdrawal Clonidine, beta-blockers, alcohol, sedative-hypnotics
Medications Erythropoietin, cyclosporine, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors,
tricyclic antidepressants, tyrosine kinase inhibitors, bevacizumab, steroids, pseudoephedrine,
anaesthetic agents (malignant hyperthermia)
Illicit drugs Cocaine, phencyclidine, sympathomimetics, amphetamines, anabolic steroids
Endocrine Pheochromocytoma, Cushing syndrome, primary hyperaldosteronism, renin-secreting tumour, carcinoid
syndrome, hyperthyroidism
Pregnancy-related Preeclampsia, eclampsia
Neurologic Head injury, cerebral infarction, cerebral haemorrhage, brain tumour, spinal cord injury, seizure
Others Pain, anxiety, burns, scleroderma, lead intoxication, neck radiation, coarctation of aorta, Guillain–Barre
syndrome, acute intermittent porphyria

short-acting beta-blockers can cause rebound tachy-
cardia and in rare instances severe rebound hyper-
tension due to the upregulation of beta-receptors
while on treatment [21].
Recreational drugs
HTN-C can occur as a consequence of the use of
illicit drugs such as cocaine, phencyclidine, sympa-
&
thomimetic drugs and amphetamine [4 ,11,17].
Hyperadrenergic state and/or vasoconstriction are
the primary mechanisms underlying increased BP
with use of these agents [3]. Over-the-counter use of
anabolic steroids in supra-pharmacological levels,
especially in body builders, can cause several adverse
cardiovascular outcomes including abrupt increases
in BP [22].
Medication-induced hypertensive crisis
Several medications are implicated in the severe
elevation of BP. Monoamine oxidase (MAO) inhibi-
tors are a class of antidepressants well known to be
associated with HTN-C if taken with food products
rich of tyramine (i.e. aged cheese, soy sauce, fava
beans, etc.). This exacerbated response carries the
risk of mortality from HTN-C. Therefore, patients
must be advised a low tyramine diet, when a MAO
inhibitor is prescribed [23,24].
HTN-C can be a manifestation of serotonin syn-
drome, a potentially life-threatening condition that
occurs after the use of medications that are involved
in the uptake, synthesis, metabolism or release of
serotonin or the activation of serotonergic recep-
tors. The clinical presentation of serotonin syn-
drome may include high body temperature,
agitation, hyperactive reflexes, tremor, sweating,
dilated pupils, diarrhoea, severely increased heart
rate and BP. Early diagnosis and prompt initiation of
therapy is crucial to prevent devastating compli-
cations of serotonin syndrome [25].
Some chemotherapeutic agents have been
implicated in development or worsening of hyper-
tension. For instance, bevacizumab (an antivascular
endothelial growth factor antibody) and some
tyrosine kinase inhibitors (such as sunitinib, sora-
fenib and pazopanib) have been associated with
severely elevated BP levels [26]. The mechanisms
that are involved in chemotherapy-induced hyper-
tension include depletion of nitric oxide, endo-
thelial dysfunction, increased vascular tone,
decreased density of microvessels and renal throm-
botic microangiopathy [26–28]. Alkylating agents
such as calcineurin and steroids can also cause a
significant elevation in BP by causing salt and fluid
retention [26]. Radiotherapy targeting the head or
neck can lead to labile BP and HTN-C by impairing
baroreflexes [29]. Cancer patients who are at risk
for chemotherapy-induced hypertension require
frequent BP monitoring. Drug–drug interactions
may potentiate the toxicity of chemotherapeutic
agents and should be considered when chemo-
therapy-induced hypertension is encountered
[26]. Physicians should take into account the path-
ophysiologic background of BP elevation when
managing patients with chemotherapy-induced
hypertension. For example, calcium-channel
blockers (CCBs) are ideal for calcineurin-induced
hypertension.
Acute stressors such as pain and psychological
& &
stress can induce sudden BP increases [4 ,30 ]. More-
over, other rare causes of HTN-C include pheochro-
mocytoma, paraganglioma, carcinoid syndrome
and scleroderma (Table 1).

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Hypertension
Pregnancy-related hypertension (preeclampsia/
eclampsia) should be considered in female HTN-C
patients at child-bearing age.
PATHOPHYSIOLOGY
The pathophysiologic basis of HTN-C remains
poorly understood. Several common mechanisms
play a role in both hypertension and HTN-C. These
mechanisms include but not limited to endothelial
dysfunction, dysregulation of nitric oxide secretion,
overactivation of the renin-angiotensin-aldosterone
system, inflammatory dysregulation and throm-
botic microangiopathy [3,31–33]. A genetic back-
ground for the risk of HTN-C has been suggested by
the association between the genotypic variations in
the angiotensin-converting enzyme (ACE) gene and
risk of HTN-C [34,35].
Patients with a history of chronic hypertension
appear to be more tolerant to the abrupt increases in
BP than those without any history of hypertension.
It has been suggested that vascular smooth muscle
hypertrophy that occurs due to chronic hyperten-
sion may provide some degree of tissue protection at
the capillary level in case of an abrupt rise in BP.
However, individuals who are normotensive at base-
line lack the same protection from the smooth
muscle hypertrophy [3,31].
PROGNOSTIC IMPLICATIONS
Mortality from HTN-C has declined significantly
with the widespread use of antihypertensive drugs.
The 5-year survival in patients diagnosed with
‘malignant HTN’ has shown improvement from
37 to 91% from 1960s to 2000s [18]. Despite this
remarkable progress, HTN-C carries significant risk
for cardiovascular morbidity and mortality. A study
by Vlcek et al. [36] demonstrated that presentation
to ED with HTN-U is associated with a more than
50% increased risk of cardiovascular events when
compared with those presenting with hypertension
below the BP limits of HTN-U. A nationwide epide-
miologic study from US reported the in-hospital
mortality rate as 2.6% among patients admitted
with HTN-C [7]. A registry data from Europe
revealed 4% mortality (30-day) in patients who
require parenteral antihypertensive therapy for
HTN-C [37]. Ninety-day readmission rate with the
same diagnosis was reported as 29% for patients who
require hospitalization for HTN-C [16].
Major complications of HTN-C include acute
ischemic stroke, subarachnoid haemorrhage, hyper-
tensive encephalopathy, AKI, retinopathy and
cardiovascular events such as acute decompensated
heart failure (ADHF), pulmonary oedema,
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myocardial ischemia, acute myocardial infarction
(MI), and acute aortic dissection [3,10,14].
CLINICAL PRESENTATION
The clinical picture of HTN-C varies from inciden-
tally identified asymptomatic severe BP elevation to
the presentation with findings of acute EOD.
Patients with HTN-C usually present with nonspe-
cific symptoms, including a headache, dizziness,
epistaxis, vomiting and palpitations [10]. Cardio-
pulmonary signs/symptoms such as dyspnoea,
angina, arrhythmias and syncope are only seen in
about 30% of the HTN-C patients, while focal neuro-
logical deficits affect nearly 16% of the patients [10].
DIAGNOSTIC WORKUP
Initial evaluation of patients with suspected HTN-C
should include BP measurement on both arms with
appropriate size cuff. Lower extremity BP should be
measured if there is a significant BP difference
between two arms as seen in the setting of acute
aortic dissection. A thorough physical examination
may help with identifying the potential causes and
complications of HTN-C. Although rarely used (10%
of patients), a fundoscopic examination should be
performed to evaluate for retinal exudates, haemor-
rhages and papilledema [10]. Fundus photography
may help with obtaining more accurate images of
the retina and facilitate a remote/quick consultation
with an ophthalmologist [38]. Initial diagnostic
workup should include a complete blood count,
basic metabolic panel, troponin and B-type natriu-
retic peptide (BNP). A urinalysis should be con-
sidered to screen for proteinuria and haematuria.
Findings of proteinuria, haematuria, increased
serum creatinine, hypokalemic metabolic alkalosis
and haemolytic anaemia should alert physicians for
the renal involvement of HTN-C [3]. Elevated BNP in
the setting of HTN-C is a strong indicator of ADHF
[39].
A 12-lead ECG should be obtained to identify
acute ischemic findings. If there is clinical suspicion
for acute aortic dissection or CVA, a computed
tomography of the chest/abdomen or head should
be obtained, respectively. A transthoracic echocar-
diography performed in the ED can help with detec-
tion of critical findings such as left ventricular
systolic dysfunction, type A acute aortic dissection
and related aortic regurgitation. Novel echocardio-
graphic techniques such as strain imaging with
speckle tracking may identify subclinical left
ventricular systolic and diastolic dysfunction in
the setting of markedly increased afterload. In
this regard, Alam et al. [40] demonstrated a high
Volume 32  Number 4  July 2017

frequency of diastolic dysfunction or impaired myo-
cardial mechanics (assessed by speckle tracking
echocardiography) in HTN-C patients. Moreover,
they observed a significant improvement in these
parameters in response to BP reduction [40].
MANAGEMENT
Well designed randomized clinical trials (RCTs) or
major society guidelines to guide the clinical
approach to patients with HTN-C are lacking. There-
fore, current recommendations regarding the man-
agement of HTN-C are based on expert opinions and
retrospective studies. The main objectives in the
management of HTN-C are distinction of HTN-E
from HTN-U and appropriate risk stratification, pre-
vention or regression of acute EOD from severely
elevated BP, prevention of recurrence of HTN-C with
an effective long-term management plan and avoid-
ance of rapid lowering of BP to decrease the risk of
impairment in cerebral, coronary and renal blood
flow.
Hypertensive urgency
HTN-U represents the majority of patients with
HTN-C and it is usually a manifestation of uncon-
trolled essential hypertension. Recent evidence has
suggested that most patients with HTN-U can be
safely managed in the outpatient setting without
exposing patients to the risks of aggressive BP low-
ering. A retrospective cohort study by Levy et al.
&
[20 ] compared the impact of rapid BP reduction
and outpatient BP management strategies in
patients who presented to the ED with HTN-U.
Patients under either treatment strategy had a
good prognosis (30-day all-cause mortality of
0.2%) and similar 30-day ED readmission rates
&
[20 ]. A larger retrospective cohort study by Patel
&&
et al.[41 ] compared the impact of hospital refer-
rals vs. outpatient management on outcomes in
asymptomatic patients diagnosed with HTN-U
in the outpatient clinic. The study found that
hospital referral was associated with a 75%
increased rate of hospitalization (within 7 days)
with no significant improvement in major adverse
cardiac events (6-month) or chance of having
controlled BP at 6-month follow-up. These
findings supported the safety of outpatient manage-
ment of asymptomatic HTN-U without ED admis-
sion or hospitalization. However, early clinic
follow-up is still recommended. ED referral may
be considered for HTN-C patients with new symp-
toms, multiple cardiovascular risk factors, history
of medication nonadherence and de-novo hyper-
tension.
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Clinical approach to hypertensive crisis Ipek et al.
The efficacy of different oral antihypertensive
agents in the setting of HTN-U has not been com-
pared by well designed RCTs. Therefore, the choice
of oral antihypertensive agents should be made on
the basis of the underlying cause of HTN-U, patient
demographics and comorbidities. Combination
antihypertensive therapy can be considered to
achieve effective BP control and help with medi-
cation compliance. It is not uncommon that
patients with HTN-U receive aggressive BP reduction
in the ED and are discharged home with the
improvement of BP levels. In that case, physicians
should keep in mind that, high oral loading doses of
antihypertensive drugs can cause hypotension even
after discharge from the ED and this may increase
risk of hypotension-related complications and lead
&& &
to medication nonadherence [2,11,41 ,42 ].
Hypertensive emergency
Prompt diagnosis and treatment are crucial to pre-
vent progression of acute EOD and limit morbidity
and mortality in patients with HTN-E [2,43]. It is
critical to confirm and document BP readings before
starting antihypertensive therapy. Parenteral, short-
acting and titratable-agents are preferred when
managing HTN-E. After initiation of antihyperten-
sive therapy, patients should ideally be admitted to
an ICU for close monitoring of BP and the findings
of acute EOD.
The ideal rate and time interval for BP reduction
in patients with HTN-E are not well known. A goal of
20–25% reduction in BP within the first hour is
usually considered appropriate [3,11]. A less aggres-
sive BP reduction approach should be pursued in
patients with acute ischemic stroke. Contrarily, a
more aggressive approach is indicated in patients
with acute aortic dissection. Following the initial
reduction, a gradual decrease [from several hours to
days (i.e. 24–48 h)] should be targeted to reach
normal BP levels unless EOD is worsening [2,5].
A retrospective study in patients with combined
HTN-E and ADHF demonstrated that a more aggres-
sive BP strategy (goal SBP of <120 mmHg achieved
within 6 h) was associated with worse outcomes
when compared with a more gradual decline in
BP [39]. Once BP stability is achieved with parenteral
drugs, the intravenous therapy should slowly be
titrated down with the initiation of oral agents [11].
Because of altered autoregulation of BP in HTN-
E, the rapid decline of BP in these patients may lead
to impaired tissue perfusion and related ischemia
and injury in some arterial beds [2,5,11]. Thus, rapid
BP reduction is usually discouraged in HTN-E.
Patients with a labile BP may benefit from the use
of intra-arterial BP monitoring. Because of the
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Hypertension
unpredictable pharmacodynamics of medications,
sublingual and intramuscular routes should be
avoided in the treatment of patients with HTN-E
[11].
Assessment and optimization of volume status is
a key component in the management of HTN-E
patients. Under normal physiologic conditions, kid-
neys have a pressure natriuresis response character-
ized by increased urinary sodium excretion in
response to acute elevations in BP [44]. Thus, an
abrupt rise in BP may lead to a variable degree of
volume depletion in HTN-E patients. This necessi-
tates careful evaluation of the volume status in
patients with HTN-E. Volume depletion in HTN-E
patients should be treated with intravenous volume
replacement to prevent an exaggerated decline in BP
and an impairment of tissue perfusion [11].
Nevertheless, an excessive decline in BP is not
uncommon during management of HTN-E. A multi-
centre registry data from Europe demonstrated that
hypotension occurred in 10% of HTN-C patients
who were managed with parenteral antihyperten-
sive agents [37]. Sublingual nifedipine and intra-
venous hydralazine must be avoided in the
treatment of HTN-E because of unpredictable effect
and risk of profound hypotension [11].
We have limited data on the efficacy and safety
of parenteral antihypertensive agents in the treat-
ment of HTN-E. A multicentre RCT compared intra-
venous nicardipine (a CCB) and labetalol (a beta-
blocker) in the treatment of HTN-C (n ¼ 226; the
proportion of HTN-E and HTN-U 63 and 37%,
respectively) and found that nicardipine was more
effective than labetalol in regards to reducing BP to
the goal at 30 min. The risk of hypotension was
similar in both arms of the study [45]. The antihy-
pertensive drugs that are commonly used in HTN-C
are summarized in Table 2 [46].
CARDIOVASCULAR COMPLICATIONS
Left ventricular dysfunction and pulmonary
oedema (22%), acute coronary syndromes (ACS,
18%) and aortic dissection (8%) are amongst the
most common complications of HTN-Es [10]. Early
initiation of parenteral vasodilator therapy is a key
component of the management of HTN-E with car-
diovascular acute EOD [47]. Intravenous nitrogly-
cerin infusion, with its preload and afterload
reducing properties at higher doses, is an ideal
option for the management of ADHF, pulmonary
oedema, ACS in the setting of HTN-E. Moreover,
supplemental oxygen (in the case of hypoxemia)
and intravenous morphine can reduce preload, sym-
pathetic drive and air hunger. Intravenous diuretics
are commonly used to treat flash pulmonary
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oedema due to HTN-E. However, its efficacy in this
situation is not well established. A small RCT in
HTN-E patients (n ¼ 59) with pulmonary oedema
found no improvement in dyspnoea with use of
intravenous furosemide [48]. HTN-E related flash
pulmonary oedema usually manifest with severe
acute respiratory failure. If respiratory distress fails
to improve with pharmacological treatment and
supplemental O2, noninvasive or invasive mechan-
ical ventilation should be considered [49].
Troponin elevation is commonly seen with
HTN-C. In a recent retrospective cohort study on
patients with HTN-C, one-third of individuals were
found to have elevated troponin-I [50]. Troponin
elevation in the setting of HTN-C indicates either
myocardial demand–supply mismatch or an ACS.
The distinction between these two conditions is
crucial for an appropriate management. Neverthe-
less, regardless of its cause, troponin elevation due to
HTN-C is a strong predictor of future adverse car-
diovascular events [50]. Beta-blockers or nondihy-
dropyridine CCBs such as diltiazem or verapamil
(CCBs if beta-blockers are not tolerated) should be
initiated early in the setting of ACS due to HTN-E.
These agents can decrease infarct size with their
effect on BP and cardiac inotropy and chronotropy
[51]. Nondihydropyridine CCBs should be avoided
if left ventricular systolic dysfunction is present.
Immediate-release nifedipine, a dihydropyridine
CCB, is contraindicated in ACS because of the risk
of increased mortality [52,53]. High-dose nitroprus-
side infusion carries the potential risk of coronary
steal from ischemic territories, therefore should also
be avoided in the setting of ACS [54].
Acute aortic dissection is a relatively uncommon
but probably the most devastating complication of
HTN-E. Acute aortic dissection is usually preceded
by aortic intramural hematoma and/or penetrating
ulcer. It has an estimated mortality of about 40%.
Acute aortic dissection involving the ascending
aorta is considered as a surgical emergency, as its
mortality risk increase by 1–2% every hour after the
onset of symptoms unless surgically repaired.
Prompt diagnosis and control of BP and heart rate
to reduce aortic wall tension are critical in the
management of aortic dissection. The heart rate
and SBP must be lowered to about 60 beats per
minute and less than 120 mmHg within minutes,
respectively [5]. Intravenous propranolol, labetalol
or esmolol (beta-blockers) are ideal first-line agents
in acute aortic dissection. Dihydropyridine CCBs are
appropriate alternatives for patients intolerant to
beta-blockers. Intravenous nitroprusside should
be added to the treatment if the goal BP levels
cannot be achieved with either beta-blockers or
CCBs [55].
Volume 32  Number 4  July 2017
 Table 2. Commonly used intravenous drugs for the management of hypertensive emergency

Onset Duration Adverse reactions

Drug Category of action of action Metabolism Dosing Special notes significant

Nicardipine CCB (second-generation
dihydropyridine)
Clevidipine CCB (third-generation
dihydropyridine
Labetalol a1-adrenergic (selective)
and b-adrenergic
(nonselective) receptor
blocker
5–15 min 3h Hepatic Initial infusion rate is 5 mg/h Highly selective for coronary Angina, peripheral
Titrated up by 2.5 mg/h every and cerebral vasculature oedema, tachycardia,
5 min It can be used in acute ischemic headache
Maximum dose of 15 mg/h stroke (if SBP >220 mmHg or
DBP >120 mmHg)
1–2 min 2–4 min RBC esterases Initial infusion rate 0.4 mg/kg/ Direct coronary vasodilator, Atrial fibrillation,
min increases stroke volume and headache, nausea,
Titrated up by doubling cardiac output vomiting, insomnia,
increments every 90 s Contraindicated in egg or soy fever
Maximum dose of allergies
3.2 mg/kg/min. Can cause hypertriglyceridemia
The maximum 24-h dosage is at higher infusion rates
2.5 g/kg because of high percentage
of fat emulsion in the formula
2–5 min 2–4 h Hepatic Loading dose 20 mg Drug of choice during Bradycardia, dizziness,
Followed either by boluses of pregnancy due to poor ability drowsiness, nausea
20–80 mg every 10 min or to cross the maternal–foetal
titrated to a continuous barrier
infusion rate of 1–2 mg/min. Contraindicated in preexisting
Maximum dose of 300 mg heart block, asthma,

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bradycardia and severe
congestive heart failure
It can be used in cocaine-
induced HTN-C with a
vasodilator
Esmolol Cardioselective beta-blocker 60 s 10–20 min RBC esterases 0.5 mg/kg loading dose for Reduces heart rate and Bradycardia, nausea,
60 s myocardial contractility injection site pain
Continuous infusion starting at without vasodilatory effect
50 mg/kg/ min Maximum Preferred agent during aortic
dose 300 mg/kg/min dissection
Phentolamine Pure a-adrenergic secs 15 min Hepatic Starting dose is 1–5 mg IV Agent of choice in the initial Bradycardia, mouth
antagonist boluses management of pain, headache,
catecholamine-induced HTN-E angina
Enalaprilat ACE inhibitor 15 min 6h Mainly hepatic Initial dose of 1.25 mg over IV ACE inhibitor Headache, cough,
5 min No reflex tachycardia and angioedema

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Maximum dose of 5 mg every minimal to no effect on
6h intracranial pressure.
Contraindicated in

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hyperkalemia, acute kidney
injury, pregnancy
Clinical approach to hypertensive crisis Ipek et al.

403
 404
Table 2 (Continued)

Onset Duration Adverse reactions

Drug Category of action of action Metabolism Dosing Special notes significant
Hypertension

Nitroglycerin Nitrate 2–5 min 3–5 min Mainly hepatic Initial dose of 5 mg/kg/min
Titrated up by 5 mg/kg/min
every 3–5 min. After the dose
20 mg/kg/min, can be
increased by 20 mg/kg/min
No dosing limits (risk of
hypotension is greater after
200 mg/kg/min)
Venodilator Headache, dizziness,
Decreases preload, increases increased intracranial
coronary blood flow, relieves pressure
coronary vasospasm,
decreases oxygen demand of
heart
Arterial vasodilator at high
doses

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Preferred agent in HTN-E in
acute coronary syndrome,
flush pulmonary oedema,
acute aortic dissection (with a
b-blocker)
Sodium Nitrate Secs 1–2 min RBCs Hepatic Initial dose of 0.25–0.3 mg/kg/ Arterial and venous dilator Coronary steal
nitroprusside Renal min It decreases both afterload and phenomenon (it may
Titrated up by 0.5 mg/kg/min preload trigger acute
until reaching BP goal Contraindicated renal failure myocardial
and hereditary optic nerve infarction), increased
atrophy intra- cranial pressure,
It should be used only when decreased cerebral
other IV antihypertensive blood flow, cyanide
drugs are not available. toxicity (avoid
infusion more than
24 h and greater than
2 mg/kg/min)
Fenoldopam Peripheral D-1 receptor 5 min 30–60 min Hepatic (without Initial dose is 0.1 mg/kg/min Renal artery vasodilator Flushing, headache,
agonist cytochrome Titrated up by 0.05–0.1 mg/ Natriuretic nausea, chest pain,
P450 kg/min Contraindicated in myocardial tachycardia,
enzyme) Maximum dose of 1.6 mg/kg/ ischemia, glaucoma and hypokalemia,
min intracranial hypertension increased in
Its solution contains sodium met intraocular pressure.
bisulfate which can be
allergic.
Agent of choice in the initial
management of
catecholamine-induced HTN-E

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ACE, angiotensin-converting enzyme; CCB, calcium channel blocker; D-1, dopamine-1; HTN-C, hypertensive crisis; HTN-E, hypertensive emergency; IV, intravenous; min, minutes; secs, seconds; RBCs, red blood cells.
Adapted from Padilla et al. [46], Johnson et al. [3] and Muiesan et al. [5].

Volume 32  Number 4  July 2017


CONCLUSION
HTN-C is commonly encountered in the clinical
practice. However, we still lack a standard definition
for HTN-C. Most of the patients who present with
HTN-C carry a prior diagnosis or essential hyperten-
sion. Medication nonadherence seems to be the
main risk factor for HTN-C. The key component
of the approach to patients with HTN-C is the dis-
tinction of HTN-E from HTN-U. The presence of
acute EOD, the hallmark finding of HTN-E, indicates
significantly increased risk of adverse outcomes and
therefore necessitates hospitalization and prompt
treatment. Conversely, many patients with asymp-
tomatic HTN-U can be safely managed in the out-
patient setting without a need for ED referral or
hospitalization. With the widespread use of antihy-
pertensive agents, the prognosis of HTN-C has
improved significantly. However, a better under-
standing of the pathophysiological basis of HTN-C
and evidence-based diagnostic and treatment algo-
rithms for HTN-C are needed.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no Conflict of interests.
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