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

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Hypertension

Nonadherence to antihypertensive medications


KEY POINTS is probably the most important risk factor for HTN-
 Despite a significant decrease in mortality and C. Other common risk factors include obesity, coro-
improvement in survival, the overall incidence of HTN-C nary artery disease, hypertensive heart disease, the
and frequency of hospitalizations continue to rise. requirement of multiple antihypertensive drugs at
baseline and not being under the care of a primary
 Nonadherence to antihypertensive medications is the
care physician [11,15]. Readmission with the same
most important risk factor promoting HTN-C.
diagnosis is not uncommon in patients who require
 Important risk factors for hypertension include excessive hospitalization for HTN-C. Medication nonadher-
salt intake, high body weight, decreased physical ence, substance abuse and dialysis treatment for
activity, lower consumption of fruits, vegetables and end-stage renal disease (ESRD) were reported to
potassium and increased alcohol consumption.
predict readmission with HTN-C [16].
 Illicit drug use remains a major public health problem
and an important cause of HTN-C.
CAUSES
 Most of the patients with asymptomatic HTN-U do not
require ED referral or hospital admission and can be HTN-C can develop de-novo or present as a compli-
managed with oral agents as outpatient. cation of essential or secondary hypertension [11].
The etiologic factors that can induce HTN-C are
listed in Table 1.

widespread use of antihypertensive drugs. Epide- Kidney disease


miological studies from the preantihypertensive Because of the essential role played by the renal
medication era reported that HTN-C would affect system in BP regulation, any type of renal paren-
nearly 7% of individuals with essential hypertension chymal or renal artery disease can lead to HTN-C [3].
with a 1-year mortality rate of 79% and a median Moreover, acute kidney injury (AKI) may be a con-
survival of nearly 10 months [5]. Despite the great &
sequence of HTN-C [3,4 ]. Patients with ESRD are at
progress made in the management of hypertension, risk for having HTN-C in the setting of inadequate
HTN-C remains an important medical emergency dialysis and related volume overload. In kidney
affecting 1–2% of patients with essential hyperten- transplant recipients, cyclosporine and corticoste-
sion [7]. roids can cause a significant increase in BP. In
Here, we review the current concepts on HTN-C patients with HTN-E complicated with AKI, the
with a focus on epidemiology, causes, pathophysi- presence of underlying renal disease at baseline
ology and prognosis. We also discuss some import- and the degree of renal impairment at admission
ant caveats in the management of HTN-C. impact the level of renal recovery after control of BP
[3].

EPIDEMIOLOGY
Owing to a strong correlation between BP and acute Rebound hypertension
stress, elevated BP is a very common finding in the Medication nonadherence, inappropriate dosing
emergency department (ED). In fact, a recent epi- intervals of antihypertensive medications and inter-
demiologic study found that severely elevated BP ruption of antihypertensive treatment (for a stress
was present in 18% of patients admitted to the ED test, procedures, etc.) are common causes of uncon-
[8]. Compared with the frequency of encounters for trolled BP [13,17,18]. Withdrawal of certain BP
severely elevated BP, true HTN-E remains uncom- medications, specifically drugs acting on the sym-
mon. A recent nationwide study demonstrated that pathetic nervous system, can cause an abrupt
the frequency of HTN-E is 0.2% of all adult ED visits increase in BP, which is referred as rebound hyper-
&
in the US [9 ]. Among all patients who are seen for tension.
the primary diagnosis of HTN-C in ED, the pro- Clonidine is a centrally acting alpha-adrenocep-
portion of those with HTN-U and HTN-E are 75 tor agonist with rapid onset of action and it is
and 25%, respectively [10]. HTN-C usually, but usually preferred in the setting of resistant hyper-
not always, affects patients with a prior diagnosis tension or intolerance to other antihypertensives.
of HTN who are treated with antihypertensive medi- The abrupt cessation of high doses of clonidine
cations [11–13]. Males, blacks and elderly are the can induce pheochromocytoma-like symptoms
demographic groups more predominantly affected and rebound hypertension with a BP above the
by HTN-C [5,11,14]. &
pretreatment levels [19,20 ]. Abrupt cessation of

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

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Hypertension

Pregnancy-related hypertension (preeclampsia/ myocardial ischemia, acute myocardial infarction


eclampsia) should be considered in female HTN-C (MI), and acute aortic dissection [3,10,14].
patients at child-bearing age.

CLINICAL PRESENTATION
PATHOPHYSIOLOGY The clinical picture of HTN-C varies from inciden-
The pathophysiologic basis of HTN-C remains tally identified asymptomatic severe BP elevation to
poorly understood. Several common mechanisms the presentation with findings of acute EOD.
play a role in both hypertension and HTN-C. These Patients with HTN-C usually present with nonspe-
mechanisms include but not limited to endothelial cific symptoms, including a headache, dizziness,
dysfunction, dysregulation of nitric oxide secretion, epistaxis, vomiting and palpitations [10]. Cardio-
overactivation of the renin-angiotensin-aldosterone pulmonary signs/symptoms such as dyspnoea,
system, inflammatory dysregulation and throm- angina, arrhythmias and syncope are only seen in
botic microangiopathy [3,31–33]. A genetic back- about 30% of the HTN-C patients, while focal neuro-
ground for the risk of HTN-C has been suggested by logical deficits affect nearly 16% of the patients [10].
the association between the genotypic variations in
the angiotensin-converting enzyme (ACE) gene and
risk of HTN-C [34,35]. DIAGNOSTIC WORKUP
Patients with a history of chronic hypertension Initial evaluation of patients with suspected HTN-C
appear to be more tolerant to the abrupt increases in should include BP measurement on both arms with
BP than those without any history of hypertension. appropriate size cuff. Lower extremity BP should be
It has been suggested that vascular smooth muscle measured if there is a significant BP difference
hypertrophy that occurs due to chronic hyperten- between two arms as seen in the setting of acute
sion may provide some degree of tissue protection at aortic dissection. A thorough physical examination
the capillary level in case of an abrupt rise in BP. may help with identifying the potential causes and
However, individuals who are normotensive at base- complications of HTN-C. Although rarely used (10%
line lack the same protection from the smooth of patients), a fundoscopic examination should be
muscle hypertrophy [3,31]. performed to evaluate for retinal exudates, haemor-
rhages and papilledema [10]. Fundus photography
may help with obtaining more accurate images of
PROGNOSTIC IMPLICATIONS the retina and facilitate a remote/quick consultation
Mortality from HTN-C has declined significantly with an ophthalmologist [38]. Initial diagnostic
with the widespread use of antihypertensive drugs. workup should include a complete blood count,
The 5-year survival in patients diagnosed with basic metabolic panel, troponin and B-type natriu-
‘malignant HTN’ has shown improvement from retic peptide (BNP). A urinalysis should be con-
37 to 91% from 1960s to 2000s [18]. Despite this sidered to screen for proteinuria and haematuria.
remarkable progress, HTN-C carries significant risk Findings of proteinuria, haematuria, increased
for cardiovascular morbidity and mortality. A study serum creatinine, hypokalemic metabolic alkalosis
by Vlcek et al. [36] demonstrated that presentation and haemolytic anaemia should alert physicians for
to ED with HTN-U is associated with a more than the renal involvement of HTN-C [3]. Elevated BNP in
50% increased risk of cardiovascular events when the setting of HTN-C is a strong indicator of ADHF
compared with those presenting with hypertension [39].
below the BP limits of HTN-U. A nationwide epide- A 12-lead ECG should be obtained to identify
miologic study from US reported the in-hospital acute ischemic findings. If there is clinical suspicion
mortality rate as 2.6% among patients admitted for acute aortic dissection or CVA, a computed
with HTN-C [7]. A registry data from Europe tomography of the chest/abdomen or head should
revealed 4% mortality (30-day) in patients who be obtained, respectively. A transthoracic echocar-
require parenteral antihypertensive therapy for diography performed in the ED can help with detec-
HTN-C [37]. Ninety-day readmission rate with the tion of critical findings such as left ventricular
same diagnosis was reported as 29% for patients who systolic dysfunction, type A acute aortic dissection
require hospitalization for HTN-C [16]. and related aortic regurgitation. Novel echocardio-
Major complications of HTN-C include acute graphic techniques such as strain imaging with
ischemic stroke, subarachnoid haemorrhage, hyper- speckle tracking may identify subclinical left
tensive encephalopathy, AKI, retinopathy and ventricular systolic and diastolic dysfunction in
cardiovascular events such as acute decompensated the setting of markedly increased afterload. In
heart failure (ADHF), pulmonary oedema, this regard, Alam et al. [40] demonstrated a high

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Clinical approach to hypertensive crisis Ipek et al.

frequency of diastolic dysfunction or impaired myo- The efficacy of different oral antihypertensive
cardial mechanics (assessed by speckle tracking agents in the setting of HTN-U has not been com-
echocardiography) in HTN-C patients. Moreover, pared by well designed RCTs. Therefore, the choice
they observed a significant improvement in these of oral antihypertensive agents should be made on
parameters in response to BP reduction [40]. the basis of the underlying cause of HTN-U, patient
demographics and comorbidities. Combination
antihypertensive therapy can be considered to
MANAGEMENT achieve effective BP control and help with medi-
Well designed randomized clinical trials (RCTs) or cation compliance. It is not uncommon that
major society guidelines to guide the clinical patients with HTN-U receive aggressive BP reduction
approach to patients with HTN-C are lacking. There- in the ED and are discharged home with the
fore, current recommendations regarding the man- improvement of BP levels. In that case, physicians
agement of HTN-C are based on expert opinions and should keep in mind that, high oral loading doses of
retrospective studies. The main objectives in the antihypertensive drugs can cause hypotension even
management of HTN-C are distinction of HTN-E after discharge from the ED and this may increase
from HTN-U and appropriate risk stratification, pre- risk of hypotension-related complications and lead
&& &
vention or regression of acute EOD from severely to medication nonadherence [2,11,41 ,42 ].
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 Hypertensive emergency
impairment in cerebral, coronary and renal blood Prompt diagnosis and treatment are crucial to pre-
flow. 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
Hypertensive urgency starting antihypertensive therapy. Parenteral, short-
HTN-U represents the majority of patients with acting and titratable-agents are preferred when
HTN-C and it is usually a manifestation of uncon- managing HTN-E. After initiation of antihyperten-
trolled essential hypertension. Recent evidence has sive therapy, patients should ideally be admitted to
suggested that most patients with HTN-U can be an ICU for close monitoring of BP and the findings
safely managed in the outpatient setting without of acute EOD.
exposing patients to the risks of aggressive BP low- The ideal rate and time interval for BP reduction
ering. A retrospective cohort study by Levy et al. in patients with HTN-E are not well known. A goal of
&
[20 ] compared the impact of rapid BP reduction 20–25% reduction in BP within the first hour is
and outpatient BP management strategies in usually considered appropriate [3,11]. A less aggres-
patients who presented to the ED with HTN-U. sive BP reduction approach should be pursued in
Patients under either treatment strategy had a patients with acute ischemic stroke. Contrarily, a
good prognosis (30-day all-cause mortality of more aggressive approach is indicated in patients
0.2%) and similar 30-day ED readmission rates with acute aortic dissection. Following the initial
&
[20 ]. A larger retrospective cohort study by Patel reduction, a gradual decrease [from several hours to
&&
et al.[41 ] compared the impact of hospital refer- days (i.e. 24–48 h)] should be targeted to reach
rals vs. outpatient management on outcomes in normal BP levels unless EOD is worsening [2,5].
asymptomatic patients diagnosed with HTN-U A retrospective study in patients with combined
in the outpatient clinic. The study found that HTN-E and ADHF demonstrated that a more aggres-
hospital referral was associated with a 75% sive BP strategy (goal SBP of <120 mmHg achieved
increased rate of hospitalization (within 7 days) within 6 h) was associated with worse outcomes
with no significant improvement in major adverse when compared with a more gradual decline in
cardiac events (6-month) or chance of having BP [39]. Once BP stability is achieved with parenteral
controlled BP at 6-month follow-up. These drugs, the intravenous therapy should slowly be
findings supported the safety of outpatient manage- titrated down with the initiation of oral agents [11].
ment of asymptomatic HTN-U without ED admis- Because of altered autoregulation of BP in HTN-
sion or hospitalization. However, early clinic E, the rapid decline of BP in these patients may lead
follow-up is still recommended. ED referral may to impaired tissue perfusion and related ischemia
be considered for HTN-C patients with new symp- and injury in some arterial beds [2,5,11]. Thus, rapid
toms, multiple cardiovascular risk factors, history BP reduction is usually discouraged in HTN-E.
of medication nonadherence and de-novo hyper- Patients with a labile BP may benefit from the use
tension. of intra-arterial BP monitoring. Because of the

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Hypertension

unpredictable pharmacodynamics of medications, oedema due to HTN-E. However, its efficacy in this
sublingual and intramuscular routes should be situation is not well established. A small RCT in
avoided in the treatment of patients with HTN-E HTN-E patients (n ¼ 59) with pulmonary oedema
[11]. found no improvement in dyspnoea with use of
Assessment and optimization of volume status is intravenous furosemide [48]. HTN-E related flash
a key component in the management of HTN-E pulmonary oedema usually manifest with severe
patients. Under normal physiologic conditions, kid- acute respiratory failure. If respiratory distress fails
neys have a pressure natriuresis response character- to improve with pharmacological treatment and
ized by increased urinary sodium excretion in supplemental O2, noninvasive or invasive mechan-
response to acute elevations in BP [44]. Thus, an ical ventilation should be considered [49].
abrupt rise in BP may lead to a variable degree of Troponin elevation is commonly seen with
volume depletion in HTN-E patients. This necessi- HTN-C. In a recent retrospective cohort study on
tates careful evaluation of the volume status in patients with HTN-C, one-third of individuals were
patients with HTN-E. Volume depletion in HTN-E found to have elevated troponin-I [50]. Troponin
patients should be treated with intravenous volume elevation in the setting of HTN-C indicates either
replacement to prevent an exaggerated decline in BP myocardial demand–supply mismatch or an ACS.
and an impairment of tissue perfusion [11]. The distinction between these two conditions is
Nevertheless, an excessive decline in BP is not crucial for an appropriate management. Neverthe-
uncommon during management of HTN-E. A multi- less, regardless of its cause, troponin elevation due to
centre registry data from Europe demonstrated that HTN-C is a strong predictor of future adverse car-
hypotension occurred in 10% of HTN-C patients diovascular events [50]. Beta-blockers or nondihy-
who were managed with parenteral antihyperten- dropyridine CCBs such as diltiazem or verapamil
sive agents [37]. Sublingual nifedipine and intra- (CCBs if beta-blockers are not tolerated) should be
venous hydralazine must be avoided in the initiated early in the setting of ACS due to HTN-E.
treatment of HTN-E because of unpredictable effect These agents can decrease infarct size with their
and risk of profound hypotension [11]. effect on BP and cardiac inotropy and chronotropy
We have limited data on the efficacy and safety [51]. Nondihydropyridine CCBs should be avoided
of parenteral antihypertensive agents in the treat- if left ventricular systolic dysfunction is present.
ment of HTN-E. A multicentre RCT compared intra- Immediate-release nifedipine, a dihydropyridine
venous nicardipine (a CCB) and labetalol (a beta- CCB, is contraindicated in ACS because of the risk
blocker) in the treatment of HTN-C (n ¼ 226; the of increased mortality [52,53]. High-dose nitroprus-
proportion of HTN-E and HTN-U 63 and 37%, side infusion carries the potential risk of coronary
respectively) and found that nicardipine was more steal from ischemic territories, therefore should also
effective than labetalol in regards to reducing BP to be avoided in the setting of ACS [54].
the goal at 30 min. The risk of hypotension was Acute aortic dissection is a relatively uncommon
similar in both arms of the study [45]. The antihy- but probably the most devastating complication of
pertensive drugs that are commonly used in HTN-C HTN-E. Acute aortic dissection is usually preceded
are summarized in Table 2 [46]. by aortic intramural hematoma and/or penetrating
ulcer. It has an estimated mortality of about 40%.
Acute aortic dissection involving the ascending
CARDIOVASCULAR COMPLICATIONS aorta is considered as a surgical emergency, as its
Left ventricular dysfunction and pulmonary mortality risk increase by 1–2% every hour after the
oedema (22%), acute coronary syndromes (ACS, onset of symptoms unless surgically repaired.
18%) and aortic dissection (8%) are amongst the Prompt diagnosis and control of BP and heart rate
most common complications of HTN-Es [10]. Early to reduce aortic wall tension are critical in the
initiation of parenteral vasodilator therapy is a key management of aortic dissection. The heart rate
component of the management of HTN-E with car- and SBP must be lowered to about 60 beats per
diovascular acute EOD [47]. Intravenous nitrogly- minute and less than 120 mmHg within minutes,
cerin infusion, with its preload and afterload respectively [5]. Intravenous propranolol, labetalol
reducing properties at higher doses, is an ideal or esmolol (beta-blockers) are ideal first-line agents
option for the management of ADHF, pulmonary in acute aortic dissection. Dihydropyridine CCBs are
oedema, ACS in the setting of HTN-E. Moreover, appropriate alternatives for patients intolerant to
supplemental oxygen (in the case of hypoxemia) beta-blockers. Intravenous nitroprusside should
and intravenous morphine can reduce preload, sym- be added to the treatment if the goal BP levels
pathetic drive and air hunger. Intravenous diuretics cannot be achieved with either beta-blockers or
are commonly used to treat flash pulmonary CCBs [55].

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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 5–15 min 3h Hepatic Initial infusion rate is 5 mg/h Highly selective for coronary Angina, peripheral
dihydropyridine) 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)
Clevidipine CCB (third-generation 1–2 min 2–4 min RBC esterases Initial infusion rate 0.4 mg/kg/ Direct coronary vasodilator, Atrial fibrillation,
dihydropyridine 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
Labetalol a1-adrenergic (selective) 2–5 min 2–4 h Hepatic Loading dose 20 mg Drug of choice during Bradycardia, dizziness,
and b-adrenergic Followed either by boluses of pregnancy due to poor ability drowsiness, nausea
(nonselective) receptor 20–80 mg every 10 min or to cross the maternal–foetal
blocker 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 Venodilator Headache, dizziness,
Titrated up by 5 mg/kg/min Decreases preload, increases increased intracranial
every 3–5 min. After the dose coronary blood flow, relieves pressure
20 mg/kg/min, can be coronary vasospasm,
increased by 20 mg/kg/min decreases oxygen demand of
No dosing limits (risk of heart
hypotension is greater after Arterial vasodilator at high
200 mg/kg/min) 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


Clinical approach to hypertensive crisis Ipek et al.

9. Janke AT, McNaughton CD, Brody AM, et al. Trends in the incidence of
CONCLUSION & hypertensive emergencies in US Emergency Departments from 2006 to
HTN-C is commonly encountered in the clinical 2013. J Am Heart Assoc 2016; 5:e004511.
This is a descriptive epidemiological analysis reporting the recent trends in the
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for HTN-C. Most of the patients who present with most remarkable finding of this study is that the total number and frequency of
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HTN-C carry a prior diagnosis or essential hyperten- 2006 and 2013.
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