c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4

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journal homepage: www.elsevier.com/locate/cqn

Review Article

Hypertension emergencies and urgencies

Sudeep Kumar a,*, Tanuj Bhatia b, Aditya Kapoor c

a
Additional Professor, Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road,
Lucknow 226014, UP, India
b
Senior Resident, Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India
c
Professor, Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, UP, India

article info abstract

Article history: Where at one hand, the vast majority of hypertensive patients succumb to the complica-
Received 20 November 2012 tions of hypertension like atherosclerosis, cerebrovascular diseases and congestive heart
Accepted 25 January 2013 failure, a subset of these have an exacerbation in this gradual course that needs acute
Available online 15 March 2013 management in the blood pressure control and plays a role in short term outcomes. These
hypertensive crises are now encountered more frequently, in more diverse and aging
Keywords: population than in earlier times.
Hypertensive crises Despite the recognized unmet need of timely evaluation and management, fewer than
Hypertensive emergency 10% receive the recommended investigations and appropriate treatment often gets
Hypertensive urgency delayed. This review emphasizes the therapeutic implications of correct diagnosis, various
Malignant hypertension treatment options and targets in different clinical circumstances.
Nicardipine, clevidipine, esmolol and fenoldopam have emerged as potentially superior
drugs in most hypertensive emergencies as compared to other conventional drugs. For
hypertensive urgencies, blood pressure lowering at a gradual pace with oral drugs &
adequate follow up are two important facets of management, making sure that the blood
pressure has been lowered out of a potentially dangerous range.
Impact of optimal management of hypertensive crisis should translate into lesser target
organ damage and eventually fewer complications of stroke, myocardial infarction, or
congestive heart failure.
Copyright 2013, Reed Elsevier India Pvt. Ltd. All rights reserved.

1. Introduction elevations in blood pressure can result in acute organ damage

Hypertension no longer affects the middle aged & older adults
predominantly, but with the rapidly expanding epidemic of
obesity & sedentary lifestyles, now equally affects the young
adults & teenagers as well.1 Around 27e30% of population over
the age of 20 years is affected by this chronic medical condition.2
While chronic hypertension is a major risk factor for car-
diovascular & cerebrovascular outcomes & ESRD, accelerated
& dysfunction. Prompt & precise management of such situa-
tions is essential to prevent permanent organ damage.
Numerous reports in late nineties estimated that around
1% of hypertensive individuals experience hypertensive crisis
at some point of time during their lifetime3,4 although before
the advent of antihypertensive therapy figures were probably
as high as 7%.3,5 Nonetheless, the absolute number of such
individuals has been gradually increasing over the period of

* Corresponding author. Tel.: 91 522 2495198 (O), 91 522 2495199 (R); fax: 91 522 2668573, 91 522 2668017.
E-mail address: Sudeep@sgpgi.ac.in (S. Kumar).
2211-9477/$ e see front matter Copyright 2013, Reed Elsevier India Pvt. Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.cqn.2013.01.004
2 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4
time, due to absolute increase in number of hypertensive
patients, coupled with better survival from major adverse
cardiovascular & cerebrovascular events.
Unfortunately, there is a lack of randomized trials & little
long term follow up data.6 Additionally, diagnosis overlap
with other cardiac, neurologic, renal or multisystem syn-
dromes makes it difficult to follow & remove confounding
factors while assessing long term follow up. Questions
regarding mortality & morbidity hence remain unanswered.7,8
Moreover, the impact of these clinical situations is often
underappreciated, such that timely evaluation & treatment
are often not instituted, leading to serious adverse outcomes.
2. Terminology
The various terminologies used in context to acute elevations
in blood pressures have often been misused. The consensus
definitions of the various terms are discussed in succession
below.
Hypertensive crises are defined as clinical scenarios associ-
ated with severe elevations in systolic & diastolic blood pres-
sure, usually above 180/120 mmHg.2,9,10
Hypertensive crises are further classified as hypertensive
emergencies & urgencies.
Hypertensive emergency is defined as marked elevation in BP
complicated by acute target organ damage such as coronary
ischemia, acute pulmonary edema, dissecting aortic aneu-
rysm, hypertensive encephalopathy, cerebral hemorrhage &
acute renal failure.7,11e14
BP should be reduced promptly, preferably within minutes,
& with rapidly acting parenteral drugs to limit target organ
damage.
Hypertensive urgency is a less clearly defined condition
characterized by severe elevation in blood pressure in an in-
dividual who may have evidence of previous end organ
damage related to hypertension, but in whom there exists no
evidence of on-going or imminent acute target organ dam-
age.11 These patients do not require hospital admission and
the reduction in blood pressure can be gradual, & by oral
medications, as per individual patient characteristics.2,9,11,12,15
2.1. Malignant hypertension
The usage of the term malignant with hypertension by Keith &
Wagener, as early as in 1928,16 was to emphasize that the
downhill course would be similar to most cancers. However,
with improvement in inpatient & outpatient management of
hypertension,14 the prognosis of malignant hypertension has
dramatically improved, & it will not be wrong to say that with
appropriate management instituted at the right time, malig-
nant hypertension is no more malignant. Hence, the usage of
terms hypertensive emergencies & urgencies is more in
vogue.2
This clinical entity is characterized by marked elevation of
blood pressure with widespread acute arteriolar injury that
reveals itself as hypertensive neuroretinopathy with striate
haemorrhages, cotton-wool exudates, and often papilledema
in funduscopy.17 All these three funduscopic findings portend
a poor prognosis.18e20
No matter how high the blood pressure, a patient cannot be
labeled to have malignant hypertension in absence of hyper-
tensive neuroretinopathy.17 However, some authors believe
presence of papilledema to be essential for diagnosis of ma-
lignant hypertension, & use the term accelerated hypertension
for patients with haemorrhages, exudates, arteriolar narrow-
ing & spasm but without evidence of papilledema.21,22 Prac-
tically, although, malignant hypertension & accelerated
hypertension are terms used interchangeably for each other.17
Hypertensive encephalopathy is a clinical syndrome with
cerebral malfunction due to severe elevation of blood pres-
sure. Though mostly associated with malignant hyperten-
sion, it may at times occur without neuroretinopathy.19 The
first use of this term was by Oppenheimer & Fishberg in
1928.23 Clinical features include severe headache, blurred
vision or blindness, nausea, vomiting, and mental confusion.
The most dramatic feature is prompt clinical response to
antihypertensive therapy & in case aggressive treatment is
not initiated, stupor, convulsions, and death can ensue
within hours.
At times, even in absence of hypertensive neuro-
retinopathy, if acute end-organ dysfunction occurs in the
presence of even moderate hypertension, it may still qualify
as a hypertensive crisis.
3. Pathophysiology of hypertensive crisis
Hypertensive crisis can be the first clinical presentation of hy-
pertension or may punctuate the clinical course of long stand-
ing essential, or more commonly, secondary hypertension.
Volhard & Fahr24 first described the rapidly fatal course of
hypertensive crisis and noticed how its pathophysiology dif-
fers from the changes of chronically elevated blood pressure.
Situations that qualify as hypertensive emergencies in
clinical practice are enlisted in Table 1. The theme of pre-
sentation of hypertensive emergencies is quite expressive, but
variable, depending on the target organ involvement, super-
scripted with R in the below mentioned table. The triggering
causative factors are superscripted with C in the table
below.
Chronic elevations in blood pressure causes compensatory
structural & functional changes in arterial cerebral circula-
tion27 & renal microcirculation28 that maintains autor-
egulation & avoids excessive blood flow at higher BP levels.14
These are the subset of patients of presenting with no recent
evidence of acute target organ damage, & need appropriate
management, with slow and gradual reduction in blood
pressure.
In contrast are hypertensive emergencies, in which the
mechanisms leading to severe and rapid elevations in blood
pressure coupled with failure of autoregulatory mechanisms29
lead to target organ damage. The triggering factor could be
delineated in few cases like release of a humoral vasoactive
factors.30,31 However, in many cases; the hypertensive emer-
gency is a non-specific consequence of chronically elevated
blood pressure.13
The endothelial injury occurring as a response to chroni-
cally elevated blood pressure leads to further vascular damage
and tissue ischemia by increasing vascular permeability &
 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4
Table 1 e Common hypertensive emergencies or
urgencies.
Malignant e accelerated hypertension with papilledemaR
Cardiovascular conditions
Acute MI/unstable anginaR
Acute LVF/pulmonary edemaR
Acute aortic dissectionR, C
Severe hypertension after CABG/vascular surgeryR
Renal conditions
Rapidly progressive glomerulonephritisC
Renovascular hypertensionC
Scleroderma renal crisisC
Post renal transplantation severe hypertensionC
Neurological conditions
Hypertensive encephalopathyR
Intracerebral & Subarachnoid haemorrhageC,R
Acute head injuryC
Atherothrombotic strokeC, R
GuillaineBarre syndromeC
Catecholamine excess states
Pheochromocytoma crisisC
MAO Inhibitor e tyramine interactionsC
Alpha-2 agonists drug (Clonidine, alpha methyl dopa)C with-
drawal leading to rebound hypertension
Automatic hyperreflexia after spinal cord injury C
Use of sympathomimetic drugs (Cocaine,
phenylpropanolamine)C
Surgical conditions
Perioperative hypertensionC more commonly with cardiovas-
cular & neurosurgical procedures25
Postoperative bleeding from vascular suture lines26 R
Hypertension after organ transplantationC
Hypertension associated with severe burnsC
R
e result of hypertensive emergency.
C
e cause of hypertensive emergency.
activation of platelets & coagulation cascade.13,30e33 Various
vasoactive substances that contribute to this vascular injury
are catecholamines, renin, angiotensin,34 endothelin, vaso-
pressin35,36 and more recently added to this list are ouabain,
digoxin,37,38 marinobufagenin & telocinobufagin. These newer
chemicals are grouped under the category of CTS (cardiotonic
steroids) that have short term effects on vascular & cardiac
smooth muscle cells, resulting in BP elevation & cardiac ac-
tivity modulation.37,38 The activation of the RAAS & other
vasoactive mediators lead to further vasoconstriction & pro-
duction of proinflammatory cytokines such as IL-6.39,40
NADPH oxidase activity that generates reactive oxygen spe-
cies are increased, leading to oxidative stress.41
Besides this, endothelial dysfunction is a common de-
nominator of these hypertensive emergencies and may
persist for a long time after the index event.42,43
The typical lesion of the hypertensive crisis is fibrinoid
necrosis of small arteries and arterioles.29,44 In the cerebral
vasculature, cerebral perfusion seems to affect primarily the
white matter in the parieto-occipital areas of the brain45 &
brainstem,46 possibly because of decreased sympathetic
innervation of vessels in the parieto-occipital region.47
3
4. Epidemiology
Exact figures regarding this commonly faced medical emer-
gency are largely unknown.32,48 They constitute approximately
one fourth of all medical emergencies.49 Of the hypertensive
crisis, three fourths were urgencies & one fourth were emer-
gencies in an Italian study50 while Brazilian series quotes pro-
portion of emergencies to be three fifths of hypertensive crisis.51
Despite recent advances & awareness, both at physician &
patient level, hypertension control is poorly attainable. It is
estimated that only approximately 30% of hypertensive pa-
tients achieve good control of the blood pressure, although
clinical trials say that control rates of 60e70% are attainable.
Despite these discouraging facts, widespread outpatient use
of antihypertensive drugs has reduced the incidence of hy-
pertensive emergencies.6,52 In US, hospitalization for hyper-
tensive emergencies is reported at the rate of 1e2 cases/
million population/year.29 However, poor compliance to
antihypertensive regime53e55 & inability to access health care
sources56 contribute to increased incidence of hypertensive
crisis in the developing nations.
5. Diagnostic evaluation
Hypertensive crisis is thematically a hot topic. From pediatric
to geriatric, from medical to surgical e all subgroups of pa-
tients either have or are on verge of having target organ
damage. The primary goal, hence, is to differentiate between
true hypertensive emergency from hypertensive urgency, as
the therapeutic approaches are different. Our approach, clin-
ical and investigative, should at least help us to overcome this
ambiguity. Another goal is to accurately assess the type and
severity of target organ damage.
This includes a speedy history, current blood pressure &
clinical examination, ECG, chest roentgenogram, basal
biochemistry, funduscopy & urinalysis as essential in-
vestigations & targeted investigations as per clinical hints for
ruling out causes of secondary hypertension or analyzing
target organ damage.
History should essentially include assessment of severity
of hypertension, duration of treatment,9,13 patients medica-
tion & compliance to treatment including history of over the
counter medications & recreational drugs. Not to be forgotten
is a thorough and targeted history for any clue to target organ
damage (chest or back pain, dyspnea, throbbing headache,
pulsatile abdominal mass). Liquorice, nasal drops, cocaine,
amphetamines, oral contraceptives, steroid, NSAIDs, eryth-
ropoietin and cyclosporine are drugs that may trigger an acute
hypertensive emergency. Dietary and smoking history can be
of additional information. Concomitant medical history &
history of sleep apnea syndrome should be explored.57,58
BP recordings in both sitting & standing position & in the leg
are essential.2,59 Recordings need to be done with an appro-
priate sized cuff as the use of a cuff too small for the arm size,
as in obese individuals, or use of arm cuff over the thigh
may give spuriously high recordings.49,60 Needless to over-
emphasize, that meticulously done clinical examination may
sometimes be extremely helpful in instituting early treatment.
4 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4
Swift cardiac, pulmonary, peripheral vessel & neurological ex-
amination inclusive of fundoscopic inspection essentially
needs to be done. Gallop rhythm (suggestive of heart failure)
and new murmurs of aortic insufficiency (associated with
aortic dissection) and mitral regurgitation (ischemic MR)
deserve special importance in cardiovascular examination.
Some classical signs of secondary hypertension should not be
missed in first examination.10,61 These include abdominal bruit
(renovascular hypertension), radiofemoral delay (aortic coarc-
tation), palpable abdominal mass (pheochromocytoma/poly-
cystic kidney disease), central obesity & abdominal striae
(Cushings syndrome) & exophthalmos (hyperthyroidism).57,58
Laboratory evaluation of such patients should be expedi-
tious. It should include full blood count with peripheral smear
and a metabolic panel inclusive of renal function indices and
electrolytes9,10,13 Nephritic urinary sediment suggests acute
glomerulonephritis as a potential cause. Endocrinology eval-
uation for plasma renin activity, aldosterone (in patients who
are not on diuretics)62 & catecholamines may guide treatment
in selected cases.
ECG to rule out myocardial ischemia and left ventricular
hypertrophy and strain & Chest X-ray to assess cardiac size &
pulmonary edema are indispensable investigations and
should be routinely performed for each patient.9,10,13
As per clinical status & results of preliminary in-
vestigations, Echocardiography (for regional wall motion
analysis, left ventricular hypertrophy, systolic or diastolic
dysfunction & degree of mitral regurgitation), CT scan or MRI
Brain (in neurologic syndromes), Thoracoabdominal CT/MRI
or Abdominal ultrasound (for suspected aortic dissection) may
be needed.63
Notwithstanding, we should remember that prompt ther-
apy should take priority over detailed history, unnecessary
physical evaluation & irrelevant time consuming diagnostic
studies. The pursuit of etiology should never deprive a patient
of hypertensive emergency from receiving the appropriate
antihypertensive drug at the minimum time possible after
contact with the medical care team, especially after knowing
that most of these complications are largely reversible with
appropriate treatment being rendered at the appropriate
time.64,65
6. Treatment of hypertensive emergencies
What is crucial regarding management of hypertensive
emergencies is the need of immediate reduction in blood
pressure levels so as to reverse, or at least, halt the on-going
target organ damage. This usually requires a short acting
intravenous drug that helps in tight control of the blood
pressure, and can be titrated easily by the clinician both for
rate of control of blood pressure and the ultimate target. It is
generally accepted that such a patient should be admitted to
an ICU or a high dependency unit (HDU) for monitoring &
administration of an appropriate parenteral agent.2,9,11,12
The ideal agent to treat hypertensive crisis should be fast
acting, rapidly reversible and titrable without any significant
side effects. There is no single ideal agent & the choice of
pharmacologic agent to treat hypertensive crisis should be
tailored to each individual based on risks, comorbidities and
end organ damage. Table 2 depicts the various agents used for
this purpose.
Instead of the absolute value of blood pressure, the gov-
erning factor for immediate institution of management is the
presence of target organ damage, as patients with recent
onset or rapidly rising hypertension develop target organ
damage earlier than chronically hypertensive patients who
tolerate equal or higher blood pressures due to structural &
functional autoregulatory changes.14,28,29
Understanding these autoregulatory mechanisms is
equally important from therapeutic point of view, as sudden
lowering of blood pressure may actually lead to inadequate
tissue perfusion, which may lead to renal, cerebral or coronary
ischemia.9 According to current American & European
guidelines, the mean BP should be reduced by no more than
20e25% within minutes to 1e2 h2,9 A diastolic blood pressure
between 100 and 110 mm Hg or 25% of initial baseline,
whichever is higher, should be the target in the next 6 h116
Achieving final target blood pressures gradually in 24e48 h
allows autoregulatory mechanisms to reset, and thence-
forth the parenteral medications may be replaced by oral
medications. Abrupt lowering of blood pressure is not favor-
able, and this fact is exemplified by the fact that sublingual
nifedipine, known for its potent, but unpredictable & precip-
itous hypotensive effect, increased mortality & morbidity
when used for this indication.117
Patients presenting with hypertensive emergencies may be
volume depleted owing to pressure natriuresis, and prior to
administering parenteral therapy, volume deficit must be
assessed & corrected as it avoids precipitous fall in blood
pressure and maintains adequate organ perfusion.61
Currently, evidence is insufficient to label one drug or drug
class superior over other in reducing morbidity or mortality
related to hypertensive crisis, however logical & consensus
opinion regarding choice of pharmacological agent in specific
clinical scenarios exist.
7. Specific hypertensive emergencies
7.1. Hypertensive emergencies involving acute coronary
syndromes
The target blood pressure for hypertensive emergencies
involving cardiac ischemia is that which improves myocardial
perfusion.29
Intravenous nitroglycerin & nitroprusside were previously
proposed as first line drugs.9,67 Nicardipine that can selec-
tively dilate cerebral & coronary arteries71,72 and clevidipine
that can protect against ischemia-reperfusion injury118 are
successful alternatives.
In presence of acute LVF, vasodilator agents that reduce
afterload like nitroglycerine, nitroprusside & fenoldopam are
preferred agents. Concomitant loop diuretics & ACE inhibition
are essential.
Diazoxide & hydralazine that cause reflex tachycardia
should be avoided.9,29,61,67 Drugs that reduce myocardial
contractility like beta blockers (labetalol, esmolol) should also
be avoided, especially when associated with heart failure,
except in cases with diastolic dysfunction29 or those without
 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4 5

Table 2 e Drugs used in hypertensive emergencies.

Dosage & pharmacokinetics Adverse Effects & Caution Comments & Special Uses

Vasodilators
1. Nicardipine hydrochloride: second generation dihydropyridine calcium channel blocker
Dose: Adverse Effects: Comments:
1e3 mg/kg/min IV, alternatively  Flushing, hypotension, palpitations,  Strong cerebral & coronary vasodilatory property68
5e15 mg IV every hour (bolus dosing angina, syncope, peripheral edema,  Considered as effective as nitroprusside68,69
independent of body weight) headache, vomiting66  Associated with decreased norepinephrine levels70
Onset of action:
5e15 min Caution: Special Uses:
Duration of action:  Post operative patients as it potentiates  Particular use in CAD patients as it increases
15e30 min; may last for up to 3e4 h effects of curare & interacts with inhalant stroke volume & coronary blood flow with favor-
anesthetics61,67 able effect on myocardial oxygen balance71e74
 Avoid in acute heart failure  Postoperative state75

2. Fenoldopam mesylate: dopamine D1 receptor agonist (10 times more potent than dopamine) promoting natriuresis & diuresis76
Dose: Adverse Effects: Comments:
0.8e1.2 mg/kg/min intravenously  Tachycardia, hypotension, flushing,  Action mainly in renal & splanchnic arteries & less
Begin with 0.1 mg/kg/min headache, hypokalemia, nasal congestion in coronary & cerebral arteries36e38
Increase by 0.1e0.2 at 20 min  Poorly lipid soluble, does not cross blood brain
intervals Caution: barrier (so no CNS activity)80
Onset of action:  Caution in glaucoma 29,67

>5 min Special Uses:

Duration of action:  Most useful in patient with renal impairment81
30 min to 1 h without rebound  Acute heart failure76,82e84
hypertension when infusion is  Those undergoing vascular surgery85
discontinued.77
Tachyphylaxis after 48 h78,79

3. Clevidipine butyrate: L-type calcium channel blocker

Dose: Adverse Effects: Comments:
0.5e3.5 mg/kg/min Intravenously  Headache, nausea, vomiting, hypotension  Reduces PVR without affecting venous vascular
Onset of action:  Heart failure deterioration tone, increases cardiac output with little influence
2e4 min e ultra short acting on left ventricular filling pressure86e89 & without
Duration of action: Caution: causing reflex tachycardia90
5e15 min  Severe aortic stenosis  Rapid metabolism by esterase in blood &
 Acute heart failure extravascular tissues

Special Uses:
 Critically ill patients, minimizing risk of prolonged
hypotension & overshoot hypotension32,86
 Post anesthesia hypertension90

4. Sodium nitroprusside: direct arteriolar & venous dilator by releasing nitric oxide, increases cGMP, blocks intracellular calcium release91
Dose: Adverse Effects: Comments:
0.5e10 mg/kg/min I.V with light  Hypotension, palpitations, headache,  For years considered first choice drug9,13,29,67
resistant delivery system15,74,92 nausea, vomiting.  Now relatively abandoned10,32
Onset of action:  Obliterates cerebral autoregulation
Immediate  Thyroid suppression Special Uses :
Intraarterial BP monitoring  Coronary steal phenomenon78  Hypertensive encephalopathy96
recommended because of  Thiocyanate and cyanide toxicity (when  Aortic dissection
tachyphylaxis & rapidity of action used for > 72 h)10,61  Acute heart failure
Duration of action: Cyanide removal requires bioavailability
1e2 min of thiosulphate & normal liver & renal
functions.79,93
Caution:
 High intracranial pressure94
 Hepatic or renal failure
 Acute coronary syndrome94,95

5. Nitroglycerin: powerful venodilator & at higher doses is an arteriolar vasodilator. Acts by increasing nitrate receptor.
Dose: Adverse Effects : Comments:
5e100 mg/kg/min I.V  Profound headache, vomiting, methemo-  Adheres to plastic containers & tubings,61,67
Onset of action: globinemia, tachyphylaxis.
2e5 min Special Uses:
Duration of action:  Coronary ischemia & pulmonary edema
5e10 min

(continued on next page)

6 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4

Table 2 e (continued )
Dosage & pharmacokinetics Adverse Effects & Caution Comments & Special Uses

6. Enalaprilat: Angiotensin-converting enzyme inhibitor

Dose: Adverse Effects: Special Uses:
5e10 mg/kg/dose every 8e24 h  Hypotension, hyperkalemia, oliguria, rash,  Acute left ventricular failure (non ischemic)98
Alternatively 1.25e5 mg every 6 h angioedema, agranulocytosis, neutropenia,
Onset of action: cough, fatal hepatic necrosis (rare)
15e30 min
Duration of action: Caution:
6e12 h  Avoid in acute myocardial infarction
 Abrupt BP reduction in patients with renal
artery stenosis & hypovolemia13,44
 Contraindicated in pregnancy.97,98

7. Hydralazine hydrochloride: direct arteriolar vasodilator e K channel opener

Dose: Adverse Effects: Comments:
0.1e0.6 mg/kg/dose every 4e6 h  Palpitations, flushing, tachycardia  Limited use owing to side effects & unpredictable
intravenously  Fever, rash, headache, arthralgia, SLE-like action61,67,99,100 with precipitous drop in blood
Onset of action: syndrome, positive ANA pressure that may last for 12 h
10e20 min  Peripheral neuropathy
Duration of action:  Fluid retention by activating RAAS34
1e4 h

8. Diazoxide: direct acting vasodilator

Dose: Adverse Effects:
50e150 mg every 5 min I/V or 15  Nausea, flushing
e30 mg/min I/V infusion  Reflex sympathetic stimulation101 &
Onset of action: aggravation of angina
1e5 min  Sodium retention, hyperglycemia
Duration of action:
4e12 h Caution:
 Avoid in angina, acute MI, aortic dissection

9. Isradipine: Second generation calcium channel blocker

Dose: Adverse Effects: Special Uses:
0.15 mg/kg/min I.V., increase by  Headache, flushing, peripheral edema,  Perioperative states & pregnancy102,103
0.0025 mg/kg/min every 15 min. dizziness, tachycardia
Maintenance 0.15 mg/kg/min
Onset of action:
1e10 min
Duration of action:
1e2 h

Adrenergic inhibitors

10. Labetalol hydrochloride: combined alpha 1 and beta blocker (1:7 ratio)104
Dose: Adverse Effects: Comments:
20e80 mg I/V bolus every 10 min  AV conduction disturbances, headache,  Reduces PVR without reflex increase in systolic
or 0.25e3 mg/kg/h intravenously bronchospasm, nasal congestion, scalp volume while cerebral, coronary and renal blood
Onset of action: tingling flow is mantained92,104,106,107
5e10 min13,61  Does not require intraarterial BP monitoring
Duration of action: Caution:  Metabolized in liver by formation of inactive
3e6 h13,61,105  Not to be used in acute heart failure, heart glucuronide conjugate105
block & COPD9,13,61  Maintains cardiac output unlike pure beta adren-
ergic blockers107

Special Uses:
 Aortic dissection
 Acute coronary syndrome
 Hypertensive encephalopathy
 Adrenergic crises
 Preeclampsia related crises61,92

11. Esmolol hydrochloride: cardioselective beta-1 adrenergic blocker

Dose: Adverse Effects: Comments:
125e500 mg/kg/min intravenously  AV Conduction disturbance, bronchocon-
0.5e2 mg/kg over 1 min followed striction, skin necrosis after extravasation,  Metabolism independent of renal or hepatic
by 50e100 mg/kg/min61,67 Raynauds phenomenon function
 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4 7

Table 2 e (continued )
Dosage & pharmacokinetics Adverse Effects & Caution Comments & Special Uses

Onset of action:  Metabolized by rapid hydrolysis of ester linkages

1e2 min by RBC esterase
Duration of action:
Caution:
10e20 min108,109 Special Uses:
 Heart failure
 Heart block  Considered by some as ideal beta adrenergic
 COPD blocker to be used in critically ill patients32
 Aortic dissection
 Perioperative states110,111
 Any hypertensive crisis with increased heart
rate/cardiac output
 Acute MI112
12. Urapidil: selective post synaptic alpha-1 blocker, 5 HT1A receptor agonist
Dose: Adverse Effects: Special Uses:
12.5e25 mg I.V. bolus followed by  Headache, dizziness  Perioperative states113
5e40 mg/h I/V infusion
Onset of action:
3e5 min
Duration of action:
4e6 h

13. Phentolamine: Non selective alpha-adrenergic blocker

Dose: Adverse Effects: Special Uses:
0.05e0.1 mg/kg/dose intravenously  Tachycardia, palpitations,  Special use in catecholamine excess states114,115
(maximum of 5 mg per dose)67 flushing, headache  Once initial control is achieved, oral
Onset of action:  Nasal congestion phenoxybenzamine a long acting alpha
1e2 min  Exacerbation of peptic ulcer adrenergic antagonist must be used
Duration of action:
15e30 min

heart failure with an intent to reduce myocardial oxygen 7.3. Hypertensive emergencies presenting with acute
consumption9,61,67 where it may be helpful. neurologic syndromes

7.2. Hypertensive emergencies associated with aortic
dissection
The blood pressure should be rapidly reduced to
systolic < 120 mmHg or < 100 mmHg if tolerated.119,120 A
vasodilator alone is not ideal as this can promote reflex
tachycardia, increase aortic ejection velocity & promote
dissection propagation. Therefore, the standard treatment is a
combination of beta blocker & vasodilator recommended to
effectively reduce BP, heart rate & cardiac contrac-
tility9,29,67,119,120 that lowers the pulsatile load as well as aortic
stress.
Esmolol is the drug of choice although metoprolol is a
reasonable alternative.121,122 Although nitroprusside has
traditionally been used as the vasodilator of choice, fenoldo-
pam or nicardipine are less toxic & equally effective
alternatives.122,123
Even presumptive diagnosis of acute aortic dissection
should prompt us to start parenteral anti hypertensives as
soon as possible. Not invariably, pharmacologic treatment is
only a bridge to surgery, especially in Type A dissection
involving ascending aorta.124,125 Therefore, all patients of
aortic dissection of Type A dissection deserve active surgical
consideration. However, patients with Type B dissections can
be managed with aggressive BP control unless complications
like leak, rupture and impaired flow to vital organs
ensues.125,126
Prompt improvement in patients condition with BP reduction
is the only definite criterion to diagnose hypertensive
encephalopathy.127
Currently, fenoldopam, nicardipine & labetalol are advo-
cated.29,61,67 Clevidipine has also emerged as an effective
alternative128,129 to be preferred over nitroprusside that was
typically chosen for many years. Since nitroprusside can in-
crease intracranial pressure & reduces cerebral blood flow in
areas with a fixed arterial narrowing130 & recent evidence of
an increase in mortality in ECLIPSE study when compared to
clevidipine,131 its use for this indication has declined.
In patients with acute ischemic stroke, however, aggressive
reduction in blood pressure is controversial, as elevated BP
likely represents an adaptive mechanism to maintain blood
flow to the affected area132 and aggressive lowering of blood
pressure has even documented to expand the ischemic pen-
umbra61,127,133 that may have deleterious and sometimes
catastrophic consequences. Overall, there is no convincing
evidence that elevated blood pressure affects the outcome
during the acute phase of an ischemic stroke,127,134 not even
when initiated in the first few hours of stroke onset.29,61,135,136
Blood pressure usually declines spontaneously to pre-
stroke levels within 4 days of an acute ischemic stroke
without any antihypertensive treatment.137
The current recommendations are to administer antihy-
pertensive treatment in ischemic stroke only if blood pressure
is more than 220/120 with mean BP is more than 130 mmHg, &
8 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4
to reduce blood pressure by no more than 10e15% in the first
24 h127,134,138
However, if concomitant non cerebral target organ damage
is present, other rules may apply & patients who are planned
to receive thrombolytic therapy, BP should be kept below
185/110 mmHg.9,61,67,134,138
ACCESS study assessed candesartan (angiotensin receptor
blocker) & found lower 12 month mortality when used in acute
phase of stroke.139 However, in the SCAST trial, there was no
reduction in the composite of vascular death, myocardial
infarction or stroke in 6 month follow up with use of cande-
sartan in first 7 days of stroke.140
Use of labetalol or nicardipine was previously suggested if
SBP is >220 mm Hg, DBP is 121e140 mmHg & nitroprusside if
DBP is >140 mmHg.61,67
In intracerebral bleed, rapid BP reduction, although at the
expense of risk of cerebral hypoperfusion141,142 should be
aimed with intent to prevent further bleeding, & this strategy
of intensive BP lowering significantly attenuated hematoma
growth over 72 h in the INTERACT study.143
Blood pressure more than 180/105 need to be treated in
cases of intracranial bleed, except in cases of subarachnoid
hemorrhage with normotensive prehaemorrhage status,
where target is 130e160 mmHg systolic.9,29,144
In the setting of haemorrhagic stroke with intracranial
bleed BP of more than 200/110 mm Hg need to be
controlled127,134 However, rapid decline in BP within 24 h is
independently associated with increased mortality.141
In general, if neurologic function worsens, the therapy
should be suspended, and blood pressure should be allowed to
increase.
7.4. Hypertensive emergencies associated with renal
disease
Either renal arterial disease, acute glomerulonephritis or
autoimmune vascular diseases are commonly followed by
further deterioration of remnant renal function, even when BP
is properly lowered.
Because of its renal vasodilator effects & lack of toxic me-
tabolites, fenoldopam is preferred in this setting.76 Nicardi-
pine, labetalol or clevidipine are other alternatives. Loop
diuretics are to be used only if there is associated volume
overload.13,29,61
ACE inhibitors are usually contraindicated due to the risk
of further deterioration of renal function, except in the case
of scleroderma renal crisis where it is the drug of choice.
The renin-angiotensin-aldosterone system is critically
responsible for hypertension associated with renovascular
disease & some models62 propose a possible explanation of
involvement of this axis in other forms of hypertensive crisis
as well. Even very old reports of surgical removal of an
ischemic kidney preventing hypertensive surges have been
documented.145
7.5. Hypertensive emergencies due to catecholamine
excess states
These situations are best managed with an intravenous alpha
blocker (phentolamine) with a beta blocker added if
necessary.146,147 Caution needs to be exercised in giving beta
blocker prior to adequate alpha blockade as unopposed alpha-
adrenergic stimulation can be dangerous.9,29
Although labetalol was traditionally considered ideal for
this purpose due to its combined alpha & beta adrenergic
blocking properties, but experimental studies do not support
its use in this clinical setting.148,149
Specifically in cocaine induced hypertensive emergency,
use of beta adrenergic antagonists can increase coronary
vasoconstriction, fail to control heart rate, increase BP and
decrease survival.150,151
Nicardipine, fenoldopam and verapamil in combination
with benzodiazepines are agents preferred in this setting.152,153
Diuretics are generally avoided as these patients are generally
volume depleted.
7.6. Perioperative hypertensive emergencies
Severe perioperative hypertension can occur in conjunction
with anesthesia induction, intraoperatively due to sympa-
thetic vasoconstriction, early postoperatively or after 24e48 h
due to pain or volume overload.154
Perioperative hypertensive emergencies most commonly
occur with carotid surgery, abdominal aortic surgery, periph-
eral vascular procedures, intraperitoneal & intrathoracic
surgeries155& approximately 50% of patients after cardiac sur-
geries. Amongst these, carotid surgery is notorious for being
associated with hypertensive emergences, and actually repre-
sents a face of baroreflex failure.156 Regardless of cause, post-
operative hypertension may be associated with increased risk
of cardiac & neurologic complications. A conservative target is
to control BP up to 10% above the baseline preoperative mean
BP levels.48 However, patients with heart failure & those who
are at high risk of bleeding will benefit from afterload reduction,
and the target in them should be more aggressive.
Postoperative hypertension also seems to be related to
catecholamine surge & sympathetic nervous system stimu-
lation 172 & usually requires treatment for 6 h or less.25 Careful
monitoring of patient response and temporal adjustments of
treatment are of paramount importance for safe management
of hypertensive emergencies in perioperative period.
7.7. Hypertensive emergencies during pregnancy
Preeclampsia affects nearly 7% of pregnancies157 and should be
managed with utmost caution, & conservatively, due to presence
of the developing fetus. The objective of treatment is to prevent
intracerebral bleed and cardiac failure without compromising
cerebral perfusion and uteroplacental blood flow.158
Hence a target SBP of 140e160 mmHg and DBP between 90
and 105 mmHg is recommended by most authorities & current
guidelines from American College of Obstetricians and
Gynaecologists.158,159
Hydralazine, though was earlier considered as the drug of
choice,160 has gone out of use due to increased risk of maternal
hypotension & fetal heart rate abnormalities.100,161 Associa-
tion with excess of cesarean sections, placental abruptions &
low APGAR scores were noted.161 Labetalol, Urapidil100 &
Nicardipine162,163 have emerged as superior alternatives to
 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4 9

Table 3 e Drugs used in hypertensive urgencies.

Dosage & Pharmacokinetics Adverse Effects & Caution Comments & Special Uses

1. Captopril: ACE inhibitor

Dose: Adverse Effects: Special Uses:
12.5e25 mg P/O every 1e2 h  Angioedema, cough,  Preferable for patients with evidence
Onset of action: acute renal failure9,44 of left ventricular dysfunction
15e30 min
Duration of action: Caution:
4e6 h  Contraindicated in pregnancy97,98

2. Clonidine: central alpha 2 agonist

Dose: Adverse Effects: Comments:
0.1e0.2 mg P/O every 1e2 h  Sedation, dry mouth, bradycardia,  Poorly lipid soluble, does not cross
Onset of action: rebound hypertension blood brain barrier, No CNS activity
30e60 min
Duration of action:
6e8 h

3. Labetalol: combined alpha 1 and beta blocker (1:7 ratio)104

Dose: Adverse Effects: Special Uses:
200e400 mg P/O every 2e3 h  Bronchoconstriction, Heart block, CHF  Preeclampsia related crises61,92
Onset of action:
30e120 min
Duration of action:
6e8 h

4. Furosemide: loop diuretic

Dose: Adverse Effects: Comments:
20e40 mg P/O every 2e3 h  Volume depletion, hyponatremia,  Not a primary drug but to be
Onset of action: hypokalemia9,11,12 considered as an add on therapy
30e60 min
Duration of action:
8e12 h

5. Isradipine: second generation calcium channel blocker

Dose: Adverse Effects: Special Uses:
5e10 mg P/O every 4e6 h  Headache, tachycardia, flushing,  May be considered in preeclampsia
Onset of action: peripheral edema related crisis & perioperative states102,103
30e90 min
Duration of action:
8e16 h

hydralazine.162,164 Oral treatment with methyldopa, long
acting nifedipine & magnesium sulfate may also be useful.
ACE inhibitors & nitroprusside are contraindicated due to
their teratogenic effects.
8. Treatment of hypertensive urgencies
Hypertensive crisis without evidence of target organ damage
can usually be treated with orally acting antihypertensive
agents with close ambulatory care.29 The lowering of blood
pressure, if done precipitously, can do more harm than good9
by causing a shift in the pressure/flow auto-regulatory curve
to the right.27
In essence, if BP lowering at a gradual pace is impor-
tant,11,12 equally important is assuring adequate follow up to
an appropriate site of care of chronic hypertension2,29 making
sure that the blood pressure has been lowered out of a
potentially dangerous range.11,12
Moreover, placebo-controlled trials have shown that BP
decreases spontaneously in a substantial proportion of
patients. This raises concern whether BP lowering, even
gradual, does, at all confer any benefit to a patient presenting
with hypertensive urgency.29,165
Notwithstanding, the potential of every hypertensive ur-
gency to transform into a hypertensive emergency should be
kept in mind & appropriate management of hypertension
with slow and controlled reduction of the blood pressure
should be the cornerstone in management of any form of
witnessed severe hypertension.
The drug of choice for a hypertensive urgency should be
effective, quick acting and unlikely to cause alterations in
mental status or produce hypotension. This widens the
armamentarium of drugs available for this purpose. These
drugs are summarized in Table 3 below.
Although evidence regarding the preferred time to reach
goal BP and type of BP lowering medication is limited, there is
evidence that a steep decrease in BP, such as reported with
sublingual nifedipine tablets, can lead to cerebral, cardiac and
renal ischemia166 & use of nifedipine immediate-release for-
mulations must be abandoned as a treatment option of any
form of hypertensive crises.58,167,168
10 c l i n i c a l q u e r i e s : n e p h r o l o g y 2 ( 2 0 1 3 ) 1 e1 4
9. Conclusion
To summarize, hypertensive crisis as a clinical presentation of
hypertension is far less common than routinely detected
chronic hypertension. Hypertensive emergencies are a po-
tential threat for permanent organ damage, significant
morbidity & mortality. Triage of these emergencies from ur-
gencies is crucial to ensure delivery of appropriate therapy to
the appropriate candidate in timely fashion.
Still, the potential threat of permanent target organ damage
associated with this clinical diagnosis, if not detected & treated
in time, should make the optimal implementation of recom-
mended therapy a commitment on part of the treating physi-
cian. The appropriate therapeutic approach needs to be
individualized for every patient. However, admission to ICU,
use of titratable IV hypotensive agents, and expeditious eval-
uation are cornerstone in management of hypertensive emer-
gencies. The pharmacological evolution in the last decade has
witnessed the transition of usage from nifedipine, hydralazine
& nitroprusside to esmolol, nicardipine & fenoldopam that are
equally potent, if not more, and have fewer adverse effects. It
should be stressed that the use of oral or sublingual nifedipine
should be avoided to prevent increased mortality.
Conflicts of interest
All authors have none to declare.
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