Journal of Geriatric Cardiology (2018) 15: 504512

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Review 
Open Access 

Management of hypertensive crises in the elderly

Abbas Alshami1, 2, Carlos Romero1, 3, America Avila1, 4, Joseph Varon5, 6, 7

1
Dorrington Medical Associates, Houston, Texas, USA
2
University of Baghdad/College of Medicine, Baghdad, Iraq
3
Universidad Autónoma de San Luis Potosí, San Luis Potosí, México
4
Universidad Durango Santander, Hermosillo, Sonora, México
5
The University of Texas Health Science Center at Houston, USA
6
The University of Texas Medical Branch at Galveston, USA
7
Critical Care Services, United Memorial Medical Center / United General Hospital, Houston, Texas, USA

Abstract

Hypertensive crises are elevations of blood pressure higher than 180/120 mmHg. These can be urgent or emergent, depending on the
presence of end organ damage. The clinical presentation of hypertensive crises is quite variable in elderly patients, and clinicians must be
suspicious of non-specific symptoms. Managing hypertensive crises in elderly patients needs meticulous knowledge of the pathophysiologi-
cal changes in them, pharmacological options, pharmacokinetics of the medications used, their side effects, and their interactions with other
medications. Clevidipine, nicardipine, labetalol, esmolol, and fenoldopam are among the preferred choices in the elderly due to their efficacy
and tolerability. Nitroprusside, hydralazine, and nifedipine should be avoided, unless there are no other options available, due to the high risk
of complications and unpredictable responses.

J Geriatr Cardiol 2018; 15: 504512. doi:10.11909/j.issn.1671-5411.2018.07.007

Keywords: Beta-blockers; Calcium channel blockers; Clevidipine; Elderly; Esmolol; Fenoldopam; Hypertensive crises; Labetalol; Nicardi-
pine; Nitroprusside

manage these crises in the elderly is associated with signifi-

1 Introduction
cant morbidity and mortality.[4]
Hypertension (HTN) remains a common illness around
the World.[1] Uncontrolled HTN can lead to hypertensive
2 Epidemiology and pathophysiology
crises. These are divided into two groups, urgencies and
emergencies.[2] Both of them involve severe elevations of HTN is one of the most important diseases among in the
blood pressure (BP) more than 180/120 mmHg.[3] The core elderly population. According to the National Health and
difference between them is whether severe HTN causes any Nutrition Examination Survey during 2015–2016, 63.1% of
organ dysfunction (hypertensive emergency) or not (ur- American people aged > 60 years have elevated blood
gency).[1,3] These crises are common among the elderly. pressure.[5] The vast majority of these patients have essential
Management of hypertensive crises in elderly patients HTN.[6] In addition, HTN remains a major risk factor for
should integrate a comprehensive set of pharmacological cerebrovascular as well as cardiovascular diseases, two of
strategies, depending on the core pathophysiological changes the leading causes of death in the United States causing
related to aging, preexisting risk factors, coexistent comor- about 770,000 deaths only in 2016.[7]
bidities, speed of progression of the condition, and the ex- The incidence of HTN, and hence, its complications such
tensiveness of organs involvement. Failure to successfully as hypertensive crises, is different among different groups,
and is higher in the elderly and African-Americans.[8–11]
Hypertension is not just more prevalent in elderly people,
Correspondence to: Joseph Varon, MD, The University of Texas Health
but mortality and morbidity are more significant as well.[12]
Science Center at Houston, 2219 Dorrington Street, Houston, Texas 77030,
USA. E-mail: [email protected] The investigators of the multicenter STAT registry reported
Telephone: +1-713-669-1670 Fax: +1-713-669-1671 a hospital mortality rate of 6.9% among patients with acute
Received: May 30, 2018 Revised: May 30, 2018 hypertensive crises requiring hospitalization and a cumula-
Accepted: May 30, 2018 Published online: July 28, 2018 tive 90 day mortality of 11% among these patients.[13]
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Alshami A, et al. Management of hypertensive crises in the elderly 505

Severe HTN is predominant among patients with history must be aware of the pathophysiology of this entity. The
of HTN in the majority of cases.[10] Many of them have in- regulation of BP is a concert of several organs/systems. The
adequate previous medical management, or poor compli- most important mechanisms are the cardiac output and sys-
ance to treatment.[12] Those preventable causes should be temic vascular resistance (SVR).[14] Elderly people suffer
addressed and treated, as the recurrence rate of acute hyper- increased SVR and, hence, elevated BP.[15] Several mecha-
tensive crises is high. The STAT investigators reported a nisms have been suggested to explain the increase in SVR,
90-day readmission rate of 37%, of which, 25% were due to such as endothelial dysfunction, neuro-hormonal dysregula-
recurrent acute hypertensive crises.[13] tion, and a reduction in renal homeostatic mechanisms due
To understand the extent of HTN among the elderly, one to decreased glomerular filtration rate (Figure 1).[14,16,17]

Figure 1. Pathophysiological mechanisms of acute hypertensive crises.

3 Clinical manifestations quires prompt understanding of the pathophysiology of the

disease, the physiological changes among them, and me-
Many elderly patients with severe uncontrolled HTN are
chanism of action and side effects of the medications avail-
totally asymptomatic. Pinna and collaborators, in a study of
able (See Table 1). Most experts advise to generally reduce
1,546 patients (mean age = 69 years) presented with acute
the mean arterial pressure by approximately 10%–15% dur-
hypertensive crises, reported that 55.6% of the patients re-
ing the first hour, and another 10%–15% during the next 2
ferred non-specific symptoms such as dizziness, palpitations,
to 4 hours due to the risk of hypoperfusion if the BP is low-
and headache.[18] Whereas symptoms related to end-organ
damage, such as chest pain and focal neurologic deficits, ered too suddenly or too far (e.g., into the range of < 140/90
were evident in 28.3% and 16.1% of patients, respec- mmHg).[19–21] However, faster drop in BP is required in cer-
tively.[18] Elderly patients are more likely to have hyperten- tain conditions, such as aortic dissection, in which BP
sive emergencies, rather than urgencies, than the general should be kept between 100 and 120 mmHg systolic and
population.[13] less than or equal to 60 to 70 mmHg diastolic as fast as pos-
The most frequent end-organ damage associated with sible.[20,22,23] While in the acute phase of ischemic stroke, it
hypertensive emergencies are cerebral infarction, acute has been recommended that lowering of BP should be de-
pulmonary edema, and hypertensive encephalopathy (24%, layed unless BP is > 220/120 mmHg or > 200/100 mmHg
23%, and 16%, respectively).[2] with end organ damage or if the patient will receive throm-
bolytics.[24] In hemorrhagic stroke, the target BP is variable
but generally systolic blood pressure (SBP) can be reduced
4 Management
safely to  140 mmHg.[25] The INTERACT2 trial showed
The management of hypertensive crises in elderly re- that a rapid decrease of BP does not have a representative

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506 Alshami A, et al. Management of hypertensive crises in the elderly

Table 1. Pharmacokinetics of different medications used in the management of hypertensive crises in the elderly.
Medication Mechanism(s) Dosage Onset Half-life
Nitroglycerin Activation of guanylyl cyclase via NO 5 to 200 µg/min 2–5 min 1–4 min
Nitroprusside Activation of guanylyl cyclase via NO 0.3 to 10 mcg/kg/min < 2 min –2 min
Nifedipine 1st generation dihydropyridine calcium-channel blocker 10 to 20 mg 3 times daily –20 min 2.5–5 h
Nicardipine 1st generation dihydropyridine calcium-channel blocker 5–25 mg/h 5–15 min 4–6 h
Clevidipine 3rd generation dihydropyridine calcium-channel blocker 1–2 mg/h Increase every 10 min up to 16 mg/h 2–4 min 5–15 min
Selective α1-adrenergic receptor blocker and
Labetalol 200–400 mg per o.s. every 2–3 h 30–120 min 2–6 h
nonselective β-adrenergic blocker
0.5–1 mg/kg loading dose.
Esmolol Beta1 receptor blocker 60 s 20 min
50–300 µg/kg/min infusion
Clonidine Alpha2 adrenergic agonist and imidazoline I1 receptor agonist 500 µg/kg in bolus and 25–300 µg/kg/min 30 min 12–16 h
Fenoldopam Dopamine type-1 receptor agonist 0.05–1.6 μg/Kg/ min 5–10 min 5 min
3h
Hydralazine Inhibition of calcium influx in vascular smooth muscle cells 20 mg initial bolus; 20–80 mg repeat boluses 5–15 min

NO: Nitric oxide.

reduction in primary outcome of mortality or severe disability Regardless of the target BP, the pharmacological man-
in patients with an acute intracerebral hemorrhage, however, agement must include agents that are titratable and easily
their analysis of modified Rankin scores revealed that patients reversible. The choice of the medications also depends on
had a better functional outcome when their BP was inten- the patient’s comorbidities, availability, and end-organ in-
sively decreased.[26] volvement (Table 2).

Table 2. Specific indications and adverse effects of different drugs used in the management of acute hypertension in the elderly.
Medication Specific Indications Adverse Effects
Nitroglycerin Acute coronary syndrome, pulmonary edema, volume overload Headache, vomiting reflex tachycardia and methemoglobinemia
Nitroprusside Use only in the elderly when other alternatives are not available Thiocyanate and cyanide intoxication, coronary steal syndrome
Nifedipine Not recommended in the elderly patient Hypotension, coronary steal syndrome, reflex tachycardia
Nicardipine Most hypertensive crises as a potent vasodilator Headache, local phlebitis, vomiting
Clevidipine Most hypertensive crises Headache, tachycardia, heart failure
Labetalol Acute aortic dissection Heart block and bronchoconstriction
Esmolol Post-operative hypertension, useful in increased cardiac output, easily titration Heart block and heart failure
Clonidine Severe hypertension associated with pain and anxiety Rebound hypertension and sedative effects
Renal arterial disease, glomerulonephritis or vascular diseases with
Fenoldopam Headache, tachycardia, nausea and exacerbation of glaucoma
impaired renal function, very useful
Hydralazine Not recommended in elderly patients Reflex tachycardia and severe hypotension

In patients presenting with hypertensive urgencies, a less Cyclic guanosine monophosphate (cGMP) via release of
drastic approach can be considered. Some authors suggest a nitric oxide (NO).[27] The hypotensive effects are secondary
decrease of BP over a period of 24–48 hours with an oral to a decrease in the preload and cardiac output.[27–29] Based
short-acting agent, such as angiotensin-converting enzyme on the data from the Euro-STAT registry, nitroglycerin is
inhibitor or angiotensin II receptor blocker, followed by the most commonly drug used for acute HTN in the inten-
close monitoring of the patient for several hours.[1,21] sive care unit.[30] This agent is available in different routes
The following paragraphs describe some of the common of administration including intravenous, oral, sublingual,
agents used to treat this condition. and transdermal.[27] The onset action of nitroglycerin is 2–5
minutes, and it has a plasma half-life of 1–4 minutes with
half-life of metabolites of 40 minutes.[27] It metabolizes via
5 Common agents
erythrocytes, hepatic, and vessels walls.[27] The recom-
mended intravenous dose of nitroglycerin for the treatment
5.1 Nitroglycerin of hypertensive crises is from 5 to 200 µg/min.[31] Tachy-
Nitroglycerin is a potent vasodilator prodrug that acts on phylaxis is common. The most common adverse effects

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Alshami A, et al. Management of hypertensive crises in the elderly 507

include headache, vomiting, reflex tachycardia and methe- type calcium channel blocker.[41] It is highly selective to
moglobinemia.[32] Nitroglycerin is particularly useful in vessels without affecting cardiac contractility.[46] It is a po-
clinical practice in acute coronary syndromes and pulmo- tent coronary dilator as it is more selective to coronary beds
nary edema as an adjunctive agent.[1,4,16,33,34] than systematic beds.[33] In a retrospective analysis to com-
pare nicardipine to labetalol in managing HTN in criti-
5.2 Sodium nitroprusside
cally-ill patients, Malesker and Hilleman found that
Nitroprusside is a potent vasodilator that elicits its effects nicardipine was as efficacious as labetalol with significantly
on both arteries and veins.[35] It is comprised of a ferrous ion fewer side effects, which were mainly hypotension and
center complexed with five cyanide moieties and a nitrosyl bradycardia.[47] Although it has been reported to cause bra-
group. Once infused, it can interact with oxyhemoglobin, dycardia in elderly patients,[48] tachycardia is a more com-
dissociating immediately and forming methemoglobin while mon side effect.[49] Animal studies have shown a direct
releasing cyanide and NO.[35] Nitric oxide causes then vaso-
sympathetic activator effect, in addition to its effects
dilation, and mediates the antihypertensive properties of the
through baroreflex.[50] Additional side effects include head-
medication while cyanide can accumulate potentially to
ache, flushing, and local phlebitis after prolonged infusion
toxic levels.[36] For years, it used to be the gold standard;
in a single site.[49] Nicardipine is rapidly and extensively
however, because the cyanide toxicity is so significant, the
Food and Drug Administration placed a black box warning metabolized by the liver and should be avoided in patients
in 1991.[37] Nevertheless, this medication is still being used, with hepatic impairment.[33] The manufacturer dose range is
although less than before.[35] In the STAT registry, nitro- between 5–15 mg/hr, but in our experience, up to 25 mg/hr
prusside was the 4th most commonly used drug (13%) in can be tolerated safely.[1,51]
management of hypertensive crises with neurological mani-
5.5 Clevidipine
festations.[38]
Wood and coworkers showed that elderly patients are at Clevidipine is the newest, ultrashort, dihydropyridine
a particular risk for developing complications when re- calcium channel blocker.[52] It is a pure arteriodilator, and
ceiving nitroprusside; and that hypotension is very common does not affect the venous tone or cardiac muscle contractil-
among them.[39] The ECLIPSE trial compared nitroprusside ity.[53] It is given as a lipid emulsion as it is water inso-
versus other antihypertensives; it showed that this agent luble.[54] This agent should be avoided in patients with egg
caused higher mortality when compared with other agents.[40] and soybean allergy.[55] It has rapid onset and offset of ac-
From our standpoint, nitroprusside should only be used tion. It has been shown to achieve the first 15% reduction in
when other safer alternatives are not available, especially SBP within 5–6 minutes of intravenous administration.[56,57]
among elderly patients. Its antihypertensive effects are abolished 5–15 minutes after
weaning off the medication in most patients.[55]
5.3 Nifedipine
Clevidipine had also achieved significant reduction in BP
Nifedipine is a first generation calcium channel blocker.[41] in patients with acute HTN when compared to placebo in
For a period of time, it had been used widely through oral
the ESCAPE I & II trials.[56,57] When compared to nitro-
and sublingual capsules for the management of hypertensive
glycerin, nitroprusside, and nicardipine in ECLIPSE trial, it
crises.[16] However, it is poorly soluble, and poorly absorbed
showed comparable safety profile to them, and a significant
through the buccal mucosa, and swallowing the drug is the
reduction in mortality.[40] Indeed, it was more effective than
only effective method of administration.[42] The American
Geriatrics Society, in the updated Beers criteria, strongly nitroglycerin (P = 0.0006) and nitroprusside (P = 0.003) in
recommended avoiding nifedipine in patients older than 65 maintaining BP within the predetermined range.[40] This
years, due to the potential risk of hypotension, which may agent was as effective as nicardipine, in maintaining BP
precipitate for myocardial ischemia.[43] In addition, in eld- within a predetermined range.[40] The VELOCITY trial
erly patients, it can cause a rapid fall in BP, coronary steal showed a rapid and effective reduction in BP, with a de-
syndrome, and reflex tachycardia.[44,45] Given those serious crease of 6% of BP within three minutes, 15% within 9.5
side effects and complete lack of outcome data, Grossman minutes and a 27% reduction in BP 18 hours after infusion
and coworkers pointed out that in true hypertensive emer- initiation.[58] Clevidipine does not induce a reflex increase in
gencies, this agent is contraindicated.[44] heart rate. It has coronary vasodilatory properties.[53] These
anti ischemic properties make clevidipine one of the best
5.4 Nicardipine options for elderly patients presenting with hypertensive
Nicardipine is a second generation dihydropyridine L- crises.

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508 Alshami A, et al. Management of hypertensive crises in the elderly

5.6 Labetalol almost completely absorbed after oral administration.[66] The

Labetalol is a combined α1-adrenergic and β-adrenergic metabolism of this agent is primarily by hepatic (-50%) and
receptors blocker, with greater effect on β-receptors as the excretion is 40%–60% in the urine, and 20% in feces.[69]
compared to α-receptors.[1] Labetalol can be administered Clonidine is used in severe HTN associated with pain and
anxiety, due to its sedative-analgesic effects. Rapid with-
either as a bolus or continuous infusion.[59] It has negative
drawal from this medication may cause rebound HTN.[28,34,65]
chronotropic and inotropic effects, which made it one of the
This agent must be used with caution in the elderly, as con-
preferred agents in the management of hypertensive crises
fusion may be a significant side effect.[70]
in acute aortic dissection.[16,23] Labetalol was compared with
nicardipine in the CLUE trial; and results showed that 5.9 Fenoldopam
nicardipine is more likely than labetalol to achieve target
Fenoldopam is a selective dopamine type-1 receptor
blood pressure within 30 minutes.[60] Reported side effects
agonist that works by increasing renal blood flow, improv-
include hypotension, bradycardia nausea, vomiting, scalp
ing renal function, and stimulating natriuresis.[71,72] This
tingling, and burning sensation in the groin.[61] In elderly,
drug has an onset of action of 5–10 minutes with a half-life
labetalol’s side effects are even more significant, mainly due
of five min.[73] It is rapidly metabolized by hepatic methyla-
to delayed clearance of the agent in elderly.[62]
tion without participation of cytochrome P450 enzymes, and
5.7 Esmolol the excretion is mostly by urine (90%).[65] Fenoldopam is
preferred in hypertensive emergencies mediated by renal
Esmolol is an ultrashort cardioselective beta-blocker.[16] arterial disease, glomerulonephritis, or vascular diseases
It is mainly used for post-operative HTN; and in combina- with impaired renal function.[23] Fenoldopam can be used
tion with nicardipine or nitroglycerin to maintain hemody- also in hypertensive emergencies in perioperative situa-
namic stability in the perioperative period.[63] tions.[32] Recommended dosage of this agent is 0.01–1.5
Esmolol is well tolerated in patients with myocardial in- µg/kg/min and the titration is recommended by increase of
farction and patients with contraindications for other beta- 0.05–0.1 µg/kg/min every 15 min.[34]
blockers.[64] This agent is contraindicated in congestive heart Intravenous fenoldopam has no effect on the central
failure, bradycardia, and chronic obstructive pulmonary nervous system, and does not cross the blood-brain barrier.[32]
disease.[32,64] In the authors’ experience, these contraindica- Due to its properties, it is considered a choice of treatment
tions are relative.[34] Esmolol is particularly useful in situa- in elderly to reduce BP in severe HTN with acute kidney
tions in which the cardiac output, BP, and heart rate are injury, heart failure, and in perioperative situations, specifi-
increased.[28] The onset of action is within 60 seconds, and cally in vascular surgery.[32]
the duration of action is upon 20 minutes.[16] The loading
dose is 0.5–1 mg/kg over 1 minute, and the maintenance is 5.10 Hydralazine
infusion of 50 µg/kg/min.[28] The metabolism of esmolol is Hydralazine is a vasodilator that elicits effects purely on
through hydrolysis of ester linkages by esterases of eryth- the arterial system.[14] It is thought that it inhibits calcium
rocytes.[34] Esmolol is safe in elderly patients because it can influx in vascular smooth muscle cells, causing hyperpo-
be easily titrated.[65] larization of the cell membrane, or induces cGMP.[65] Hy-
dralazine has an onset of action of 5–15 min and a half-life
5.8 Clonidine of only three hours.[74] However, its antihypertensive effects
Clonidine was first used as a nasal decongestant, but be- are completely unpredictable, and can last up to 24 hours.[75]
cause of its other effects, such as hypotension, bradycardia, Hydralazine remains a common agent in the treatment of
and sedation, is now used in other conditions.[66] This drug preeclampsia and eclampsia.[76] However, new evidence
is an alpha2-adrenergic agonist (affinity 200:1 vs. alpha1 shows that hydralazine can cause maternal hypotension and
receptors) and an agonist at the imidazoline receptors.[67] Its is harmful to fetus.[32] Other adverse effects of hydralazine
hypotensive effect is secondary to stimulation of the al- include reflex tachycardia, severe hypotension, and oxygen
pha-adrenergic receptors in the vasomotor center of medulla consumption.[28] Hydralazine should be avoided in patients
oblongata, and a decrease in renin and aldosterone.[67] These with cardiomyopathies.[77] Recommended dosage of intra-
effects are elicited within 30 minutes of oral administration, venous hydralazine is 10–20 mg.[32] Because of its large
with peak plasma levels achieved within 2–4 hours, and number of adverse effects, poor safety of dosage, and un-
half-life is 12 to 16 hours.[28,34,65] However, the antihyper- predictable antihypertensive effects, we do not recommend
tensive effects may persist 24 hours or more.[68] Clonidine is its use in the elderly patients.[1,34,51]

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Alshami A, et al. Management of hypertensive crises in the elderly 509

5.11 Phentolamine ommend using easily titratable agents, such as clevidipine,

Phentolamine is a reversible α1- and α2 antagonist re- nicardipine, esmolol, and fenoldopam as first choices and
ceptor.[78] It is mostly used to treat hypertensive emergen- avoid agents such as nitroprusside, hydralazine, and
cies due to a sympathetic crises, such as pheochromocytoma, nifedipine due to their established side effects.
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