Curr Hypertens Rep (2016) 18:43

DOI 10.1007/s11906-016-0651-8

HYPERTENSION AND EMERGENCY MEDICINE (T RAINER, SECTION EDITOR)

Therapies to Reduce Blood Pressure Acutely

Joseph B. Miller 1,2,3 & Harish Kinni 1,2,3 & Ahmed Amer 1 & Phillip D. Levy 4

# Springer Science+Business Media New York 2016

Abstract Clinicians make frequent treatment decisions re-
garding acute blood pressure reduction for the critically ill.
Key to the decision making process is a balance between
reducing arterial wall stress and maintaining perfusion to vital
organs. In this article, we review the physiological consider-
ations underlying acute blood pressure management, includ-
ing the concept of cerebral autoregulation and its adaptations
to chronic hypertension. We then discuss available pharmaco-
logical interventions suited for reducing blood pressure acute-
ly. We also discuss specific blood pressure targets in common
critical illnesses and consider future directions in this thera-
peutic area.
This article is part of the Topical Collection on Hypertension and
Emergency Medicine
Dr. Phillip Levy is currently funded by the National Institute on Minority
Health and Health Disparities (PI: Levy—MD 5 R01 MD005849-05).
* Joseph B. Miller
jmiller6@hfhs.org
Keywords Hypertension . Hypertensive emergencies .
Antihypertensive . Blood pressure
Introduction
In the management of critically ill, hypertensive patients,
rapid blood pressure reduction is often indicated to re-
duce further decompensation. Clinical trials to guide
management are challenging for these disease processes,
and treatment recommendations are largely based on
physiological considerations and experience. In this arti-
cle, we review the physiological background behind
acute blood pressure management goals and the available
pharmacological agents. We additionally discuss disease-
specific goals and future directions in acute blood pres-
sure management.

Harish Kinni Case Snapshot

hkinni2@hfhs.org
Ahmed Amer A 66-year-old male with a history of hypertension, dia-
aamer1@hfhs.org betes, and transient ischemic attack presents with right-
Phillip D. Levy sided hemiparesis and dysarthria. He was out with his
plevy@med.wayne.edu son hunting, and his son noticed the symptoms acutely
develop while they were in a field about 4 h prior to
1
Department of Emergency Medicine, Henry Ford Hospital, arrival. His blood pressure at triage in the emergency
Detroit, MI, USA department was 225/124 mmHg and his National
2
Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, Institute of Health stroke scale was 12. He is immediate-
USA ly taken for a non-enhanced computer tomography scan
3
Wayne State University, Detroit, MI, USA of the head, and the treating team prepares for transfer to
4
Department of Emergency Medicine, Wayne State University, endovascular therapy. What is the optimal blood pressure
Detroit, MI, USA management strategy?
43 Page 2 of 8
Background
Multiple pathologies in acute care mandate rapid blood pres-
sure reduction. Of particular concern are cardiovascular and
neurological emergencies, such as aortic dissection and stroke.
Regardless of the specific condition, this goal of blood pres-
sure reduction is largely the same: to minimize further organ
damage while maintaining blood flow to the brain and other
vital organs.
The two primary risks of blood pressure reduction are ce-
rebral ischemia and renal injury, and the concept of autoregu-
lation is central to defining these risks. Given the potential for
devastating consequences of brain hypoperfusion, cerebral
autoregulation is the dominant concern [1, 2]. In the traditional
model of cerebral autoregulation, the brain maintains constant
flow to cerebral tissue over a range of mean arterial pressure
(MAP). This range is typically thought to be from MAP of 50
to 160 mmHg [3].
Complicating this model, however, is right-shifting of auto-
regulation due to chronic hypertension. The mechanisms for
cerebral autoregulation occur at the microvascular level, and
with persistently high blood pressures, these mechanisms reset
to a higher overall range of MAP under which cerebral perfu-
sion is regulated [4•]. Hence, a patient with uncontrolled hy-
pertension may autoregulate through a range of MAP of 80 to
180 mmHg rather than 50 to 160 mmHg [5]. Such a patient
could tolerate a MAP of 175 mmHg without developing ce-
rebral edema but could not tolerate a MAP of 55 mmHg with-
out risking hypoperfusion.
In the acute setting, treatment is largely blinded to the im-
mediate effects on cerebral perfusion. Nevertheless, because
of these concerns, goals of blood pressure reduction are usu-
ally set at modest reduction rather than normalization. Such
goals reduce the likelihood of complications while providing
reduction in arterial wall stress that could lead to further car-
diovascular or neurovascular injury. In the next sections, we
review the available antihypertensive agents best suited for
rapid blood pressure lowering and targets for specific critical
diagnoses.
Antihypertensive Selection for Acute Blood Pressure
Reduction
Most medication recommendations in hypertensive emergen-
cies stem from expert experience using drugs that have been
available for over 40 years. Although there have been a num-
ber of new oral antihypertensive medications over the past
decade, there is more limited drug development of intravenous
agents for rapid blood pressure reduction [6]. Clevidipine is
the most notable exception, a short-acting intravenous, fourth
generation dihydropyridine calcium channel blocker [7].
Curr Hypertens Rep (2016) 18:43
The available antihypertensive medications for rapid blood
pressure reduction are generally divided into vasodilators and
adrenergic blockers. Table 1 lists common antihypertensive
agents available for acute blood pressure control. The intrave-
nous infusion calcium channel blockers have had increasing
relevance for acute blood pressure reduction, most notably in
management of neurological emergencies [8–10]. Current
American Heart Association guidelines for the acute manage-
ment of blood pressure in stroke include nicardipine as a pre-
ferred option, along with more traditional medications such as
labetalol [11]. Both nicardipine and clevidipine require less
intensive monitoring and dose titration compared to nitroprus-
side [12].
Certain medications are best paired to the disease process
according to their expected effects on cardiac output,
chronotropy, or safety in pregnancy. Although cardiac output
is rarely directly measured in the emergency department, pa-
tients with known or suspected heart failure and low cardiac
output may benefit from specific agents that do not reduce
contractility. Direct-acting vasodilators such as hydralazine,
nitroprusside, and nitroglycerin cause reflexive increases in
chronotropy but do not cause reduced myocardial contractility
[13, 14]. Beta-blockers, on the other hand, have a universally
negative effect on chronotropy and various effects on myocar-
dial contractility, dependent on their intrinsic sympathomimet-
ic activity and alpha blockade [15]. Labetalol, for instance, is
relatively contraindicated in patients with suspected low car-
diac output that have acute heart failure due to its negative
inotropic properties [16].
Other key factors in choosing a medication for blood pres-
sure reduction include the onset and duration of action, the
route of administration, and potential adverse effects. The
acuity of conditions such as aortic dissection demands rapidly
efficacious treatment. Generally, oral and transdermal routes
should be avoided due to their slow onset of action and incon-
sistent kinetics. Oral medications are particularly problematic
in neurological emergencies due to the risk of aspiration. In
addition, the management of critical disease processes re-
quires predictable treatment effects. In the authors’ experience
and in the limited literature available, certain medications such
as hydralazine and enalaprilat have unpredictable effects.
Treatment with these medications can lead to either no effect
or rapid, sustained drops below blood pressure goals [17, 18].
Disease-Oriented Blood Pressure Targets
Recognizing the balance of maintaining perfusion to vascular
beds that have become accustomed to higher blood pressure
ranges versus reducing immediate risks associated with vessel
wall stress, the general rule for managing hypertensive emer-
gencies is to gradually reduce the MAP by 10–20 % in the first
hour with a further 5–15 % decrease over the next 23 h [19].
Curr Hypertens Rep (2016) 18:43 Page 3 of 8 43

Table 1 Common antihypertensive medications for acute blood pressure reduction [55–57]

Drug Dose range Onset Duration Adverse effects Notes

Vasodilators
Clevidipine 1 to 2 mg/h (max 16 mg/h)
Enalaprilat 1.25 to 5 mg q 6 h
Fenoldopam 0.05 to 1.6 mcg/kg/min
Hydralazine 10 to 20 mg IV q 4 to 6 h
Nicardipine 5 to 15 mg/h
Nitroglycerin 5 to 400 mcg/min
Nitroprusside 0.25 to 10 mcg/kg/min
Adrenergic inhibitors
Esmolol 250 to 500 mcg/kg load
over one min then 25 to
300 mcg/kg/min
Labetalol 10–20 mg bolus q 15 min
up to 300 mg, 0.5 to
2 mg/min infusion
Metoprolol 1.25 to 5 mg IV followed by
2.5 to 15 mg q 3–6 h
Phentolamine 5 to 15 mg IV bolus q 5 to
15 min
Urapidil 10–25 mg slow IV bolus
every 5 min to goal BP
then 5–40 mg/h infusion
2–4 min 5 to 15 min
Increased incidence of atrial
fibrillation, nausea
15– 6 to 12 h Drastic fall in BP in high renin Avoid in renal impairment
30 min states; variable response, and pregnancy
headache, dizziness
5–10 min 30 to 60 min Tachycardia, headache, flushing, Avoid in glaucoma or
nausea increased ICP
10– 1 to 8 h Sudden drop in BP, tachycardia, Unpredictable effect on BP
20 min flushing, headache, vomiting
5–15 min 1.5 to 4 h Tachycardia, headache, dizziness,
nausea, flushing, edema
2–5 min 5 to 10 min Tachycardia, headache, vomiting, Primary role in acute heart
tolerance after prolonged use failure
0.5–1 min 1 to 10 min Increased ICP, cyanide and Caution in renal and hepatic
thiocyanate toxicity with renal failure
impairment
1–2 min 10 to 30 min Nausea, flushing, bronchospasm, Caution in decompensated
1st degree heart block, prolonged heart failure
half-life in anemia
5–10 min 2 to 4 h Nausea, paresthesias, bronchospasm, Caution in decompensated heart
dizziness, heart block failure or reactive airway disease
20 min 5 to 8 h Nausea, paresthesias, bronchospasm, Caution in decompensated heart
dizziness, heart block failure
1-2 min 10 to 30 min Tachycardia, flushing, headache, First line for pheochromocytoma
nausea
3–5 min 2–6 h Headache, dizziness Caution in renal and hepatic failure,
not available in USA

BP blood pressure, IV intravenous, q every, h hour, min minute

Exceptions to this rule exist and are detailed below in the
management of acute aortic dissection and acute ischemic
stroke.
Cardiovascular
Aortic Dissection
Acute aortic dissection represents a major exception to grad-
ual blood pressure lowering over the first day because of its
high short-term mortality risk [19]. The danger of aortic wall
stress outweighs concern for cerebral perfusion. Expert opin-
ion recommends rapid lowering of the systolic blood pressure
(SBP) to 100–120 mmHg within 20 min [20]. This goal is
shared with a primary aim to reduce the heart rate below
60 beats/min, which will consequently reduce aortic wall
shear stress to avoid propagating the dissection. Intravenous
esmolol or labetalol are excellent first steps to lower heart rate
and blood pressure, though the blood pressure lowering ef-
fects of esmolol are limited. In patients who cannot tolerate
beta-blockers, verapamil or diltiazem may be used as alterna-
tives. Adequate chronotropic control is essential to avoid re-
flex activation of the sympathetic nervous system due vasodi-
lation, which contributes to aortic wall stress [20]. If the blood
pressure is not adequate with such agents, nitroprusside has
classically been added. Clevidipine and nicardipine are attrac-
tive alternatives to nitroprusside and require less minute to
minute titration [21]. Other direct vasodilators, such as hydral-
azine, increase aortic wall stress and should be avoided. In our
opinion, the most attractive agents for managing aortic dissec-
tion are esmolol followed by clevidipine, as both are short-
acting agents with reliable decreases in chronotropy and blood
pressure.
Acute Decompensated Heart Failure and Pulmonary
Edema
In the setting of hypertensive acute heart failure, acute blood
pressure reduction is indicated for patients with significant
pulmonary congestion and dyspnea due to excessive afterload
[22]. Reductions in MAP of 15–20 % can produce significant
43 Page 4 of 8
improvements in dyspnea [23, 24]. Nitroglycerin is a first-line
treatment for reducing severely elevated blood pressure in
acute heart failure and improves dyspnea symptoms, though
a Cochrane review notes that the data on the effectiveness of
nitrates is limited [25]. In small studies and in our experience,
repeated sublingual or intravenous nitroglycerin provides rap-
id symptom improvement [26–28]. Patients with acute hyper-
tensive pulmonary edema may further benefit from high-dose
nitroglycerin (2 mg boluses repeated every 2–5 min) to rapidly
improve dyspnea symptoms [26]. Clevidipine and nicardipine
are additional options for rapid blood pressure reduction, of
which clevidipine has greater safety and efficacy data for
blood pressure and dyspnea reduction [23]. Of note, there is
a lack of evidence that nitrates or any intravenous vasodilators
have mortality benefit for acute heart failure [29].
Obstetric
Hypertensive emergency in pregnancy is rare but can occur in
patients with preeclampsia and eclampsia. Severe elevations
of blood pressure can cause hypertensive encephalopathy or
acute heart failure in these patients. In order to avoid an abrupt
decrease in pressure to the placenta, which can lead to poten-
tial harmful fetal defects, the goal reduction in MAP is 20 %
over minutes to hours and further reaching a blood pressure
≤160/110 mmHg over the subsequent day [30]. Prior to deliv-
ery, it is desirable to maintain the diastolic blood pressure
above 90 mmHg to allow for adequate utero-placental perfu-
sion. The choice of antihypertensive depends largely on expe-
rience as there is insufficient data to demonstrate the superi-
ority of one agent over another in hypertensive emergencies in
pregnancy [30]. The American College of Gynecology cur-
rently regards oral nifedipine as first-line treatment [31]. For
more rapid reductions with intravenous agents and treatment
of refractory hypertension, we recommend labetalol and
nicardipine due to their safety in pregnancy and reliable effi-
cacy. Though traditionally a first-line medication in pregnan-
cy, hydralazine is a less favorable option as it may be associ-
ated with higher rates of adverse fetal effects [32].
Cerebrovascular
Hypertensive Encephalopathy
Hypertensive encephalopathy is rare and typically occurs in
patients with MAP >150 mmHg, although it can occur at
lower blood pressures in newly diagnosed hypertensive pa-
tients and pregnant women [33]. For the treatment of hyper-
tensive encephalopathy not complicated by cerebrovascular
accident, the MAP should be reduced by approximately
20 % in the first hour using intravenous agents such as
Curr Hypertens Rep (2016) 18:43
labetalol, nicardipine, clevidipine, or nitroprusside. Due to
its need for continuous monitoring, nitroprusside is rarely
used for this indication in the emergency department setting.
In the authors’ experience, nicardipine is a reliable and proven
medication for managing hypertensive encephalopathy given
its potency and ease of titration.
For most patients, this level of reduction should return
blood pressure to the autoregulatory range and reduce cerebral
edema caused by loss of autoregulation. However, further
reductions in blood pressure may be needed to reverse ongo-
ing neuronal cell damage. More aggressive blood pressure
reduction is generally well tolerated in patients with hyperten-
sive encephalopathy as they, by virtue of their condition, are
on the ascending portion of the autoregulation curve, far
above the point where blood flow decreases may occur with
antihypertensive therapy.
Intracerebral Hemorrhage
Blood pressure management in intracerebral hemorrhage
(ICH) is one of the few hypertensive emergencies with a sig-
nificant influx of data. In particular, the Rapid Blood Pressure
Lowering in Patients with Acute ICH (INTERACT) 2 trial
tested whether a target SBP <140 mmHg versus a target
<180 mmHg would lead to reduced death or major disability
[34•]. The trial was a multi-national study with over 2800
patients and used open-label antihypertensive agents to reduce
blood pressure within 6 h of symptom onset. Although the
trial did not find statistically significant improvement in its
primary outcome of death or severe disability, it was clear that
a target SBP of 140 mmHg is safe in this patient population.
Furthermore, secondary analysis from the trial indicated that
patients with the greatest reduction in early blood pressure had
the best associated neurological outcomes [35•]. The
INTERACT 2 trial was one of the largest ICH trials ever
performed and provides the most robust safety data to date
on targeting a SBP of 140 mmHg. When considering safety,
it is notable that patients in the trial had presenting SBP
<220 mmHg and small intracerebral hematomas (median vol-
ume 11 ml) on average.
There will soon be a second large influx of data with the
Antihypertensive Treatment in Acute Cerebral Hemorrhage
(ATACH) 2 trial coming to completion. This multicenter trial
tests the same blood pressure targets in ICH as INTERACT 2
but aims to initiate treatment at earlier time points and admin-
isters nicardipine as the primary antihypertensive agents [8].
The trial was halted prior to completion due to futility and
final results will be published in 2016.
Current guidelines recommend aggressive reduction of
blood pressure for patients with ICH [36]. For most patients,
the treatment goal is a SBP of 140–160 mmHg. As
INTERACT 2 demonstrated, the target of 140 mmHg is safe
in patients without large intracerebral hematomas and
Curr Hypertens Rep (2016) 18:43
presenting SBP <220 mmHg. Treatment should occur with
continuous IV medications, such as labetalol, nicardipine, ni-
troprusside, and clevidipine [36, 37, 38•]. Nicardipine is com-
monly used in the emergency department setting and is the
authors’ first-line choice for ICH blood pressure control. Two
caveats for blood pressure control in ICH are notable. First, for
patients with clinical suspicion for high intracranial pressure,
blood pressure reduction below a SBP of 180 mmHg should
occur judiciously with neurological surgery consultation and
intracranial pressure monitoring. High intracranial pressure
may require higher blood pressure levels to maintain cerebral
perfusion pressure. Second, for patients presenting with SBP
>220 mmHg, there is less data to guide treatment and SBP
goals of 160–180 mmHg are reasonable.
Acute Ischemic Stroke
Due to physiological concern for loss of cerebral perfu-
sion with blood pressure lowering, current American
Heart Association (AHA) guidelines for the management
of cute ischemic stroke are conservative regarding blood
pressure targets [11]. Blood pressure reduction is indi-
cated only for patients whose blood pressure exceeds
220/120 mmHg. For patients that are candidates for
thrombolytic or endovascular therapy, however, treat-
ment is indicated to keep blood pressure <185/110 mmHg.
The acute hypertensive response in ischemic stroke common-
ly decreases without treatment over the first 12–24 h from
symptom onset.
These treatment goals vary significantly with blood pres-
sure management in ICH because of key differences in stroke
pathophysiology. In ischemic stroke, there is usually an
area of tissue surrounding a core infarct that is electri-
cally silent and at risk for further ischemia called the
penumbra [39]. In addition, cerebral autoregulation is
disrupted [40, 38•]. Hence, large drops in blood pres-
sure may decrease perfusion and increase ischemic inju-
ry. In ICH, there is less risk as an analogous penumbra
does not exist around the primary area of hemorrhage
and autoregulation is often preserved [41, 42]. Finally,
clinical trials testing blood pressure reduction below
current AHA guideline targets have failed to show ben-
efit [43, 44]. A recent meta-analysis of antihypertensive
trials in ischemic stroke indicated no outcome benefit
and potential harm with acute blood pressure reduction
[45].
In the authors experience, a minority of ischemic stroke
patients require acute blood pressure reduction, and for those
that do, the ideal antihypertensive agents are labetalol and
nicardipine [38•]. Although there is less experience in stroke
care with its use, clevidipine is another reasonable agent.
Nicardipine and clevidipine may be advantageous in transfer-
ring severely hypertensive patients for endovascular care
Page 5 of 8 43
given their ease of titration. For patients not receiving throm-
bolytic or endovascular therapy, blood pressure <220/
120 mmHg is acceptable for the first 24 h, after which oral
antihypertensive agents can be started or restarted. Because an
exaggerated response to antihypertensive agents can occur in
dehydrated stroke patients, intravenous fluids are recommend-
ed for patients with acute hypertension that have clinical signs
of volume depletion [38•].
Subarachnoid Hemorrhage
The current American Stroke Association guidelines do
not define a definitive target blood pressure for hyper-
tension as a result of subarachnoid hemorrhage (SAH)
and suggest decreasing SBP 160 mmHg [46]. The op-
timal therapy is not clear, but labetalol and nicardipine
are preferred. Vasodilators such as nitroprusside or ni-
troglycerin should be avoided because of their propen-
sity to increase intracranial pressure (ICP) as a conse-
quence of increased cerebral blood volume [46]. The
overall goal of blood pressure reduction is to reduce
the risk of re-bleeding of an unstable aneurysm without
potentially contributing to hypoperfusion due to reduction in
cerebral perfusion pressure (CPP). Though often thought of as
an acute therapy, oral nimodipine should be started within the
first 48–72 h in all patients due to its adjunctive neuroprotec-
tive effects [47].
Future Directions
Decision making in acute hypertension management has rest-
ed on the concept of reducing mechanical stress on vessels and
afterload while respecting physiological concerns for cerebral
perfusion. Future directions include increased tailoring of
medications and endpoints to measured effects on cerebral
perfusion and patient phenotypes.
Emergent treatment is largely blind to the effect on ce-
rebral blood flow. Methods of monitoring cerebral blood
flow in the acute setting have largely been reserved to
research and rarely implemented to guide antihypertensive
therapy. Advances in non-invasive methods of measuring
cerebral flow may change clinician monitoring towards in-
dividualized therapy (Table 2). Two categories of cerebral
monitors available for bedside clinical use are of note.
First, transcranial Doppler (TCD) has been available for
many years. Through insonation of the middle cerebral ar-
teries, one can track changes in flow velocity as an indica-
tor of cerebral flow [48]. Hence, it is feasible to test if a
patient has experienced significant drops in cerebral flow
due to antihypertensive medications. The primary limitation
of TCD monitoring is the difficulty obtaining adequate sig-
nals and maintaining these signals for repeat measurements.
43 Page 6 of 8 Curr Hypertens Rep (2016) 18:43

Table 2 Non-invasive methods

of assessing continuous cerebral
flow
Method Advantages
Transcranial Doppler Bedside, dynamic flow velocity
measurements
Near-infrared spectroscopy Local cerebral oxygen saturation
measurement, bedside, dynamic
UTLightTM Local cerebral perfusion
measurement, bedside, dynamic
Diffusion correlation Local cerebral perfusion
spectroscopy measurement, dynamic, beside
Limitations
Only measures large vessel flow,
not obtainable in approximately
15 % of patients
Only measures near surface oxygen
saturation, skin interference can
decrease fidelity of measurements,
minimal clinical validation
Only measures near surface, ultrasound
tagging of near-infrared light improves
fidelity of cerebral measurement,
minimal clinical validation
Local, near surface measurements, not
yet commercially available

In addition, approximately 10 to 15 % of patients will not
have adequate temporal windows for insonation.
Second, near-infrared spectroscopy is currently available
for cerebral perfusion monitoring [49, 50]. First genera-
tion near-infrared spectroscopy measures perfusion in
the frontal lobes proximal to the skull. Perfusion measure-
ments correlate well with classical methods of measuring cere-
bral perfusion, but interference can occur due to changes in skin
perfusion. Later generation spectroscopy combines near-
infrared spectroscopy with ultrasound (UTLight) to pinpoint
measurements from the frontal lobes proximal to the skull and
may reduce interference of skin perfusion change [51]. The
primary advantage of these devices is ease of placement and
allowance for continuous bedside monitoring. The main disad-
vantage is the limitation to monitoring perfusion of the frontal
lobes. Future development in this area may allow for accurate
bedside monitoring of the cerebrovascular effects of blood pres-
sure reduction.
In addition to individual attention to cerebral physiology,
improved systemic physiological profiling is currently
possible. Non-invasive devices such as arterial wave-
form analysis, impedance cardiography, and bedside
echocardiography allow for more precise assessment of
the effects of acute blood pressure lowering beyond
measurements of blood pressure alone. Individual re-
sponse of systemic vascular resistance and cardiac out-
put is accessible for tailored therapy. Whereas beta-
blocker agents may be more appropriate for a hyperdynamic
heart discovered by bedside monitoring, vasodilators may be
more appropriate for those with low cardiac output and high
systemic vascular resistance that would not otherwise be rec-
ognized. Lastly, genomic and proteomic profiling in hyperten-
sion is in its infancy, but may define patient phenotypes that
have differing responses to certain antihypertensive agents
[52].
These and other key issues will drive emergency care re-
search in hypertensive emergencies. The success of
endovascular stroke trials raises the question of what the op-
timal blood pressure goal should be in ischemic stroke patients
undergoing endovascular treatment [28]. A role for nitrates in
hyperacute ischemic stroke treatment is also being investigat-
ed [53]. In heart failure, new vasodilatory agents, such as
seralaxin, are currently being tested and may alter our ap-
proach to hypertensive heart failure patients [54].
Case Review
Current guidelines for acute ischemic stroke management call
for a systolic blood pressure <185 mmHg in patients under-
going endovascular interventions or receiving thrombolysis.
Hence, it is appropriate to acutely reduce the blood pressure in
this patient with a blood pressure of 225/124. Available med-
ications to accomplish a goal systolic blood pressure
<185 mmHg include labetalol, nicardipine, and clevidipine.
This patient received a continuous infusion of nicardipine and
was maintained at a systolic blood pressure of 175 throughout
transport to receive endovascular care.
Conclusions
Acute reduction of blood pressure is reserved for a small but
critically ill cohort of patients. Treatment is aimed at balancing
the risk of ongoing arterial wall stress with the risk of hypo-
perfusion, especially in the cerebral circulation. Although fu-
ture management may incorporate technology to monitor ce-
rebral effects, current approaches empirically accounts for the
risk of cerebral hypoperfusion by focusing on a maximal de-
crease in MAP of 10–20 %. While a number of agents are
available to acutely lower blood pressure, newer calcium
channel blockers are frequently seen as the Bgo-to^ class for
this purpose.
Curr Hypertens Rep (2016) 18:43
Compliance with Ethical Standard
Conflict of Interest Drs. Kinni and Amer declare no conflicts of inter-
est. Dr. Miller declares personal fees from The Medicines Company. Dr.
Levy declares personal fees and non-financial support from The
Medicines Company and Chiesi USA.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
References
Papers of particular interest, published recently, have been
highlighted as:
• of importance
1. Inscho EW, Lewis K. Dahl Memorial Lecture. Mysteries of renal
autoregulation. Hypertension. 2009;53(2):299–306. doi:10.1161/
HYPERTENSIONAHA.108.119982.
2. Ono M, Arnaoutakis GJ, Fine DM, Brady K, Easley RB, Zheng Y,
et al. Blood pressure excursions below the cerebral autoregulation
threshold during cardiac surgery are associated with acute kidney
injury. Crit Care Med. 2013;41(2):464–71. doi:10.1097/CCM.
0b013e31826ab3a1.
3. Paulson OB, Waldemar G, Schmidt JF, Strandgaard S. Cerebral
circulation under normal and pathologic conditions. Am J
Cardiol. 1989;63(6):2C–5C.
4.• Faraco G, Iadecola C. Hypertension: a harbinger of stroke and de-
mentia. Hypertension. 2013;62(5):810–7. doi:10.1161/
HYPERTENSIONAHA.113.01063. This manuscript provides a
succinct and current review of the cerebrovascular changes
induced by chronic hypertension.
5. Strandgaard S. Autoregulation of cerebral circulation in hyperten-
sion. Acta Neurol Scand Suppl. 1978;66:1–82.
6. Perez MI, Musini VM. Pharmacological interventions for hyperten-
sive emergencies: a Cochrane systematic review. Journal of human
hypertension. 2008;22(9):596–607. doi:10.1038/jhh.2008.25.
7. Keating GM. Clevidipine: a review of its use for managing blood
pressure in perioperative and intensive care settings. Drugs.
2014;74(16):1947–60. doi:10.1007/s40265-014-0313-6.
8. Qureshi AI, Palesch YY. Antihypertensive Treatment of Acute
Cerebral Hemorrhage (ATACH) II: design, methods, and rationale.
Neurocrit Care. 2011;15(3):559–76. doi:10.1007/s12028-011-
9538-3.
9. Graffagnino C, Bergese S, Love J, Schneider D, Lazaridis C,
LaPointe M, et al. Clevidipine rapidly and safely reduces blood
pressure in acute intracerebral hemorrhage: the ACCELERATE
trial. Cerebrovascular diseases. 2013;36(3):173–80. doi:10.1159/
000351149.
10. Varelas PN, Abdelhak T, Corry JJ, James E, Rehman MF, Schultz
L, et al. Clevidipine for acute hypertension in patients with sub-
arachnoid hemorrhage: a pilot study. The International journal of
neuroscience. 2014;124(3):192–8. doi:10.3109/00207454.2013.
836703.
11. Jauch EC, Saver JL, Adams Jr HP, Bruno A, Connors JJ,
Demaerschalk BM, et al. Guidelines for the early management of
patients with acute ischemic stroke: a guideline for healthcare pro-
fessionals from the American Heart Association/American Stroke
Page 7 of 8 43
Association. Stroke. 2013;44(3):870–947. doi:10.1161/STR.
0b013e318284056a.
12. Hottinger DG, Beebe DS, Kozhimannil T, Prielipp RC, Belani KG.
Sodium nitroprusside in 2014: a clinical concepts review. J
Anaesthesiol Clin Pharmacol. 2014;30(4):462–71. doi:10.4103/
0970-9185.142799.
13. Cohn JN, McInnes GT, Shepherd AM. Direct-acting vasodilators.
Journal of clinical hypertension. 2011;13(9):690–2. doi:10.1111/j.
1751-7176.2011.00507.x.
14. Kandler MR, Mah GT, Tejani AM, Stabler SN, Salzwedel DM.
Hydralazine for essential hypertension. The Cochrane database of
systematic reviews. 2011;11:CD004934. doi:10.1002/14651858.
CD004934.pub4.
15. Frishman WH, Saunders E. Beta-adrenergic blockers. Journal of
clinical hypertension. 2011;13(9):649–53. doi:10.1111/j.1751-
7176.2011.00515.x.
16. Sladen RN, Klamerus KJ, Swafford MW, Prough DS, Mann HJ,
Leslie JB, et al. Labetalol for the control of elevated blood pressure
following coronary artery bypass grafting. Journal of cardiothoracic
anesthesia. 1990;4(2):210–21.
17. Hirschl MM, Binder M, Bur A, Herkner H, Brunner M, Mullner M,
et al. Clinical evaluation of different doses of intravenous
enalaprilat in patients with hypertensive crises. Arch Intern Med.
1995;155(20):2217–23.
18. Salgado DR, Silva E, Vincent JL. Control of hypertension in the
critically ill: a pathophysiological approach. Ann Intensive Care.
2013;3(1):17. doi:10.1186/2110-5820-3-17.
19. Elliott WJ. Clinical features in the management of selected hyper-
tensive emergencies. Prog Cardiovasc Dis. 2006;48(5):316–25.
doi:10.1016/j.pcad.2006.02.004.
20. Tsai TT, Nienaber CA, Eagle KA. Acute aortic syndromes.
C i r c u l a t i o n . 2 0 0 5 ; 11 2 ( 2 4 ) : 3 8 0 2 – 1 3 . d o i : 1 0 . 11 6 1 /
CIRCULATIONAHA.105.534198.
21. Kim KH, Moon IS, Park JS, Koh YB, Ahn H. Nicardipine hydro-
chloride injectable phase IV open-label clinical trial: study on the
anti-hypertensive effect and safety of nicardipine for acute aortic
dissection. J Int Med Res. 2002;30(3):337–45.
22. Viau DM, Sala-Mercado JA, Spranger MD, O’Leary DS, Levy PD.
The pathophysiology of hypertensive acute heart failure. Heart.
2015;101(23):1861–7. doi:10.1136/heartjnl-2015-307461.
23. Peacock WF, Chandra A, Char D, Collins S, Der Sahakian G, Ding
L, et al. Clevidipine in acute heart failure: results of the A Study of
Blood Pressure Control in Acute Heart Failure—a Pilot Study
(PRONTO). Am Heart J. 2014;167(4):529–36. doi:10.1016/j.ahj.
2013.12.023.
24. Weintraub NL, Collins SP, Pang PS, Levy PD, Anderson AS,
Arslanian-Engoren C, et al. Acute heart failure syndromes: emer-
gency department presentation, treatment, and disposition: current
approaches and future aims: a scientific statement from the
American Heart Association. Circulation. 2010;122(19):1975–96.
doi:10.1161/CIR.0b013e3181f9a223.
25. Wakai A, McCabe A, Kidney R, Brooks SC, Seupaul RA, Diercks
DB, et al. Nitrates for acute heart failure syndromes. The Cochrane
database of systematic reviews. 2013;8:CD005151. doi:10.1002/
14651858.CD005151.pub2.
26. Levy P, Compton S, Welch R, Delgado G, Jennett A, Penugonda N,
et al. Treatment of severe decompensated heart failure with high-
dose intravenous nitroglycerin: a feasibility and outcome analysis.
Ann Emerg Med. 2007;50(2):144–52. doi:10.1016/j.
annemergmed.2007.02.022.
27. Beltrame JF, Zeitz CJ, Unger SA, Brennan RJ, Hunt A, Moran JL,
et al. Nitrate therapy is an alternative to furosemide/morphine ther-
apy in the management of acute cardiogenic pulmonary edema.
Journal of cardiac failure. 1998;4(4):271–9.
28. Cotter G, Metzkor E, Kaluski E, Faigenberg Z, Miller R, Simovitz
A, et al. Randomised trial of high-dose isosorbide dinitrate plus
43 Page 8 of 8
low-dose furosemide versus high-dose furosemide plus low-dose
isosorbide dinitrate in severe pulmonary oedema. Lancet.
1998;351(9100):389–93. doi:10.1016/S0140-6736(97)08417-1.
29. Alexander P, Alkhawam L, Curry J, Levy P, Pang PS, Storrow AB,
et al. Lack of evidence for intravenous vasodilators in ED patients
with acute heart failure: a systematic review. Am J Emerg Med.
2015;33(2):133–41. doi:10.1016/j.ajem.2014.09.009.
30. American College of Obstetricians and Gynecologists, Task Force
on Hypertension in Pregnancy. Hypertension in pregnancy. Report
of the American College of Obstetricians and Gynecologists’ Task
Force on Hypertension in Pregnancy. Obstet Gynecol. 2013;122(5):
1122–31. doi:10.1097/01.AOG.0000437382.03963.88.
31. Al Khaja KA, Sequeira RP, Alkhaja AK, Damanhori AH. Drug
treatment of hypertension in pregnancy: a critical review of adult
guideline recommendations. J Hypertens. 2014;32(3):454–63. doi:
10.1097/HJH.0000000000000069.
32. Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P.
Hydralazine for treatment of severe hypertension in pregnancy:
meta-analysis. BMJ. 2003;327(7421):955–60. doi:10.1136/bmj.
327.7421.955.
33. Olson-Chen C, Seligman NS. Hypertensive emergencies in preg-
nancy. Crit Care Clin. 2016;32(1):29–41. doi:10.1016/j.ccc.2015.
08.006.
34.• Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, et
al. Rapid blood-pressure lowering in patients with acute intracere-
bral hemorrhage. N Engl J Med. 2013;368(25):2355–65. doi:10.
1056/NEJMoa1214609. This study was the largest study ever
performed to test blood pressure targets in intracerebral
hemorrhage.
35.• Wang X, Arima H, Heeley E, Delcourt C, Huang Y, Wang J, et al.
Magnitude of blood pressure reduction and clinical outcomes in
acute intracerebral hemorrhage: intensive blood pressure reduction
in acute cerebral hemorrhage trial study. Hypertension. 2015;65(5):
1026–32. doi:10.1161/HYPERTENSIONAHA.114.05044.
Important secondary analysis from the largest intracerebral
hemorrhage study ever published with evidence of efficacy for
early and significant blood pressure reduction.
36. Hemphill 3rd JC, Greenberg SM, Anderson CS, Becker K, Bendok
BR, Cushman M, et al. Guidelines for the management of sponta-
neous intracerebral hemorrhage: a guideline for healthcare profes-
sionals from the American Heart Association/American Stroke
Association. Stroke. 2015;46(7):2032–60. doi:10.1161/STR.
0000000000000069.
37. Morgenstern LB, Hemphill 3rd JC, Anderson C, Becker K,
Broderick JP, Connolly Jr ES, et al. Guidelines for the management
of spontaneous intracerebral hemorrhage: a guideline for healthcare
professionals from the American Heart Association/American
Stroke Association. Stroke. 2010;41(9):2108–29. doi:10.1161/
STR.0b013e3181ec611b.
38.• Miller J, Kinni H, Lewandowski C, Nowak R, Levy P. Management
of hypertension in stroke. Ann Emerg Med. 2014;64(3):248–55.
doi:10.1016/j.annemergmed.2014.03.004. This review article on
the management of hypertension in stroke expands
significantly upon the discussion in this article, including
analysis of the literature supporting current guidelines for
blood pressure control in ischemic and hemorrhagic stroke.
39. Fisher M, Bastan B. Identifying and utilizing the ischemic penum-
bra. Neurology. 2012;79(13 Suppl 1):S79–85. doi:10.1212/WNL.
0b013e3182695814.
40. Strandgaard S, Paulson OB. Regulation of cerebral blood flow in
health and disease. J Cardiovasc Pharmacol. 1992;19 Suppl 6:S89–93.
41. Zazulia AR, Diringer MN, Videen TO, Adams RE, Yundt K,
Aiyagari V, et al. Hypoperfusion without ischemia surrounding
Curr Hypertens Rep (2016) 18:43
acute intracerebral hemorrhage. J Cereb Blood Flow Metab.
2001;21(7):804–10. doi:10.1097/00004647-200107000-00005.
42. Powers WJ, Zazulia AR, Videen TO, Adams RE, Yundt KD,
Aiyagari V, et al. Autoregulation of cerebral blood flow surround-
ing acute (6 to 22 hours) intracerebral hemorrhage. Neurology.
2001;57(1):18–24.
43. He J, Zhang Y, Xu T, Zhao Q, Wang D, Chen CS, et al. Effects of
immediate blood pressure reduction on death and major disability in
patients with acute ischemic stroke: the CATIS randomized clinical
trial. JAMA. 2014;311(5):479–89. doi:10.1001/jama.2013.282543.
44. Sandset EC, Bath PM, Boysen G, Jatuzis D, Korv J, Luders S, et al.
The angiotensin-receptor blocker candesartan for treatment of acute
stroke (SCAST): a randomised, placebo-controlled, double-blind
trial. Lancet. 2011;377(9767):741–50. doi:10.1016/S0140-
6736(11)60104-9.
45. Wang H, Tang Y, Rong X, Li H, Pan R, Wang Y, et al. Effects of
early blood pressure lowering on early and long-term outcomes
after acute stroke: an updated meta-analysis. PloS one. 2014;9(5):
e97917. doi:10.1371/journal.pone.0097917.
46. Connolly Jr ES, Rabinstein AA, Carhuapoma JR, Derdeyn CP,
Dion J, Higashida RT, et al. Guidelines for the management of
aneurysmal subarachnoid hemorrhage: a guideline for healthcare
professionals from the American Heart Association/american
Stroke Association. Stroke. 2012;43(6):1711–37. doi:10.1161/
STR.0b013e3182587839.
47. Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC, et
al. Cerebral arterial spasm—a controlled trial of nimodipine in pa-
tients with subarachnoid hemorrhage. N Engl J Med. 1983;308(11):
619–24. doi:10.1056/NEJM198303173081103.
48. Panerai RB. Transcranial Doppler for evaluation of cerebral auto-
regulation. Clin Auton Res. 2009;19(4):197–211. doi:10.1007/
s10286-009-0011-8.
49. Mazzeo AT, Di Pasquale R, Settineri N, Bottari G, Granata F,
Farago G, et al. Usefulness and limits of near infrared spectroscopy
monitoring during endovascular neuroradiologic procedures.
Minerva Anestesiol. 2012;78(1):34–45.
50. Moerman A, De Hert S. Cerebral oximetry: the standard monitor of
the future? Curr Opin Anaesthesiol. 2015;28(6):703–9. doi:10.
1097/ACO.0000000000000256.
51. Schytz HW, Guo S, Jensen LT, Kamar M, Nini A, Gress DR, et al.
A new technology for detecting cerebral blood flow: a comparative
study of ultrasound tagged NIRS and 133Xe-SPECT. Neurocrit
Care. 2012;17(1):139–45. doi:10.1007/s12028-012-9720-2.
52. Kotchen TA, Cowley Jr AW, Liang M. Ushering hypertension into
a new era of precision medicine. JAMA. 2016;315(4):343–4. doi:
10.1001/jama.2015.18359.
53. Ankolekar S, Fuller M, Cross I, Renton C, Cox P, Sprigg N, et al.
Feasibility of an ambulance-based stroke trial, and safety of glyc-
eryl trinitrate in ultra-acute stroke: the rapid intervention with glyc-
eryl trinitrate in Hypertensive Stroke Trial (RIGHT,
ISRCTN66434824). Stroke. 2013;44(11):3120–8. doi:10.1161/
STROKEAHA.113.001301.
54. Wilson SS, Ayaz SI, Levy PD. Relaxin: a novel agent for the treat-
ment of acute heart failure. Pharmacotherapy. 2015;35(3):315–27.
doi:10.1002/phar.1548.
55. Adebayo O, Rogers RL. Hypertensive emergencies in the emergen-
cy department. Emerg Med Clin North Am. 2015;33(3):539–51.
doi:10.1016/j.emc.2015.04.005.
56. Varon J. Treatment of acute severe hypertension: current and newer
agents. Drugs. 2008;68(3):283–97.
57. Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet.
2000;356(9227):411–7. doi:10.1016/S0140-6736(00)02539-3.