Acute Severe Arterial Hypertension Current Drug Targets, 2009, Vol. 10, No. 8 789
Table 2. Causes of Secondary Hypertension increase in CO (Fig. 1) . Chronic adrenergic stimulation
induces vascular remodelling and smooth muscular cells
• Autonomic hyperactivity (spinal cord injury, Guillain-Barré proliferation, thus increasing diastolic pressure, while arterial
syndrome, diabetes mellitus) vessels thicken and stiffen due to lipid, calcium and collagen
accumulation and deposition in vascular walls .
• Intracranial hypertension and brain edema
Moreover, chronically increased vascular tone leads to
• Pheochromocytoma increased myocardial mass (e.g., left ventricular hypertro-
• Tumors secreting renin or aldosterone phy) and oxygen consumption, which in turn can lead to
• Eclampsia and preeclampsia chronic ischemia or acute myocardial infarction. At renal
level, increased sympathetic activity enhances sodium and
• Vasculitis and scleroderma
water retention, further contributing to maintain elevated
• Parenchymal renal disease (e.g., acute glomerulonephritis) blood pressure.
• Renal vascular disease (e.g., renal artery stenosis or thrombosis)
• Drugs (e.g., cocaine, amphetamine, phencyclidine)
• Drug interaction (e.g., monoamine oxydase inhibitor with The RAA system greatly influences cardiovascular
tyramine, tryciclics antidepressants or sympathomimetics) homeostasis (Fig. 2). Angiotensin II (AT-II) acts as direct
vasoconstrictor on systemic and renal vessels, thus
• Abrupt withdrawal of anti-hypertensive drugs (e.g., clonidine)
contributing to initiate and maintain elevated blood pressure.
• Alcohol withdrawal Moreover, AT-II stimulates adrenaline and noradrenaline
release at pre-synaptic level. It also contributes to left
Sympathetic Activity ventricular hypertrophy and myocardial ischemia through
increased left ventricular wall tension. On renal vessels, AT-
Noradrenaline and adrenaline, either from sympathetic
II-induces alterations of arterial and capillary walls and leads
neurons or epirenal medullar cells, interact with peripheral
to progressive glomerular ischemia, parenchymal damage,
smooth cell- 1 adrenergic receptors increasing vascular tone
proteinuria and end-stage renal failure . AT-II stimulates
at pre-capillary level. They also increase heart rate and
aldosterone and antidiuretic hormone release, which both
contractility through interaction with cardiac- 1 adrenergic
contribute to hypervolemia and hypertension. This condition
receptors. The net effect of sympathetic stimulation is an
Increases Increases Induces
vascular tone at sodium and vascular
precapillary water remodelling
contractility level reabsorption
Vasoconstriction Increased left Increase
Increase increasing ventricular diastolic
cardiac output peripheral vascular hypertrofy and pressure
Fig. (1). Effect of increased sympathetic activity cardiovascular homeostasis.
790 Current Drug Targets, 2009, Vol. 10, No. 8 De Gaudio et al.
Vasoconstriction Alteration of renal
on systemic and arterial and capillary
renal vassels vessels’ wall
Increase left Glomeruar ischemia, Sodium and
ventricular wall parenchymal damage, water renal
tension proteinuria, end-stage retention
Left ventricular hypervolemia
ischemia Increase BP
Fig. (2). Effect of renin-angiotensin system on cardiovascular homeostasis.
contributes to myocardial remodelling and cell fibrosis. increase of blood pressure raises shear stress on arteriolar
Aldosterone leads to increased sodium and water renal and capillary vessels and leads to endothelial inflammation
retention, with hypokalemia and metabolic alkalosis . and fibrosis with altered permeability . In sustained
Hyperaldosteronism “per se” promotes renal vessel inflam- crisis, endothelial damage occurs, and coagulation cascade
mation and fibrosis, leading to microvascular renal injury activates . This can further impair tissue hypoperfusion
[11, 12]. Furthermore, during hypertensive crisis, abrupt and precipitate acute organ damage.
increase in renal vessels shear forces leads to reflex
glomerular capillary constriction and renal hypoperfusion End-Organ Damage in Hypertensive Crisis
which, in turn, can be responsible for a further increase of
Hypertensive associated end-organ damage can be the
RAA system activity with sudden worsening of renal acute complication of chronic hypertension or the clinical
manifestation of a hypertensive emergency (Table 3).
Endothelial Function Table 3. End Organ Damage in Arterial Hypertension
Vascular endothelium plays a role in regulating
• Hypertensive encephalopathy
microvascular tone (Fig. 3). Nitric oxide exhibits
vasodilating activity, while endothelin-1 is a powerful • Stroke
vasoconstrictor. In physiological condition the two effects • Subarachnoid and intraparenchymal haemorrhage
are well balanced. In hypertensive patients, increase in • Hypertensive retinopathy
arteriolar and capillary shear forces, due to peripheral • Myocardial ischemia
transmission of elevated blood pressure, leads to an
increased endothelin-1 release by the endothelium, with a
• Acute congestive heart failure and pulmonary oedema
progressive increase in vasoconstriction. The consequent
reduction in blood-oxygen supply can lead to tissue • Aortic dissection
hypoperfusion/ischemia and organ dysfunction . In insulin
resistant patients hyperinsulinemia inhibits endothelial nitric • Renal injury and chronic renal failure
oxide release thus leading to a predominant endothelin-1
effect . Vasoconstrictive endothelial tone might contri- • Eclampsia
bute to maintain high blood pressure and precipitate renal
injury . During hypertensive emergencies, an abrupt
Acute Severe Arterial Hypertension Current Drug Targets, 2009, Vol. 10, No. 8 791
Activation of coagulative
Endothelial Increased shear
inflammation forces on arterioles
and fibrosis and capillaries
Alterated vasocostrictive effect Hyperinsulinemia
Fig. (3). Effects of hyperinsulinemia on endothelial dysfunction.
Brain and Retina
Chronically elevated peripheral vascular resistance leads
Normotensive individuals maintain a normal cerebral
to increased left ventricular mass because of the increased
blood flow between mean arterial pressures (MAP) of 60 and
left wall tension . Aldosterone and angiotensin II can
120 mm Hg . A chronically high MAP induces cerebral
directly stimulate left ventricular hypertrophy and
microvascular thickening and stiffening, increasing cerebral
vascular resistance. Consequently hypertensive patients are remodelling. Thickening of the ventricular wall increases
myocardial oxygen consumption, limiting diastolic blood
more prone to suffer from cerebral hypoperfusion when
flow and myocardial oxygen delivery. These phenomena
blood pressure lowers . On the other hand, an abrupt
lead to a chronic myocardial ischemia, with progressive wor-
increase in blood pressure leads to elevated cerebral blood
sening of left ventricular function and deposition of inters-
flow and intracranial pressure, with consequent blood brain
titial collagen, with further impairment of myocardial oxy-
barrier disruption, fluid leakage and brain oedema [7, 18].
Clinical manifestation of such hypertensive encephalopathy gen delivery . Left ventricular hypertrophy can lead to
mitral regurgitation, left atrial dilatation and atrial fibrilla-
is an acute neurologic syndrome associated to severe hyper-
tion, which further reduce blood flow to the coronaries.
tension. Clinical manifestations include headache, nausea
During hypertensive crisis, a raise in myocardial serum
and vomiting which are associated to elevated blood
troponin-I is commonly observed as the result of impaired
pressure. If the syndrome is left untreated, confusion,
myocardial cells oxygen supply, even in absence of overt
delirium or seizures can manifest, and risk of stroke or
cerebral haemorrhage is high . On the retina, chronic ischemia or infarction . However, during acute crisis,
shear stress on coronary walls leads to intimal damage and
hypertension leads to arterial narrowing and intimal
accelerated atherosclerosis which can precipitate plaque
thickening. In hypertensive crisis, blood-retina disruption
rupture and intravascular thrombosis causing myocardial
occurs, with necrosis, retinal ischemia and optic disk oede-
infarction . Both left ventricular hypertension and
ma. Fundoscopic examination reveals haemorrhage, “cotton
myocardial ischemia lead to left ventricular failure and
wool spots” and papilledema .
congestive heart failure. In hypertensive crisis, the already
792 Current Drug Targets, 2009, Vol. 10, No. 8 De Gaudio et al.
failing left ventricle can be overcome by acutely increased of surgery and usually requires treatment for no more than 6
vascular resistance and acute congestive failure with pulmo- hours . Cardiothoracic, vascular, head and neck surgery
nary edema . Clinically, patients are hypoxic and crack- and neurosurgical procedures are most commonly involved
les are heard on chest auscultation, limbs can be cool as a . Perioperative neuro-hormonal stress response leading
sign of hypo-perfusion and oedematous as fluid overload to increased sympathetic tone is thought to be responsible
occurs . . Other involved factors include activation or RAA
system, baroreceptor dysfunction or withdrawal of central
Aorta acting antihypertensive therapies . Anaesthetic factors
include poorly controlled postoperative pain, hypothermia,
Untreated hypertension may lead to aortic dilation and
urinary distention and discontinuation of anaesthetic drugs.
intimal tearing, i.e. aortic dissection . Blood flows into
the aortic media and false and true aortic lumen become Postoperative crisis require aggressive treatment in case of
the fear of vascular suture leak and rupture [13, 30].
evident. Dissection can involve the ascending aorta
(proximal, type A of Stanford) or not (distal, type B of
Stanford) . In type A dissection, tearing can involve
carotid artery, with stroke and/or syncope as clinical Arterial hypertension without signs of acute organ
manifestations. Coronary arteries can be involved, and damage can be managed conservatively . Control of
myocardial infarction can be seen . If aortic rupture precipitating factors and wait for a progressive reduction of
occurs, massive intra - pericardial bleeding leads to cardiac blood pressure values is the more rational approach. In
tamponade, obstructive shock and cardiac arrest. When already hypertensive patients, reinitiating oral therapy may
aortic valve is involved in dissection, acute regurgitation can be the key to restore normal blood pressure. In the
lead to pulmonary edema and acute heart failure. In type B postoperative period, pain, anxiety, hypothermia, hypoxia,
dissection limbs ischemia or anuria can occur as a hypercapnia and hypoglycaemia have all to be ruled out and
consequence of involvement of aortic branch vessels . treated in order to control the hypertensive status that can be
associated to them . Because of the risk of organ
Kidneys hypoperfusion associated to the use of parenteral
hypotensive drugs, postoperative volume status should be
Acute glomerulonephritis, renal artery stenosis or
optimized before starting the intravenous therapy .
cyclosporine use in renal transplant patients, may lead to
arterial hypertension and hypertensive crisis . On the In the setting of hypertensive emergencies, when organ
other hand, kidneys are usually involved as target organs of damage is pending or actual, there is a general consensus that
chronic hypertensive status. Afferent arterioles of lowering blood pressure may limit damage [4, 13]. However,
hypertensive patients tend to progressively narrow in the even in this case, arterial pressure should be lowered slowly,
attempt of limiting overflow to glomerular capillaries. targeting a 20% reduction in mean arterial pressure over
Moreover, chronic stimulation from the adrenergic system several minutes-hours . To rapidly lower high blood
and AT-II leads to vessel wall thickening. Vessel structural pressure values, can be harmful in chronic hypertensive
changes are seen that lead to progressive reduction of patients, where autoregulation thresholds of the brain are
glomerular blood flow and filtration rate. Microalbuminuria higher than normotensive individuals. In this case, brain
is the landmark of progressive glomerular damage . End- hypoperfusion can complicate institution of anti-hyperten-
stage renal failure and need for dialysis may follow. sive therapy . Moreover, there is not enough evidence
Moreover, chronic glomerular ischemia stimulates renin that anti-hypertensive treatment reduces mortality or associa-
release and the consequent activation of the RAA system ted morbidity in hypertensive emergencies . The only
leads to further renal vasoconstriction and fluid retention, situation in which blood pressure should be quickly lowered,
thus maintaining and worsening hypertension . As auto - is aortic dissection, in order to reduce tearing forces on aortic
regulatory renal system is lost, glomerular blood flow starts wall, thus limiting the extension of dissection itself .
to vary directly with variations of systemic arterial pressure. Many different pharmacological options are available, and
At this point, any abrupt reduction in blood pressure may each patient should have the treatment tailored to the aim of
lead to acute renal failure. lowering blood pressure in a safe manner. Evidence in terms
of best drug and best infusion regimen is still lacking .
Preeclampsia and Eclampsia
Calcium Antagonists: Nicardipine and Clevidipine
The preeclamptic syndrome is characterized by hyperten-
sion associated to interstitial oedema and proteinuria, while Nicardipine is a second-generation dihydropyridine
in eclamptic syndrome, neurological signs, such as visual calcium-channel antagonist (Table 4). It shows high vascular
alterations and seizures, ensue [18, 25]. Altered trophoblast selectivity and a strong cerebral and coronary vasodilatory
implantation seems to initiate a cascade in which placental activity, with no negative inotropic properties. Nicardipine
vessels vasoconstriction induces a raise in peripheral reduces both cardiac and cerebral ischemia . Nicardipine
resistances, leading to hypertension. Moreover, endothelial increases stroke volume and coronary blood flow, thus
dysfunction, with activation of coagulative pathways and contributing to a better oxygen supply to the heart . This
inhibition of fibrinolisis, occurs as well . might be useful in patients suffering from coronary heart
diseases and congestive heart failure. Its use has been
Postoperative Arterial Hypertension advocated in hypertensive patients undergoing vascular
surgery, either abdominal, neuro- or cardiovascular .
Postoperative Arterial hypertension is defined as an
Moreover, it has been used to prevent cerebral vasospasm in
hypertensive crisis which occurs within 2 hours from the end
Acute Severe Arterial Hypertension Current Drug Targets, 2009, Vol. 10, No. 8 793
Table 4. Drugs Receptor Interaction and Mechanism of Action
Calcium Channel Alfa 1 Alfa 2 Beta 1 Beta 2 D1 5-HT NO
Antagonist Partial Agonist Antagonist Agonist
(+++) (++) (+) (++)
Agonist Agonist Agonist
(+++) (+) (+)
Antagonist Antagonist Antagonist
(+++) (+++) (+)
Antagonist Antagonist Antagonist Antagonist
(+++++++) (+++++++) (+) (+)
Antagonist Antagonist Agonist
(+) (+) (+++)
subarachnoid hemorrhage. Nicardipine has been recommen- advantage when treating patients suffering from ischemic
ded as agent of choice to reduce blood pressure in patients heart disease, in whom any reflex tachycardia can increase
with ischemic stroke when DBP > 120 mmHg or SBP > 220 myocardial oxygen consumption. Similarly, clevidipine was
mmHg . When administered intravenously, nicardipine’s found to reduce blood pressure without influencing cardiac
onset ranges from 5 to 15 minutes, and its action lasts index or filling pressures . The drug showed both a rapid
between 4 to 6 hours . Patient weight does not influence onset and offset in patients admitted to postoperative
nicardipine dose, which starts from 5mg/h, up to a 15 mg/h, intensive care. Authors concluded that clevidipine may be
with an increasing rate of 2.5 mg/h every 5 minutes (Table useful in treatment of acute postoperative hypertension. The
5). The main adverse effect is abrupt reduction in blood same results were found in the ECLIPSE trials on acute
pressure and reflex tachycardia, which can be harmful in hypertension treatment in cardiac surgery patients .
patients with coronary heart disease. Clevidipine showed to be more effective than nitroglycerin
(p=0.0006) and sodium nitroprusside (p=0.003) in maintai-
Clevidipine is a third-generation dihydropyridine calcium-
channel antagonist [4, 35] (Table 4). Acting as arteriolar ning a blood pressure target. Compared to nicardipine, it
showed the same efficacy, but more stability in terms of less
smooth muscle cells relaxant, clevidipine reduces peripheral
blood pressure excursions. No differences were found in the
vascular resistance. As a result, blood pressure lowers and
incidence of myocardial infarction, stroke or postoperative
cardiac output increases. Being metabolized by the esterases
of red blood cells, it exhibits an ultra short activity, with an
half life of about 2 minutes (Table 5). This makes
Alpha-Adreno Receptors Agonists and Antagonists:
clevidipine very suitable in those conditions when blood
Urapidil, Phentolamine and Clonidine
pressure needs to be tightly controlled, such as in intensive
care and perioperative care . Moreover, clevidipine Urapidil acts as a peripheral 1 post-synaptic receptor
exerts a protective role in ischemic tissues limiting antagonist and as a central 5-hydroxytryptamine receptor
reperfusion injury, either scavenging oxygen free radicals or agonist [4, 41] (Table 4). It induces a reduction in both
reducing intracellular calcium overflow toxicity . preload and afterload, thus lowering cardiac output and
Clevidipine is effective in reducing blood pressure in blood pressure, without reflex effects on heart rate (Table 5).
hypertensive crises in surgical and intensive care patients It is used to control hypertensive crisis either in surgical
and at the emergency department . In hypertensive patients or during pregnancy . Urapidil has been
patients scheduled for cardiac surgery, pre-operative compared to nitroprusside in its efficacy in reducing blood
clevidipine was given to control high blood pressure . It pressure during hypertensive emergencies . It showed to
showed to rapidly decrease blood pressure without be as effective as nitroprusside, with a slower effect and a
significant increases in heart rate (median of 6 minutes, CI lower incidence of adverse hypotensive events. In light of
95% 6-8 min.). This last effect must be taken as an this, Authors recommended its use in patients with
794 Current Drug Targets, 2009, Vol. 10, No. 8 De Gaudio et al.
Table 5. Antihypertensive Agents’ Synopsis
Drug Dynamic Dose Onset (min) Metabolism Offset Adverse Effects
5mg/h, up to a 15 mg/h, with 5-15
calcium-channel abrupt reduction in blood pressure
Nicardipina an increasing rate of 2.5 hepatic 4-6 h
antagonist and reflex tachycardia
mg/h every 5 minutes
0.4 g/kg/min doubling 1-2 esterases of
Clevidipine every 90 seconds to a red blood 5-15 min
maximum of 8 g/kg/min cells
peripheral 1 post-
bolus of 10-50 mg or 2 2-5
Urapidil mg/min titrated up to 9 hepatic 1-2 h hypotension, cardiac arrhythmias
antagonist and central
5HT receptor agonist
tachyphylaxis, reflex thachycardia,
-1 and -2 2-5 mg 1-2 hours before an increase of circulating levels of
Phentolamine adrenoreceptors pheochromocytoma surgery 1-2 hepatic 15-30 min noradrenaline cardiac arrhythmias,
antagonist repeating if necessary ischemic cardiac events abdominal
Clonidine starting at 0.2 mg/kg/min
2-adrenergic receptors bradycardia and hypotension, dry
and titrated up to a 5-10 hepatic 6-8 h
agonist mouth and sedation
maximum of 0.5 mg/kg/min
initial dose of 20 mg,20-80
1-adrenergic and mg can follow every 10
nonselective - minutes. Continuous
Labetalol 2-5 hepatic 2-4 h bradycardia and bronchospasm
adrenergic blocking infusion starting at 1-2
agent mg/hrs after the loading dose
bolus of 0.5 to 1 mg/kg
followed by a
1-adrenergic red blood
continuous infusion starting
Esmolol 1 cells 10-20 min bradycardia and bronchospasm
blocking agent at 50 g/kg/min and titrated
to 300 g/kg/min
5 g/min, titrated by 5 hypotension, tachycardia,
Nitroglycerine NO donors g/min every 5-10 min to 2-5 hepatich 10-20 min hypoxemia , tachyphylaxis and
maximum of 60 g/min headache
starting at 0.5 g/kg/min, cyanide toxicity
Sodium breaken down
NO donors and titrated up to a <1 1-2 min
Nitroprusside in erythrocyte
maximum of 2 g/kg/min
dopamine-1 receptor starting dose of 0.1
Fenoldopam 5 hepatic 40 min pressure,tachycardia, hypotension
cerebrovascular and cardiovascular diseases, in whom a drug. Phentolamine can be used for short-term control of
gradual and cautious reduction of blood pressure is hypertension in patients with Pheochromocytoma . To
indicated. Urapidil-mediated 1-block proved to be useful in control high blood pressure, 5 mg of the drug are injected
patients undergoing laparoscopic surgery for pheocromo- intravenously 1 or 2 hours before surgery and repeated if
cytoma. The drug prevented cathecolaminergic crises during necessary (Table 5). Tachyphylaxis, reflex thachycardia and
gland manipulation and resection . Urapidil use is an increase in circulating levels of noradrenaline counter
contraindicated in aortic stenosis . indicate its use for prolonged blood pressure control in peri-
Phentolamine is a competitive receptor antagonist that operative period .
shows affinity for both -1 and -2 adreno-receptors (Table Rapid infusions of phentolamine may cause severe
4). It exerts also an 5-HT and K+ channels blocking effect. hypotension, and the drug should be administered cautiously.
Phentolamine has an half-life of 19 minutes following In addition, reflex cardiac stimulation may cause alarming
intravenuos administration and approximately 13 % of a tachycardia, cardiac arrhythmias, and ischemic cardiac
single intravenous dose appears in the urine as unchanged events, including myocardial infarction. GI stimulation may
Acute Severe Arterial Hypertension Current Drug Targets, 2009, Vol. 10, No. 8 795
result in abdominal pain, nausea, and exacerbation of peptic Due to the rapid onset and offset, esmolol is considered as
ulcer. the anti-hypertensive of choice in intensive care and
postoperatively, when a tight control on blood pressure has
Clonidine is a direct and selective agonist of 2-
to be kept . This hemodynamic stabilizing effect was
adrenergic receptors (Table 4). Intravenous administration of
clonidine leads to an acute and transient elevation in blood recently evidenced in neurosurgical patients treated with
esmolol during emergence from general anesthesia .
pressure, due to peripheral post-sinaptic 2-adrenergic
Authors found that a loading dose of the drug followed by a
stimulation . However this effects is followed by a
continuous infusion, effectively treated tachycardia and
prolonged hypotensive effect which is related to its
hypertension (p<0.05). The same effect has been observed
adrenergic stimulation on brain stem receptors. Both heart
during endotracheal intubation or skin incision, when
rate and contractility are reduced by clonidine. Secondary
effects are linked to excessive sympathetic block, such as esmolol can prevent any raise in intracranial pressure
associated to excessive adrenergic stimulation . A
bradycardia and hypotension (Table 5). Clonidine exerts
“myocardial sparing effect” has been observed in brain dead
analgesic and sedative effects . Those combined effects
organ donors, in whom esmolol can be used to avoid the
make clonidine useful in controlling the postoperative
effect of associated “autonomic storm” .
hypertension associated to pain and agitation . Moreover
it has shown to reduce anesthetic requirements both in non As an antiarrhythmic drug, esmolol has been employed to
cardiac and cardiac surgery [48, 49]. Clonidine infusion reduce heart rate in supraventricular tachyarrhtymias 
leads to hemodynamic stability due to the sympathetic block and its use has been recommended particularly in decreasing
and it seems to reduce perioperative cardiac risk for patients ventricular rate in high rate atrial fibrillation in post-CABG
undergoing non cardiac surgery . Interestingly, patients patients .
undergoing regional anesthesia for carotid endoarterectomy
Perioperatively, esmolol infusion contributes to a better
treated with clonidine had a significantly reduced cortisol, pain control, reducing opioid requirements. Recently, it has
epinephrine and norepinephrine plasma concentration
been used as a continuous infusion in hypertensive patients
(p<0.05) . Same results were observed in hypertensive
undergoing laparoscopic cholecystectomy . In this trial,
patients undergoing general anesthesia for major vascular
Authors found that esmolol exerted an opiod-sparing effect,
surgery , in whom clonidine showed to reduce anesthetic
both intraoperatively (p=0.001) and post-operatively
requirements and plasma level of adrenergic stress
(p=0.012). Esomolol is administered as a slow (one minute
mediators. This blunt in adrenergic response to surgical long) bolus of 0.5 to 1 mg/kg, followed by a continuous
stress, might be helpful when managing peri-operative
infusion starting at 50 g/kg/min and titrated up to 300
g/kg/min, targeting a desired blood pressure . As with
labetalol, bradycardia and bronchospasm may follow its
Beta-Blockers: Labetalol and Esmolol
administration, and its use in congestive heart failure must be
Labetalol is a -blocker with selective 1 -adrenergic and judicious .
nonselective -adrenergic blocking activity, with a / -
blocking ratio of 1:7  (Table 4). Following intravenous Nitroglycerin
administration, labetalol exerts its effects in 2-5 minutes,
Nitroglycerin is a venous dilator which reduces dilate
peaking at 5-15 minutes and lasting 2-4 hrs (Table 5). Reflex
arterioles only at high doses  (Table 4). It reduces blood
tachycardia is blunt by the -blocking effect, and heart rate
pressure reducing preload and, thus, cardiac output.
can also be slightly reduced . Labetalol reduces the Nitroglycerin onset starts in 2-5 minutes after administration,
systemic vascular resistance without, thus increasing cardiac
and lasts 10-20 minutes after withdrawal [4, 53]. Its
output. Moreover, it maintains cerebral, renal, and coronary
elimination is hepatic (Table 5). When administered to
blood flow . Its use is safe in pregnancy, due to little
volume depleted patients (e.g., postoperative patients),
placental transfers . Labetalol is administered as an
Nitroglycerin tends to cause hypotension and reflex
initial dose of 20 mg. Next doses of 20-80 mg can follow
tachycardia, particularly harmful in the setting of coronary
every ten minutes, targeting a desired BP. Continuous heart disease . Moreover, reduction of cardiac output can
infusion is suitable as well, starting at 1-2 mg/hr after the
impair peripheral blood flow, particularly to kidneys and
loading dose of 20 mg, and titrating it to the desired blood
brain. Due to its potential detrimental effects, use of
pressure values [4, 53]. Adverse effects include bradycardia
nitroglycerin in critical care patients must be cautious, and a
and bronchospasm, while caution must be used in treating
low-dose administration is advised only in patients with
patients with congestive heart failure to avoid acute heart
hypertensive emergencies associated with acute coronary
failure . syndromes or acute pulmonary edema . Dosing regimens
Esmolol is cardioselective, -adrenergic blocking agent start at 5 g/min, titrated by 5 g/min every 5-10 min to
(Table 4). Following its administration, the effect starts maximum of 60 g/min . Adverse effect include
within one minute and lasts up to 10-20 minutes  Table hypotension and tachycardia, hypoxemia due to ventilation-
5. Esmolol reduces blood pressure reducing heart rate and perfusion mismatch (it blunts hypoxemic vasoconstriction in
myocardial contractility, thus reducing cardiac output. lungs), tachyphylaxis and headache.
However, peripheral blood flow is maintained. Esmolol
exerts no vasodilating effect . Being metabolized by the Sodium Nitroprusside
red blood cells esterases, its elimination is not dependant on
Sodium nitroprusside acts as arterial and venous
hepatic or renal function. However, any reduction in the
vasodilator, decreasing cardiac after-load and preload [4, 64]
number of circulating red cells might prolong its half-life.
(Table 4). Nitroprusside is a very effective anti-hypertensive
796 Current Drug Targets, 2009, Vol. 10, No. 8 De Gaudio et al.
agent. Its effect begins seconds after starting the intravenous reducing blood pressure while maintaining organ blood flow,
infusion and lasts for 1-2 minutes after its withdrawal. e.g., avoiding coronary, brain or renal hypo-perfusion. In
Nitroprusside use should be limited to manage very severe order to do so, many different agents are suitable, and
hypertensive crisis, starting as an infusion rate of 0.5 therapeutic strategies must be undertaken considering both
g/kg/min, and up to a maximum of 2 g/kg/min [4, 18] severity of the crisis and clinical features of the single
Table 5. Due to its direct vasodilatory effects, nitroprusside patients. Faster agents, like clevidipine, might be of
tends to decrease peripheral blood flow to tissues. This effect particular benefit when arterial pressure control must be
may be detrimental in coronary heart disease, where a “steal” achieved quickly.
of blood can occur from ischemic to healthy myocardium
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Received: March 28, 2009 Revised: March 31, 2009 Accepted: March 31, 2009