Emergency care and patient management

tactics with various types of hypertensive

crisis. A doctor’s tactic. Applied
therapeutic drugs, their mechanism of
action, side effects, formulation.
Made by 531-B’s:
- Lorraine Shose David Maimu
- Ezzine Youssef Abderahmen
- Fouad Maher Salem AL Marshoud
Hypertensive Crisis
Hypertensive urgencies can be defined as severe elevations in BP that do not exhibit
evidence of target-organ (cardiovascular, renal, CNS) dysfunction or damage.
Urgencies can be managed by the administration of oral medications, most often in
the emergency department (ED), and follow-up on an outpatient basis. Hypertensive
emergencies are severe elevations in systolic and diastolic BP associated with acute
target-organ damage that require immediate management in a hospital setting.

Hypertensive crises encompass a spectrum of clinical situations that have in common

blood pressure (BP) that is elevated, and progressive or impending target organ
damage. Most hypertensive urgencies or emergencies are preventable and are the
result of inadequate treatment of mild-to-moderate hypertension or nonadherence
to antihypertensive therapy.
Some of examples of hypertensive crises
Traditionally, hypertensive crises have been divided into
• Emergencies
• Urgencies
Hypertensive emergencies
are severe elevations in blood pressure (BP) that are complicated by evidence
of progressive target organ dysfunction, and will require immediate BP
reduction (not necessarily to normal ranges) to prevent or limit target organ
damage. Examples include: hypertensive encephalopathy, intracranial
hemorrhage, unstable angina pectoris, or acute myocardial infarction, acute
left ventricular failure with pulmonary edema, dissecting aneurysm, or
eclampsia. While the level of BP at the time of presentation is usually very
high (greater than 180/120 mm Hg), keep in mind that it is not the degree of
BP elevation, but rather the clinical status of the patient that defines a
hypertensive emergency. For example, a BP of 160/100 mm Hg in a 60-year-
old patient who presents with acute pulmonary edema represents a true
hypertensive emergency.
Hypertensive urgencies
are severe elevations of BP but without evidence of progressive target organ
dysfunction and would be better defined as severe elevations in BP without acute,
progressive target organ damage. A traditional term “urgency” has led to aggressive and
often excessive treatment of the majority of patients who present to Emergency
Departments (ED) with severe hypertension. While these patients may present with
levels of BP similar to the hypertensive emergency, and may have evidence of target
organ involvement, they do not display evidence of ongoing progressive target organ
damage. Most of these patients are, in fact, nonadherent to drug therapy or are
inadequately treated hypertensive patients and often present to the ED for other
reasons. Patients with severe elevations of BP can be managed in the ED with oral
agents and appropriate follow-up within 24 hours to several days depending upon the
individual characteristics of the patient. It is the correct differentiation of these two
forms of hypertensive crises, however, that presents the greatest challenge to the
physician.
Initial Assessment
A brief but thorough history should address the duration as well as the severity of hypertension,
all current medications including prescription and nonprescription drugs and, of particular
importance, the use of recreational drugs. A history of other comorbid conditions and prior
cardiovascular or renal disease is essential to the initial evaluation. Direct questioning regarding
the level of compliance with current antihypertensive medications may establish inadequacy of
treatment or frank noncompliance.

Frequent or continuous monitoring of BP should be established. Look for historical information

suggestive of neurologic, cardiovascular, and/or renal symptoms. Check for specific manifestations
such as headache, seizures, chest pain, dyspnea, and edema. The clinical characteristics of a
hypertensive emergency are listed here. The level of BP alone does not determine a hypertensive
emergency; rather, it is the degree of target organ involvement that will determine the rapidity
with which BP should be reduced to a safer level to prevent or limit target organ damage. Initial
therapy will be for a presumptive diagnosis based on the information available during the initial
triage evaluation.
Symptoms that suggest a cardiovascular problem include:

• Chest pain and/or syncope (suggests myocardial ischemia/unstable angina or aortic dissection).
• Back pain (suggests aortic dissection).
• Dyspnea (suggests pulmonary edema or congestive heart failure).

Symptoms that suggest a neurologic problem include:

• Seizure/altered mental status (suggests hypertensive encephalopathy).
• Focal weakness and/or speech change (suggests cerebrovascular accident or transient ischemic attack).
• Headache and/or visual disturbance (suggests CNS compromise).

Symptoms that suggest a renal problem include:

• Decreased urinary output.
• Bloody or frothy urine.
• Nonspecific abdominal pain.
• Malaise.
If the patient has a history of hypertension, find out when BP elevations began, how the hypertension has
been treated, what degree of BP control was achieved, and whether there has been any previous target
organ damage. This information can help assess risk and guide treatment. For example, patients with
chronic hypertension in whom a hypertensive emergency develops are more likely to experience cerebral
ischemia and other negative consequences if BP is reduced abruptly. Hypertensive patients may have poor
outcomes even if their BP is reduced to a range tolerated by most normotensive persons.4

A thorough history taking also attempts to uncover the cause of acutely elevated BP (Table 2). To investigate
possible toxicologic causes, ask about:
• Recent illicit drug use (eg, cocaine, methamphetamine).
• Recent sympathomimetic use.
• Concurrent use of monoamine oxidase inhibitors and ingestion of foods that contain tyramine (eg, wine,
aged cheese, and canned meats).

To investigate possible iatrogenic causes, inquire about:

• Use of exogenous glucocorticoid therapy (which can precipitate Cushing syndrome).
• Use of weight loss medications (either prescription or over-the-counter).
• Discontinuation of antihypertensive medications (especially clonidine and β-blockers).
Algorithm helps the clinician identify those patients who meet the
criteria of a hypertensive emergency that requires immediate admission
to an ICU for continuous monitoring of BP and initiation of parenteral
antihypertensive therapy.
For patients with uncontrolled hypertension (urgency), evidence of
target organ damage may or may not be present but these patients do
not demonstrate any evidence of deterioration of target organ function.
They can be observed for several hours in the ED during which time their
oral medications can be resumed, if discontinued, or if untreated, an oral
regimen can be initiated.
On occasion, increasing presently inadequate dosages of medication may
be appropriate. Appropriate outpatient follow-up can then be arranged
within 24 hours to several days as needed, and if no prior evaluation has
been performed on this patient for hypertension, an outpatient
appointment should be established. Failure to follow-up on this large
group of patients is a missed opportunity from the standpoint both of
keeping patients in the healthcare system, and establishing optimal BP.
Physical Examination
The physical examination should begin with an assessment of BP, with an
appropriate-size cuff in both upper extremities and in a lower extremity if
peripheral pulses are markedly reduced. Brachial, femoral, and carotid pulses
should be assessed. A careful cardiovascular examination as well as a
thorough neurologic examination, including mental status, should be
conducted. This assessment will aid in establishing the degree of involvement
of affected target organs and should provide clues to the possible existence
of a secondary form of hypertension, such as renovascular hypertension. If a
secondary cause of hypertension is suspected, appropriate blood and urine
samples should be obtained before aggressive therapy is initiated. A careful
funduscopic examination should be performed to detect the presence of
hemorrhages, exudates, and/or papilledema.
Initial Laboratory Studies
Initial laboratory studies should be limited and rapidly expedited.
• urinalysis with microscopic examination of the urinary sediment; The urinalysis may
reveal significant proteinuria, red blood cells, and/or cellular casts. Cellular casts are
suggestive of renal parenchyma disease.
• Immediate Biochemistry; Electrolyte abnormalities, particularly hypokalemia or
hypomagnesemia, increase the risk of cardiac arrhythmias, and the chemistry panel will
also provide evidence of renal and/or hepatic dysfunction.
• Electrocardiogram;The electrocardiogram should identify evidence of coronary
ischemia and/or left ventricular hypertrophy and may reveal pulse deficits, raising the
question of aortic dissection.
When the clinical examination suggests cerebrovascular ischemia or hemorrhage, or if
the patient is comatose, a computed tomographic scan of the head should be
immediately obtained.
 Initial Treatment of the Hypertensive
Emergency
The initial goal for BP reduction is not to obtain a normal BP but rather to achieve a
progressive, controlled reduction in BP to minimize the risk of hypoperfusion in cerebral,
coronary, and renovascular beds. Under normal conditions, blood flow to these organs
remains relatively constant despite wide fluctuations in BP. In the presence of severe
hypertension, the autoregulatory range is shifted upward so that higher levels of BP are
tolerated, but organ circulation may be put at risk with sudden reductions in BP. As an
example, studies on the autoregulation of cerebral blood flow suggest that the lower limit
of autoregulation is about 25% below the resting mean arterial pressure in normotensive
subjects and in those with uncomplicated essential hypertension. These observations have
led to the suggestion that initial reduction in mean arterial pressure should not exceed 20%
to 25% below the pretreatment BP. As an alternative, mean arterial pressure can be
reduced within the first 30 to 60 minutes to 110 to 115 mm Hg. If this level of BP is well
tolerated and the patient is clinically stable, further gradual reductions toward a normal BP
can be implemented over the next 24 hours.
Excessively rapid reductions in BP have been associated with acute
deterioration in renal function, ischemic cardiac or cerebral events, and
occasional retinal arterial occlusion and acute blindness.
A significant exception to the above recommendations should be
recognized for patients with ischemic stroke, with the awareness that
cerebral autoregulation is disrupted in ischemic tissue. There is no clear
evidence from clinical trials to support the use of antihypertensive
treatment during an acute stroke in the absence of other concurrent
disorders such as aortic dissection or heart failure. Antihypertensive
treatment may adversely affect cerebral autoregulation in acute stroke.
Hypertension associated with an acute ischemic stroke spontaneously
decreases to pre-stroke levels within several days.
How Urgent is Urgent Hypertension?
most patients seen in the ED with severe hypertension did not meet the criteria for hypertensive
emergency and were therefore classified as having hypertensive urgencies. Most were treated
aggressively in the ED and many were, in fact, admitted to the hospital for control of BP. The
important caveat is that elevated blood pressure alone rarely requires emergency therapy. Initial
triage should identify those patients who have an elevated BP without any evidence of significant
target organ damage or any other impending cardiovascular events, and these patients clearly
represent the majority of those seen in the ED. They are often asymptomatic and can be
observed for a brief period in the ED to initiate or resume medication in the noncompliant patient
or to increase dosages for those being inadequately treated. Follow-up can be arranged within
several days in the outpatient department.

The occasional patient who presents to the ED with uncontrolled hypertension and symptoms
such as headache, shortness of breath, or epistaxis, may benefit from observation in the ED over
a period of several hours and/or an increase in current medications or added medication to
further lower BP under observation and monitoring of current symptoms.
When clinically stable, the patient may safely be sent home with oral agents
and arrangements for follow-up. There are several oral agents available that
can provide rapid response in blood pressure within one to several hours.
These include agents such as the short-acting ACE inhibitor, captopril,
clonidine, Labetalol, or in selected patients the alpha-adrenergic blocking
agent prazosin. Some of the pharmacologic characteristics of these oral
agents are listed below.

In either case, to discharge the patient from an ED without a confirmed

follow-up appointment represents a missed opportunity to get that patient
back into treatment for optimal control of BP, which should be a
management goal. There is little justification today to admit patients with
hypertensive urgency or high BP to a hospital for further evaluation and
management when these issues can be efficiently and cost-effectively
addressed in the outpatient setting.
Oral Agents for Severe Hypertensive
• Captopril an angiotensin-converting enzyme inhibitor, is well tolerated and can effectively reduce BP
in a hypertensive urgency. Given by mouth, captopril is usually effective within 15 to 30 minutes and
may be repeated in 1 to 2 hours, depending on the response. The drug has been administered
sublingually, in which case the onset of action is within 10 to 20 minutes, with a maximal effect
reached within 1 hour. Responsiveness to captopril can be enhanced by the coadministration of a loop
diuretic such as furosemide. Administration may lead to acute renal failure in patients with high-grade
bilateral renal artery stenosis, and some reflex tachycardia may be observed.

• Clonidine is a centrally acting alpha-adrenergic agonist with onset of action 30 to 60 minutes after
oral administration, and maximal effects are usually seen within 2 to 4 hours. This agent is most
commonly administered as a loading dose of 0.1 or 0.2 mg followed by 0.1 mg hourly for several hours
until an appropriate BP level is attained. Evidence suggests that a comparable response may be seen
with a single 0.2 mg dose.5 The most common adverse effect in the acute setting is drowsiness,
affecting up to 45% of patients. Clonidine may be a poor choice when monitoring of mental status is
important. Dry mouth is a common complaint, and light-headedness is occasionally observed.
• Labetalol, a combined alpha- and beta-adrenergic blocking agent, can be
effectively administered orally in a dose of 200 to 400 mg with BP
response observed within 2 to 3 hours. However, the onset of effect may
be observed within 1 to 2 hours. Like other beta-blocking agents, labetalol
has the potential to induce heart block and to worsen the symptoms of
bronchospasm in the asthmatic patient. Caution must be observed in
patients who have more than first-degree heart block, symptomatic
bradycardia, or congestive heart failure.

• Prazosin is an alpha-adrenergic blocking agent that can have limited

benefit in the early management of a patient with a pheochromocytoma.
Side effects include first-dose syncope, palpitations, tachycardia, and
orthostatic hypotension.
 Parenteral Agents for Hypertensive
Emergencies
• Labetalol is effective when administered as 20- to 40-mg bolus intravenous (IV) injections and can provide a
step-wise, controlled reduction in BP to a predetermined goal. Once the goal BP is achieved, injections are
stopped, and the long duration of action facilitates conversion to effective oral therapy. A continuous
infusion of labetalol at 2 mg/min offers an alternative method of administration and is also associated with
a gradual yet controlled reduction in BP. Since the beta-blocking effects predominate with this agent,
bradycardia or heart block may be observed in patients with intrinsic heart disease.

• Sodium nitroprusside has an extremely rapid onset of action, within seconds of initiating an infusion, and a
rapid offset of effect within 1 to 2 minutes, which necessitates constant supervision of BP during
administration. This agent is particularly effective in reducing preload and afterload in patients with
impaired left ventricular function, and a carefully titrated infusion can achieve any desired goal BP.
Nitroprusside does not cause sedation or somnolence but is rapidly degraded by light, requiring periodic
exchange of solutions.

In patients with significant renal impairment, accumulation of a major metabolite, thiocyanate, may occur
over several days with toxic effects. In the presence of poor tissue perfusion and depressed hepatic function,
an intermediate metabolite in the form of cyanide can accumulate and occasionally lead to cyanide poisoning.
• Nicardipine is an IV form of the dihydropyridine calcium antagonist and is effective in a high
percentage of hypertensive emergencies, particularly at higher infusion rates. Its growing popularity
can be attributed to its ease of administration. Infusion rates can be increased by 2.5 mg/hr at intervals
of 15 to 20 minutes until the maximal recommended dosage of 15 mg/hr is obtained or until the
desired reduction in BP is achieved. Dosing of nicardipine is not dependent on body weight.
Nicardipine has been shown to reduce both cerebral and coronary ischemia although headache,
nausea, and vomiting may occasionally be observed.
• Nitroglycerin may be of particular benefit in hypertensive emergencies with coexisting coronary
ischemia. Since this agent dilates collateral coronary vessels and, like nitroprusside, has a rapid onset
and offset of effect, its use requires close nursing supervision. Unfortunately, at low infusion rates,
nitroglycerin has its primary effect on capacitance vessels in which much higher infusion rates are
required to effect arteriolar vasodilitation. Infusion rates may be increased at 3- to 5-minute intervals
until the desired effect is achieved. Nitroglycerin may be particularly useful in patients with severe
coronary ischemia whose BPs are only modestly elevated or in patients with acute hypertension
following postcoronary artery bypass surgery. Tolerance to IV nitroglycerin may be observed within 24
to 48 hours of instituting an infusion.

• Fenoldapam is a selective, peripheral dopamine1-receptor agonist that induces systemic vasodilation,

particularly in the renal circulation.10 This agent also has effects on renal proximal and distal tubules.
Fenoldapam does not bind to dopamine2 receptors or beta-adrenergic receptors; it has no alpha-
adrenergic agonist effects but is an alpha1 antagonist. This drug does not cross the blood/brain barrier.
 Fenoldapam's unique effects on the kidney provide increased urine flow rate, sodium
and potassium excretion, and improved creatinine clearance, making this agent particularly
attractive in hypertensive emergencies associated with significant renal impairment.

Fenoldapam provides clinical effects similar to those of nitroprusside in improving

cardiac hemodynamics in patients with acute congestive heart failure. Onset of clinical effect is
seen within 5 minutes, and effects tend to dissipate within 30 minutes of discontinuing the
infusion. The most common side effects include headache, flushing, tachycardia, and dizziness.
A dose-related increase in intraocular pressure has been observed in normotensive and
hypertensive patients. Inactive metabolites are eliminated in the urine, and no dosage
adjustments are required for patients with renal or hepatic impairment.

• Hydralazine finds limited use today in pregnant women with preeclampsia. Five to 20 mg may
be administered IV as a bolus injection, and may be repeated. The major advantage is this
agent's ability to improve uterine blood flow. Hydralazine is contraindicated in patients who
have coronary atherosclerosis, as administration is associated with reflex tachycardia and
sodium and water retention, together with intense flushing. Headache and increased
intracranial pressure have also been observed.
Other Parenteral Agents
• Enalaprilat is administered in an IV dose of 1.25 mg and may be repeated at 6-hour
intervals. Onset of action is within 30 minutes. Response to enalaprilat in hypertensive
emergencies is unpredictable, in part because of variable degrees of plasma volume
expansion. This agent may be particularly suitable in hypertensive emergencies
associated with congestive heart failure or with high plasma angiotensin II
concentrations.

• Esmolol is an ultra-short-acting beta-adrenergic blocker that is administered

intravenously. Onset of effect is seen within 1 to 5 minutes, with a rapid offset of effect
within 15 to 30 minutes after discontinuation. Esmolol may be administered as a 500-
µg/kg bolus injection, which may be repeated after 5 minutes. Alternatively, an infusion
of 50 to 100 µg/kg/min may be initiated and increased to 300 µg/kg/min as needed.
Adverse effects include increased heart block, precipitation of congestive heart failure,
and bronchial spasm.
• Phentolamine is a nonselective alpha-adrenergic blocking agent that is still used when
excess catecholamine states, such as pheochromocytoma, are suspected. It is useful as a
diagnostic agent when administered as a bolus injection of 5 to 10 mg in patients with
suspected pheochromocytoma. Acute BP lowering will be seen within several minutes
and may last 10 to 30 minutes. Tachycardia is common and on occasion may precipitate
myocardial ischemia. Nitroprusside and labetalol are more easily titrated in the
management of hypertensive emergencies associated with high circulating levels of
catecholamines, and therefore phentolamine is rarely used therapeutically today.

• Diazoxide is rarely used any longer in the treatment of hypertensive emergencies.

Although a potent vasodilator, large doses of 300 mg were often associated with severe
hypotension. Smaller miniboluses of 50 mg administered at 10- to 15-minute intervals
can provide controlled reduction of BP but are usually associated with reflex tachycardia,
hyperglycemia, hyperuricemia, and sodium and water retention. In view of these side
effects, diazoxide offers little advantage over several other agents that have more
acceptable adverse-effect profiles.
Hypertensive emergencies can carry a poor prognosis unless the BP is reduced quickly, whereas hypertensive urgencies
pose less immediate danger. Hypertensive emergencies are considered to be clinical circumstances in which the BP should
be reduced immediately (within a matter of a few hours), whereas in hypertensive urgencies, BP reduction can be
accomplished gradually (within several hours or even days). There is no arbitrary level of BP that separates hypertensive
emergencies from urgencies. The presence of acute target-organ damage is more indicative of an emergency than an
urgency. In either circumstance, the complications of hypertensive crisis are reversible, if the treatment is provided
efficiently.

Any type of hypertensive disorder may be complicated by the development of hypertensive crisis. The important proviso is
that it is the level of the BP—rather than the cause of hypertension—that is the main determinant of hypertensive crisis.4
(In select forms of hypertensive crises, however, the rapidity with which the BP rises seems to be more relevant than the
actual level of the BP.) In most clinical circumstances, immediate BP reduction is indicated, not because of its absolute level
but because the coexisting complications may make any level of hypertension risky. The risk-benefit ratio of immediate
therapy in many forms of hypertensive crisis is not well-established due to the paucity of controlled clinical trials.

The most critical decision in the management of hypertensive emergencies is to assess the patient's clinical state and to
ascertain whether the patient's condition dictates emergency management. The absolute indications for treatment and
optimal management depend on the underlying and concomitant conditions. A patient with a true hypertensive crisis
should be treated in an ICU.

The choice of oral versus parenteral drug therapy depends on the urgency of the situation, as well as on the patient's
general condition. The level to which the BP should be lowered varies with the type of hypertensive crisis and should be
individualized. The choice of parenteral drug is governed by the clinical manifestations and concomitant medical problems
associated with hypertensive crisis. There is no predetermined level for the goal of therapy.
Complications of therapy, mainly hypotension and ischemic brain damage, can occur in
patients given multiple potent antihypertensive drugs in large doses without adequate
monitoring.5 Such complications should be minimized by gentle lowering of BP, careful
surveillance, and individualization of therapy.

A relatively asymptomatic patient who presents with severe hypertension, (a diastolic

BP of 130-140 mm Hg), need not be treated with parenteral drugs. These patients
should be managed on an individual basis, and the usual course would be to intensify or
alter the previous antihypertensive therapy.

Once the hypertensive crisis is resolved and the patient's clinical condition is stable, the
physician should look into factors that might have contributed to the dangerous
elevation of BP (nonadherence to prescribed therapy or the presence and/or
progression of a secondary form of hypertension such as a renal artery stenosis or renal
failure, for example). The physician should discuss long-range and periodic outpatient
follow-up plans with the patient, as close follow-up is extremely important.
Accelerated and malignant hypertension Accelerated hypertension is clinically
identified by severe retinopathy (without papilledema), exudates, hemorrhages,
arteriolar narrowing, and spasm. Malignant hypertension is considered a deterioration
of the accelerated form and is distinguished by papilledema. Both the accelerated and
malignant forms of hypertension are associated with severe vascular injury to the
kidney and other target organs. The diagnosis of accelerated or malignant
hypertension is best made clinically on the basis of history and clinical examination.
Simple investigations such as chest radiography, ECG, urinalysis, and laboratory tests to
determine blood count, serum nitrogen level, creatinine clearance, and electrolyte
concentrations are generally sufficient.

The BP level in malignant hypertension is often quite high, with diastolic levels in the
range of 130 to 140 mm Hg (stage 2 hypertension), but the degree of BP elevation is an
unreliable diagnostic feature Rather, it is the degree and extent of vascular injury that
determines the clinical manifestations. Severe headache, with or without coexisting
encephalopathy, is one symptom. Weight loss may occur in some patients with
malignant hypertension as a result of initial natriuresis.
Some patients with malignant hypertension report visual problems ranging from blurring to blindness;
drowsiness and altered mental status are also common. Worsening symptoms may indicate
progression to encephalopathy or other cerebral complications, such as stroke. Congestive heart
failure can be a feature of malignant hypertension, either as a consequence of left ventricular
dysfunction, or due to volume retention from concomitant renal failure. Azotemia, a frequent feature
of malignant hypertension, may be associated with proteinuria. Renal function deteriorates rapidly in
many patients without appropriate therapeutic intervention.
Patients with accelerated/malignant hypertension should ideally be treated in the hospital, since the
goal of management is not only to lower the BP but to stabilize it, reverse the target-organ damage,
and exclude any reversible causes. Preferably, these patients should be treated in an ICU; but in the
absence of significant target-organ dysfunction, they can be managed safely on the wards under
supervision
Although IV therapy is widely used in the initial treatment of malignant hypertension, various oral
therapies can also be used successfully. ACE inhibitors, minoxidil, clonidine, prazosin, labetalol, and
nifedipine have all been used for initial treatment of malignant hypertension, but there are no
controlled prospective studies to offer precise guidelines on the preferred therapeutic options. The
choice between oral and parenteral therapy depends on the monitoring facilities, condition of the
patient, and coexisting complications. Once the BP is brought to safe levels, appropriate oral therapy
must be initiated on the basis of the patient's renal, cardiac, and neurologic status.
TREATMENT OF A PATIENT WITH
HYPERTENSIVE EMERGENCY
Whether or not to hospitalize the patient, the therapeutic choices, and the choice of IV versus oral therapy
depend on the clinical evaluation of the patient and available facilities. Patients with hypertensive emergencies
should be hospitalized, and those with hypertensive urgencies may not always require admission to the hospital.

The therapeutic premise underlying the management of hypertensive emergency is not only to lower the BP
quickly but to prevent, arrest, and reverse the target-organ damage. Therefore, close supervision of the patient
is required while the BP is being lowered. There are no firm guidelines as to the degree of desired BP reduction,
but a reasonable goal for most hypertensive emergencies is to lower the diastolic BP to 100 mm Hg (or to
reduce the mean arterial pressure by 20%) over a period of minutes to hours.

Hypertensive emergencies should preferably be managed in an ICU to allow for continuous monitoring of the
general hemodynamic status of the patient. Even though a secondary form of hypertension, such as renal artery
stenosis or adrenal hypertension, may be a causative factor, the immediate goal should be to lower the BP to a
safe level rather than undertaking a diagnostic workup. The rapidity of onset and duration of action of the
chosen drug are important considerations in treating patients with hypertensive emergencies. The physician
should be familiar with the hemodynamic and pharmacologic actions of the available drugs.
 Role of concomitant diuretic therapy
Diuretics have a limited role in the management of hypertensive emergencies; however, they potentiate the therapeutic response of
nondiuretic agents. When the BP does not respond satisfactorily to an adequate dose of the primary agent, adding a diuretic (such as
furosemide) may be helpful. In volume overload states such as heart failure, concomitant administration of a loop diuretic is indicated
for optimal results. Diuretics should not be used routinely in the management of hypertensive crises, as prior volume depletion may
be present in some conditions, such as malignant hypertension. The need for diuretic therapy, therefore, should be individualized on
the basis of the hemodynamic and renal function status of the patient.

Orally effective drugs

Clinical experience has shown that antihypertensive drugs given orally as either single or multiple doses can lower the BP immediately
in patients with severe hypertension. Obviously, this therapeutic opportunity is most suitable for patients with hypertensive
urgencies, not emergencies.

• Nifedipine, a calcium channel blocker given either orally or sublingually, has been shown to lower the BP rapidly and can be useful
in the management of hypertensive crisis. Immediate reduction in BP can be accomplished with sublingual (a punctured capsule, or
nifedipine liquid drawn out of the capsule with a syringe) or oral administration of the capsules. The drug is also effective when the
capsule is bitten and then swallowed. The advantages of nifedipine are rapid onset of action and lack of CNS depression. It may
cause reflex tachycardia. As the duration of action of nifedipine is short, patients who receive this drug for hypertensive
emergencies should be monitored for several hours to consider re-administration of the drug. An abrupt fall in the BP induced by
nifedipine administration can cause certain adverse effects—symptomatic hypotension, tachycardia, and ischemic events—so the
clinical need to use nifedipine capsules to lower the BP urgently should be carefully assessed and avoided, if possible.
• Clonidine has been shown to produce an immediate antihypertensive effect when given in repetitive doses. Typically, clonidine loading
was accomplished in the ED by administering it orally at a dosage of 0.1 mg q1h until the desired goal was obtained. The use of
clonidine loading therapy has declined due to the availability of safer and better-tolerated alternative therapies that do not cause
drowsiness.

• Captopril is an ACE inhibitor that has been found to be effective in the immediate treatment of severe hypertension and hypertensive
crises. Captopril lowers the BP promptly without causing tachycardia, and thus offers a distinct hemodynamic advantage over direct
arteriolar dilators. The maximal effect from orally administered captopril may not be attained for as long as 2 hours. There are some
reports documenting the effectiveness of sublingual captopril in the treatment of hypertensive crisis, but further data needs to be
generated to define its role in the acute management of hypertensive crisis.

• Minoxidil, a powerful direct vasodilator, has been successfully used in the treatment of refractory or severe hypertension. Because of
its relatively rapid onset of action and sustained duration, this drug has been used for the treatment of hypertensive crises. Minoxidil
in dosages ranging from 2.5 to 10 mg can be given every 4 to 6 hours initially in the treatment of severe hypertension. It works best
when given along with a diuretic, and an adrenergic blocker is necessary to counteract the reflex tachycardia. Minoxidil should be used
with caution in patients with acute coronary syndromes unless the patient is beta-blocked.

• Labetalol can be administered orally in doses of 100 to 300 mg for the treatment of hypertensive urgencies. Because of its dual
adrenergic blockade, the fall in BP is not accompanied by reflex tachycardia. This attribute can be especially beneficial in patients with
CAD. Oral labetalol is effective within 1 to 3 hours and may be useful for hypertensive urgencies, but it has an unpredictable dose
response and thus may not be ideal for acute situations. Labetalol is contraindicated in patients with bronchospasm, heart block,
significant bradycardia or heart failure.

IV drugs for hypertensive emergencies Several IV drugs are effective for use in hypertensive crisis. The patient's clinical presentation will
determine the agent of choice in an individual situation. Parenteral drugs for rapid control of severe hypertension
• Nitroprusside is a powerful BP-lowering drug that possesses the properties of rapid onset and offset of action. The hypotensive response occurs
within seconds after the infusion is started and disappears almost as rapidly when the infusion is discontinued. The initial infusion rate should be 0.3
mcg/kg/min, which can be increased every 5 minutes until a desired BP level is obtained. Once the desired effect is achieved, the BP should be
continuously monitored. Hypotension is the most common—but avoidable—adverse effect of nitroprusside therapy. Cyanide toxicity from
nitroprusside is possible, although extremely rare. Prophylactic infusion of cyanocobalamin (vitamin B12a) 25 mg/h, has been shown to decrease the
cyanide concentration and tissue hypoxia resulting from nitroprusside infusion during surgery. Thiocyanate toxicity secondary to nitroprusside is
uncommon and occurs only with high doses and in the presence of renal failure. Treatment should be interrupted when the thiocyanate level is close
to 10 mg/dL. Monitoring of plasma thiocyanate levels is not mandatory, as long as the patient's clinical status is closely assessed. Treatment of
suspected thiocyanate toxicity requires discontinuation of the drug and institution of dialysis.

• Labetalol can be used parenterally or orally for the treatment of hypertensive emergencies. IV labetalol administered as either a continuous infusion
or as bolus injections reduces the BP promptly because of its rapid onset of action. Controlled smooth reduction in BP may be obtained by
continuous infusion of labetalol at the rate of 0.5 to 2 mg/min. As with nitroprusside, close monitoring of the patient is required during the infusion
of labetalol. Rapid (but not abrupt) lowering of BP can also be accomplished with bolus injections of labetalol. Labetalol should not be used when
beta-blockers are contraindicated—for example, in patients who may have heart failure, atrioventricular block, asthma, or chronic obstructive
pulmonary disease.

• Nicardipine is a dihydropyridine calcium antagonist that exerts a prompt hemodynamic effect when given IV in patients with severe hypertension.
Nicardipine infusion is started at 5 mg/h, and can be titrated upwards gradually to obtain the desired therapeutic effect.11 Once a stable BP is
reached, most patients do not require further dosage alterations. Thus, nicardipine pharmacodynamics resemble those of nitroprusside in terms of
the onset, and duration and offset of action. Because of its mechanism of action (calcium channel blockade), nicardipine may be beneficial in
preserving tissue perfusion. It is a good option in the management of severe hypertension with or without target-organ damage.

• Hydralazine has an antihypertensive action that results from a direct relaxation of the vascular smooth muscle and it is accompanied by reflex
increases in stroke volume and heart rate, which can precipitate myocardial ischemia. Either IM or IV administration of hydralazine causes an
unpredictable but definite fall in BP. In the treatment of hypertensive emergencies, the initial IV dose should be 10 to 20 mg. The onset of the
hypotensive effect occurs within 10 to 30 minutes, and its duration of action ranges from 3 to 9 hours. The dose and frequency of administration
necessary to control the BP are highly variable. The delayed onset and unpredictable degree of hypotensive effect present difficulties in titration.
Nevertheless, hydralazine continues to be successfully utilized in the treatment of eclampsia.
• Phentolamine is an alpha receptor-blocking agent that is specifically indicated for treating hypertensive crises associated with increased
circulating catecholamines. These include, for example, pheochromocytoma crisis, certain cases of clonidine withdrawal syndrome, and crises
resulting from an MAOI and drug-food interaction. The hypotensive effect of a single bolus injection is short-lived and lasts less than 15 minutes.
This drug may precipitate angina or cardiac arrhythmias.

• Nitroglycerin is a weak systemic arterial dilator with a greater effect on large arteries than on smaller arteries. Low doses cause venodilation;
much higher doses are required to produce a fall in systemic BP. Because of its pharmacologic actions, nitroglycerin infusion may be particularly
beneficial in patients with CAD either with or without hypertension. Nitroglycerin improves coronary perfusion. Although there are no
controlled studies, nitroglycerin therapy can be considered in the management of severe hypertension associated with CAD. The usual initial
dosage of nitroglycerin is 5 to 15 mcg/min, and the dosage is titrated upward to a desired therapeutic end point. It has a rapid onset (2-5
minutes) and offset of action. Although nitroglycerin has been used to achieve controlled hypotension, its main use continues to be in patients
with unstable angina and acute MI. Prolonged use may result in tolerance. Isosorbide dinitrate therapy has also been utilized for immediate
treatment of severe hypertension but its precise role and guidelines on how to use it are not fully delineated.12

• Enalaprilat, by its mechanism of action, prevents conversion of angiotensin I to angiotensin II by blocking angiotensin converting enzyme and
thus lowering BP. Enalaprilat is the only available parenteral ACE inhibitor. For hypertensive emergencies, it is given at a dosage of 0.625 to 1.25
mg IV over 5 minutes and may be repeated every 6 hours. ACE inhibitors are contraindicated in patients with renal artery stenosis and in
pregnant patients. ACE inhibitors can cause precipitous falls in BP in patients who are hypovolemic. These drugs are especially valuable in
treating hypertensive emergencies in patients with chronic heart failure.

• Fenoldopam is a relatively new drug that is a selective dopamine (DA1) receptor agonist and causes significant vasodilation. It is a short-acting,
parenteral arteriolar vasodilator that lowers BP by reducing peripheral vascular resistance.13,14 By the mode of its action on the DA1 receptor,
fenoldopam causes remarkable renal vasodilation and promotes diuresis and natriuresis. The half-life of fenoldopam is estimated to be 5
minutes, and the recommended starting dosage is 0.1 mcg/ kg/min. Its onset of action is 5 minutes and maximum response is achieved within
15 minutes. The dosage should be titrated to gradually attain the goal BP. It can lower BP in hypertensive emergencies safely and effectively and
at the same time preserve or improve renal blood flow and cause diuresis and natriuresis. Therefore, it may offer important advantages. A
number of early comparative studies between nitroprusside and fenoldopam showed that while both are equally effective in reducing the BP,
fenoldopam offers important renal advantages over nitroprusside.
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