DEFINITION :

HYPERTENSIVE CRISIS
A severe elevation in BP, generally a SBP > 220 mm Hg and / or
DBP > 120 mm Hg. (JNC-VI, 1997)

HYPERTENSIVE EMERGENCIES
Severe elevation in BP complicated by acute target organ
dysfunction, such as coronary ischemia, stroke, intracerebral
hemorrhage, pulmonary edema, or acute renal failure.

HYPERTENSIVE URGENCIES
Severe elevations in BP without evidence of target organ
deterioration.

Colhum DA. Oparil S, New Engl. J. Med, 323 : 1177, 1990

PREVALENCE :
1. Hypertensive crisis reprensented 27 % of all medical
emergencies encountered over a year interval (zampaglione et al,
Turin, Italy, 1996)

2. In Patients with untreated primary hypertension before the

availability of modern antihypertensive therapies, the incidency
of accelerated hypertension with papiledema was 7% (Cahhoun
DA, Oparil S, N. Engl. J. Med 332 : 1029, 1995)

3. Hypertensive emergencies occur most frequently in patients

previously diagnosed with primary hypertension but who are
non compliant.
4. At present + 1 % of patient with primary hypertension will
progress to an accelerated-malignant form

PROGNOSIS :
1. In 1939, Keith et al found that patients with hypertension
and grade IV retinopathy had a mean survival of 10.5
months, with no survivors at 5 years.
2. In 1958, Dustan at al found that among 84 patients being
treated for malignant hypertension, 70 % survived 1 year
and 33 % survived 5 years.
3. In the 1960s, with use of more effective and better tolerated
anti hypertensive agents, 5 year survival rates were 50 to
60 %.
4. 1970s, with increase use of dialysis 5 year survival rates +
75 %.
5. Current survival of patients with severe hypertension
approaches that of patients with uncomplicated primary
hypertension.

HYPERTENSIVE CRISIS
DBP >120 mmHg

URGENCY

BP within hours < 24 hours

(PARENTERAL / ORAL)

KAPLAN NM . Lancet 344:1335,1994

EMERGENCY

BP within minutes < 1 hours

(PARENTERAL)
- Accelerated malignant hypertension
- Hypertensive encephalopathy
- Intracerebral/Subarachnoid hemorrhage
- Acute aortic dissection
- Acute left ventricular failure
- Acute myocardial infarction
- Acute glomerulonephritis
- Eclampsia
- Severe epistaxis
- Perioperative hypertension, etc

End-Organ Damage Associated Hypertensive Emergencies

End-Organ Damage Type

No of Cases (%)

Cerebral Infarction

26 (24.5)

Intracerebral or sub-arachnoid
hemorrhage

5 (4.5)

Hypertensive encephalopathy

18 (16.3)

Acute pulmonary edema

24 (22.5)

Acute congestive heart failure

15 (14.3)

Acute myocardial infarction or unstable

angina pectoris

13 (12.0)

Eclampsia

5 (4.5)

Aortic dissection

2 (2.0)
Zampaglione, et al. AHA ; 27 (1) : 144

PATHOPHYSIOLOGY

Critical Degree of Hypertension

Local Effects
(Prostaglandins, Free Radical, etc.

Systemic Effects
(Renin-angiotensin, Cathecol,
Vasopression

Endothelial Damage
Pressure Natriuresis

Platelet Deposition
Hypovolemia
Mitogenic and Migration
Factors
Further Increase in
Vasopressure

Myointimal Proliferation

Further Rise in Blood Pressure

And
Vascular Damage
Tissue Ischemia
M. Kaplan, Clinical Hypertension, 7th edition, Baltimore, 266 : 1998

Putative Vascular Pathophysiology of Hypertensive Emergencies

Lancet 2000; 356: 41117

Initial Evaluation of Patients with a Hypertensive

Emergencies
HISTORY

Prior diagnosis and treatment of hypertension.

Intake of pressor agent : street drugs, sympathomimetics.
Symptom of cerebral, cardiac, and visual dysfunction.

PHYSICAL EXAMINATION

Blood Pressure
Funduscopy
Neurologycal Status
Cardiopulmonary status
Body fluid volume assessment
Peripheral pulses

LABORATORY EVALUATION

Packed cell volume and blood smear

Urine analysis
Chemistry : creatinine, glucose, electrolytes
Electrocardiogram
PRA and aldosterone (if primary aldosteronism is suspected)
PRA before and 1 hour after 25 mg Captopril (if renovascular hypertension is
suspected).
Spot urine for metanephrine (if pheochromocytoma is suspected)
Chest radiograph (if heart failure or aortic dissection is suspected)
M. Kaplan, Clinical Hypertension, 7th edition, Baltimore, 267 : 1998

Plasma Renin Activity in Hypertensive Crisis

DISORDERS WITH HIGH RENIN

Malignant Hypertension
OTHER MEDIUM TO HIGH RENIN STATES

Unilateral renovascular hypertension

Renal vasculitis (scleroderma, lupus, polyarteritis)

Renal trauma

Renin secreting tumors

Adrenergic crises ; pheochromocytoma, cocaine abuse, clonidine or methyl DOPA

withdrawal.
PROBABLE MEDIUM to HIGH RENIN STATE : PRA 0.65 ng/mL/hour

Hypertensive encephalopathy

Hypertension with cerebral hemorrhage

Hypertension with (impending) stroke

Hypertension with pulmonary edema

Hypertension with acute myocardial infarction or with unstable angina.

Dissecting aortic aneurysm

Peri-operative hypertension.
PROBABLE MEDIUM to HIGH RENIN STATE : PRA 0.65 ng/mL/hour

Acute tubular necrosis

Acute glomerulonephritis

Urinary tract obstruction

Primary aldosteronism

Low renin essential hypertension

Pre-eclampsia/eclampsia (PRA values falls from 6 to 10 range of normal pregnancy,

to 1 ng/mL/hour.
Laragh J.H., AJH 2001; 14 : 1154-1167

Circumstances Requiring Rapid

Treatment of Hypertension (DBP > 120 mmHg)
Accelerated-malignant hypertension with papilloedema
Cerebrovascular
Hypertensive encephalopathy
Atherothrombotic brain infarction with severe hypertension.
Intracerebral hemorrhage, subarachnoid hemorrhage.
Cardiac
Acute aortic dissection
Acute left ventricular failure
Acute or impending myocardial infarction
After coronary bypass surgery
Renal
Acute glumerulonephritis
Renal crisis from collagen-vascular diseases.
Severe hypertension after kidney transplantation

Circumstances Requiring Rapid

Treatment of Hypertension (cont)
Excessive circulating cathecolamines

Pheochromocytoma crisis
Food and drug interactions with monoamine oxidase inhibitor
Sympathomimetic drug use (cocaine)
Rebound hypertension after suddent cessation of antihypertensive drugs.

Eclampsia, Surgical
Severe hypertension in patients requiring immediated surgery.
Post-operative hypertension
Post-operative bleeding from vascular suturelines

Severe body burns, Severe epistaxis.

Kaplan NM : Management Hypertension Emergencies, LANCET, 344, 1994 : 1335

Treatment
1. The goal of therapy is to reduce systemic vascular
resistance.
2. The approach is to initially reduce mean arterial pressure
by about 25 % with further reductions accomplished more
gradually.

3. In general the initial reduction should be achieved over a

period of 1 to 2 hours with less rapid reduction over the
ensuring 6 hours to a DBP of + 100 mm Hg.
4. With the exception of patients with aortic dissection, the
BP should not be reduce to normotensive and especially
hypotensive levels, as target organ hypoperfusion may
results.

Current Recommendation of the

AHA :
Hypertension in the setting of acute ischemic
stroke should only be treated rarely and
cautiously .
Treat : DBP > 120-130 mmHg , objective
reduction 20 % in the first 24 hours.
Abandon oral nifedipine.
Short
actingIV.(labetalol,nicardipine,fenoldopam )
SNP increase ICP,cyanide poisoning

Intracerebral Hematoma
Hypertension serve to protect CBF in
the setting of high ICP.
Treat if : systolic blood pressure > 200
mmHg or DBP > 110 mmHg.
The rate of decline in blood pressure
was independently associated with
increased mortality.

MANAGEMENT OF HYPERTENSIVE EMERGENCIES

JNC-VI RECOMMENDATION

Reduce Mean Arterial BP no More than 25 %

over 2 hours then Reduce to 160 / 100 mm Hg
within 2-6 hours.
Avoid excessive falls in Blood Pressure
Titrate with Intravenous antihypertensives.

Guideline of treatment based on concensus

expert.

Profile of an ideal IV
antihypertensive
Preserves GFR and renal blood flow
Few or no drug reactions
Little or no potential for exacerbation of co-morbid
conditions
Rapid onset and offset of action
Minimal hypotension overshoot
Minimal need for continuous BP monitoring and
frequent dose titration
No acute tolerance
Ease of use and convenience
Safe and no toxic metabolites
Multiple formulations for short and long term use
Minimal symphathetic activation

End-Organ Complication of
Hypertensive Emergencies
ENDORGAN

COMPLICATIONS

THERAPEUTIC CONSIDERATIONS

Aortic

Aortic dissection

-BLOCKADE, labetolol (decrease dp/dt), SODIUM

NITROPRUSSIDE with -BLOCKADE, avoid isolated
use of pure vasodilators.

Brain

Hypertensive encephalopathy
Cerebral infarction or
Haemorrhage

Avoid centrally acting antihypertensive drugs such

as CLONIDINE.
Avoid centrally acting agents : avoid rapid
decreases in blood pressure

Heart

Myocardial ischaemia
Myocardial infarction
Heart failure

Intravenous GLYCERYL TRINITRATE, -BLOCKADE.

Kidney

Renal insufficiency

DIURETICs with cautions, CALCIUM Antagonists

useful.

Placenta

Eclampsia

HYDRALAZINE, LABETOLOL, CALCIUM Antagonists

useful; avoid sodium nitroprusside.

dp/dt = change in pressure / change in time

DIURETICs & ACE inhibitors useful, -BLOCKERS

with caution.

LANCET 2000; 356 : 411-417

Autoregulation of Cerebral Blood Flow

Lancet 2000; 356: 41117

Auto regulation
Difficulty in balancing between organ :
Brain , heart and kidney.
Different organ depending on the
preexisting lesion has a different
threshold of perfusion pressure.

Intravenous Drugs
for Hypertensive Emergency
DRUGS

DOSAGE

ONSET of ACTION

Nitropruside

0.25 10 g/kg/min as IV Infusion

Instantaneous

Nitroglycerin

5 100 g/min as IV Infusion

2 5 min

Nicardipine

5 15 mg/hours IV

5 10 min

Hydralazine

10 20 mg IV

10 20 min

10 50 mg IM

20 30 min

1.25 5 mg q 6 hours

15 min

Fenoldopam

0.1 0.3 g/kg/min

< 5 min

Phentolamine

5 15 mg IV

1 2 min

Esmolol

500 g/kg/min for 4 min, then 150

300 g/kg/min IV

1 2 min

Labetolol

20 80 mg IV bolus every 10 min

2 mg/min IV Infusion

5 10 min

Enalapril

Braunwald , 2001

Commonly Used Parenteral Antihypertensive Drugs

Lancet 2000; 356: 41117

Intravenous Drugs for Hypertensive

Emergencies Available in Indonesia

Vasodilators

Clonidine
Nitroglicerin

Sodium Nitropruside
Ca-Antagonist

Diltiazem Hydrochloride

COMMONLY USED DRUG IN

HYPERTENSIVE EMERGENCY

DILTIAZEM I.V. (HERBESSER)

Useful for hypertensive emergency and urgency.
Acts as calcium slow-channel blockers.
Dose-dependent :

Predictable onset of action

Rapidly reduced BP.

No rebound on withdrawn

Adverse effect : bradycardia, hypotension, headache, flushing.

Has antiischemic and antiarrhythmic effect (class-IV)

Organ Target

HER

CLON

NTG

NIFE

++
++
+
++

++
-

+
+

AntiIschemic

Cardioprotective
Heart rate
Dilate: coroner
collateral
Antiarrhytmic
Antivasospasm

Renoprotective
Afferent
RBF
Efferent
CGP

Cerebroprotective
CBF
Epstein M, 1991, Bakris GL, 1993, Mancia G, 1996, Messerly FH, 1996

DILTIAZEM-Injection
Dosage and Administration
Each ampoule of DILTIAZEM-Injection should be dissolve in
at least 5 mL aquadest or NaCl or glucose solution before use.

BOLUS I.V. INJECTION

0.20 0.35 mg/kg BW
Adult (50kg) : 1 Ampoule (1 3 minutes)
DRIP I.V. INFUSION (Flat)
5 15 mcg/kg BW/min
Adult (50kg) : 15mg/hour 45 mg/hour
DRIP I.V. INFUSION (maintenance)
1 5 mcg/kg BW/min
Adult (50kg) : 5mg/hour 15 mg/hour

Bolus I.v.
0.2 mg/kg
10

10% MBP reduction

From Baseline

20

20% MBP reduction

From Baseline

30

Target MBP
Level

Drip infusion
50 mg/hour

Drip infusion
30 mg/hour

Drip infusion
5-10 mg/hour
Every 30-60 minutes observation

Switch to Oral
DILTIAZEM 180SR

COMMONLY USED DRUG IN

HYPERTENSIVE EMERGENCY
CLONIDINE I.V.
Reduce peripheral sympathetic tone by central
stimulation of 2- receptor.
Unpredictable onset of action.
Adverse effect : sedation, dry mouth, constipation
and a tendency to a overshoot or rebound hypertension
on withdrawn.
W.H. Frishman, et al., Cardiovascular Pharmacotherapy, 1996

COMMONLY USED DRUG IN

HYPERTENSIVE EMERGENCY
NITROGLISERIN I.V.

Strongth vasodilator (arterial- and veno-dilator).

Direct interacting with nitrate receptors on vascular

smooth muscle.

A rapid onset and duration of action.

Adverse effect : headache, tachycardia, nausea,

vomiting.

Conclusion :
1. Hypertensive emergencies require immediate BP reduction. This
is most safely accomplished in the intensive care setting with
use of an Intravenous agent.
2. With the advent of better tolerated, long-acting anti
hypertensive agents, hypertensive crisis become less common,
with an estimated prevalence rate of 1% among hypertensive
patients.
3. Diltiazem IV is scalable and predictable effective to lower BP
faster in avoiding complications of hypertensive emergency.
4. In hypertensive urgencies BP should be reduced more gradually
with an fast-acting agents per os in an out patient setting.