Ketut Suwitra

Dr dr Haerani Rasyid, MKes, SpPD, KGH, SpGK

Hasanuddin University Hospital
Makassar
Division of Nephrology Department of Medicine
School of Medicine University of Udayana /Sanglah Hospital
Denpasar

Hypertensive
patients
Severe
hypertension

Hypertensive
urgency

Hypertensiv
e emergency

(70-75%)

(25-30%)

Hypertensive
Crisis

Severe hypertension
- Blood pressure 180/110 mmHg
- Absence of symptoms beyond mild or
moderate headache
- Without evidence of acute target organ
damage

Prim Care Clin Office Pract 2008; 35: 4754

Hypertensive urgency
- Blood pressure 180/110 mmHg
- Presence of symptoms beyond mild or
moderate headache
- Without evidence of acute target organ
damage

Prim Care Clin Office Pract 2008; 35: 4754

Hypertensive emergency

- Very high blood pressure (often >

220/140 mmHg)
- Accompanied by evidence of
threatening organ dysfunction

life-

Prim Care Clin Office Pract 2008; 35: 4754

Malignant hypertension
Represents markedly elevated blood
pressure accompanied by papiledema
(grade 4 retinopathy)

Accelerated hypertension
Present if markedly elevated blood
pressure is accompanied by grade 3
retinopathy, but no papilledema

Prim Care Clin Office Pract 2008; 35: 4754

Comparison of Hypertensive
Emergencies and Urgencies
Variable

Hypertensive
Emergency

Hypertensiv
e Urgency

Symptoms
Acute BP elevation
Acute organ damage
Hospitalizazion
Intensive care
Route of therapy
Arterial line
Rate of BP lowering
Evaluate for secondary
hypertension

Yes
Yes
Yes
Yes
Yes
Intravenous
Yes
Minute to hours
Yes

Non or minimal
Yes
No
No
No
Oral
No
Hours to days
Yes

Epidemiology
Less than 1 % of hypertensive population
Hypertensive crises are more prevalent
in :
- Elderly
- Afro-American
- Men (affected 2 times more often than
women)
- Noncompliant individuals
- Persons of lower socioeconomic status
Cardiol Rev 2010; 18: 102-107

Precipitating factors in hypertensive crisis

1. Accelerated sudden rise in blood pressure in patient
with preexisting essential hypertension
2. Renovascular hypertension
3. Glomerulonephritis-acute
4. Eclampsia
5. Pheochromocytoma
6. Antihypertensive withdrawl syndromes
7. Head injuries
8. Renin secreting tumors
9. Ingestion of cathecolamine precursor in patients
taking MAO inhibitors

HYPERTENSIVE URGENCY
- Accelerated malignant hypertension

- Hypertension associated CAD

- Perioperative hypertension
- Severe hypertension in renal disease
- Severe hypertension in the organ transplant
- patient
- Hypertension associated with burns
- Severe, uncontrolled hypertension
Kaplan NM . Lancet 344:1335,1994
Venkata C, Silverstein RL , Curr Hypertens Rep 2009, 11:307-314

HYPERTENSIVE EMERGENCY
-

Hypertensive encephalopathy
Intracerebral/Subarachnoid hemorrhage
Acute aortic dissection
Acute left ventricular failure
Acute myocardial infarction
Acute glomerulonephritis
Eclampsia
Hemorrhage : Post surgical, Severe epistaxis
MAO inhibitor + tyramine interaction
Head trauma
Catecholamine excess states :
Beta blocker or clonidine withdrawal, Cocaine,
phencyclidine hydrochloride use,
Phaeochromocytoma Crisis
Kaplan NM . Lancet 344:1335,1994
Venkata C, Silverstein RL , Curr Hypertens Rep 2009, 11:307-314

Patophysiology of a
hypertensive crisis is not
well known.

Normotensive : arteries dilate or constrict in respons to changes

pressure to maintain a constant flow to the tissue bed.
Chronic hypertension : functional and structural changes in the a
that shift autoregulatory curve to the right, to maintain normal
in important organs and avoid an increase in local blood flow a
higher blood pressures.
Hypertensive emergency : blood pressure increased above the
the autoregulatory mechanisms to compensate by vasoconstr
tissue damage, ischemia or loss of vascular integrity.

Known stimuli or
Unknown stimuli

The pressure
hypothesis

Severe blood
pressure
elevation

The humoral
hypothesis

- Vasoconstrictors :

- Vasodilators

Endothelin,
Norepinephne,
Angiotensin II,
Vasopressin
Nitric oxide

Endothelial dysfunction
Myointimal proliferation
Fibrinoid necrosis

End organ
damage

Cardiol Rev 2010; 18: 102-107

The most widespread signs and

symptoms at presentation for
hypertensive urgency (Zampaglione et.al,
Hypertension 1996;27:144-147)
-Headache (22%)
-Epistaxis (17%)
-Faintness (10%)
-Psychomotor agitation (10%)
-Chest pain (9%)
-Dyspnea (9%)
-Others : arrhytmias and paresthesias

The most widespread signs and symptoms at

presentation for hypertensive emergency
(Zampaglione et.al, Hypertension 1996;27:144147) :
-Chest pain (27%)
-Dyspnea (22%)
-Neurologic deficits (21%)
-Associated end-organ damage includes
cerebral infarction (24.5%), acute
pulmonary edema (22.5%), hypertensive
encephalopathy (16.3%), and congestive
heart failure (12.0%)

Comprehensive Clinical Nephrology, 2010

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)

Goal of Treatment
1.The goal of treatment in a hypertensive
emergencies is to
restore blood pressure to a range in which
autoregulatory forcesmay be re-established.
2. The treatment target is often not a normal
blood pressure, but instead one that is only
moderately lower, just sufficient to allow
autoregulation to be restored.

Table Oral drugs for hypertensive urgencies

Drug

Class

Captopril

Angiotensinconverting
enzyme
inhib.

Clonidine

Central agonist

Furosemide

Diuretic

20-40 mg

0.5-1.0 h

6-8

Labetalol

- and Blocker

100-200 mg

0.5-2.0 h

8-12

Propanolol

-Blocker

Dose

Onset

Duration (h)

6.5-50.0 mg

15 min

4-6

0.2 mg initially, 0.2-2.0 h

then 0.1 mg/h,
up to 0.8 mg
total

20-40 mg

15-30
min

6-8

3-6

Management of
Hypertensive Emergency (general)

Patients should be admitted to an Intensive Care

Unit for continuous monitoring of BP and parenteral
administration of an appropriate agent

The initial goal therapy is to reduce mean arterial BP

by no more than 25% (within minutes to 1 hour).

Then if stable, to 160/100 to 110 mmHg within the

next 2 to 6 hours.
Excessive falls in pressure that may precipitate
renal, cerebral, or coronary ischemia should be
avoided.

Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

Management of
Hypertensive Emergency (general)

1.
2.
3.

If this level of BP is well tolerated and the

patients is clinically stable , further gradual
reductions toward a normal BP can be
implemented in the next 24 to 48 hours.
Exceptions :
Patients with ischemic stroke
Aortic dissection SBP should < 100 mmHg
Patients whom BP is lowered to enable the
use of thrombolytic agents
Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

Parenteral drugs for treatment of hypertensive emergency

Drug

Dose

Diuretics
Furosemide

Vasodilators
Nitropruside
(Nipride,
Nitropress)

Onset of
actions

Duration
of action

Special indications

20-40 mg in 1-2 min, 5-15 min

repeated and higher
doses with renal
insufficiency

2-3 h

Ussually needed to
maintain efficacy of
other drugs

0.25-10.00
g/min/kg/min as
i.v. infusion

Immediate

1-2 min

Most hypertensive
emergencies; caution
with high intracranial
pressure or azotemia

Nitroglycerin
(Nitro-bid IV)

5-100 g/min as i.v.

infusion

2-5 min

5-10 min

Coronary ischemia

Fenoldopam
(Corlopam)

0.1-0.6 g/kg/min as
i.v. infusion

4-5 min

10-15 min

Renal insufficiency,
after surgery

Nicardipine
(Cardene IV)

5-15 mg/h i.v.

5-10 min

1-4 h

Most hypertensive
emergencies; caution
with acute heart failure

Parenteral drugs fortreatmentf o hypertensiveemergency(contd)

Drug

Dose

Onset of
actions

Duration
of action

Special indications

Hydralazine
(Apresoline)

10-20 mg i.v.
10-20 mg IM

10-20 min
20-30 min

3-8 h

Eclampsia; caution with

high intracranial
pressure

Enalaprilat
(Vasotec IV)

1.25-5.00 mg every 6 h

15 min

6h

Acute left ventricular

failure

5-15 mg i.v.
200-500 g/kg/min for 4
min, then 50-300
g/kg/min i.v.
20-80 mg i.v. bolus
every 10 min
2 mg/min i.v. infusion

1-2 min
1-2 min

3-10 min Catecholamine excess

10-20 min Aortic dissection, after
operation

5-10 min

3-6 h

Adrenergic
inhibitors
Phentolamine
Esmolol
(Brevibloc)
Labetalol
(Normodyne, Trandate

Most hypertensive
emergencies except
acute heart failure

Parenteral Drugs for Treatment of

Hypertensive Emergencies based on JNC 7
Drugs

Dose

Onset

Duration of
Action

Sodium
nitroprusside

0.25-10 ugr/kg/min

Immediate

1-2 minutes after

infusion stopped

Nitroglycerin

5-500 ug/min

1-3 minutes

5-10 minutes

Labetolol HCl

20-80 mg every 10-15 min

or 0.5-2 mg/min

5-10 minutes

3-6 minutes

Fenoldopan HCl

0.1-0.3 ug/kg/min

<5 minutes

30-60 minutes

Nicardipine HCl

5-15 mg/h

5-10 minutes

15-90 minutes

Esmolol HCl

250-500 ug/kg/min IV
bolus, then 50-100
ug/kg/min by infusion;
may repeat bolus after 5
minutes or increase
infusion to 300 ug/min

1-2 minutes

10-30 minutes

Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70

Parenteral Drugs for Treatment of

Hypertensive Emergencies based on
ASA Guideline
Drug

I.V. Bolus Dose

Continous Infus
Rate

Labetalol
Nicardipine
Esmolol
Enalapril
Hydralazine
Nipride
NTG

5 20 mg every 15
NA
250 ug/kg IVP loading dose
1,25-5 mg IVP every 6 h
5 20 mg IVP every 30
NA
NA

2 mg/min (max 300mg/d)

5-15 mg/h
25-300 ug/kg/m
NA
1,5-5 ug/kg/m
0,1-10 ug/kg/m
20-400 ug/m

This parenteral drugs are approved for hypertensive emergency

in acute ischemic stroke and intracerebral hemmorhage
AHA/ASA Guideline, 2007 update. Stroke. 2007;38: 2001-2023.

Parenteral Drugs for Treatment of

Hypertensive Emergencies based on CHEST 2007
Acute Pulmonary edema /
Systolic dysfunction

Nicardipine, fenoldopam, or nitropruside combined with

nitrogliceryn and loop diuretic

Acute Pulmonary edema/

Diastolic dysfunction

Esmolol, metoprolol, labetalol, verapamil, combined with

low dose of nitrogliceryn and loop diuretics

Acute Ischemia Coroner

Labetalol or esmolol combined with diuretics

Hypertensive encephalopaty

Nicardipine, labetalol, fenoldopam

Acute Aorta Dissection

Labetalol or combined Nicardipine and esmolol or combine

nitropruside with esmolol or IV metoprolol

Preeclampsia, eclampsia

Labetalol or nicardipine

Acute Renal failure /

microangiopathic anemia

Nicardipine or fenoldopam

Sympathetic crises/ cocaine

oveerdose

Verapamil, diltiazem, or nicardipine combined with

benzodiazepin

Acute postoperative
hypertension

Esmolol, Nicardipine, Labetalol

Acute ischemic stroke/

intracerebral bleeding

Nicardipine, labetalol, fenoldopam

Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62

USE OF NICARDIPINE
Nicardipine :
. Dihydropiridine class of CCB
Reduce peripheral resistance --- blood pressure
water soluble, light insensitive, -- can be
parenteraly used (deference with nifedipine /
sodium nitroprusid)

Classification Calcium Antagonists

Generation:
First
Second
Verapamil
Nifedipine
Diltiazem

Prototype

Felodipine
Isradipine
Nicardipine
Nimodipine
Nisoldipine
Nitrendipine

Third

Latest

Amlodipine Lercanidipine
(hydrophilic) (lipophilic)

Tissue selectivity Tissue selectivity Tissue selectivity

gradual onset
gradual onset
Plasma controlled membrane-controlled

Strong cerebral and coronary vasodilating activity

J Clin Basic Cardiol 1999;2:155

PRIMARY HEMODYNAMIC OF
NICARDIPINE EFFECT
peripheral vasodilatation
preserve or enhanced cardiac pump activity
------ improve tissue perfusion
fall in systemic blood pressure, maintain at desired
level
in comparison with sodium nitropruside equally
effective, but no cyanide toxic effect in long term use
not associated adverse effect on cardiovascular and
renal function

Comparison between Calcium Antagonist

Drug

Coronary
Vasodilation

Suppression
of Cardiac
Contractility

Suppression
of SA Node

Suppression
of AV Node

Verapamil
(phenylalkylamine)

++++

++++

+++++

+++++

Diltiazem
(benzothiazepin)

+++

++

+++++

++++

Nicardipine
(dihydropyridine )

+++++

Kerins DM. Goodman Gilmans.10th ed.2001:843-70

Tissue selectivity between

Calcium Antagonist

Bristow et al. Br J Pharmacol1984; 309:82

Comparison Study with

Intravenous Diltiazem
Subjects:
Patients requiring a rapid reduction in BP (DBP 115 mmHg)
Design:
Multicenter, randomized, single-blind comparative study
Dosage
Nicardipine: Started at 0.5 g/kg/min
Increased up to 10 g/kg/min if necessary
Diltiazem: Started at 5 g/kg/min
Increased up to 15 g/kg/min if necessary
Duration of drug administration
Dose titration: 1 hour
Maintenance infusion: 24 hours

Yoshinaga K. et al. Igaku no Ayumi 1993: 165:437

Stability of antihypertensive
effect better than Diltiazem

Yoshinaga K. et al. Igaku no Ayumi 1993: 165:437

Nicardipine vs Nitrovasodilators
Drug

Nicardipine
(Perdipine IV)

Nitroprusside

Nitroglycerin

Rapid Onset of Peak Effect

++++

++++

+++

Afterload Reduction

++++

++++

Preload Reduction

++

++++

Coronary Steal Reported

Coronary Dilation: Large Vessel

+++

++++

Coronary Dilation: Small Vessel

+++

+/-

+/-

Tachycardia

++

++

Potential for Symptomatic

Hypotension

++

+++

++++

++

+++

++++

Ease of Administration
Cyanide Toxicity

Pepine CJ. Intravenous nicardipine: cardiovascular effects and clinical relevance. Clin Ther.
1988;10:316-25.

Prevention
- Hypertensive crisis are largely preventable
- Risk factors of hypertensive crises :
1. Inadequate management of hypertension by
the
physician
2. Poor adherence to therapy by the patient
3. Insufficient access to care

Prim Care Clin Office Pract 2008; 35: 4754

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TAKE CARE OF YOUR HEART, BRAIN, AND KIDNEY