Dr I Ketut Sujana SpPD

COMPLICATIONS OF HYPERTENSION

Acute Complication

Chronic complication

- Abruptly

- Gradually

- Related with accelerated

- Related with duration

elevation of BP
- BP must be decreased

aggressively

of hypertension
- BP managed smartly

COMPLICATIONS OF HYPERTENSION

Acute Complication

Chronic complication

- Abruptly

- Gradually

- Related with accelerated

- Related with duration

elevation of BP
- BP must be decreased

aggressively

Hypertensive Crisis

of hypertension
- BP managed smartly

Definition :
Hypertensive crisis :

Severe elevation of blood pressure, which must be

reduced immediately
Classification :
Hypertensive emergency :

accompanied by acute target organ damage

BP must be reduced within minutes
Hypertensive urgency :
no acute organ damage
BP must be reduced within hours
Clinical Hypertension, Kaplan 2003

Hypertensive Crises

Hypertensive Urgency

Markedly elevated BP
Without severe symptoms or
progressive target organ damage
BP should be reduced within hours
Oral agents

Hypertensive Emergency

Markedly elevated BP
With acute or progressing
target organ damage
BP should be reduced immediate
Parenteral agents

Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9th Ed,

Lippincott Williams & Wilkins 2006:609-630

Definition :
Not determined by BP level, but rather the imminent

compromise vital organ function

Formerly when :
systolic

180 mm Hg

diastolic

110 mm Hg
(stage III ESH)

The Kidney and Hypertension, Bakris, 2004

High blood pressure in asymptomatic chronic hypertension

IS NOT A HYPERTENSIVE CRISES

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 EMERGENCY
Accelerated-malignant hypertension with papilledema
Cerebrovascular conditions
Hypertensive brain infarction with severe hypertension
Intracerebral hemorrhage
Subarachnoid hemorrhage
Head trauma
Cardiac conditions
Acute aortic dissection
Acute left ventricular failure
Acute or impending myocardial infarction
After coronary bypass surgery
Renal conditions
Acute glomerulonephritis
Renovascular hypertension
Renal crises from collagen-vascular diseases
Severe hypertension after kidney transplantation

Hypertensive emergency (contd)

Excess circulating catecholamines
Pheochromocytoma crisis
Food or drug interactions with monoamine oxidase inhibitors
Sympathomimetic drug use (cocaine)
Rebound hypertension after sudden cessation of antihypertensive drugs
automatic hyperreflexia after spinal cord injury

Eclampsia
Surgical conditions
Severe hypertension in patients requiring immediate surgey
Postoperative hypertension

Postoperative bleeding from vascular suture lines

Severe body burns
Severe epistaxis
Thrombotic thrombocytopenic purpura

Sign and symptom in various types of hypertensive emergency

Type of
hypertensive emergency

Typical symptoms

Typical signs

Comment

Acute stroke in evolution

(thrombotic or embolic)

Weakness, altered
motor skill(s)

Focal neruological
deficit(s)

Hypertension not
usually treated

Suibarachnoid hemorrhage

Headache,
delerium

Altered mental
status, meningeal
signs

Lumbar puncture
typically shows
xanthochromia or red
blood cells

Acute head injury/trauma

Headache, altered
sensorium or
motor skills

Lacerations,
ecchymoses,
altered mental
status

Computed
tomographic (CT)
scan is helpful to
determine extent of
intracranial injury

Hypertensive
encephalopathy

Headache, altered
mental status

papilledema

Usually a diagnosis of
exclusion

Cardiac ischemia/infraction

Chest discomfort,
nausea, vomiting

Abnormal EKG
(esp. T-wave
elevations)

Sign and symptom in various types of hypertensive emergency (contd)

Type of
hypertensive emergency

Typical symptoms

Typical signs

Comment

Acute left ventricular

failure/pulmonary edema

Shortness of
breath

Rales auscultated
in chest

Aortic dissection

Chest discomfort

Widened aortic
knob on chest xray

Echocardiogram,
chest CT, or
angiogram usually
needed to confirm

Recent vascular surgery

Bleeding,
tenderness at
suture lines

Bleeding at suture
lines

Often require surgical

revision of vascular
anastamosis

Pheochromocytoma

Headache,
sweating,
palpitations

Pallor, flushing,
rare skin signs
(phakomatoses)

Phentolamine is very
useful

Drug related catecholamine

excess state

Headache,
palpilations

tachycardia

History regarding
drug exposure is key

Preeclampsia / eclampsia

Headache, uterine
irritability

Edema,
hyperreflexia

New treatment
guidelines exist

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 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

Nitroglycerin
Nitroglycerin is a potent venodilator and only at high doses affect
arterial tone. It reduces BP by reducing cardiac
ouput and preload which are undesirable effects in patient with
compromised cerebral and renal perfusion

Nifedipine
Nifedipine has been widely used via oral or sublingual
administration in the management of hypertensive
emergencies. This mode of administration has not been
approved by FDA and since JNC VI because it may cause
sudden uncontrolled and severe reductions in blood pressure
may precipitate cerebral, renal, and myocardial ischemia that
have been associated with fatal outcomes

Clonidine
Central

alfa blocker, sedative effect

CI : in patient with Cerebrovascular
accident
Rebound effect

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)

Calcium Channel Blocker Mechanism

Ca++

Blocking
effect of CCB

Ca++

Ca++ plus Calmodulin

Myosin Kinase

Ca++ plus Calmodulin

Myosin Kinase

Actin-Myosin Interaction
Contraction

Ca++

Ca++

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

NICARDIPINE
CHARACTERISTIC
1.VASOSELECTIVITY
Nicardipine selectivity 30.000 x in smooth muscle cells
blood vessels compared with myocardium
2. Myocardial depression (-)
3. Negative inotropic (-)
4. Rapid and stable antihypertensive effects, reduce blood
pressure gradually < 25% in 2 hours, minimal effects to
heart rate
5. Increase blood flow in major organ : Renal, coroner,
cerebral

Actions to increase organ blood flow

Pharmacodynamic action

Perdipine: 3 g/kg/min 20 min

%)
Blood flow change rate

60
40

Mean blood
pressure

Vertebral
artery
blood flow

Renal
blood flow

Coronary
blood flow

(Hypertensive patients, n = 9)

Baseline value
Mean blood pressure

Mean blood pressure

change rate

20
0

-10

103 11 mmHg

Vertebral artery
blood flow

183 65 mL/min

Renal artery
blood flow

563 29mL/min

Coronary artery
blood flow

121 42 mL/min

-20

(%)
(Shoji Suzuki, et al., The 20th Annual Scientific Meeting of the Japanese Society of Hypertension: 1997)

Tissue selectivity between

Calcium Antagonist

Bristow et al. Br J Pharmacol1984; 309:82

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

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
Stability Effect
120
100

80

Perdipine
Diltiazem

95.8
69

60
40

24.1

20

4.2

6.8

0
Stable

Slightly unstable

Undeterminable

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.

Perdipine for preeclampsia

DOSIS

PERDIPINE
DIV
(g/kg/min)

Bolus
(g/kg)

Acute hypertensive crises during surgery

2 - 10

10 30

Hypertensive emergencies

0.5 6

Acute hypertensive crises during surgery

Hypertensive emergencies

0.5

(g/kg/min)

10

Dosage and Administration

Start with the lowest dose.
Eg 0.5 mcg/BW/min 15 drops monitoring, if in 5-15
minutes theres no significant blood pressure reducing
Increasing drip until 20 drop , and then can be increased
until desirable blood pressure achieved ( about 3-5 drops
each after monitoring)
Monitoring blood pressure and heart rate frequently
Before choose to switch to oral, 1 hour before Perdipine
is stopped, give oral drugs and Perdipine is tappered of

PERDIPINE
The 1st line treatment of Hypertensive Emergency

Could be used :
Sodium Chloride / NaCl
( OTSU-NS : 100/250/500 ml )
Dextrose 5%
( OTSU-D5 : 100 / 250 / 500 ml )
Glucose 5%
Potacol R

Ringer Asetat
KN 1A / 1B / 4A

Couldnt be used :
Sodium bicarbonat
Ringer Laktat

SUMMARY

Hypertensive Crises is an urgent situation that need rapid

management to prevent organ damage

Antihypertensive agent that preffered in this condition should

be fast action, parenteral, and titratable

Nicardipine is the only Calcium Antagonist recommended by

JNC 7, AHA, 2007, CHEST 2007 to manage hypertensive
emergency

Nicardipine has favorable antiischemic profile

because of
an increase myocardial , brain, and kidney oxygen supply

THANK YOU FOR YOUR ATTENTION

TAKE CARE OF YOUR HEART, BRAIN, AND KIDNEY