Divisi Kardiologi

Bag Ilmu Penyakit Dalam

FK Universitas Islam Sultan Agung
Semarang
Target
Target Organ
Organ Damage
Damage of
of Hypertension
Hypertension
Brain
Brain

Eye
Eye

Heart
Heart

Kidney
Kidney Blood
Blood vessel
vessel
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
 HYPERTENSIVE CRISIS
DBP >140 mmHg

URGENCY EMERGENCY
 BP
BP within
within hours
hours << 24
24 hours
hours  BP
BP within
within minutes
minutes << 11 hours
hours
(PARENTERAL / ORAL) (PARENTERAL)
-- Accelerated
Accelerated malignant
malignant hypertension
hypertension
-- Hypertensive
Hypertensive encephalopathy
encephalopathy
-- Intracerebral/Subarachnoid
Intracerebral/Subarachnoid hemorrhage
hemorrhage
-- Acute
Acute aortic
aortic dissection
dissection
-- Acute
Acute left
left ventricular
ventricular failure
failure
-- Acute
Acute myocardial
myocardial infarction
infarction
-- Acute
Acute glomerulonephritis
glomerulonephritis
-- Eclampsia
Eclampsia
-- Severe
Severe epistaxis
epistaxis
KAPLAN NM . Lancet 344:1335,1994 -- Perioperative
Perioperative hypertension,
hypertension, etc
etc
PATHOPHYSIOLOGY
Critical Degree of Hypertension

Local Effects Systemic Effects

(Prostaglandins, Free Radical, etc. (Renin-angiotensin, Cathecol,
Vasopression

Endothelial Damage
Pressure Natriuresis

Platelet Deposition

Hypovolemia
Mitogenic and Migration
Factors
Further Increase in
Myointimal Proliferation Vasopressure

Further Rise in Blood Pressure

And
Vascular Damage

Tissue Ischemia
M. Kaplan, Clinical Hypertension, 7th edition, Baltimore, 266 : 1998
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
13 (12.0)
angina pectoris
Eclampsia 5 (4.5)

Aortic dissection 2 (2.0)

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

 CLINICAL CHARACTERISTIC OF
HYPERTENSIVE CRISIS

Blood pressure : Usually > 140 mm Hg diastolic

Funduscopic findings : Hemorrahage ,exudate , papilledema
Neurological status : Headache , confusion , somnolence ,
stupor , visual loss , focal deficits ,
seizures , coma
Cardiac findings : Prominent apical impulse , cardiac -
enlargement , congestive failure
Renal : Oliguria , azotemia
Gastrointestinal : Nausea , vomiting

From Kaplan NM : Clinical Hypertension , 6th ed .Baltimore ,Williams & Wilkins , 1994 , p 283
 CIRCUMSTANSCES REQUIRING RAPID
TREATMENT OF HYPERTENSION
Accelerated - malignant hypertension with papilledema
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 glomerulonephritis
Renal crises from collagen - vascular diseases
Severe hypertension after kidney transplantation
 CIRCUMSTANSCES REQUIRING RAPID
TREATMENT OF HYPERTENSION, Con`t

Excessive circulating - cathecholamines

Phoechromocytoma crisis
Food or drug interactions with monoamine oxidase inhibitor
Sympathomimetic drug use ( cocaine )
Rebound hypertension after sudden cessation of antihyperten
sive drugs
Eclampsia , Surgical
Severe hypertension in patients requiring immediated surgery
Postoperative hypertension
Postoperative bleeding from vascular suture lines
Severe body burns , Severe epistaxis

From Kaplan NM : Management Hypertensive Emergencies , Lancet 344: 1335,1994

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

TAHAP PENURUNAN TEK DRH GDH
Tek darah awal
2 jam
MAP 25 %
6 – 12 jam
Td diast :
110 – 100 mmHg
bbrp hari
+ OATDTO
Normotensif
PARENTERAL DRUGS FOR TREATMENT OF
HYPERTENSIVE EMERGENCY
DRUG DOSE ONSET OF ACTION

Nitroprusside 0,25 - 10 g / kg/min as IVinfusion Instantaneous

Nitroglycerin 5 - 100 g / min as IV infusion 2 - 5 min
Nicardipine 5 - I5 mg / hr IV 5 - 10 min
Hydralazine 10 - 20 mg IV 10 - 20 min
10 - 50 mg IM 20 - 30 min
Enalapril 1.25 - 5 mg q 6 hr 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 1 - 2 min
150 - 300 g / kg / min IV
Labetalol 20 - 80 mg IV bolus every 10 min 5 - 10 min
2 mg / min IV infusion

Braunwald , 2001
 COMMONLY USED DRUG IN
HYPERTENSIVE EMERGENCY

CLONIDINE I.V.
• Reduce peripheral sympathetic tone by central
stimulation of alpha-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 Vena- dilator).

• Direct interacting with nitrate receptors on vascular
smooth muscle.
• A rapid onset and duration of action.
• Adverse effect : headache, tachycardia, nausea,
vomiting.
 COMMONLY USED DRUG IN
HYPERTENSIVE EMERGENCY

NIFEDIPINE S.L

• May be useful for hypertensive urgency only.

• Acts as calcium slow-channel blockers.
• Sub-lingual : Unpredictable target BP.
• Adverse effect : oedema, tachycardia, hypotension,
headache, flushing.
• May precipitate myocardial ischemia.
 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 targets HER CLON NTG NIFE
Cardioprotective
Heart rate
Ischemic

Dilate: coroner ++ - ++ +
Anti-

collateral ++ - - -
Antiarrhytmic + - - -
Antivasospasm ++ - - +
Renoprotective
Afferent + - - +
RBF - -
Efferent + - - -
CGP - -
Cerebroprotective
CBF
Epstein M, 1991, Bakris GL, 1993, Mancia G, 1996, Messerly FH, 1996
DILTIAZEM INTRAVENOUS
The role in Renoprotection:
•Maintenance Renal Blood Flow
•Maintenance Glomerular Filtration Rate
•Normalized Intraglomerular Pressure
•Inhibit Proteinuria
•Inhibit cyclosporine nephrotoxicity
The role in Cardioprotection:
•Maintenance Cardiac Index
•Increase Coronary Blood Flow
•Inhibit Coronary spasm
•Without Reflex Tachycardia
•Has Antiarrhythmic Effect
The role in Cerebroprotection:
•Maintenance Cerebral Blood Flow
•Normalized Intracranial Pressure
•Inhibit Vasospasm
Epstein M. 1991 Wagner K., et al.; Amer J Nephrol 1987; Fasol R, et al.Drug of Today 1998;
Hirayama T., et al; Neurol Res 1994;Kuroda K.; et al; Neurol Res 1997;
 DILTIAZEM-Injection
Applicable
Applicable in
in ::

••Hypertensive
Hypertensive Peri-Operative,
Peri-Operative,
••Hypertensive
Hypertensive Emergency,
Emergency,
••Supraventricular
Supraventricular Tachycardia,
Tachycardia,
••Atrial
Atrial Fibrillation,
Fibrillation, Atrial
Atrial Flutter,
Flutter,
••Unstable
Unstable Angina
Angina Pectoris,
Pectoris,
••PTCA,
PTCA, CABG
CABG
 DILTIAZEM-Injection
Dosage and Administration
Each
Each ampoule
ampoule of of DILTIAZEM-Injection
DILTIAZEM-Injection should
should be
be
dissolve
dissolve in
in at
at least
least 55 mL
mL aquadest
aquadest or
or NaCl
NaCl or
or glucose
glucose
solution
solution before
before use.
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% MBP reduction
10’
From Baseline
Drip infusion
50 mg/hour
20% MBP reduction
20’ From Baseline
Drip infusion
30 mg/hour
Target MBP
30’ Level
Drip infusion
5-10 mg/hour
Every 30-60 minutes observation

Switch to Oral
DILTIAZEM 180SR
DILTIAZEM INJECTION
Contraindications
• Severe bradycardia (sick sinus syndrome, 2nd or 3rd degree
of AV-block)
• Hypotension (SBP <90 mmHg)
• MI associated with CHF
• Pregnancy
• Hypersensitivity to diltiazem

Precautions
• Bradycardia (Heart rate <50 bpm), 1st degree of AV-block
• severe liver dysfunction

Possible adverse reactions

• Bradycardia 0.24% Hypotension 0.19%
• headache 0.17% Flushing
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.
PATHOPHYSIOLOGY
Critical Degree of Hypertension

Local Effects Systemic Effects

(Prostaglandins, Free Radical, etc. (Renin-angiotensin, Cathecol,
Vasopression

Endothelial Damage
Pressure Natriuresis

Platelet Deposition

Hypovolemia
Mitogenic and Migration
Factors
Further Increase in
Myointimal Proliferation Vasopressure

Further Rise in Blood Pressure

And
Vascular Damage

Tissue Ischemia
M. Kaplan, Clinical Hypertension, 7th edition, Baltimore, 266 : 1998
 DILTIAZEM-Injection
Indication and Dosage
Hypertensive Peri-Operative
•Bolus I.v. injection 0.20 - 0.35 mg/kg
•over 1-3 minutes, followed by : Drip I.v. infusion
5 - 15 mcg/kg/min

Hypertensive Emergency or UAP

•Drip intravenous infusion : 5 - 15 mcg/kg/min

Tachyarrhytmias
•Paroxysmal Supraventricular Tachycardia (PSVT)
•Atrial Fibrillation
•Atrial Flutter
•Bolus I.v. injection 0.20 - 0.25 mg/kg over 1-3
minutes