RUBIN SURACHNO GONDODIPUTRO

Divisi Ginjal Hipertensi

Departemen Ilmu Penyakit Dalam

RSUP Dr. Hasan Sadikin / Universitas Padjadjaran

Bandung

Di USA Hipertensi mengenai 50 juta orang

Di tahun 2000 menimbulkan 250 ribu kematian

akibat kerusakan organ target

30% dari populasi tidak mengetahui dirinya

menderita hipertensi

Hanya 34% berobat dan dapat mencapai tek.

darah < 140/90 mm Hg

HAL-HAL YANG AKAN

DIBICARAKAN PAGI INI

ADALAH:

PREVALENSI

DEFINISI

PATOFISIOLOGI

ETIOLOGI HIPERTENSI KRISIS

CONTOH-CONTOH MANIFESTASI KLINIK

PRINSIP TERAPI DAN OBAT-OBATAN

PREVALENSI

JNC VII melaporkan :

30% tidak menyadari menderita hipertensi

30% tidak pernah berobat dengan baik

Hipertensi emergensi insidensinya tak jelas di

duga hanya 1% saja

PREVALENSI

SULIT MENGELOLA HIPERTENSI EMERGENSI

OLEH KARENA

Definisi tidak pernah konsisten

Dasar literatur sudah tua (20 - 40 tahun)

Sifat yang heterogen, kemungkinan akibat

pengelolaan buruk dari sekelompok kecil

hipertensi esensial atau hipertensi sekunder

PREVALENSI

Laki-laki : Wanita = 2 : 1

Insidensi pada populasi kulit putih menurun

(Australia & New Zealand)

Insidensi pada populasi kulit hitam, Asia dan

Suku Indian meningkat

DEFINISI

Stadium JNC Rentang TDS/TDD

(mmHg)

JNC VI

Normal Tinggi

Stadium 1

Stadium 2

Stadium 3

JNC VII

Prehipertensi

Stadium 1

Stadium 2

130-139/85-89

140-153/90-99

160-179/100-109

180+/110+

120-139/80-89

140-159/90-99

160+/100+

DEFINISI UMUM

Krisis hipertensi : TDD > 120 mm Hg

Termasuk : Hipertensi Emergensi

Hipertensi Urgensi

Hipertensi Berat

DEFINISI

Hipertensi Emergensi :

• Hipertensi berat dengan TDD > 120 mm Hg

• Terdapat KOT AKUT (otak, jantung, Ginjal)

• Menurunkan TD dalam menit – jam

menggunakan obat intravena

• Perlu perawatan di ICU

DEFINISI

Hipertensi Urgensi :

• Hipertensi berat dengan TDD > 120 mm Hg

• Tidak terdapat KOT AKUT

• Bisa bergejala / tanpa gejala (sakit kepala

hebat, cemas, sesak nafas)

• Menurunkan TD dalam 24 – 48 jam

menggunakan obat oral

• Tidak perlu perlu perawatan di ICU

DEFINISI

Hipertensi Maligna :

• Hipertensi Berat

• Disertai kelainan retina Keith – Wagener –Barker stad IV :

- papil edema

- pendarahan retina

- eksudasi retina

• Biasa menggambarkan hipertensi emergensi dengan kelainan SSP

DEFINISI

Hipertensi Akselerasi :

• Hipertensi berat disertai kelainan retina

• Keith – Wagener – Barker stad III :

- perdarahan retina

- eksudasi retina

- tanpa papil edema

DEFINISI

Klasifikasi retinopati : Keith – Wagener – Barker

• Tidak menggambarkan secara akurat dari

beratnya ke TD

• Terminologi / definisi jarang digunakan lagi

Nilai absolut dari kenaikan TD itu sendiri tidaklah begitu

penting, sebab kenaikan TD tiba-tiba yang sedang saja

pada orang yang sebelumnya normotensif sudah dapat

menyebabkan KOT yang kritis (contohnya: preeklamsia

atau glomerulonefritis akut) atau pada pasien dengan

penyakit penyerta seperti aorta desekans atau infark

miokard akut.

PATOFISIOLOGI

• Peran langsung dari ke TD

• Peran mediator endokrin dan parakrin

Patofisiologi – peran kenaikan TD

Local effects

(prostaglandins, free

radical, etc

Systemic effects

(Renin-angiotensin,

catechol, vasopressin)

Endothelial damage

Platelet deposition

Mitogenic and migration

factors

Myointimal proliferation

Pressure natriuresis

Hypovolemia

Further increase in

vasoprossors

Further rise In blood pressure

and

Vascular damage

Tissue ischemia

Critical Degree of Hypertension

Patofisiologi – peran kenaikan TD

Gangguan auto

regulasi

Ke tekanan darah

mendadak

KOT Akut

Resistensi perifer

vascular

Patofisiologi – peran kenaikan TD

Local effects

(prostaglandins, free

radical, etc

Systemic effects

(Renin-angiotensin,

catechol, vasopressin)

Endothelial damage

Platelet deposition

Mitogenic and migration

factors

Myointimal proliferation

Pressure natriuresis

Hypovolemia

Further increase in

vasoprossors

Further rise In blood pressure

and

Vascular damage

Tissue ischemia

Critical Degree of Hypertension

Patofisiologi peran ke TD

Kenaikan mendadak TD

Stress pd

Vaso konstriksi

hipertropi dd pd

NO

Kerusakan

endotel pd

Pelepasan vaso-aktif

gangguan fibrinolisis

aktifasi sistem koagulasi

Isemia jaringan

Tekanan darah

makin tinggi

Nekrosis fibrinoid

adhesi platelet

agregasi

Patofisiologi peran mediator

Endokrin & Parakrin

Local effects

(prostaglandins, free

radical, etc

Systemic effects

(Renin-angiotensin,

catechol, vasopressin)

Endothelial damage

Platelet deposition

Mitogenic and migration

factors

Myointimal proliferation

Pressure natriuresis

Hypovolemia

Further increase in

vasoprossors

Further rise In blood pressure

and

Vascular damage

Tissue ischemia

Critical Degree of Hypertension

“Break through Vasodilatation”

Cerebral Auto-regulation in Hypertensive

Patients

60 120 180

Normotension

Chronic hypertensive

Mean Arterial Pressure (mmHg)

Cerebral Blood

Flow

Increased risk of

encephalopathy

Increased risk of

ischemic

Autoregulasi

• Autoregulasi (perfusi jaringan) diotak, jantung

dan ginjal relatif stabil

• Hipertensi autoregulasi bergeser untuk

melidungi kerusakan jaringan

• Pada keadaan normal atau hipertensi batas

terendah untuk terjadinya hipoperfusi jaringan

adalah 20 – 25% dibawah dari ke TD yang

sedang berlangsung (prinsip pengobatan)

Etiologi

Hipertensi :

95% tak diketahui – essensial

5% diketahui - sekunder

Keduanya berpotensi untuk terjadinya Hipertensi

Emergensi

Etiologi

Kelainan neurologis :

Hiperaktivitas saraf otonom (Sindroma Guillain Barre, spinal cord injury)

Gagal baroreflektor

Cardiovascular accident

Trauma kapitis

Kelainan hormonal:

Pheochromocytoma

Renin atau aldosteron secreting tumors

Kehamilan:

Eklamsia

Preeklamsia

Kelainan autoimmun:

Skleroderma atau kelainan vaskular kolagen

Vaskulitis

Kelainan ginjal:

Glomerulonefritis

Kelainan renovaskular

Obat-obatan :

Interaksi MAO dengan tyramine atau simpatomimetik

Cocaine, amphetamine, phencyclidine

Penghentian tiba-tiba dari obat:

Obat antihipertensi

Alkohol

Manifestasi klinik

Tipe Kasus(%)

Infark serebral

Perdarahan intraserebral dan Subarakhnoidal

Hipertensi Ensefalopati

Edema pulmonal akut

Gagal jantung kongestif akut

Infark miokardial akut dan angina tak stabil

Aorta disekans

Eklamsia

24,5

4,5

16,3

22,5

14,3

12,0

2,0

2,0

Manifestasi klinik

Keterlibatan satu organ target 83%

Keterlibatan dua organ target 14%

Keterlibatan lebih dari dua organ target 3%

Zampaglione

Gejala Klinik Hipertensi Emergensi

Type of

hypertensive emergency

Typical symptoms Typical signs Comment

Acute stroke in evolution

(thrombotic or embolic)

Weakness, altered

motor skill(s)

Focal neroulogical

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)

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 x-

ray

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

Gejala Klinik Hipertensi Emergensi

Evaluasi Klinis Hipertensi

Emergensi

1. Anamnesis lengkap dan terarah

2. Pemeriksaan fisik yang teliti

3. Pemeriksaan penunjang

Severe Hypertension in Emergency

Departement

End Organ Compromise?

Heart Failure

Renal Failure

Encephalopathy

Papiledema

NO YES

Concurrent condition which may mandate

intensive BP control?

Cardiovascular

Aortic dissection

Acute MI

Cerebrovascular

SAH / IC hemorrhage

Acute cerebral infarction

Other

Acute removascular hypertension

Pheochromacytoma crisis

Severe burns

Severe epitaxis

Eclampsia

NO YES

Conservative Management

Monitor BP, Oral

Antihypertensive Rx

Consider Intravenous

Antihypertensive Rx and

invasive Monitoring

Prinsip Pengobatan

Hipertensi Emergensi

• Segera berikan obat yang tepat dan sudah

tersedia walaupun diagnosis belum tegak benar

• Tim di ICU sudah biasa mengelola hipertensi

emergensi

• Pilih pemberian obat yang praktis bila pasien

harus mobile

• first do not harm (Hippocrates)

Prinsip Pengobatan Hipertensi Emergensi

• Goal: cegah progresivitas kerusakan organ

• Harus menggunakan obat intravena

• Utamakan keuntungan pengobatan terhadap perfusi

jaringan terutama otak, miokardium dan ginjal

MIMS Cardiovascular Guide, 2005

Pengobatan Hipertensi Emergensi

Name Dosing Onset of

Action

Duration

of Action

Preload Afterload Cardiac

Output

Renal

perfusion

Sodium

nitroprusside

Labetolol

Fenoldopam

Nicardipine

Esmolol

Methyldopa

Hydralazine

IV 0.25-10 mg/kg/min

IV (20-to 80-mg

bolus/10 min)

IV 0.1-0.6 mg/kg/min

IV 2-10 mg/hr

IV 80-mg bolus over 30

second, followed by 150

mg/kg/min infusion

IV (250-to 1000-mg bolus

every 6 hr)

IV bolus (10-20 mg)

Within

seconds

5-10 min

10-15 min

5-10 min

6-10 min

3-6 hr

10 min

1-2 min

2-6 hr

10-15 min

2-4 hr

20 min

up to 24 hr

2-6 hr

decreased

no effect

no effect

no effect

no effect

no effect

no effect

decreased

decreased

decreased

decreased

no effect

decreased

decreased

no effect

decreased

increased

increased

decreased

decreased

Increased

decreased

no effect

increased

no effect

no effect

no effect

no effect

Condition Preferred antihypertensive agent

Acute pulmonary edema Fenoldopam or nitroprusside in combination

with nitroglycerin (up to 60 g/min) and a loop

diuretic

Acute myocardial ischemia Labetalol or esmolol in combination with

nuitroglycerin (up to 60 g/min)

Hypertensive encephalopathy Labetalol, nicardipine, or fenoldopam

Acute aortic dissection Labetalol or combination of nicardipine or

fenoldopam and esmolol or combination of

nitroprusside with either esmool or

intravenous metoprolol

Eclampsia Labetalol or nicardipine. Hydralazine may be

used in a non-ICU setting

Acute renal failure/

microangiopathic anemia

Fenoldopam or nicardipine

Sympathetic crisis/cocaine

overdose

Verapamil, diltiazem, or nicardipine in

combination with a benzodiazepine

Table Recommended antihhypertensive agents for hypertensive crisis

Pengobatan Hipertensi Emergensi

Modes of

comparison

Hypertensive encephalopathy,

cardiovascular accident,

intracranial hemorrhage

Acute congestive heart

failure or pulmonary

edema

Acute myocardial

infarction or acute

coronary syndrome

Aortic dissection Acute cocaine or

sympathomimetic

intoxication

Therapeutic goal

Suggested agents

Risk of therapy

Pearls

First do no harm, avoid

hypoperfusion

Do not exceed 20%

reduction of BP

Nicardipine: reduces,

cerebral ischemia

Consider ultra short acting

agents (esmolol or

nitroprusside)

Cerebral autoregulation is

disrupted in the ischemic

brain

Patients demonstrate

marked lability of BP with

any agent, and

hypoperfusion of the brain

can occur

There is no clear evidence of

benefit with intensive control

of BP in the setting of stroke

Reduction of BP,

especially by

vasodilatation

Promote diuresis

IV nitroglycerin

Morphine

IV angiotensin

converting enzyme

inhibitor

IV diuretic

Diuretics and

angiotensin converting

enzyme inhibitor can

exacerbate renal

dysfunction

Diuretics are slow to

work

Angiotensin converting

enzyme inhibitor has

rapid onset of action

IV nitrates dilate

capacitance vessels at

low doses, higher

doses dilate arterioles

and lower BP

Redution of BP

Decrease

myocardial

oxygen demand

IV blocker

IV nitroglycerin

Blocker can

exacerbate left

ventricular failure

Blockade also

reduces mortality

associated with

ventricular

arrhythmia

Reduction of

shear orces by

reduction of BP

and tachycardia

IV labetalol

IV blocker

Nitroprusside

Nitroprusside is

extremely potent

and requires

continuous intra-

arterial BP

monitoring

Avoid volume

depletion in

patients requiring

IV dye or going

for general

anesthesia

Reduction of

excessive

sympathomimetic

drive

Benzodiazepine

IV nitroglycerin

IV labetalol

Unopposed blockade

can cause alpha

storm and increase

cocaine toxicity

Measure core

temperature and treat

hyperthermia if

present

Consider the

possibility of

multidrug use

Pengobatan Hipertensi Emergensi

Name Comments Major Side Effects

Sodium nitroprusside

Labetolol

Nicardipine

Esmolol

Methyldopa

Hydralazine

Need to measure thiocyanate

levels, caution in renal

insufficiency

Alpha and beta blocker,

contraindicated in acute

heart failure

Safe in coronary bypass

patients

Short-acting beta blocker,

contraindicated in acute

heart failure

Safe in pregnancy needs

renal dosing

Safe in pregnancy

Cyanide toxicity: nausea, vomiting,

altered mental status, lactic

acidosis, death

Bradycardia, bronchospasm, nausea

Reflex tachycardia, flushing

Bradycardia bronchospasm

Drowsiness, fever, jaundice

Reflex tachycardia, lupus-like

syndrome

TERAPI HIPERTENSI URGENSI

Beberapa hal yang harus diperhatikan :

1. Pengukuran TD akurat

2. Hipertensi reaktif ?

3. Tentukan adakah penyakit dasar

4. Tentukan apakah kenaikan TD. ini hanya

sesaat / seterusnya

5. Prinsip terapi TD harus diturunkan dalam

beberapa jam

6. Tidak perlu terburu-buru

7. Kita memiliki cukup waktu untuk

menurunkan TD sampai tingkat yang

optimal

8. Cegah penggunan obat nifedipine

sublingual

Nifedipine ?

1. 16 pasien diamati : meninggal 2, stroke

4, infark miokard 9, dan aorta diseksi 1

2. Bioavibilitas oral atau bukal buruk

3. 1985 FDA melarang penggunannya

untuk hipertensi emergensi

4. 1996 FDA boleh digunakan dengan

pengawasan ketat apabila tidak ada obat

lain

Grossman E et.al, JAMA, 1996 Oct 3-30; 276(16):1328-31. Review

INGAT TINGKAT URGENSINYA TETAP

BERLAKU SEHINGGA PEMERIKSAAN

PENUNJANG HARUS DILAKUKAN DENGAN

TERARAH DAN LENGKAP

”Diskusi untuk membedakan antara hipertensi berat dan

hipertensi urgensi belum bisa dipecahkan. Pertanyaannya

apakah ada keadaan atau kelainan tertentu yang dapat

membedakan antara hipertensi urgensi dengan

hipertensi berat ?”

“Tidak meragukan bahwa pemeriksaan penunjang

ini harus dilakukan tetapi apakah hasilnya dapat

mendiagnosis suatu hipertensi urgensi masih tetap

dipertanyakan”.

KELUHAN - KELUAHAN

Tak Khas

Sering tanpa gejala

Sakit kepala 12 %

Nyeri otot 18 %

Walaupun tanpa gejala dan KOT pengawasan

harus tetap dilakukan dan tidak memerlukan

perawatan di ICU

BP(mmHg) Follow up

140-159/90-99

160-179/100-109

180-209/110-119

210+/120+

observe and confirm within 2 month

confirm and treat within 1 month

confirm and treat within 1 week

confirm. Evaluate, and initiate th/ immediately with

close follow up

Hypertensive urgencies and treatment

Type of Urgency Drugs of Choice Alternative or

Second-Line

Drugs

Relative

Contraindications

Uncomplicated

malignant

hypertension

Acute renal failure

Perioperative

hypertension

Labetalol, ACEI

Labetalol, minoxidil

+ beta-blocker

Nitroglycerin

nitroprusside

Nifedipine,

clonidine

ACEI, diuretics, or

hemofiltrationa

Labetalol,

nicardipine

Nitroprussideb

a Diuretics should be considered in patients with volume overload only. In oliguric patients, hemofiltration

may be necessary.

b Nitroprusside may be considered if no alternatives are available, but the dose and duration must be

limited to avoid toxicity.

Oral drugs for hypertensive urgencies

Drugs Dosage Onset /

Duration

Indications Adverse effects

Captropril

Clonidine

Labetalol

6.25-25 mg

q6 h

0.1-0.2 mg

hourly, to

max 0.8

mg in 24 h

100-200 mg

q12h

15-30 min/

6 h

30-60 min/

6-12 h

30-120 min/

8-12 h

Well tolerated in

most

scenarios

Severe

uncomplicated

hypertension

Well tolerated in

most

scenarios

Hypertension in

high rennin

states

Sedation,

bradycardia,

dry mouth

Heart failure, heart

block,

bronchospasm

KESIMPULAN

1. Kunci keberhasilan pengobatan adalah

dapat membedakan antara hipertensi

emergensi dan urgensi

2. Ingat kita mengobati pasien dan bukan

angka

3. Pengawasan lebih lanjut perlu

dilakukan untuk mengobati hipertensi

secara komprihensif