How to Overcome

Hypertension Crisis?
Dr. Rinelia Minaswary, SpJP - FIHA
RS Syafira Pekanbaru
 SEJARAH
Presiden AS FD. Roosevelt:
Penderita severe hypertension
Meninggal karena HT emergensi
 Blood pressure goal JNC 8 guideline
Patient characteristics BP threshold for starting BP goal
drug therapy

<60 yrs/CKD/DM 140/90 <140/90

60 yrs * 150/90 <150/90

 Severe Hypertension
Emergency or Not?
Most hypertensive crises are preventable
Result from inadequate management hypertension or non-
adherence to therapy
About 1% of adults with hypertension have a hypertensive
crisis
Hypertensive crises constitute as many as 25% of all visits
to busy metropolitan emergency departments (EDs)
Hypertensive emergencies account for 25% to 30% of these
cases
 Definitions
Hypertensive Crises
Acute increasing of BP
>180/110 mmHg
Need immediate treatment

Hypertensive Urgency Hypertensive Emergency

Markedly elevated BP Markedly elevated BP

Without severe symptoms or With acute or progressing
progressive target organ damage target organ damage
BP should be reduced within hours BP should be reduced immediate
ORAL AGENTS PARENTERAL AGENTS

Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9 th Ed, Lippincott Williams & Wilkins 2006:609-630
 Faktor Risiko Krisis Hipertensi

Riwayat hipertensi : Operasi , seperti :

konsumsi antihipertensi tidak operasi cardiothoracic, vascular,
teratur kepala, leher & neurosurgical

Krisis hipertensi Kerusakan pada aorta

Penyakit jantung
(seperti : aortic dissection)
Gagal jantung
Serangan jantung
(infark miokard)

Eklamsia/
Penyakit ginjal
preeklamsia
 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
Damages caused by Vascular Damage
Hypertension
Tissue Ischemia

M. Kaplan, Clinical Hypertension, 7th edition, Baltimore, 266 : 1998

 Clinical Presentation of Hypertension
Emergency
30%

25%
25%
23%

20%
16%
14%
15%
12%

10%

5%
5%
2%

0%
Cerebral ICH or SAH Hypertensive Acute Acute CHF AMI or UAP Aortic
Infarction encephalopathy pulmonary dissection
edema

Zampaglione B, Pascale C et al. Hypertension 1996;27:144-7

 Organ involved in Hypertensive
Emergency

Single-organ involvement 83%

Two-organ involvement 14%
Multi-organ failure which means
failure of at least 3 organ systems 3%
 Gejala hipertensi urgensi dan emergensi

Hipertensi Urgensi Hipertensi emergensi

Bisa juga asimptomatik Gejala :
Gejala- gejala , seperti : Mual-muntah(cerebral edema)
Sakit kepala parah Nyeri dada
Nafas pendek Nafas pendek (dyspnea)
Mimisan Pandangan mata kabur
Ansietas Confusion (bingung)
Kehilangan kesadaran
Tanda : Tanda:
Peningkatan TD Retinal hemorrhages atau papilledema
Gangguan renal (malignant nephrosclerosis) dengan
Acute Kidney Injury (AKI), proteinuria, hematuria
Cerebral edema kejang dan koma
Pulmonary Edema
Myocardial Infarction
Hemorrhagic Stroke, lacunar infarcts
Pemeriksaan Awal
ANAMNESIS
Riwayat hipertensi dan terapi sebelumnya.

Konsumsi obat-obatan: Simpatomimetik, Obat Warung

Anamnesis gejala keterlibatan organ target: otak, jantung, pandangan, BAK

PEMERIKSAAN FISIK
Tekanan Darah

Funduskopi penting. SERING TERLUPAKAN

Status neurologis

Status Kardiopulmonal

Status fluid volume

Pulsus perifer

M. Kaplan, Clinical Hypertension, 7th edition, Baltimore, 267 : 1998

PEMERIKSAAN LABORATORIUM
Darah Rutin
Urinalisis
Ureum/Kreatinin, GDS, Elektrolit
EKG
Foto Thorax
Kadar aldosterone (jika dicurigai aldosteronisme primer)
Pemeriksaan metanephrine (jika dicurigai phaekromsitoma)
TENTUKAN TARGET
ORGAN

- Stroke
- Sindroma Koroner Akut
- Diseksi Aorta
- Gagal ginjal akut
- Perdarahan retina
 Management of Hypertensive Emergency
o Patients should be admitted to an Intensive Care Unit for
continuous monitoring of BP and parenteral administration
of an appropriate agent
o The initial goal therapy is to reduce mean arterial BP by no
more than 25% (within minutes to 1 hour).
o Then if stable, to 160/100 to 110 mmHg within the next 2 to
6 hours.
o Excessive falls in pressure that may precipitate renal,
cerebral, or coronary ischemia should be avoided.
o 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

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

Obat Antihipertensi Apa yang Dipakai ??
 Parenteral Drugs for Treatment of
Hypertensive Emergencies based on JNC 8
Duration of
Drugs Dose Onset
Action
1-2 minutes after
Sodium nitroprusside 0.25-10 ugr/kg/min Immediate
infusion stopped

Nitroglycerin 5-200 ug/min 1-3 minutes 5-10 minutes

20-80 mg every 10-15 min or 0.5-2

Labetolol HCl 5-10 minutes 3-6 minutes
mg/min

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

250-500 ug/kg/min IV bolus, then

50-100 ug/kg/min by infusion;
Esmolol HCl may repeat bolus after 5 minutes 1-2 minutes 10-30 minutes
or increase infusion to 300
ug/min
Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70
 Parenteral Drugs for Treatment of
Hypertensive Emergencies based on CHEST 2007
Acute Pulmonary edema / Systolic Nicardipine, fenoldopam, or nitropruside combined with nitrogliceryn and
dysfunction loop diuretic
Acute Pulmonary edema/ Diastolic Esmolol, metoprolol, labetalol, verapamil, combined with low dose of
dysfunction 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 Nicardipine or fenoldopam
anemia
Sympathetic crises/ cocaine oveerdose Verapamil, diltiazem, or nicardipine combined with benzodiazepin

Acute postoperative hypertension Esmolol, Nicardipine, Labetalol

Acute ischemic stroke/ intracerebral Nicardipine, labetalol, fenoldopam
bleeding

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

 Calcium Channel Blocker

Nicardipine antihipertensi golongan calcium channel blocker dihidropiridine generasi

kedua.
 Cardiac vs Vascular Selectivity of CCB

Arteriole
Aorta

Great Veins (SVC)

Pulmonary Artery

SA node
Diltiazem
Coronary Artery
Verapamil
AV node Nifedipine Felodipine,
Isradipine,
Amlodipine
Myocardium Nicardipine,
Lecarnidipine Nisoldipine
(100:1)

Non Dihydropyridine Dihydropyridine

SA dan AV nodes > Myocardium = Vessels Vessels > Myocardium > SA & AV nodes
 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 BP
gradually < 25% in 2 hours, minimal effects to heart rate
5. Increase blood flow in major organ : Renal, coronary,
cerebral
EFEK NICARDIPINE

Tidak berpengaruh terhadap :

HEART RATE
PRELOAD

Sedikit berpengaruh terhadap Myocardial

contractility

Berefek terhadap systemic vascular resistance

Salgado et al. Annals of Intensive Care 2013, 3:17

http://www.annalsofintensivecare.com/content/3/1/17
 Comparison between Calcium Antagonist

Suppression
Coronary Suppression Suppression
Drug Vasodilation
of Cardiac
of SA Node of AV Node
Contractility

Verapamil
++++ ++++ +++++ +++++
(phenylalkylamine)

Diltiazem
+++ ++ +++++ ++++
(benzothiazepin)

Nicardipine
+++++ 0 + 0
(dihydropyridine )

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

 Mekanisme Kerja Nicardipin

Nicardipin
Ca2+ masuk dari
Menghambat influks (masuknya ion
luar sel kalsium) ke dalam sel otot, sehingga
tidak terjadi kontraksi otot pada
pembuluh darah
Membran sel

Ca2+ yg masuk
menstimulasi
pelepasan
penyimpanan Ca2+
internal
Resistensi Perifer

Tekanan darah

Kontraksi otot
pembuluh darah
 Nicardipine Increase Organ Blood
Flow
Pharmacodynamic
%) action
Mean blood Vertebral artery Renal Coronary
pressure blood flow blood flow blood flow
60
Blood flow change rate

Nicardipine: 3 g/kg/min 20 min

40
(Hypertensive
Mean blood pressure 103 patients,
11 mmHg n = 9)
20 Vertebral artery
183 65 mL/min
blood flow
Renal artery
563 29mL/min
Baseline value
0 blood flow
Mean blood pressure

Coronary artery
121 42 mL/min
change rate

blood flow
-10

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

JNC 8
American Stroke Association 2007
American Stroke Association 2010
Guideline Stroke PERDOSSI 2007
Konsensus INASH 2008
Guideline POGI 2010
 KONTRAINDIKASI

Pasien dengan suspected incomplete hemostasis diikuti dengan

intracranial hemorrhage
Pasien dengan tekanan intrakranial yang meningkat pada tahap
akut stroke serebral. Tekanan intrakranial dapat lebih lanjut menjadi
meningkat.
Pasien riwayat hipersensitivitas terhadap nicardipine hidroklorida.
 Pemakaian untuk Populasi tertentu

Geriatrik
Diawali dengan terapi dengan dosis rendah (0.5 mcg/kg/menit) dan dilanjutkan
dengan monitoring seksama.

Pediatrik
Keamanan nicardipine hidroklorida pada prematur, bayi baru lahir, bayi
menyusui dan anak-anak belum diketahui

Wanita hamil dan menyusui

Nicardipine hidroklorida hanya diberikan pada wanita hamil dan yang diduga hamil
jika dirasakan benefit lebih besar dibandingkan dengan risiko dari terapinya
Tidak direkomendasikan selama laktasi. Jika selama laktasi harus diberikan, maka
pasien harus berhenti menyusui
 ILUSTRASI KASUS
Tn SUH, 35 thn
Pasien lama dg Dx: CKD ST IV ec HT & GNK, HHD.
Tanda Vital
CM,
Renogram: CCT 18 ml/mnt. Sempat HD 4 x, namun tidak
dianjurkan HD rutin. TD 210/110 mmHg,
Kontrol rutin dengan terapi: Nifedipin 3x10 mg, ISDN 3 x 5 Frekuensi nadi 110 x/mnt teratur
mg, Vit B12 1 x 1 tab, caps camp 1 x 1 tab, Furosemid 1xI Frekuensi nafas 40 x/mnt,
Suhu 38 C.
Kel Utama: Sesak nafas berat.
Sesak nafas 1 hari, timbul setelah sholat,
DOE (+), PND (+). Mual (+). Batuk (+). Hari II perawatan,
BAK biasa, bening. BAB dbn. TD 270/120 mmHg,
Nadi 100 x/mnt, Nafas 20 x/mnt,
suhu afebris.
Keluhan: mual
Pemeriksaan Fisik:
Konjungtiva pucat
JVP 5 + 3 cmH2O.
Paru: ronkhi basah halus lapangan paru, dengan ronkhi basah
kasar di paru kanan bagian tengah disertai mengi.
Jantung: kesan kardiomegali, bunyi Jantung I dan II reguler cepat,
BJ 2 (P2) mengeras,
PSM 3/6 di apex dan parasternal kiri mengeras dengan Laboratorium:
inspirasi Hb; 6.9
Abdomen: asites, hepar teraba 4-5 jari bac. Ht: 24

Ekstremitas: oedema berat. Leukosit: 22.200

GDS: 119
Eritrosit: 3,7

Trombosit: 187.000 AGD

MCV/MCH/MCHC: 65/19/29 pH 7.002
Ureum/kreatinin: 241/17,8 pCO2 20.6
Na/K/Cl: 131/5,5/119 pO2 93
HCO3 5.0

BE -24.8
Sat O2 92.7
 Pemeriksaan Opthalmologist
Retinopati hipertensi grade III ODS dan
pterigium grade II ODS non-inflamed.
Anjuran untuk kontrol tekanan darah dan gula
darah.

CTR 65 %
Segmen Aorta melebar
Kesan: Hypertensive Heart Disease. Segmen pulmonal N
Apex downward
Infiltrat di paru kiri medial
Kongesti (++)
Diagnosis
Acute on CKD st IV-V dengan asidosis metabolik berat,
hiperkalemia dan anemia MH
ADHF pada CHF fc III-IV ec HHD, Suspek MR, TR, PH

Hipertensi Emergency

Pneumonia Lobaris Kanan medial

Hiponatremia hipervolume

Terapi:
O2 Mask 10 Liter/mnt,
Inj morfin 2 mg perlahan iv,
Lasix 2 Ampul iv,
Natrium Bikarbonat 300 mEq,
Nitrogliserin drip mulai 5 g/menit, uptitrasi sesuai dengan
klinis dan tekanan darah,
Lasix drip 5 mg/jam.
HD cito
Menunggu HD Cito
NTG dititrasi 150 g/mnt TD 190/90 mmHg.
NTG stop. Ganti Nicardipine drip
Dosis Nicardipine 0,5 g/kgBB/jam, hingga 1 g/kgBB/jam.
TD tercapai 160/90 mmHg
TD dipertahankan 160/90 mmHg.

Pasien di-HD selama 2 jam,

Ditarik cairan 250 cc.
Paska HD
TD 150/80 mmHg,
Nadi 100 x/mnt,
Nafas 30 x/mnt
Suhu 36,8oC,
 DISKUSI
Pasien I, Pria 35 tahun.
HT Emergensi dengan target organ:
Jantung -- Acute Heart Failure

Penyulit:
CKD st IV-V dengan asidosis dan overload
Infeksi Paru

Antihipertensi :
Parenteral Nitrogliserin drip hingga 150 g/mnt
Target TD belum tercapai
NTG stop.
Nicardipine hingga 1 g/kgBB/jam
TD 150/90 mmHg
HD cito
 PENTING UNTUK DIINGAT

Pastikan adanya Organ Target

FIRST, do no Harm
Tentukan Target TD
Tentukan obat:
Ketahui dosis, cara kerja, efek samping
Cara memberikan obat
Cara titrasi
Pengawasan adekuat
Ruang intensif
Cek TD & nadi setiap 15 menit pada fase akut
 SUMMARY
Hypertensive Emergency is an urgent situation that need rapid
management to prevent organ damage
Antihypertensive agent preferred in this condition should be fast
action, parenteral, and titrate-able
Nicardipine is recommended by JNC 8, ASA 2007, CHEST 2007, ASA
2010 and also national guideline to manage hypertensive emergency
Nicardipine has excellent safety profile to preserve major organs
THANK YOU
KERUSAKAN ORGAN

Flanigan JS, Vitberg D. Hypertensive Emergency and Severe Hypertension: What to Treat, Who to Treat, and How to Treat. Med Clin N Am
2006;90:439-451
Putative Vascular Pathophysiology of Hypertensive Emergencies

Vasodilator VS Vasoconstrictor
Lancet 2000; 356: 41117
Lancet 2000; 356: 41117
Kurva Aliran Darah Serebral pada Hipertensi Kronik

Kurva bergeser ke kanan pada hipertensi kronik

Ruland S, Aiyagari. Cerebral Autoregulation and Blood Pressure Lowering. Hypertension;2007:977-978.

Kaplan NM. Kaplans Clinical Hypertension. 8th ed. 2002; p345
 Anjuran JNC VII
Penurunan tekanan darah < 25% dalam 1 jam.
Jika stabil, target:
160/110 mmHg dalam 2 6 jam.
Antihipertensi IV berdasarkan literatur
 APA YANG TERSEDIA ??
JENIS OBAT DOSIS TARGET ORGAN PERHATIAN KHUSUS

Nitroglycerin Bolus 200-300 mcg ACS, AHF Peningkatan tekanan

Drip 5 150 mcg/menit Diseksi Aorta intrakranial

Nicardipine 5 15 mg per jam Stroke Refleks takikardia, hati-hati

ACS pada heart failure.
Diseksi Aorta
Verapamil Bolus 5 10 mg, lanjut drip 3 Diseksi aorta Hati-hati pada heart failure,
25 mg/jam bradikardia

Metoprolol Bolus 2.5 5 mg boleh diulang Diseksi aorta Hati-hati pada heart failure,
3x, ACS bradikardia, gangguan
Lanjut dengan oral. konduksi
Furosemide Bolus 1-2 mg/kgBB, dilanjutkan Heart failure, Hipovolemik, gangguan
drip 3-20 mg/jam Stroke dengan peningkatan elektrolit
TIK
Isosorbid dinitrate Drip 2 10 mg/jam ACS, AHF
Diseksi Aorta
Management of Hypertension
in Acute Cardiovascular
and Renal diseases

Critical Pathways in Cardiology, vol.6;4,Dec 2007

Flanigan JS, Vitberg D. Hypertensive Emergency and Severe Hypertension: What to Treat, Who to Treat, and How to Treat.
Med Clin N Am 2006;90:439-451
Opie LH, Gersh BJ Drugs for the Heart, Elsevier Inc, Philadelphia, Pennysilvania,
2005