Zulkhair Ali

Dept. Of Medicine, Div. Nephrology & Hypertension

FK Unsri/ RSMH
 SBP >180 or DBP >120
 Urgency = no signs of end-organ damage
 Days to Weeks
 Emergency = signs of end-organ damage
 Minutes to Hours

 Need to know pt’s baseline before crisis

 Incidence: only <1%
 But HTN: >50 million!
 Definition
 HYPERTENSION 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 oedema, 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, 1999
Krisis hipertensi:
 Suatu keadaan peningkatan tekanan darah
yang mendadak (sistole ≥180 mmHg dan/atau
diastole ≥120 mmHg), pd penderita hipertensi,
yg membutuhkan
penanggulangan segera.

InaSH (Indonesian Society of Hypertension) 2008

 Hypertension Crisis
DBP >120 mmHg
URGENCY
 BP within hours < 24 hours
( PARENTERAL / ORAL )
1. KAPLAN NM., Lancet 344:1335,1994
2. KAPLAN NM., 8th edition., 2002 p : 339-40
EMERGENCY
 BP within minutes < 1 hours
( PARENTERAL )
- Accelerated malignant hypertension
- Hypertensive encephalopathy
- Intracerebral / Subarachnoid hemorrhage
- Acute aortic dissection
- Acute left ventricular failure
- Acute myocardial infarction
- Acute glomerulonephritis
- Eclampsia
- Severe epistaxis
- Perioperative hypertension, etc
End Organ Damage Type Case (%)

Cerebral Infarction 24,5

Intracerebral or Subarachnoid Bleed 4,5
Hypertensive Encephalopathy 16,3
Acute Pulmonary Edema 22,5
Acute Congestive Heart Failure 14,3
Acute Myocardial Infarction or Unstable Angina 12,0
Aortic Dissection 2,0
Eclampsia 2,0

Clanigan JS & Vitberg D. Med Clin N Am 2006

 BP Elevation
+
End-Organ Damage
 Therapy Approach
in Hypertensive Crises
As there have been no large clinical trials investigating
the optimum therapy, treatment is dictated by consensus
on the basis of case-controlled studies and expert’
opinion
We should consider :
- particular features of the clinical situation
- end-organ complications,
And not purely the absolute value of blood pressure
 Therapy of Hypertensive Crises
HYPERTENSIVE EMERGENCY
PATIENTS should be hospitalized
BP should be reduced :
- immediately
- Gradually
- Specifically
DRUGS should be used i.v :
- take care of the fluid homeostatis
Recommended Rate of Decrease
in Blood Pressure

EXTRACEREBRAL END-ORGAN DYSFUNCTION

- rapid lowering of BP by no more than 20-25 % of mean BP in 2 hrs
- the decrease of DBP to 100-110 mmHg in 2 hrs

CEREBRAL END-ORGAN DYSFUNCTION

- in patient with stroke antihypertensive therapy is not recommended
routinely !
- gradually decrease BP only if it is extremely high ( > 220 / 130 mmHg )
- in patient with hypertensive encephalopathy we should lower BP by 20% or
to DBP 100 mmHg within 2 hrs
 The Initial Goal of Therapy in Hypertensive
Emergency Is to Reduce MABP by No More Than
25% (within minute to 1 hour), then if stable, to
160/100-110 within the next 2-6 hours.

JNC 7, The Lancet 2003

 The mean arterial pressure (MAP) is defined as the average
arterial pressure during a single cardiac cycle.
MAP = (CO x SVR) + CVP

 Estimation
MAP= DP+ 1/3 (SP-DP)
MAP= 2/3(DP)+ 1/3(DP)
MAP= (2xDP) + SP/3
MAP = DP + 1/3 PP

 Clinical significance
 MAP is considered to be the perfusion pressure seen by
organs in the body.
 MAP is normally between 70 to 110 mmHg[6]
 If the MAP falls significantly below , the end organ will not
get enough blood flow, and will become ischemic.
Blood Pressure reduction target of crisis
hypertensive patients:
 Parenteral anti hypertension is given based
on the procedure of crisis hypertensive
treatment with MAP reduction 20-25%
from the baseline in the first hour.
 Target of BP reduction is 160 mmHg for
Systolic and 90 mmHg for Diastolic.

•Konsensus Penanggulangan Krisis Hipertensi (InaSH 2008)

 Lower B.P. over hours
 Initial goal B.P.  160’s/90’s
 Too rapid lowering may cause dire
consequences (CVA, MI)
 May take several days to get to
reasonable levels
 Avoid medications that cannot be
controlled (sublingual nifedipine)
 Parenteral Drugs for Treatment of
Hypertensive Emergencies ( Vasodilators )

Drugs Onset of action Duration of action

Nicardipine * 5 min 1 hr
Sodium Nitropruside immediate 1-2 min
Fenoldopam < 5 min 30 min
Nitroglycerin * 2-5 min 2-3 min
Enalaprilat 15-30 min 6 hr
Hydralazine 10-20 min 4-6 hr
Diltiazem * 5 min 30 min
Trimetaphan 5-10 min 10 min

* Available in Indonesia
1. Vasodilators
• Sodium nitroprusside
• Nitroglycerin
• Nicardipine
• Fenoldapam
• Hydralazine
• Enalapril

2. Adrenergic inhibitors
• Labetalol
• Esmolol
• Phentolamine
 COMMONLY USED DRUG IN
HYPERTENSIVE EMERGENCY

CLONIDINE I.V.
• Reduce peripheral sympathetic tone by central
stimulation of 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

NITROGLYCERIN I.V.
• Strong vasodilator ( arterial- and veno-dilator )
with rapid onset and duration of action.
• Adverse effect : headache, tachycardia, nausea,
vomiting
• Caution in coronary artery disease and low SBP
• It may increase ICP in anesthetized normotensive
patients.

1. Nathan Saphiro, Hypertensive Emergencies, 2002

2. George A. Mansoor et.al., Heart Disease : A Journal of Cardiovasbular medicine ., 2003
 COMMONLY USED DRUG IN
HYPERTENSIVE EMERGENCY

NICARDIPINE I.V
• Useful for hypertensive emergency and urgency.
• Acts as dihydropyridine calcium channel blockers.
• Dose-dependent :
Predictable onset of action
Rapidly reduced BP.
No rebound on withdrawn
• Adverse effect : tachycardia, hypotension and headache.
• Contraindication to patient with elevated ICP at the acute
stage of cerebral stroke.

1) Nicardipine product information

2) Nathan Saphiro, Hypertensive Emergencies, 2002
3) George A. Mansoor et.al., Heart Disease : A Journal of Cardiovasbular medicine ., 2003
 COMMONLY USED DRUG IN
HYPERTENSIVE EMERGENCY
DILTIAZEM I.V.
 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)
 COMMONLY USED DRUG IN
HYPERTENSIVE EMERGENCY

NIFEDIPINE SUBLINGUAL
• JNC VI and FDA does not recommend the use
of sublingual nifedipine for the management of
hypertensive crisis should be abandoned in
daily practice.
• Serious adverse reaction : reflex tachycardia,
cerebrovascular ischemia, stroke and death.
• Rapid unpredictable fall in blood pressure and
may precipitate ischemic events.
Vancouver Hospital Drug & Therapeutics Newsletter, 1998. ; JAMA 1996 ; Medscape Internal Medicine, 2002
 Lower the BP without compromising blood
flow to critical organs

 Vasodilators generally considered 1st , because

they preserve organ blood flow in the face of
reduced perfusion and also tend to increase
CO.
 Preserves GFR and renal blood flow
 Few or no drug reactions
 Little or no potential for exacerbation of co-morbid
conditions
 Rapid onset and offset of action
 Minimal hypotension “overshoot”
 Minimal need for continuous BP monitoring and
frequent dose titration
 No acute tolerance
 Ease of use and convenience
 Safe and no toxic metabolites
 Multiple formulations for short and long term use
 Minimal symphathetic activation
 2nd-generation calcium channel blocker (inhibits
influx of Ca ions into cardiac/vascular smooth
muscle)
 Selective for cerebral and coronary arteries
 Dose-dependent decrease in systemic vascular resistance
 Continuous infusion: 5mg/hr
 May increase by 2.5 mg/hr q 15 min. until target pressure or
dose of 15 mg/hr is reached.
 Onset: 5-10 min.
 Duration: 1-4 hours.
 Safe in neurologic hypertensive emergencies
 Doesn’t increase ICP
 Favorable effect on myocardial oxygen balance
 Avoid with IV β-blockers
 Caution in CHF, aortic stenosis.
 Flowrate (tetes/menit)

Dosis (mcg/kgBB/menit)
BB (kg) 0.5 1 2 3 4 5 6 7 8 9 10
40 4 8 16 24 32 40 48 56 64 72 80
50 5 10 20 30 40 50 60 70 80 90 100
60 6 12 24 36 48 60 72 84 96 108 120
70 7 14 28 42 56 70 84 98 112 126 140
80 8 16 32 48 64 80 96 112 128 144 160
90 9 18 36 54 72 90 108 126 144 162 180
100 10 20 40 60 80 100 120 140 160 180 200
Pelarut yang digunakan :
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

Tidak dapat digunakan :

Sodium bicarbonat
Ringer Laktat
Diltiazem Injection
Dose Flow Chart

Intravenous bolus Dose

calculation
injection
0.2 mg / kgBW

Intravenous drip infusion 10-20 % MBP reduction

( 5-15 ug / kgBW / minute ) from baseline

Observe every 30-60 minutes

Stable BP

Switch to oral
 TABEL ALUR DOSIS PENGGUNAAN DILTIAZEM -INJ DRIP INTRAVENA
Dosis Berat Laju Infusi Mikrodrip Dosis Berat Laju Infusi Mikrodrip Dosis Berat Laju Infusi Mikrodrip
m cg/kg/m nt kg m g/jam tetes/m enit m cg/kg/m nt kg m g/jam tetes/m enit m cg/kg/m nt kg m g/jam tetes/m enit
1 50 3 3 6 50 18 18 11 50 33 33
1 60 4 4 6 60 22 22 11 60 40 40
1 70 4 4 6 70 25 25 11 70 46 46
1 80 5 5 6 80 29 29 11 80 53 53
1 90 5 5 6 90 32 32 11 90 59 59
1 100 6 6 6 100 36 36 11 100 66 66
2 50 6 6 7 50 21 21 12 50 36 36
2 60 7 7 7 60 25 25 12 60 43 43
2 70 8 8 7 70 29 29 12 70 50 50
2 80 10 10 7 80 34 34 12 80 58 58
2 90 11 11 7 90 38 38 12 90 65 65
2 100 12 12 7 100 42 42 12 100 72 72
3 50 9 9 8 50 24 24 13 50 39 39
3 60 11 11 8 60 29 29 13 60 47 47
3 70 13 13 8 70 34 34 13 70 55 55
3 80 14 14 8 80 38 38 13 80 62 62
3 90 16 16 8 90 43 43 13 90 70 70
3 100 18 18 8 100 48 48 13 100 78 78
4 50 12 12 9 50 27 27 14 50 42 42
4 60 14 14 9 60 32 32 14 60 50 50
4 70 17 17 9 70 38 38 14 70 59 59
4 80 19 19 9 80 43 43 14 80 67 67
4 90 22 22 9 90 49 49 14 90 76 76
4 100 24 24 9 100 54 54 14 100 84 84
5 50 15 15 10 50 30 30 15 50 45 45
5 60 18 18 10 60 36 36 15 60 54 54
5 70 21 21 10 70 42 42 15 70 63 63
5 80 24 24 10 80 48 48 15 80 72 72
5 90 27 27 10 90 54 54 15 90 81 81
5 100 30 30 10 100 60 60 15 100 90 90
I = ?
D = 5 mcg/kg/menit
C = 0.1 % (gr/ml) 50 mg/50 ml ~ 100 mg/100 ml
W = 50 kg
Rumus / Formula : I = D/C x W
I = 5 mcg/kg/mnt / ( 50 mg/ 50 ml ) x 50 kg
= 0.005 mg/kg/mnt x ( 50 ml/ 50 mg ) x 50 kg
= 0.25 ml/menit

Infusion Pump :
Keterangan simbol :
= 0.25 ml/menit x 60 I = Infusion rate
= 15 ml/jam D = Dosis (mcg/kg/menit)
Mikrodrip : C = Konsentrasi (%)
= 0.25 ml/menit x 60 W = Berat Badan (kg)
= 15 tetes/menit
 Hypertensive encephalopathy
 reduce MAP by 25% or diastole to 100mmHg
over 8 hrs
 If neurology worsens, suspend Rx
 Drug of choice:
 Sodium nitroprusside
 Labetalol
 Acute Ischemic stroke
 often loss of cerebral autoregulation
 ischemic region more prone to hypoperfusion
 thus BP reduction not recommended
 unless SBP>220 or DBP>120
 UNLESS planning fibrinolysis – SBP<185
and DBP< 110
 Drug of choice:
 Labetalol
 Nicardipine
 Sodium Nitroprusside
I. Guidance in the acute ischemic
stroke:
1. Management of HypertensionBlood
Pressure elevation:
 For patient with Diastolic Blood Pressure >
140 mmhg (or > 110 mmhg if in
trombolytic treatment) is treated as
emergency hypertensive patient and
should receive drip continue; nikardipin,
diltiazem, nimodipine, etc.
Guideline Stroke PERDOSSI 2007, BAB VI hal 47.
 Acutes ICH/SAH
 Treatment based on clinical/radiographic evidence
of raised ICP
 Raised ICP – MAP<130 (1st 24hrs)
 No raised ICP – MAP<110
 Drug of choice:
 Sodium Nitroprusside
 Labetalol
 Nicardipine
 ACS
 treat if SBP>160 and/or DBP>100
 Reduce MAP by 20 -30% of baseline
 nitrates should be given till symptoms
subside or until DBP<100
 Drug of choice:
 Nitroglycerine
 Labetalol
 Nicardipine
 Clinical , BP > 180/.120 mmHg
EKG, Enzim myocardial disturbance (CKMB,troponin T)

 Beta Blocker and Nytroglycerin

 CCB Parenteral; nicardipin and diltiazem
 BP reduction target TD < 130/ <80 mmHg
 Diastolik reduction not lower than 60 mmhg
 Acute HF (pulmonary edema)
 treat with vasodilator (additional to diuretics)
 Sodium Nitroprusside in conjunction with
morphine, oxygen and loop diuretic
 Enalaprilat also an option
 Aortic dissection
 anti-hypertensive Rx is aimed at reducing the
shear stress on aortic wall (BP and Pulse)
 immediate lowering of BP – lifesaving
 maintain SBP<110, unless signs of end
organ hypoperfusion
 preferred Rx is combination of Morphine,
B-blocker and vasodilator
 Nitroprusside + Labetalol
 Perioperative hypertension
 target BP to within 20% of baseline, except if potential for life
threatening arterial bleeding
 typically related to catecholamine surge post-op.
 Drug of choice:
 B-blocker
 Labetalol
 Pre-eclampsia/Eclampsia
 Goal SBP<160 and DBP<110 in pre-and- intrapartum periods.
 Platelets < 100 000, BP should be maintained < 150/100
 IV Magnesium to prevent seizures
 Drug of choice:
 Methyldopa
 Hydralazine
Hipertensi Emergensi Hipertensi Urgensi

OAH intra vena

+ Furosemid iv Diuretik loop
penyekat beta
Dalam 2 jam penghambat EKA
Agonis alfa2
 MAP < 25 % antagonis kalsium

Dalam 2-6 jam

TD 160/100 mmHg JNC 6, 1997

Ganti OAH oral