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Hypertensive Crisis
Isman Firdaus, MD
FIHA, FAPSIC, FAsCC, FESC, FSCAI
Pusat Jantung Nasional, Harapan Kita Hospital
Departement of Cardiology and Vascular Medicine
Epidemiology
Hypertensive Emergency
 Estimates are that about 1% of those
with hypertension will present with
hypertensive emergency each year
 That is >500,000 Americans per year
 Correct and quick diagnosis and
management is critical
 Mortality rate of up to 90%
Definitions:
• Hypertension:
– Stage I: 140-159/90-99
– Stage II: >160/100
• Hypertensive Urgency:
– Systolic BP >180 or Diastolic BP >120 in the
absence of end-organ damage
Definitions Continued:
• Hypertensive Emergencies:
– SBP >180 OR DBP>120 in the presence of end-
organ damage
• Malignant Hypertension: End-organ damage--
eyes, kidneys, brain (hemorrhage/infarct)
affected
• Hypertensive encephalopathy: Cerebral edema
leading to neurological symptoms
Treatment Options
• Hypertensive Urgency:
– Goal: Reduce BP to <160/100 over several hours
to day
• Elderly at high risk of ischemia from rapid
reduction of BP, therefore slower reduction in
BP in this patient population
– Previously treated hypertension:
• Increase dose of existing med or add another
med
• Reinstitution of med in non-compliant patients
Treatment Continued
• Hypertensive Emergency:
– Goal: Lower Diastolic BP to approximately 100-105
over 2-6 hours; max initial fall not to exceed 20 -
25%
• More aggressive decrease can lead to ischemic
stroke and myocardial ischemia
– If focal neurological sx presentobtain MRI to r/o
acute stroke (rapid BP correction contraindicated)
– Parenteral antihypertensives (IV Drip)
recommended over oral agents in hypertensive
emergency
 Heart failure—TH, BB, ACEI, ARB, ALDO
 Post MI—BB, ACEI, ALDO
 High CVD risk—TH, BB, ACEI, CCB
 Diabetes—TH, BB, ACEI, ARB, CCB
 Chronic Renal Failure—ACEI, ARB
 Recurrent stroke prevention—TH, ACEI
 KEY: ACEI, angiotensin converting enzyme inhibitor; ALDO, aldosterone antagonist; ARB,
angiotensin receptor blocker; BB, b blocker; CCB, calcium channel blocker; TH, thiazide.
Oral Drug Choices often Based on
Comorbid Conditions
IV Medications :
• IV, short acting, titratable.
Arterial Vasodilators
• Hydralazine, diltiazem,
nicardipine
• Mixed Arterial and Venous Vasodilators
 Nitroglycerin, Sodium nitroprusside
• Negative Inotrope/Chronotrope
 Labetolol (also vasodilates), Esmolol
• Alpha blockers (inc. sympathetic activity)
 Phentolamine
Treatment of Hypertensive Emergency with
Calcium Channel Blockers
Dihydropyridine ( DHP )
Nifedipine, Amlodipine, Nicardipine, etc.
Non-Dihydropyridine ( NDHP )
Diltiazem, Verapamil
OPIE, 2001
Calcium Channel Blockers (CCBs )
Diltiazem Multiple Effects
-
ANTI-
ANGINAL
ANTI-
ARRHYTHMIC DILTIAZEM
• Anti-arrhythmic
• Arterial dilator
• Negative inotropic
• Regression of LVH
• Post-infarct protection
if no LVF
SYSTEM
CIRCULATION
ARTERIOLAR
DILATION
AFTERLOAD 
BP 
ATRIAL FIB
(with digoxin)
PSVT
Opie, 2001
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
Pathophysiologic Effects Diltiazem
• Potent vasodilator
– Inhibits vascular smooth muscle contractility and decreases
peripheral vascular resistance
• Reduce Coronary resistance
– Dilates coronary arteries and increases coronary blood flow
• Decrease Heart rate
– Rate-Pressure Product (HR x SBP) reduce myocardial oxygen
demand
– Absence of reflex tachycardia
• No adverse effects on glucose or carbohydrate metabolism
Drugs. 1990;39:757.
• Ischemic cardiac muscle is improved by
① Increasing insufficient coronary blood volume (O2 supply)
② Decreasing cardiac performance(HER two-sided effect)
Two-sided effect for myocardial ischemia
Thick coronary vasodilating effect
Collateral vasodilating effect
BP lowering effect
HR decreasing effect
①Increasing vascular flow in
ischemic cardiac muscle
②Decreasing cardiac performance
Improvement of O2 supply and demand in
ischemic cardiac muscle
Cardioprotective Efficacy
Effective in Adjunctive Therapy
• PTCA
• CABG
• Cardiac Transplantation
• Unstable Angina Pectoris
Effective in Antiarrhythmia
• PSVT
• Atrial Fibrillation
• Atrial Flutter
Effective in Lowering Blood Pressure
• Hypertensive Emergency
• Hypertensive Peri-operative
DILTIAZEM INTRAVENOUS
Calcium Channel Blockers
Nicardipine
(dihydropyridine)
Diltiazem
(benzothiazepine)
Peripheral
Vasodilation1 +++++ +++
Coronary
Vasodilation2 +++++ +++
Suppression
of SA Node2 + +++
Suppression
of AV Node2 0 +++
Suppression
of Cardiac Contractility2 0 ++
1. Frishman WH, et al. Med Clin North Am. 1988;72:523-547.
2. Adapted from Goodman and Gilman’s: The Pharmacologic Basis of Therapeutics. 9th ed. 2001.
NICARDIPINE and DILTIAZEM
NICARDIPINE DILTIAZEM
Target organ Arteriole (ca
Channel)
Arteriole (ca
Channel)
Clinical effect Vasodilatation :
BP decreased
Vasodilatation :
BP decreased
Heart Rate
Diltiazem Injection can use for patients who have Normally HR until High
Nicardipine I.V Diltiazem I.V
< 60 60 - 80 > 80
Heart Rate
(beat/minute)
Differentiation between Diltiazem and Nicardipine on Heart Rate
Subject : 11 patients with hypertension
emergency
Design : Open study
 Diltiazem injection Drip infusion: 5~40
μg/kg/min
 Average BP reduced
224/119 mmHg to 170/95 mmHg (mean
change 27.3 +9.0 %, P<0.001)
HR controlled
Current Therapeutic Research.1987: 42:1223.
Antihypertensive drugs and Heart Rate
HERBESSER
Nitroglycerin
Introduction of infusion
• Rapidly lowers high blood
pressure
• Shows fewer side effects
than nitroglycerin
Diltiazem IV Infusion
Current Therapy Research. 1988: 43
Nicardipine i.v.
Hirayama A, Katayama Y, et al:Neurological Research 16; 97-99, 1994
35 patients who had surgical evacuation of spontaneous intracerebral haematomas after cerebral hemorrhage
Herbesser i.v.: 12, Nitroglycerin i.v.: 13, Nicardipine i.v.:10
Compare the intracranial pressure when the same blood pressure reduction level is achieved in each group.
①CPP index=△CPP/△SBP
②CPP index coming close to 1 indicates less
increase of intracranial pressure.
Comparison of intracranial pressure
change by different antihypertensives.
Change
of
intracranial
pressure
Comparison of Cerebral perfusion pressure
index (CPP index) by different antihypertensives.
CPP
index
Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v.
Herbesser i.v. Nitroglycerin i.v.
20
10
0
2.0
1.5
0.0
1.0
6.7
14.2
17.0
1.33±0.07
1.80±0.11
1.63±0.13
p<0.05
p<0.05
(mmHg)
Target
Medication
Methods
Antihypertensive drugs cause increase of ICP
Diltiazem i.v. reduced cardiac event rate
in patients with unstable angina.
Target
Gobel E, et al. Lancet 346:1653-1657, 1995
Nitroglycerin i.v. group (n=61)
Herbesser i.v. group (n=60)
Incidence
during
i.v.(%)
40
30
20
10
0
Myocardial infarction refractory angina Myocardial infarction
+
refractory angina
10
5
28
10
38
15
p=0.02*
p=0.007**
Methods
129 patients with unstable angina
Randomized, double blind comparative trial
Diltiazem i.v. group (n=60) :25mg i.v.+5mg/h continuous i.v. (increase dose to 25mg/h)
Nitroglycerin i.v. group (n=61) : Physiologic saline i.v.+1mg/h continuous i.v. (increase dose to 5mg)
Intravenous bolus injection
0.2 mg / kgBW
Intravenous drip infusion
( 5-15 µg / kgBW / minute )
10-20 % MBP reduction
from baseline
Switch to oral HERBESSER® CD 200
Diltiazem (Herbesser) Chart Injection
Dose Flow Chart
Stable BP until 1 hr
Observe every 10-20 minutes
Dose
calculation
Intravenous bolus injection
10-15 mg IV (0,2-03 mg/KgBB) 1-2 min
20-30 mg/hr (15 menit)
>20 % MAP reduction
from baseline
Switch to oral drugs
Diltiazem (Herbesser) Chart Injectio
For Hypertensive Crisis
Dose
calculation
MAP > 15% Tidak
Intravenous drip infusion 50 mg/hr (20 min)
Observe every 10 minutes
10mg/hr ( 1-4 hr)
Observe every 10 minutes
Date of download: 1/12/2014
Copyright © 2014 American Medical
Association. All rights reserved.
From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the
Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
JAMA. 2013;():. doi:10.1001/jama.2013.284427
Herbesser Listed in the Guideline of JNC 8
BPJS ?
Hipertensi.pdf

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Hipertensi.pdf

  • 1. Hypertensive Crisis Isman Firdaus, MD FIHA, FAPSIC, FAsCC, FESC, FSCAI Pusat Jantung Nasional, Harapan Kita Hospital Departement of Cardiology and Vascular Medicine
  • 2. Epidemiology Hypertensive Emergency  Estimates are that about 1% of those with hypertension will present with hypertensive emergency each year  That is >500,000 Americans per year  Correct and quick diagnosis and management is critical  Mortality rate of up to 90%
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  • 5. Definitions: • Hypertension: – Stage I: 140-159/90-99 – Stage II: >160/100 • Hypertensive Urgency: – Systolic BP >180 or Diastolic BP >120 in the absence of end-organ damage
  • 6. Definitions Continued: • Hypertensive Emergencies: – SBP >180 OR DBP>120 in the presence of end- organ damage • Malignant Hypertension: End-organ damage-- eyes, kidneys, brain (hemorrhage/infarct) affected • Hypertensive encephalopathy: Cerebral edema leading to neurological symptoms
  • 7. Treatment Options • Hypertensive Urgency: – Goal: Reduce BP to <160/100 over several hours to day • Elderly at high risk of ischemia from rapid reduction of BP, therefore slower reduction in BP in this patient population – Previously treated hypertension: • Increase dose of existing med or add another med • Reinstitution of med in non-compliant patients
  • 8. Treatment Continued • Hypertensive Emergency: – Goal: Lower Diastolic BP to approximately 100-105 over 2-6 hours; max initial fall not to exceed 20 - 25% • More aggressive decrease can lead to ischemic stroke and myocardial ischemia – If focal neurological sx presentobtain MRI to r/o acute stroke (rapid BP correction contraindicated) – Parenteral antihypertensives (IV Drip) recommended over oral agents in hypertensive emergency
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  • 13.  Heart failure—TH, BB, ACEI, ARB, ALDO  Post MI—BB, ACEI, ALDO  High CVD risk—TH, BB, ACEI, CCB  Diabetes—TH, BB, ACEI, ARB, CCB  Chronic Renal Failure—ACEI, ARB  Recurrent stroke prevention—TH, ACEI  KEY: ACEI, angiotensin converting enzyme inhibitor; ALDO, aldosterone antagonist; ARB, angiotensin receptor blocker; BB, b blocker; CCB, calcium channel blocker; TH, thiazide. Oral Drug Choices often Based on Comorbid Conditions
  • 14. IV Medications : • IV, short acting, titratable. Arterial Vasodilators • Hydralazine, diltiazem, nicardipine • Mixed Arterial and Venous Vasodilators  Nitroglycerin, Sodium nitroprusside • Negative Inotrope/Chronotrope  Labetolol (also vasodilates), Esmolol • Alpha blockers (inc. sympathetic activity)  Phentolamine
  • 15. Treatment of Hypertensive Emergency with Calcium Channel Blockers
  • 16. Dihydropyridine ( DHP ) Nifedipine, Amlodipine, Nicardipine, etc. Non-Dihydropyridine ( NDHP ) Diltiazem, Verapamil OPIE, 2001 Calcium Channel Blockers (CCBs )
  • 17. Diltiazem Multiple Effects - ANTI- ANGINAL ANTI- ARRHYTHMIC DILTIAZEM • Anti-arrhythmic • Arterial dilator • Negative inotropic • Regression of LVH • Post-infarct protection if no LVF SYSTEM CIRCULATION ARTERIOLAR DILATION AFTERLOAD  BP  ATRIAL FIB (with digoxin) PSVT Opie, 2001
  • 18. 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
  • 19. Pathophysiologic Effects Diltiazem • Potent vasodilator – Inhibits vascular smooth muscle contractility and decreases peripheral vascular resistance • Reduce Coronary resistance – Dilates coronary arteries and increases coronary blood flow • Decrease Heart rate – Rate-Pressure Product (HR x SBP) reduce myocardial oxygen demand – Absence of reflex tachycardia • No adverse effects on glucose or carbohydrate metabolism Drugs. 1990;39:757.
  • 20. • Ischemic cardiac muscle is improved by ① Increasing insufficient coronary blood volume (O2 supply) ② Decreasing cardiac performance(HER two-sided effect) Two-sided effect for myocardial ischemia Thick coronary vasodilating effect Collateral vasodilating effect BP lowering effect HR decreasing effect ①Increasing vascular flow in ischemic cardiac muscle ②Decreasing cardiac performance Improvement of O2 supply and demand in ischemic cardiac muscle Cardioprotective Efficacy
  • 21. Effective in Adjunctive Therapy • PTCA • CABG • Cardiac Transplantation • Unstable Angina Pectoris Effective in Antiarrhythmia • PSVT • Atrial Fibrillation • Atrial Flutter Effective in Lowering Blood Pressure • Hypertensive Emergency • Hypertensive Peri-operative DILTIAZEM INTRAVENOUS
  • 22. Calcium Channel Blockers Nicardipine (dihydropyridine) Diltiazem (benzothiazepine) Peripheral Vasodilation1 +++++ +++ Coronary Vasodilation2 +++++ +++ Suppression of SA Node2 + +++ Suppression of AV Node2 0 +++ Suppression of Cardiac Contractility2 0 ++ 1. Frishman WH, et al. Med Clin North Am. 1988;72:523-547. 2. Adapted from Goodman and Gilman’s: The Pharmacologic Basis of Therapeutics. 9th ed. 2001.
  • 23. NICARDIPINE and DILTIAZEM NICARDIPINE DILTIAZEM Target organ Arteriole (ca Channel) Arteriole (ca Channel) Clinical effect Vasodilatation : BP decreased Vasodilatation : BP decreased Heart Rate
  • 24. Diltiazem Injection can use for patients who have Normally HR until High Nicardipine I.V Diltiazem I.V < 60 60 - 80 > 80 Heart Rate (beat/minute) Differentiation between Diltiazem and Nicardipine on Heart Rate
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  • 26. Subject : 11 patients with hypertension emergency Design : Open study  Diltiazem injection Drip infusion: 5~40 μg/kg/min  Average BP reduced 224/119 mmHg to 170/95 mmHg (mean change 27.3 +9.0 %, P<0.001) HR controlled Current Therapeutic Research.1987: 42:1223. Antihypertensive drugs and Heart Rate
  • 27. HERBESSER Nitroglycerin Introduction of infusion • Rapidly lowers high blood pressure • Shows fewer side effects than nitroglycerin Diltiazem IV Infusion Current Therapy Research. 1988: 43
  • 28. Nicardipine i.v. Hirayama A, Katayama Y, et al:Neurological Research 16; 97-99, 1994 35 patients who had surgical evacuation of spontaneous intracerebral haematomas after cerebral hemorrhage Herbesser i.v.: 12, Nitroglycerin i.v.: 13, Nicardipine i.v.:10 Compare the intracranial pressure when the same blood pressure reduction level is achieved in each group. ①CPP index=△CPP/△SBP ②CPP index coming close to 1 indicates less increase of intracranial pressure. Comparison of intracranial pressure change by different antihypertensives. Change of intracranial pressure Comparison of Cerebral perfusion pressure index (CPP index) by different antihypertensives. CPP index Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v. Herbesser i.v. Nitroglycerin i.v. 20 10 0 2.0 1.5 0.0 1.0 6.7 14.2 17.0 1.33±0.07 1.80±0.11 1.63±0.13 p<0.05 p<0.05 (mmHg) Target Medication Methods Antihypertensive drugs cause increase of ICP
  • 29. Diltiazem i.v. reduced cardiac event rate in patients with unstable angina. Target Gobel E, et al. Lancet 346:1653-1657, 1995 Nitroglycerin i.v. group (n=61) Herbesser i.v. group (n=60) Incidence during i.v.(%) 40 30 20 10 0 Myocardial infarction refractory angina Myocardial infarction + refractory angina 10 5 28 10 38 15 p=0.02* p=0.007** Methods 129 patients with unstable angina Randomized, double blind comparative trial Diltiazem i.v. group (n=60) :25mg i.v.+5mg/h continuous i.v. (increase dose to 25mg/h) Nitroglycerin i.v. group (n=61) : Physiologic saline i.v.+1mg/h continuous i.v. (increase dose to 5mg)
  • 30. Intravenous bolus injection 0.2 mg / kgBW Intravenous drip infusion ( 5-15 µg / kgBW / minute ) 10-20 % MBP reduction from baseline Switch to oral HERBESSER® CD 200 Diltiazem (Herbesser) Chart Injection Dose Flow Chart Stable BP until 1 hr Observe every 10-20 minutes Dose calculation
  • 31. Intravenous bolus injection 10-15 mg IV (0,2-03 mg/KgBB) 1-2 min 20-30 mg/hr (15 menit) >20 % MAP reduction from baseline Switch to oral drugs Diltiazem (Herbesser) Chart Injectio For Hypertensive Crisis Dose calculation MAP > 15% Tidak Intravenous drip infusion 50 mg/hr (20 min) Observe every 10 minutes 10mg/hr ( 1-4 hr) Observe every 10 minutes
  • 32. Date of download: 1/12/2014 Copyright © 2014 American Medical Association. All rights reserved. From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8) JAMA. 2013;():. doi:10.1001/jama.2013.284427 Herbesser Listed in the Guideline of JNC 8