nicardipine rtd
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HYPERTENSIVE CRISISHYPERTENSIVE CRISISHypertensive UrgenciesHypertensive Urgencies
and Emergenciesand Emergencies
Current Challenges for the Emergency PhysicianCurrent Challenges for the Emergency Physician
Dr. Az Rifki,Dr. Az Rifki, SpAn.KIC.KMNSpAn.KIC.KMN
ICUICU SitiSiti RahmahRahmah Islamic HospitalIslamic Hospital
PadangPadang
Management ofManagement of
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HypertensionHypertension An EpidemicAn Epidemic
Affects at least 65 million AmericansAffects at least 65 million Americans
Affects at least 1 BILLION individuals worldwideAffects at least 1 BILLION individuals worldwide
Most current (2003) evidence basis for chronicMost current (2003) evidence basis for chronic
managementmanagementThe Seventh Report of the JointThe Seventh Report of the Joint
National Committee on the Prevention, Detection,National Committee on the Prevention, Detection,
Evaluation, and Treatment of High Blood PressureEvaluation, and Treatment of High Blood Pressure
Hypertension (Hypertension (JNC 7JNC 7))lacks guidance for acutelacks guidance for acute
management of patients presenting to an ED withmanagement of patients presenting to an ED withhypertension, especially severe acute elevations ofhypertension, especially severe acute elevations of
BPBP
Affects at least 65 million AmericansAffects at least 65 million Americans
Affects at least 1 BILLION individuals worldwideAffects at least 1 BILLION individuals worldwide
Most current (2003) evidence basis for chronicMost current (2003) evidence basis for chronic
managementmanagementThe Seventh Report of the JointThe Seventh Report of the Joint
National Committee on the Prevention, Detection,National Committee on the Prevention, Detection,
Evaluation, and Treatment of High Blood PressureEvaluation, and Treatment of High Blood Pressure
Hypertension (Hypertension (JNC 7JNC 7))lacks g
uidance for acutelacks guidance for acute
management of patients presenting to an ED withmanagement of patients presenting to an ED withhypertension, especially severe acute elevations ofhypertension, especially severe acute elevations of
BPBP
JNC 7, JAMA 2003; 289:2560-2572.
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JNC 7 NomenclatureJNC 7 NomenclatureJNC 7 NomenclatureJNC 7 Nomenclature
Normal BP: Systolic < 120, Diastolic < 80Normal BP: Systolic < 120, Diastolic < 80
Prehypertension: S = 120Prehypertension: S = 120--139, D = 80139, D = 80--8989
Stage 1 hypertension: S = 140Stage 1 hypertension: S = 140--159, D = 90159, D = 90--9999 Stage 2 hypertension: SStage 2 hypertension: S >> 160, D160, D >> 100100
Stage 3 hypertension (JNC 6):Stage 3 hypertension (JNC 6):
ll Systolic > 180, Diastolic > 110Systolic > 180, Diastolic > 110
ll Functionally, this isFunctionally, this is hypertensive urgencyhypertensive urgency
What aboutWhat about crisis,crisis, emergency,emergency, andand urgencyurgency??
Normal BP: Systolic < 120, Diastolic < 80Normal BP: Systolic < 120, Diastolic < 80
Prehypertension: S = 120Prehypertension: S = 120--139, D = 80139, D = 80--8989
Stage 1 hypertension: S = 140Stage 1 hypertension: S = 140--159, D = 90159, D = 90--9999 Stage 2 hypertension: SStage 2 hypertension: S >> 160, D160, D >> 100100
Stage 3 hypertension (JNC 6):Stage 3 hypertension (JNC 6):
ll Systolic > 180, Diastolic > 110Systolic > 180, Diastolic > 110
ll Functionally, this isFunctionally, this is hypertensive urgencyhypertensive urgency
What aboutWhat about crisis,crisis, emergency,emergency, andand urgencyurgency??
JNC 7, JAMA 2003; 289:2560-2572.
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JNC 7 NomenclatureJNC 7 Nomenclature
Using JNC 7 nomenclature,Using JNC 7 nomenclature, hypertensivehypertensivecrisiscrisis is an acute, severe, stage 2 or 3is an acute, severe, stage 2 or 3elevation in blood pressureelevation in blood pressure
Crisis is then differentiated into hypertensiveCrisis is then differentiated into hypertensiveemergenciesemergencies (involving some end(involving some end--organorgandamage) anddamage) and urgenciesurgencies (no end(no end--organorgan
damage)damage)
Using JNC 7 nomenclature,Using JNC 7 nomenclature, hypertensivehypertensivecrisiscrisis is an acute, severe, stage 2 or 3is an acute, severe, stage 2 or 3elevation in blood pressureelevation in blood pressure
Crisis is then differentiated into hypertensiveCrisis is then differentiated into hypertensiveemergenciesemergencies (involving some end(involving some end--organorgandamage) anddamage) and urgenciesurgencies (no end(no end--organorgan
damage)damage)
JNC 7, JAMA 2003; 289:2560-2572.
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Hypertensive Crises
Hypertensive EmergencyHypertensive Urgency
Markedly elevated BP
Without severe symptoms or
progressive target organ damageBP should be reduced within hours
Oral agents
Markedly elevated BP
With acute or progressing
target organ damageBP should be reduced immediate
Parenteral agents
Kaplan NM ,Hypertensive Crisesin : Clinical hypertension 9th Ed,
Lippincott Williams & Wilkins 2006:609-630
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EndEnd--Organ DamageOrgan Damage
CardiopulmonaryCardiopulmonaryll Acute heart failureAcute heart failure
ll Acute coronary syndromeAcute coronary syndrome
ll Acute pulmonary edema with respiratory failureAcute pulmonary edema with respiratory failure
ll Dissecting aortaDissecting aorta
CNSCNSll Hypertensive encephalopathyHypertensive encephalopathy
ll CVACVA
RenalRenalll Acute renal failureAcute renal failure
CardiopulmonaryCardiopulmonaryll Acute heart failureAcute heart failure
ll Acute coronary syndromeAcute coronary syndrome
ll Acute pulmonary edema with respiratory failureAcute pulmonary edema with respiratory failure
ll Dissecting aortaDissecting aorta
CNSCNSll Hypertensive encephalopathyHypertensive encephalopathy
ll CVACVA
RenalRenalll Acute renal failureAcute renal failure
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Definitions of HypertensionDefinitions of HypertensionDefinitions of HypertensionDefinitions of Hypertension
Mild, Uncomplicated HTNMild, Uncomplicated HTNll Diastolic BP
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Hypertensive UrgencyHypertensive Urgencyll BP at a level that may be potentially harmful,BP at a level that may be potentially harmful,
but without focal findingsbut without focal findings
ll Usually sustained diastolic > 115 mmHgUsually sustained diastolic > 115 mmHg(120mmHg)(120mmHg)
Commonly due to nonCommonly due to non--compliancecompliance
ll Ignore systolic BP: MAP= ( 2 Diastolic +Ignore systolic BP: MAP= ( 2 Diastolic +systolic) / 3systolic) / 3
ll Lower BP over 24Lower BP over 24--48 hours (give them a Rx)48 hours (give them a Rx) Avoid rapid BP reductionsAvoid rapid BP reductions
ll History, physical, and time may be all thatHistory, physical, and time may be all thatis neededis needed
Hypertensive UrgencyHypertensive Urgencyll BP at a level that may be potentially harmful,BP at a level that may be potentially harmful,
but without focal findingsbut without focal findings
ll Usually sustained diastolic > 115 mmHgUsually sustained diastolic > 115 mmHg(120mmHg)(120mmHg)
Commonly due to nonCommonly due to non--compliancecompliance
ll Ignore systolic BP: MAP= ( 2 Diastolic +Ignore systolic BP: MAP= ( 2 Diastolic +systolic) / 3systolic) / 3
ll Lower BP over 24Lower BP over 24--48 hours (give them a Rx)48 hours (give them a Rx) Avoid rapid BP reductionsAvoid rapid BP reductions
ll History, physical, and time may be all thatHistory, physical, and time may be all thatis neededis needed
Definition of HypertensionDefinition of HypertensionDefinition of HypertensionDefinition of Hypertension
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Definition of HypertensiveDefinition of HypertensiveEmergencyEmergency
Hypertensive EmergencyHypertensive Emergency
ll Increased BPIncreased BP WITHWITH end organ damageend organ damage
At risk: Brain, heart, kidneysAt risk: Brain, heart, kidneys
ll BP must be reduced within minutesBP must be reduced within minutes
ll No specific BP criteriaNo specific BP criteria
Hypertensive EmergencyHypertensive Emergency
ll Increased BPIncreased BP WITHWITH end organ damageend organ damage
At risk: Brain, heart, kidneysAt risk: Brain, heart, kidneys
ll BP must be reduced within minutesBP must be reduced within minutes
ll No specific BP criteriaNo specific BP criteria
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Presenting SymptomsPresenting Symptoms
Hypertensive UrgenciesHypertensive Urgencies
ll ArrhythmiaArrhythmia
ll EpistaxisEpistaxis
ll HeadacheHeadache
ll Psychomotor agitationPsychomotor agitation
Usual Primary EDUsual Primary EDDiagnosisDiagnosis
ll HypertensionHypertension
Hypertensive UrgenciesHypertensive Urgencies
ll ArrhythmiaArrhythmia
ll EpistaxisEpistaxis
ll HeadacheHeadache
ll Psychomotor agitationPsychomotor agitation
Usual Primary EDUsual Primary EDDiagnosisDiagnosis
ll HypertensionHypertension
Hypertensive EmergenciesHypertensive Emergencies
ll Chest painChest pain
ll DyspneaDyspnea
ll Neurologic deficitsNeurologic deficits
Usual Primary EDUsual Primary EDDiagnosisDiagnosis
ll CVACVA
ll Acute pulmonary edemaAcute pulmonary edema
ll HypertensiveHypertensiveencephalopathyencephalopathy
ll Acute heart failureAcute heart failure
Hypertensive EmergenciesHypertensive Emergencies
ll Chest painChest pain
ll DyspneaDyspnea
ll Neurologic deficitsNeurologic deficits
Usual Primary EDUsual Primary EDDiagnosisDiagnosis
ll CVACVA
ll Acute pulmonary edemaAcute pulmonary edema
ll HypertensiveHypertensiveencephalopathyencephalopathy
ll Acute heart failureAcute heart failure
Zampaglione etal, Hypertension 1996;27:144.
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Hypertensive UrgenciesHypertensive Urgenciesand Emergenciesand Emergencies
Hypertensive UrgenciesHypertensive Urgenciesand Emergenciesand Emergencies
Epidemiologic data are largely lackingEpidemiologic data are largely lacking
It is thought that ~ 1% of patients with hypertensionIt is thought that ~ 1% of patients with hypertensionwill eventually present to the ED in hypertensivewill eventually present to the ED in hypertensivecrisiscrisis
In a singleIn a single--center Italian study, HU or HE accountedcenter Italian study, HU or HE accountedfor 3% of all medicine admissions and 27.5% of allfor 3% of all medicine admissions and 27.5% of allmedical emergenciesmedical emergencies
ll HU:HE ratio of 3:1 in that studyHU:HE ratio of 3:1 in that studyll Patients with HU much more likely to be unaware of theirPatients with HU much more likely to be unaware of their
hypertension diagnosis than those with HEhypertension diagnosis than those with HE
Zampaglioneetal, Hypertension 1996;27:144.
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Precipitating factors in hypertensive crisis
1. Accelerated sudden rise in blood pressure in patient
with preexisting essential hypertension
2. Renovascular hypertension
3. Glomerulonephritis-acute
4. Eclampsia
5. Pheochromocytoma
6. Antihypertensive withdrawl syndromes
7. Head injuries
8. Renin secreting tumors
9. Ingestion of cathecolamine precursor in patients
taking MAO inhibitors
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Causes of Hypertensive CrisesCauses of Hypertensive CrisesCauses of Hypertensive CrisesCauses of Hypertensive Crises
Essential hypertensionEssential hypertensionll Medication noncomplianceMedication noncompliance
Secondary hypertensionSecondary hypertensionll Aortic coarctationAortic coarctation
ll CushingCushings syndromes syndrome
ll Elevated ICPElevated ICP
ll Renal dysfunctionRenal dysfunction
ll PregnancyPregnancyll HyperparathyroidismHyperparathyroidism
ll HyperthyroidismHyperthyroidism
ll PheochromocytomaPheochromocytoma
ll Primary aldosteronismPrimary aldosteronism
Essential hypertensionEssential hypertensionll Medication noncomplianceMedication noncompliance
Secondary hypertensionSecondary hypertensionll Aortic coarctationAortic coarctation
ll CushingCushings syndromes syndrome
ll Elevated ICPElevated ICP
ll Renal dysfunctionRenal dysfunction
ll PregnancyPregnancyll HyperparathyroidismHyperparathyroidism
ll HyperthyroidismHyperthyroidism
ll PheochromocytomaPheochromocytoma
ll Primary aldosteronismPrimary aldosteronism
JNC 7, JAMA 2003; 289:2560-2572.
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ExaminationExamination
BP in both armsBP in both arms
FundoscopyFundoscopy
examinationexamination CardiovascularCardiovascular
examinationexamination
NeurologicalNeurologicalexaminationexamination
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Clinical EvaluationClinical Evaluation
CardiovascularCardiovascularll Chest pain/syncopeChest pain/syncope
ll Back painBack pain
ll DyspnoeaDyspnoea
NeurologicalNeurological
ll Seizures/altered MSSeizures/altered MSll Focal weaknessFocal weakness
ll Headache/visual disturbanceHeadache/visual disturbance
RenalRenal
ll Decreased UODecreased UO
ll Bloody or frothy urineBloody or frothy urinell NonNon--specific abdominal painspecific abdominal pain
GeneralGeneral
ll MalaiseMalaise
MI, unstable Angina,MI, unstable Angina,dissectiondissection
DissectionDissection
Pulmonary Oedema, CHFPulmonary Oedema, CHF
EncephalopathyEncephalopathy
CVA/TIACVA/TIA
Central nervous systemCentral nervous systemcompromisecompromise
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Begin Treatment!Begin Treatment!This is a Hypertensive EmergencyThis is a Hypertensive Emergency
Begin to look for other causes of symptomsBegin to look for other causes of symptoms
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Goals of ED TherapyGoals of ED Therapyof Hypertensive Crisesof Hypertensive CrisesGoals of ED TherapyGoals of ED Therapy
of Hypertensive Crisesof Hypertensive Crises
HU can generally be managed with oralHU can generally be managed with oralmedications and requires BP lowering over 24medications and requires BP lowering over 24--4848hourshours
ll Important to prevent tooImportant to prevent too--rapid lowering due torapid lowering due to autoregulationautoregulation of flow byof flow bypressure in brain, heart, and kidneyspressure in brain, heart, and kidneys
Goal in hypertensive urgency is to reduce MAP byGoal in hypertensive urgency is to reduce MAP by1010--15% and/or to a DBP of 110 . . . within one hour15% and/or to a DBP of 110 . . . within one hour
ll Aortic dissection requiresAortic dissection requires even more rapid loweringeven more rapid loweringll Once initial reduction achieved, transition to oral agentsOnce initial reduction achieved, transition to oral agents
ll Dug of choice for initial therapy often depends on which endDug of choice for initial therapy often depends on which end--organ systemorgan systemis affected and on comorbiditiesis affected and on comorbidities
HU can generally be managed with oralHU can generally be managed with oralmedications and requires BP lowering over 24medications and requires BP lowering over 24--4848hourshours
ll Important to prevent tooImportant to prevent too--rapid lowering due torapid lowering due to autoregulationautoregulation of flow byof flow bypressure in brain, heart, and kidneyspressure in brain, heart, and kidneys
Goal in hypertensive urgency is to reduce MAP byGoal in hypertensive urgency is to reduce MAP by1010--15% and/or to a DBP of 110 . . . within one hour15% and/or to a DBP of 110 . . . within one hour
ll Aortic dissection requiresAortic dissection requires even more rapid loweringeven more rapid loweringll Once initial reduction achieved, transition to oral agentsOnce initial reduction achieved, transition to oral agents
ll Dug of choice for initial therapy often depends on which endDug of choice for initial therapy often depends on which end--organ systemorgan systemis affected and on comorbiditiesis affected and on comorbidities
JNC 7, JAMA 2003; 289:2560-2572.
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WHY?WHY? AutoAuto--regulationregulation
Maintains blood flow toMaintains blood flow tovital organs, despitevital organs, despitevariations in systemic BPvariations in systemic BP
Classically maintainedClassically maintained
between MAP 60between MAP 60--120mmHg120mmHg
However, in chronicallyHowever, in chronicallyhypertensive patients thehypertensive patients thecurve is shifted to thecurve is shifted to therightright
The average lower limit ofThe average lower limit ofautoauto--regulation is aboutregulation is about2020--25% below the resting25% below the restingMAP.MAP.
Lancet, Hypertensive Emergencies,
2000; 356(9227):411-417
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Management ofManagement ofHypertensive EmergencyHypertensive Emergency (general)(general)
Patients should be admitted to an Intensive CarePatients should be admitted to an Intensive CareUnit for continuous monitoring of BP andUnit for continuous monitoring of BP andparenteral administration of an appropriate agentparenteral administration of an appropriate agent
The initial goal therapy is to reduce mean arterialThe initial goal therapy is to reduce mean arterialBP by no more than 25% (within minutes to 1BP by no more than 25% (within minutes to 1
hour).hour).
Then if stable, to 160/100 to 110 mmHg within theThen if stable, to 160/100 to 110 mmHg within the
next 2 to 6 hours.next 2 to 6 hours. Excessive falls in pressure that may precipitateExcessive falls in pressure that may precipitate
renal, cerebral, or coronary ischemia should berenal, cerebral, or coronary ischemia should beavoided.avoided.
Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70
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Management ofManagement ofHypertensive EmergencyHypertensive Emergency (general)(general)
If this level of BP is well tolerated and theIf this level of BP is well tolerated and thepatients is clinically stable , further gradualpatients is clinically stable , further gradualreductions toward a normal BP can bereductions toward a normal BP can be
implemented in the next 24 to 48 hours.implemented in the next 24 to 48 hours. Exceptions :Exceptions :
1.1. Patients with ischemic strokePatients with ischemic stroke
2.2. Aortic dissection SBP should < 100mmHgAortic dissection SBP should < 100mmHg
3.3. Patients whom BP is lowered to enable the usePatients whom BP is lowered to enable the useof thrombolytic agentsof thrombolytic agents
Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70
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Acute BP ManagementAcute BP Management ConsiderationsConsiderations
Acute BP ManagementAcute BP Management ConsiderationsConsiderations
What is the magnitude of:What is the magnitude of:
ll Disease risk?Disease risk?
ll Treatment benefit?Treatment benefit?
ll Treatment risk?Treatment risk?
How persistent is the benefit?How persistent is the benefit?
What improved outcome isWhat improved outcome isthere for the patient?there for the patient?
What is the magnitude of:What is the magnitude of:
ll Disease risk?Disease risk?
ll Treatment benefit?Treatment benefit?
ll Treatment risk?Treatment risk?
How persistent is the benefit?How persistent is the benefit?
What improved outcome isWhat improved outcome isthere for the patient?there for the patient?
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4747--YearYear--Old Stock BrokerOld Stock Broker
Complains Of Chest PainComplains Of Chest Pain
4747--YearYear--Old Stock BrokerOld Stock Broker
Complains Of Chest PainComplains Of Chest Pain
MVO2E MAP x HR
BP 162/110BP 162/110
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Hemodynamics andHemodynamics andMyocardial IschemiaMyocardial Ischemia
Adapted from Braunwald E, ed. Heart Disease: A Textbook of CardiovascularMedicine. 6th ed. W.B.Saunders Co.; 2001.
o Afterload orSVR
o Work
o O2 consumption
Myocardial Blood Flow
q O2 delivery
Left Ventricular(LV)
Wall Tension
o Afterload orSVR
Myocardial Ischemia
Increased Afterload Increases OIncreased Afterload Increases O22 ConsumptionConsumptionand Decreases Oand Decreases O22 Delivery tothe HeartDelivery tothe Heart
Increased Afterload Increases OIncreased Afterload Increases O22 ConsumptionConsumptionand Decreases Oand Decreases O22 Delivery tothe HeartDelivery tothe Heart
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Parenteraladministration
Rapid onsetand offset (minutes)
Easy titratability
Reliableefficacy
Safeacrosspatientpopulations
Easeofuse
Costeffectiveness
Acute Hypertensive Situations
Ideal Therapeutic Agent
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IV TherapeuticsIV Therapeutics
Alpha BlockersAlpha Blockers
ACE InhibitorsACE Inhibitors
Beta BlockersBeta Blockers Calcium Channel BlockersCalcium Channel Blockers
DiureticsDiuretics
DopamineDopamine--1 Agonists1 Agonists
Ganglionic BlockersGanglionic Blockers
NitrovasodilatorsNitrovasodilators
Other VasodilatorsOther Vasodilators
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Parenteral Drugs for Treatment of HypertensiveParenteral Drugs for Treatment of HypertensiveEmergencies based on JNC 7Emergencies based on JNC 7
DrugsDrugs DoseDose OnsetOnset Duration ofDuration ofActionAction
SodiumSodium
nitroprussidenitroprusside
0.250.25--10 ugr/kg/min10 ugr/kg/min ImmediateImmediate 11--2 minutes after2 minutes after
infusion stoppedinfusion stopped
NitroglycerinNitroglycerin 55--500 ug/min500 ug/min 11--3 minutes3 minutes 55--10 minutes10 minutes
Labetolol HClLabetolol HCl 2020--80 mg every 1080 mg every 10--15 min15 min
or 0.5or 0.5--2 mg/min2 mg/min
55--10 minutes10 minutes 33--6 minutes6 minutes
Fenoldopan HClFenoldopan HCl 0.10.1--0.3 ug/kg/min0.3 ug/kg/min
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DrugDrug I.V. Bolus DoseI.V. Bolus Dose Continous InfusContinous Infus
RateRate
LabetalolLabetalol
NicardipineNicardipine
EsmololEsmolol
EnalaprilEnalapril
HydralazineHydralazine
NiprideNipride
NTGNTG
55 20 mg every 1520 mg every 15
NANA
250250 ugug/kg IVP loading dose/kg IVP loading dose
1,251,25--5 mg IVP every 6 h5 mg IVP every 6 h
55 20 mg IVP every 3020 mg IVP every 30
NANA
NANA
2 mg/min (max 300mg/d)2 mg/min (max 300mg/d)
55--15 mg/h15 mg/h
2525--300300 ugug/kg/m/kg/m
NANA
1,51,5--55 ugug/kg/m/kg/m
0,10,1--1010 ugug/kg/m/kg/m
2020--400400 ugug/m/m
AHA/ASA Guideline, 2007 update. Stroke. 2007;38: 2001-2023.
Parenteral Drugs forTreatmentof Hypertensive
Emergenciesbased on ASA Guideline
This parenteral drugs are approved for hypertensive emergency
in acute ischemic stroke and intracerebral hemmorhage
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Parenteral Drugs for Treatment ofParenteral Drugs for Treatment ofHypertensive Emergencies based on CHEST 2007Hypertensive Emergencies based on CHEST 2007
Acute Pulmonary edema /Acute Pulmonary edema /
Systolic dysfunctionSystolic dysfunction
Nicardipine,Nicardipine, fenoldopam, ornitroprusidecombined withfenoldopam, ornitroprusidecombined with
nitroglicerynand loop diureticnitroglicerynand loop diuretic
Acute Pulmonary edema/Acute Pulmonary edema/
Diastolic dysfunctionDiastolic dysfunction
Esmolol, metoprolol, labetalol, verapamil, combined withEsmolol, metoprolol, labetalol, verapamil, combined with
low doseofnitroglicerynand loop diureticslow doseofnitroglicerynand loop diuretics
Acute Ischemia CoronerAcute Ischemia Coroner Labetaloloresmololcombined with diureticsLabetaloloresmololcombined with diuretics
HypertensiveencephalopatyHypertensiveencephalopaty NicardipineNicardipine,, labetalol, fenoldopamlabetalol, fenoldopam
Acute Aorta DissectionAcute Aorta Dissection LabetalolorcombinedLabetalolorcombined NicardipineNicardipine and esmololorcombineand esmololorcombine
nitroprusidewith esmololorIV metoprololnitroprusidewith esmololorIV metoprolol
Preeclampsia, eclampsiaPreeclampsia, eclampsia LabetalolorLabetalolornicardipinenicardipine
Acute Renal failure /Acute Renal failure /
microangiopathicanemiamicroangiopathicanemia
NicardipineNicardipine orfenoldopamorfenoldopam
Sympatheticcrises/ cocaineSympatheticcrises/ cocaine
oveerdoseoveerdose
Verapamil, diltiazem, orVerapamil, diltiazem, ornicardipinenicardipine combined withcombined with
benzodiazepinbenzodiazepin
Acute postoperativeAcute postoperative
hypertensionhypertension
Esmolol,Esmolol, NicardipineNicardipine,, LabetalolLabetalol
Acuteischemicstroke/Acuteischemicstroke/
intracerebralbleedingintracerebralbleeding
NicardipineNicardipine,, labetalol,labetalol, fenoldopamfenoldopam
Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62
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NitroglycerinNitroglycerin
NitroglycerinNitroglycerin is a potentis a potent venodilatorvenodilator and only at high doses affectand only at high doses affect
arterial tonearterial tone.. It reduces BP by reducing cardiacIt reduces BP by reducing cardiac
ouputouput and preload which are undesirable effects in patient withand preload which are undesirable effects in patient with
compromised cerebral and renal perfusioncompromised cerebral and renal perfusion
NifedipineNifedipine
NifedipineNifedipine has been widely used via oral or sublingualhas been widely used via oral or sublingual
administration in the management of hypertensiveadministration in the management of hypertensive
emergenciesemergencies.. This mode of administration has not beenThis mode of administration has not beenapproved by FDA and since JNC VI because it may causeapproved by FDA and since JNC VI because it may cause
sudden uncontrolled and severe reductions in blood pressuresudden uncontrolled and severe reductions in blood pressure
may precipitate cerebral, renal, and myocardial ischemia thatmay precipitate cerebral, renal, and myocardial ischemia that
have been associated with fatal outcomeshave been associated with fatal outcomes
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ClonidineClonidine
CentralCentral alfaalfa blocker, sedative effectblocker, sedative effect
CI : in patient with CerebrovascularCI : in patient with Cerebrovascular
accidentaccident Rebound effectRebound effect
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Dihydropyridine CCB: NicardipineDihydropyridine CCB: Nicardipine
Arterial selectiveArterial selectivevasodilatorvasodilator11
ll SignificantSignificant qq SVRSVR22--66
ll Cerebral and coronary vasodilatorCerebral and coronary vasodilator
Vascular smooth muscleVascular smooth muscleselectiveselective11
ll Minimal myocardial depressionMinimal myocardial depression
ll No AV nodal depressionNo AV nodal depression
No significantNo significant oo in ICPin ICP77
Oates JA. Brown NJ. In: Hardman JG, Limbird LE,eds. Goodman andGilmans PharmacologicalBasis of Therapeutics. 10th ed. New York, NY:McGraw-Hill; 1997:645-668.
1.Clarke B, etal. BrJPharmacol. 1983;79:333P.2.Lambert CR, etal. Am JCardiol. 1987;60:471-476.3.Silke B, etal. BrJClin Pharmacol. 1985;20:169S-176S.4.Lambert CR, etalAm JCardiol. 1985;55:652-656.5. VisserCA, etal. PostgradMedJ. 1984;60:17-20.6. Silke B, etal. BrJClin Pharmacol. 1985;20:169S-176S.
7. Nishiyama MT, etal. Can JAnaesth. 2000;47:1196-1201.
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NICARDIPINE
CHARACTERISTIC
1.VASOSELECTIVITY
Nicardipineselectivity 30.000 x insmooth musclecells
blood vesselscompared with myocardium2. Myocardial depression (-)
3. Negativeinotropic (-)
4. Rapid and stableantihypertensiveeffects, reduceblood
pressuregradually < 25% in 2 hours, minimaleffectsto
heartrate5. Increaseblood flowinmajororgan : Renal, coroner,
cerebral
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NicardipineNicardipine StrategyStrategy
Start at 5 mg/h: Titrate by 2.5 mg/hStart at 5 mg/h: Titrate by 2.5 mg/hq5 minutesq5 minutes 15 mg/h max15 mg/h max
Half life:Half life:
ll Redistribution:Redistribution: tt = 2.7 minutes= 2.7 minutes
ll Intermediate:Intermediate: tt = 44 minutes= 44 minutes
ll Terminal after long infusion = 14.4Terminal after long infusion = 14.4hourshours
After d/c, concentration declinesAfter d/c, concentration declinesrapidly, at least 50% in 1rapidly, at least 50% in 1stst 2 hrs2 hrs
Start at 5 mg/h: Titrate by 2.5 mg/hStart at 5 mg/h: Titrate by 2.5 mg/hq5 minutesq5 minutes 15 mg/h max15 mg/h max
Half life:Half life:
ll Redistribution:Redistribution: tt = 2.7 minutes= 2.7 minutes
ll Intermediate:Intermediate: tt = 44 minutes= 44 minutes
ll Terminal after long infusion = 14.4Terminal after long infusion = 14.4hourshours
After d/c, concentration declinesAfter d/c, concentration declinesrapidly, at least 50% in 1rapidly, at least 50% in 1stst 2 hrs2 hrs
Cardene IV [package insert]
Onset ofOnset ofActionAction
DurationDuration Adverse EventsAdverse Events Special ConsiderationsSpecial Considerations
55--10 min10 min 1515--30 minutes:30 minutes:May exceed 4May exceed 4
hourshours
oo HR, H/A, flushingHR, H/A, flushing
local phlebitislocal phlebitis
Most hypertensiveMost hypertensiveemergencies; caution withemergencies; caution with
ACSACS
The 7th Reportofthe JNC. JAMA 2003;289:2560-2571.
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Calcium Channel BlockersCalcium Channel BlockersCalcium Channel BlockersCalcium Channel Blockers
NicardipineNicardipine
(dihydropyridine)(dihydropyridine)
DiltiazemDiltiazem
(benzothiazepine)(benzothiazepine)
VerapamilVerapamil
(phenylalkylamine)(phenylalkylamine)
PeripheralPeripheral
VasodilationVasodilation11++++++++++ ++++++ ++++++
CoronaryCoronary
VasodilationVasodilation22 ++++++++++ ++++++ ++++++++SuppressionSuppressionof SA Nodeof SA Node22 ++ ++++++++++ ++++++++++
SuppressionSuppressionof AV Nodeof AV Node22 00 ++++++++ ++++++++++
SuppressionSuppressionof Cardiacof Cardiac
ContractilityContractility2200 ++++ ++++++++
1. Frishman WH, et al. Med Clin North Am. 1988;72:523-547.2. Adapted from Goodman and Gilmans: The Pharmacologic Basis of Therapeutics. 9th ed. 2001.
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Safety Profiles of NicardipineSafety Profiles of Nicardipineand Nitroprussideand Nitroprusside
Adverse EventsAdverse Events NicardipineNicardipine11 NitroprussideNitroprusside22
HypotensionHypotension 5.6%5.6% 36.9%36.9%
FlushingFlushing NANA 9.8%9.8%
NauseaNausea 4.9%4.9% 11.0%11.0%
DizzinessDizziness 1.4%1.4% 6.8%6.8%
HeadacheHeadache 14.6%14.6% 27.6%27.6%
ThiocyanateThiocyanate NANA 14.0%14.0%
Injection site painInjection site pain 1.4%1.4% NANA
1. Cardene IV [packageinsert].2. Nitropress [packageinsert].
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Nicardipine vs Adrenergic BlockersNicardipine vs Adrenergic Blockers
DrugDrug NicardipineNicardipine EsmololEsmolol LabetalolLabetalol
AdministrationAdministrationContinuousContinuous
infusioninfusion
BolusBolus
Continuous infusionContinuous infusion
BolusBolus
ContinuousContinuousinfusioninfusion
OnsetOnset RapidRapid RapidRapid IntermediateIntermediate
OffsetOffset RapidRapid RapidRapid Slower SlowerHRHR11 Minimal increaseMinimal increase DecreasedDecreased +/+/
SVRSVR DecreasedDecreased 00 DecreasedDecreased
Cardiac outputCardiac output11 IncreasedIncreased DecreasedDecreased +/+/
Myocardial OMyocardial O22
balancebalance22PositivePositive PositivePositive PositivePositive
ContraContra--indicationsindicationsAdvanced aorticAdvanced aortic
stenosisstenosis
Sinus bradycardiaSinus bradycardia
Heart block >1Heart block >1
Overt heart failureOvert heart failure
Cardiogenic shockCardiogenic shock
SevereSeverebradycardiabradycardia
Heart block >1Heart block >1
Overt heart failureOvert heart failure
CardiogenicCardiogenicshockshock
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Comparison Study withComparison Study with
IntravenousIntravenous DiltiazemDiltiazem
Subjects:
Patientsrequiringarapid reductionin BP (DBPu 115 mmHg)
Design:
Multicenter, randomized, single-blind comparativestudy
Dosage
Nicardipine: Started at 0.5 Qg/kg/min
p Increased upto10 Qg/kg/minifnecessary
Diltiazem: Started at 5 Qg/kg/min
p Increased upto15 Qg/kg/minifnecessary
Durationof drugadministration
Dosetitration: 1 hour
Maintenanceinfusion: 24 hours
YoshinagaK. etal. Igakuno Ayumi1993: 165:437
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Stability Effect
0
69
24.1
6.8
95.8
4.2
0
20
40
60
80
100
120
Stable Slightly unstable Undeterminable
%
PerdipineDiltiazem
Stability of antihypertensive effectStability of antihypertensive effect
better than DiltiazemDiltiazem
YoshinagaK. etal. Igakuno Ayumi1993: 165:437
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AHA Stroke GuidelinesAHA Stroke Guidelines Key PointsKey Points
The management of arterial hypertension remainsThe management of arterial hypertension remainscontroversialcontroversial
ll Data is inconclusive or conflictingData is inconclusive or conflicting
ll Many patients have spontaneous BP declines in the 1st 24Many patients have spontaneous BP declines in the 1st 24 hrshrsafter a strokeafter a stroke
Until more definitive data are not available, it isUntil more definitive data are not available, it isgenerally agreed that a cautious approach to thegenerally agreed that a cautious approach to thetreatment of arterial hypertension should betreatment of arterial hypertension should berecommendedrecommended
(Class I, Level of Evidence C)(Class I, Level of Evidence C)
Patients who have other medical indications forPatients who have other medical indications foraggressive treatment of blood pressure should beaggressive treatment of blood pressure should betreatedtreated
The management of arterial hypertension remainsThe management of arterial hypertension remainscontroversialcontroversial
ll Data is inconclusive or conflictingData is inconclusive or conflicting
ll Many patients have spontaneous BP declines in the 1st 24Many patients have spontaneous BP declines in the 1st 24 hrshrsafter a strokeafter a stroke
Until more definitive data are not available, it isUntil more definitive data are not available, it isgenerally agreed that a cautious approach to thegenerally agreed that a cautious approach to thetreatment of arterial hypertension should betreatment of arterial hypertension should berecommendedrecommended
(Class I, Level of Evidence C)(Class I, Level of Evidence C)
Patients who have other medical indications forPatients who have other medical indications foraggressive treatment of blood pressure should beaggressive treatment of blood pressure should betreatedtreated
AHA St k G id liAHA St k G id li
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AHA Stroke GuidelinesAHA Stroke Guidelines If Patient is a Lytic CandidateIf Patient is a Lytic Candidate
Class I, Level of Evidence B
Blood Pressure LevelBlood Pressure LevelSystolic > 185 mm Hg or diastolic > 110 mm HgSystolic > 185 mm Hg or diastolic > 110 mm Hg
______________________________________________________________________________________________________
LabetalolLabetalol 10 to 20 mg IV over 1 to 2 minutes, may repeat x 110 to 20 mg IV over 1 to 2 minutes, may repeat x 1oror
NitropasteNitropaste 1 to 2 inches1 to 2 inches
oror
Nicardipine infusionNicardipine infusion, 5 mg/h, titrate up by 0.25 mg/h at 5, 5 mg/h, titrate up by 0.25 mg/h at 5-- to 15to 15--
minute intervals, maximum dose 15 mg/h; when desired blood pressureminute intervals, maximum dose 15 mg/h; when desired blood pressure
obtained, reduce to 3 mg/hobtained, reduce to 3 mg/h
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The1st linetreatment of HypertensiveEmergency
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
PERDIPINE
Could be used :Could be used : CouldnCouldnt be used :t be used :
Sodium bicarbonatSodium bicarbonat
Ringer LaktatRinger Laktat
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SUMMARYSUMMARY
Hypertensive Crises is an urgent situation that need rapidHypertensive Crises is an urgent situation that need rapid
management to prevent organ damagemanagement to prevent organ damage
Antihypertensive agent thatAntihypertensive agent that prefferedpreffered in this condition shouldin this condition should
be fast action, parenteral, andbe fast action, parenteral, and titratabletitratable
NicardipineNicardipine is the only Calcium Antagonist recommended byis the only Calcium Antagonist recommended by
JNC 7, AHA, 2007, CHEST 2007 to manage hypertensiveJNC 7, AHA, 2007, CHEST 2007 to manage hypertensive
emergencyemergency
NicardipineNicardipine has favorablehas favorable antiischemicantiischemic profileprofile because ofbecause of
an increase myocardial , brain, and kidney oxygen supplyan increase myocardial , brain, and kidney oxygen supply
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