nicardipine rtd

8/7/2019 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

JNC 7, JAMA 2003; 289:2560-2572.


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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


ll HypertensionHypertension

Hypertensive EmergenciesHypertensive Emergencies

ll Chest painChest pain

ll DyspneaDyspnea

ll Neurologic deficitsNeurologic deficits


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


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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nicardipine rtd

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