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The Role of Perdipine in The Management of Hypertensive Emergency

dr. Al Rasyid, Sp.S(K) Dept. Neurologi FKUI/RSCM Jakarta

Epidemiology of Hypertensive Emergency (HE)

First described by Volhard and Fahr (1914), who saw patients with severe hypertension accompanied by signs of vascular injury to the heart, brain, retina, and kidney. Prior to the introduction of antihypertensive medications, 7% of hypertensive pts had HE.

Currently, 1 to 2% of pts with hypertension will have a HE at some time in their life.
Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62
InaSH-2009 2

Definitions
Hypertensive Crisis BP > 180/120
Hypertensive Urgency Hypertensive Emergency

Markedly elevated BP without severe symptoms or progressive target organ damage. BP should be reduced within hours. Oral agents.

Markedly elevated BP with acute or progressing target organ damage. BP should be reduced immediate. Parenteral agents.
Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9th Ed, Lippincott Williams & Wilkins 2006:609-630

Definitions

Accelerated malignant hypertension represents

markedly elevated BP with papiledema (grade 4 Keith-Wagener retinopathy) and/or hemorrhages and exudates (grade 3 Keith-Wagener retinopathy). The Clinical features and prognosis are similar with grade 3 or 4 retinopathy (Ahmed et al., 1986) Hypertensive encephalopaty is a sudden, marked elevation of BP with severe headache and altered mental status, reversible reduction of BP.
Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9th Ed, Lippincott Williams & Wilkins 2006:609-630
InaSH-2009 4

Clinical Presentation
30% 25% 20% 16% 15% 10% 5% 0%
Cerebral Infarction ICH or SAH Hypertensive encephalopathy Acute Acute CHF AMI or UAP Aortic pulmonary dissection edema Zampaglione B, Pascale C et al. Hypertension
1996;27:144-7

25% 23%

14% 12%

5% 2%

Indonesia : RSCM 2011


History of HT Anti HT drug non compliance Diabetes Mellitus Alcoholism Smoking Obesity Previous stroke Cerebrovascular lesions 50-58 %
Tisdalea, 2004 Xin, 2001 Teo, 2006 Critchley, 2003 Ellenga, 2011 Bisognano, 2011

Renal failure

Hypertensive Emergency

Cardiovascular disease

PATHOPHYSIOLOGY

Hypertensive emergency occur in association with target organ complications Caucasians : 20 30 % African-Americans : 80 %

cardeneiv.com

ALTERED MECHANISMS IN HYPERTENSION AND HYPERTENSIVE EMERGENCY

TRIGGERS

NORMAL

HIPERTENSIVE EMERGENCY

TRIGGERS
NO

ENDOTHELIAL DYSFUNCTION

MECHANICAL STRETCH

INFLAMATION

INCREASED : CYTOKINES ENDOTHELIAL ADHESIVES MOLECULES ENDOTHELIN-1

Initial Evaluation of Patients with a Hypertensive Emergency

History :

Physical exam.

Prior diagnosis and treatment of HT Intake of pressor agents : street drugs, sympathomimetics Symptoms of cerebral, cardiac, and visual dysfunction BP Funduscopy Neurologic status Cardiopulmonary status Body fluid volume assessment InaSH-2009 Peripheral pulses

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Management of Hypertensive Emergency (general)

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

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

Management of Hypertensive Emergency (general)

If this level of BP is well tolerated and the patients is clinically stable , further gradual reductions toward a normal BP can be implemented in the next 24 to 48 hours. Exceptions :

1. 2. 3.

Patients with ischemic stroke Aortic dissection SBP should < 100 mmHg Patients whom BP is lowered to enable the use of thrombolytic
Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

Parenteral Drugs for Treatment of Hypertensive Emergencies based on JNC 7


Drugs
Sodium nitroprusside Nitroglycerin Labetolol HCl Fenoldopan HCl

Dose
0.25-10 ugr/kg/min 5-500 ug/min 20-80 mg every 10-15 min or 0.5-2 mg/min 0.1-0.3 ug/kg/min

Onset
Immediate 1-3 minutes 5-10 minutes <5 minutes

Duration of Action
1-2 minutes after infusion stopped 5-10 minutes 3-6 minutes 30-60 minutes

Nicardipine HCl
Esmolol HCl

5-15 mg/h
250-500 ug/kg/min IV bolus, then 50-100 ug/kg/min by infusion; may repeat bolus after 5 minutes or increase infusion to 300 ug/min

5-10 minutes
1-2 minutes

15-90 minutes
10-30 minutes

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

Parenteral Drugs for Treatment of Hypertensive Emergencies based on ASA Guideline


Drug
Labetalol Nicardipine Esmolol Enalapril Hydralazine Nipride NTG

I.V. Bolus Dose


5 20 mg every 15 NA 250 ug/kg IVP loading dose 1,25-5 mg IVP every 6 h 5 20 mg IVP every 30 NA NA

Continous Infus Rate


2 mg/min (max 300mg/d) 5-15 mg/h 25-300 ug/kg/m NA 1,5-5 ug/kg/m 0,1-10 ug/kg/m 20-400 ug/m

This parenteral drugs are approved for hypertensive emergency in acute ischemic stroke and intracerebral AHA/ASA Guideline, 2007 update. Stroke. 2007;38: 2001-20 hemmorhage

Parenteral Drugs for Treatment of Hypertensive Emergencies based on CHEST 2007


Acute Pulmonary edema / Systolic dysfunction Acute Pulmonary edema/ Diastolic dysfunction Acute Ischemia Coroner Hypertensive encephalopaty Nicardipine, fenoldopam, or nitropruside combined with nitrogliceryn and loop diuretic Esmolol, metoprolol, labetalol, verapamil, combined with low dose of nitrogliceryn and loop diuretics Labetalol or esmolol combined with diuretics Nicardipine, labetalol, fenoldopam

Acute Aorta Dissection


Preeclampsia, eclampsia Acute Renal failure / microangiopathic anemia Sympathetic crises/ cocaine oveerdose Acute postoperative hypertension Acute ischemic stroke/ intracerebral bleeding

Labetalol or combined Nicardipine and esmolol or combine nitropruside with esmolol or IV metoprolol
Labetalol or nicardipine Nicardipine or fenoldopam Verapamil, diltiazem, or nicardipine combined with benzodiazepin Esmolol, Nicardipine, Labetalol Nicardipine, labetalol, fenoldopam
Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62

Nitroglycerin
Nitroglycerin is a potent venodilator and only at high doses affect arterial tone. It reduces BP by reducing cardiac ouput and preload which are undesirable effects in patient with compromised cerebral and renal perfusion

Nifedipine

Nifedipine has been widely used via oral or sublingual administration in the management of hypertensive emergencies. This mode of administration has not been approved by FDA and since JNC VI because it may cause sudden uncontrolled and severe reductions in blood pressure may precipitate cerebral, renal, and myocardial ischemia that have been associated with fatal outcomes

USE OF NICARDIPINE
Nicardipine : . Dihydropiridine class of CCB Reduce peripheral resistance --- blood

pressure
water soluble, light insensitive, -- can be parenteraly used (deference with nifedipine / sodium nitroprusid)

DOSIS

PERDIPINE
DIV (g/kg/min) Bolus (g/kg) 10 30

Acute hypertensive crises during surgery Hypertensive emergencies

2 - 10 0.5 6

Acute hypertensive crises during surgery

Hypertensive emergencies
(g/kg/min)

0.5

10

Dosage and Administration


Start with the lowest dose.
Eg 0.5 mcg/BW/min 15 drops monitoring, if in 5-15 minutes theres no significant blood pressure reducing Increasing drip until 20 drop , and then can be increased until desirable blood pressure achieved ( about 3-5 drops each after monitoring) Monitoring blood pressure and heart rate frequently Before choose to switch to oral, 1 hour before Perdipine is stopped, give oral drugs and Perdipine is tappered of

PERDIPINE
The 1st line treatment of Hypertensive Emergency

Could be used :
Sodium Chloride / NaCl ( OTSU-NS : 100/250/500 ml ) Dextrose 5% ( OTSU-D5 : 100 / 250 / 500 ml ) Glucose 5% Potacol R

Couldnt be used :
Sodium bicarbonat Ringer Laktat

Ringer Asetat
KN 1A / 1B / 4A

Kasus

Seorang laki-laki 31 tahun datang diantar keluarga dalam keadaan tidak sadar sejak 3 jam yll. Pasien saat mau ke kamar mandi mendadak mengeluh sakit kepala hebat, kemudian diikuti kejang-kejang dan selanjutnya tidak sadar. Dari pemeriksaan kesadaran sopor, TD 210/110; HR 104x/menit, febris (-). Kaku kuduk (-), gerakan tangan dan kaki kanan kurang aktif dibandingkan kiri. BB 75 kg Stroke?
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Kasus

Seorang laki-laki, 70 th, pagi hari saat ke kamar mandi mengeluh tungkai kiri terasa lemah. Ia masih dapat berjalan, beberapa saat kemudian kaki bertambah lemah disertai dengan kelemahan pada tangan kiri dan bicara pelo. Dari pemeriksaan kesadaran composmentis, TD 200/110; HR 104x/menit, febris (-). Kaku kuduk (-), ekstremitas kanan lebih lemah dibandingkan kiri. BB 61 kg Sebulan yang lalu pasien mengalami hal yang sama tapi pulih kembali dalam beberapa menit.

SUMMARY

Hypertensive Crises is an urgent situation that need rapid

management to prevent organ damage

Antihypertensive agent that preffered in this condition should be fast action, parenteral, and titratable Nicardipine is the only Calcium Antagonist recommended by JNC 7, AHA, 2007, CHEST 2007 to manage hypertensive emergency Nicardipine has favorable antiischemic profile because of an increase myocardial , brain, and kidney oxygen supply

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