HYPERTENSIVE EMERGENCY

Dwi Lestari PartiningrumNephrology and Hypertension Division, Internal Medicine Department

Medical Faculty Diponegoro University/ Kariadi Hospital

Definitions Pathophysiology and Clinical Manifestation Parenteral Agents for Hypertensive Emergencies Management of Spesific Hypertensive

Emergencies

Dwi Lestari

Definition

Hypertensive Crisis Hypertensive Emergencies Hypertensive Urgencies (Accelerated) Malignant Hypertension

?

JNC VII 2003 ≥ 180/110 Recognition of hypertensive crisis depends on

the clinical state of the patients, not on the absolute level of blood pressure

Included Hypertensive Emergency and Hypertensive Urgency

Hypertensive Crisis

Dwi Lestari

Definition Hypertensive crises

A severe elevation in blood pressure (BP), such as a diastolic BP above 120 to 130 mmHg, and is classified as either an emergency or urgency

E Grossman & FH Messerli, Comprehensive Hypertension Mosby, 2007Dwi Lestari

Definition Hypertensive urgency

A situation with markedly elevated BP but without severe symptoms or progressive target organ damage, wherein the BP should be reduced within hours, often with oral agents

or

When severe elevation in BP is not associated with end-organ injury

MN.Kaplan; Clin.Hypt 9th ed.2006

E Grossman & FH Messerli, Comprh Hypert Mosby, 2007Dwi Lestari

Clinical implicationHypertensive urgency

Common and no scientific evidence showed that acute BP lowering is beneficial.

The appropriate approach is to lower BP gradually over 12 to 24 hours with oral AHAs.

Any drug that lower BP precipitously should be avoided

MN.Kaplan; Clin.Hypertension 9th ed.2006Dwi Lestari

Definition Hypertensive emergency

A situation that requires immediate reduction in blood pressure with parenteral agents because of acute or progressing target organ damage

When BP elevation confers an immediate threat to the integrity of the cardiovascular system

Relatively rare, and immediate reduction in BP is required to avoid further end-organ damage, generally by IV therapy in an IC setting to lower the MAP by 25% over the initial 2 to 4 hours with the most specific AHA

MN.Kaplan; Clin.Hypt 9th ed.2006

E Grossman & FH Messerli, Comprehensive Hypertension Mosby, 2007Dwi Lestari

(Accelerated) Malignant Hypertension

Elevated BP associated / manifested clinically with retinal hemorrhages, exudates and papilledema (grade 3 Keith-Wagener retinopathy and grade 4 KW retinopathy)

Most often occur in patients with long-standing uncontrolled hypertension

Maybe difficult to detect, subject to observer interpretation

Dwi Lestari

Pathophysiology and Clinical Manifestation

Failure of the normal autoregulatory function Abrupt increases in systemic vascular resistant

End organ damage and severity of BP elevation Fibrinoid necrosis Activation of endothelial vasoactive systems: endothelin,

oxidative stress, RAS

Dwi Lestari

Severe hypertension

Critical levelor

rapid rate of rise and increased

vascular resistance

Decrease in vasodilators,nitric oxide, prostacyclin

Severe bloodpressure elevation

Tissue ischemia

End-organ dysfunction

Essential hypertension

Renal disorders

Spontaneous natriuresis

Intravascular volumedepletion

Increase is vasoconstrictors(renin-angiotensin,

catecholamines)

Further increase inblood pressure

Endocrine disorders

Pregnancy

Drugs

Endothelial damage

Endothelial permeability

Platelet and fibrindeposition

Fibrinoid necrosis andintimal proliferation

Kitiyakara, JASN 1998Dwi Lestari

Critical degree of hypertension

Endothelial damageIncrease in vasoconstrictors(renin-angiotensin, vasopressin, catecholamines)

Further blood pressure increase

Pressure natriuresis

hypovolemia

Further release of vasoconstrictors

Platelet and fibrin deposition

Intravascular hemolysis

Fibrinoid necrosis and intimal proliferation

Increase in blood pressure and

ischemia

Mechanisms of malignant hypertensionDwi Lestari

Drugs that can increase BP Withdrawl of antihypertensive medications:

clonidine rebound (methyldopa,reserpine), nifedipine, propanolol

Phenylpropanolamine (cold preparations) Sympathomimetics amines Oral contraceptive, erythropoieten Corticosteroids, anabolic steroids NSAIDS, Cox2 inhibitors Cocaine, amphetamine, ethanol NaCl

Dwi Lestari

Prevalence of Hypertensive CrisisPrevalence of Hypertensive Crisis

Mainly due to more effective treatment ?

Hypertensive crisis

( % of all pts )

1950’s 1990’s

1

2

4

3

Zampaglione, et al. AHA ; 27 (1) : 144Dwi Lestari

Retinal findings in hypertensive encephalopathy

Dwi Lestari

Fundoscopic appearance of grade IV hypertensive retinopathy, papilloedema (1), arteriovenous nipping (2), flame-shaped hemorrhages (3), soft (4) and hard (5) exudates

Clinical Manifestation of Hypertensive Emergency

Hypertensive encephalopathy Dissecting (acute) aortic aneurysm Acute left ventricular failure with pulmonary edema Acute myocardial infarction & acute coronary

syndrome Eclampsia, HELLP sndrome, Pre-eclampsia

severe Acute renal failure Symptomatic microangiopathic hemolytic anemia

Dwi Lestari Haas, Seminars in Dialysis 2006

Evaluation

Initial evaluation for patients with HTN emergencyHistory• Prior diagnosis & treatment of HTN• Intake of pressor agents; street drugs, sympathomimetics• Symptoms of cerebral, cardiac, pulmonal, and visual

dysfunctionPhysical examination• Blood pressure• Funduscopy• Neurologic status• Cardiopulmonary status• Blood fluid volume assessment• Peripheral pulses

Dwi Lestari

Laboratory evaluation Hematocrit and blood smear Urine analysis Automated chemistry : creatinin, glucose, electrolytes ECG Plasma renin activity & aldosterone (if primary

aldosteronism is suspected) Plasma renin activity before & 1 h after 25 mg captopril

(if renovascular HTN issuspected) Spot urine or plasma for metanephrine (if

pheochromocytoma is suspected) Chest radiograph (if heart failure or aortic dissection is

suspected)

Dwi Lestari

SIMPLE APPROACH TO HYPERTENSIVE CRISIS

BP > 220/120 mmHg

Neurological sign(encephalopathy or stroke)

Retinopathy grade 3-4Severe chest pain

(Ischemia or dissecting aneurism)

Pulmonary edemaEclampsia

Cathecolamine excessAcute renal failure

HeadacheNo neurological signs

No target organ damage

EMERGENCY

URGENCY

Intravenous therapy

Identify the causeIn panic attacks or anxiety use

analgesic, anxiolyticsOtherwise use oral

antihypertensive agentsrecheck in 6-24 hours

Dwi Lestari

Principles of Therapy for Hypertensive Emergencies

Patients must be hospitalized for monitoring Direct consequences of lowering BP too quickly Treated with parenteral Lower MAP {1/3(SBP-DBP)+DBP} by no more than 25%

within minute to 2 hours or diastolic 110 mmHg, then 160/100 mmHg within 2-6 hours (JNC VII). Exception for ischemic stroke

IV infusion is prefer than bolus

Hypertension.,Brian C. Poole and Anitha Vijayan in Nephrology and Subspeciality Consult,2004Dwi Lestari

Parenteral Agents for Hypertensive Emergencies

Pheripheral Vasodilatation Sodium Nitroprusside Nitroglycerin * Nicardipine * Diltiazem * Diazoxide Fenoldopam mesylate Enaprilat

Parenteral Adrenergic Inhibitor Labetalol Esmolol Phentolamine

Dwi Lestari

Centrally acting : Clonidin

Tatalaksana Hipertensi Emergensi

Harus dilakukan di rumah sakit Pengobatan secara parenteral baik bolus atau

infus. Tekanan darah diturunkan dalam hitungan menit

– jam.

Konsensus InaSHDwi Lestari

Tatalaksana Hipertensi emergensi

Langkah penurunan tekanan darah :

− 5-120 menit pertama tekanan darah arteri rata-rata (Mean Arterial Pressure, MAP) diturunkan 20-25 %

− 2 s/d 6 jam berikutnya tekanan darah diturunkan sampai 160 / 100 mm Hg

− 6-24 jam berikutnya lagi sampai ≤140 / 90 mmHg. (tidak boleh ada tanda-tanda iskemia organ)

− Target penurunan tekanan darah tergantung faktor risiko krisis hipertensi.

Dwi Lestari

Obat parenteral pd Hipertensi emergensi

Clonidine

Centrally acting -2 Agonist Good oral bioavailability, a relatively rapid onset of oral

action. Disadvantage : acute use parogressive sedation, dry

mouth, somnolence, “rebound hypertension’ Use oral, transdermal (FDA) 0.1 – 0.2 po repeat hourly as required Dose 0.15–0.3 mg over a period of 5 minutes . Reduced

MAP in 25% within minutes to 1 hour

Dwi Lestari

Clonidin (Catapres) IV (150 mcg/ampul) Clonidin 900 mcg (6ampul) dalam glucosa 5 % dengan

tetesan mikro disesuaikan dengan kebutuhan. Dosis awal 12 tetes / menit dan setiap 15 menit dapat dinaikkan 4 tetes.

Bila sasaran tekanan darah tercapai dilakukan observasi 4 jam dan diteruskan dengan tablet oral sesuai kebutuhan.

Clonidin tidak boleh dihentikan mendadak. Dosis diturunkan - perlahan-lahan oleh karena bahaya “rebound phenomen “ dimana tekanan darah naik kembali secara cepat bila obat dihentikan.

Dwi Lestari

Nitroglycerin

A venous dilator and slight arteriolar dilatation Most useful in patients with symptomatic

coronary disease and in those with hypertension following coronary bypass.

Initial dose 5 µg/min, max dose 100 µg/min. Onset 2 to 5 minutes, duration action 5 to 10

minutes Side effect : headache and tachycardia

Dwi Lestari

Diltiazem

Inhibit the influx Ca during membran depolarization of cardiac and smooth muscle cell

Contra indication : sick sinus syndrome, second and third degree AV block

Dwi Lestari

Diltiazem IV (10 dan 50mg/ ampul). Diltiazem 10 mg IV bolus diberikan dalam 1-3 menit

diteruskan dengan infus 50 mg /jam selama 20 menit Bila penurunan tekanan darah mencapai 20-25 %

dosis diberikan 30 mg/jam sampai sasaran tekanan darah tercapai.

Berikutnya diberikan dosis pemeliharaan 5-10 mg/ jam, selama 4 jam, kemudian diganti tablet sesuai kebutuhan.

Perlu perhatian khusus pada gangguan konduksi dan gagal jantung.

Dwi Lestari

Nicardipine

Dihydropyridine CCB Initial dose :5 mg/h to a maximum 15 mg/h Increased by 2.5 mg/h Limitation : longer half life time (precludes rapid

titration) Side effect : reduced both cerebral and coronary

ischemia, tachycardia, increase myocardial oxigen demand, headache, nausea and vomiting

Cannot use in severe coronary ischemia

Dwi Lestari

Nicardipin (Perdipin) IV (2 dan 10 mg / ampul)

Nicardipin bolus diberikan 10-50mcg/Kg BB Diteruskan dengan 0.5-6mcg/kg BB/menit

sampai mencapai sasaran tekanan darah. Kemudian diganti dengan antihipertensi oral.

Dwi Lestari

DOSIS PERDIPINE

0.5 – 6Hypertensive emergencies

10 – 302 - 10Acute hypertensive crises during surgery

Bolus(g/kg)

DIV(g/kg/min)

(g/kg/min)0.5 1 2 6 10

Hypertensive emergencies

Acute hypertensive crises during surgery

Dwi Lestari

Dwi Lestari

Conditions Preferred Antihypertensive Agents

Acute pulmonary edema/systolic dysfunction

Nicardipine, fedoldopam, or nitroprusside in combination with nitroglycerin and a loop diuretic

Acute pulmonary edema/diastolic dysfunction

Esmolol, metoprolol, labetalol, diltiazem, verapamil in combintaion with low-dose nitroglycerin and a loop diuretic

Acute myocardial ischemia Labetalol or esmolol in combination with nitroglycerin

Hypertensive encephalopathy Nicardipine, Diltiazem, labelatol, or fenoldopam

Acute aortic dissection Labetalol or combination of nicardipine and esmolol or combination of nitroprusside with either esmolol or IV metoprolol

Pre-eclampsia, eclampsia Labetalol or nicardipine

Acute renal failure/microangiopathic anemia

Nicardipine or fenoldopam

Sympathetic crisis/cocaine overdose

Verapamil, diltiazem, or nicardipine in combination with a benzodiazepine

APH Esmolol, nicardipine, or labetalol

Acute ischemic stroke/intracerebral bleed

Nicardipine, Diltiazem, labetalol, or fenoldopam

Recommended Antihypertensive Agents for Hypertensive Crises

Dwi Lestari

Summary

Hypertension Crisis included Hypertensive Emergency and Hypertensive Urgency

HE required immediate reduction in BP to avoid further end-organ damage, by IV therapy to lower the MAP by 25

Parenteral agents for hypertensive emergency : Clonidin, Nitroglycerin, Diltiazem, Nicardipine

Dwi Lestari

Dwi Lestari