You are on page 1of 37


Dwi Lestari Partiningrum

Nephrology 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



Crisis Hypertensive Emergencies Hypertensive Urgencies (Accelerated) Malignant Hypertension

Hypertensive Crisis

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

Dwi Lestari

Hypertensive crises Definition

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

Dwi Lestari

E Grossman & FH Messerli, Comprehensive Hypertension Mosby, 2007

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

Dwi Lestari

E Grossman & FH Messerli, Comprh Hypert Mosby, 2007

Hypertensive Clinical implication 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

Dwi Lestari

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

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
Dwi Lestari

E Grossman & FH Messerli, Comprehensive Hypertension Mosby, 2007

(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

Endocrine disorders Pregnancy Drugs

Severe hypertension

Essential hypertension Renal disorders

Endothelial damage

Critical level or rapid rate of rise and increased vascular resistance

Spontaneous natriuresis Intravascular volume depletion

Endothelial permeability

Platelet and fibrin deposition

Decrease in vasodilators, nitric oxide, prostacyclin

Increase is vasoconstrictors (renin-angiotensin, catecholamines)

Further increase in blood pressure

Fibrinoid necrosis and intimal proliferation

Severe blood pressure elevation Tissue ischemia End-organ dysfunction Dwi Lestari

Kitiyakara, JASN 1998

Critical degree of hypertension

Endothelial damage Increase in vasoconstrictors (renin-angiotensin, vasopressin, catecholamines) Further blood pressure increase Pressure natriuresis

Platelet and fibrin deposition

Intravascular hemolysis
Fibrinoid necrosis and intimal proliferation


Increase in blood pressure and ischemia

Further release of vasoconstrictors

Dwi Lestari

Mechanisms of malignant hypertension

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 Crisis

Hypertensive crisis ( % of all pts ) Mainly due to more effective treatment ?

4 3 2

1950s Dwi Lestari 1990s Zampaglione, et al. AHA ; 27 (1) : 144

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
Haas, Seminars in Dialysis 2006

Dwi Lestari

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


BP > 220/120 mmHg Neurological sign (encephalopathy or stroke) Retinopathy grade 3-4 Severe chest pain (Ischemia or dissecting aneurism) Pulmonary edema Eclampsia Cathecolamine excess Acute renal failure EMERGENCY Intravenous therapy
Dwi Lestari

Headache No neurological signs No target organ damage

Identify the cause In panic attacks or anxiety use analgesic, anxiolytics Otherwise use oral antihypertensive agents recheck in 6-24 hours

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

Dwi Lestari

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

Parenteral Agents for Hypertensive Emergencies

Pheripheral Vasodilatation Sodium Nitroprusside Nitroglycerin * Nicardipine * Diltiazem * Diazoxide Fenoldopam mesylate Enaprilat Parenteral Adrenergic Inhibitor Labetalol Esmolol Phentolamine

Centrally acting : Clonidin

Dwi Lestari

Tatalaksana Hipertensi Emergensi

Harus dilakukan di rumah sakit Pengobatan secara parenteral baik bolus atau infus. Tekanan darah diturunkan dalam hitungan menit jam.

Dwi Lestari

Konsensus InaSH

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


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 0.150.3 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


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 g/min, max dose 100 g/min. Onset 2 to 5 minutes, duration action 5 to 10 minutes Side effect : headache and tachycardia
Dwi Lestari


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


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)


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


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



Dwi Lestari

Dwi Lestari

Recommended Antihypertensive Agents for Hypertensive Crises

Conditions Acute pulmonary edema/systolic dysfunction Acute pulmonary edema/diastolic dysfunction Acute myocardial ischemia Hypertensive encephalopathy Acute aortic dissection Pre-eclampsia, eclampsia Acute renal failure/microangiopathic anemia Sympathetic crisis/cocaine overdose APH Acute ischemic stroke/intracerebral bleed
Dwi Lestari

Preferred Antihypertensive Agents Nicardipine, fedoldopam, or nitroprusside in combination with nitroglycerin and a loop diuretic Esmolol, metoprolol, labetalol, diltiazem, verapamil in combintaion with low-dose nitroglycerin and a loop diuretic Labetalol or esmolol in combination with nitroglycerin Nicardipine, Diltiazem, labelatol, or fenoldopam Labetalol or combination of nicardipine and esmolol or combination of nitroprusside with either esmolol or IV metoprolol Labetalol or nicardipine Nicardipine or fenoldopam

Verapamil, diltiazem, or nicardipine in combination with a benzodiazepine Esmolol, nicardipine, or labetalol Nicardipine, Diltiazem, labetalol, or fenoldopam


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