Management of hypertensive Emergencies and Urgencies

DR VISHNU RS

7/19/07

Blood Pressure Measurement Stephen Hales

1733 Hollow glass tube

in neck artery of horse

Blood rose 9 feet in glass tube

Medicine, an Illustrated History 1987

Malignant hypertension The term malignant hypertension first appeared in 1928 to

describe patients with very high blood pressure (BP) values.

“Malignant” was used to compare the prognosis of these patients with that of most cancers because they had such rapid target organ deterioration, such as retinal hemorrhages or exudates and papilledema, usually associated with encephalopathy, acute renal failure, and microangiopathic hemolytic anemia.

Dramatic advancements of both in-hospital and outpatient treatment of hypertensive emergencies have led to an improved prognosis.

Decrease in 1-year mortality from 80% in 1928 to 50% in 1955 and 10% in 1989.

Terms such as malignant and accelerated hypertension have been replaced by the terms hypertensive emergency and hypertensive urgency.

Hypertensive emergency A hypertensive emergency is defined as marked elevation in BP

complicated by evidence of acute life-threatening target organ damage, such as coronary ischemia, dissecting aortic aneurysm, pulmonary edema, hypertensive encephalopathy, cerebral hemorrhage, and eclampsia.

In this clinical condition, BP should be reduced by at least 20 to 40 mm Hg within 10 to 30 minutes with parenteral drug therapy in an intensive care unit.

Hypertensive urgency Hypertensive urgency is a clinical setting of significant BP

elevation,generally above 180/110 mm Hg, without life-threatening target organ dysfunction (i.e., papilledema, evidence of early heart failure, acute renal failure), although some evidence of target organ damage is usually present (hemorrhages and exudates in fundi, headaches).

The approach to hypertensive urgency is a gradual BP reduction within hours, usually with oral medications

In a study with more than 14,000 emergency department visits during 12 months showed that hypertensive urgencies accounted for 76% and emergencies for 24% of hypertension-related visits.12

The most common presentations of hypertensive emergencies were associated with cerebral infarction (24.5%), acute pulmonary edema (22%), hypertensive encephalopathy (16%), and acute heart failure (14%), myocardial infarction (12%), cerebral hemorrhage (5%), eclampsia (5%), and aortic dissection (2%).

PATHOPHYSIOLOGY Hypertensive Emergency

Failure of normal autoregulatory function Leads to a sharp increase in systemic vascular resistance Endovascular injury with arteriole necrosis Ischemia, platelet deposition and release of vasoactive

substances Further loss of autoregulatory mechanism Exposes organs to increased pressure

MECHANISM OF HYPERTENSIVE CRISIS

Sudden severe increase in blood pressure

Endothelial injury/dysfunction

Pressure natriuresis

Increase vasoconstrictors and

decrease in vasoldilators

Activation of procoagulation cascade

and inhibition of fibronolytic mechanism

Release of inflammatory markers and

reactive oxygen species

Volume depletion and positive feedback to

reninangiotensin system

Fibroinoid necrosis and myo-proliferation

Further increase in blood pressure

General Principles for Management Therapy with parenteral antihypertensive agents should be

initiated in the emergency department. patients with a hypertensive emergency should be admitted to

an intensive care unit for continuous BP monitoring, clinical surveillance, and continued parenteral administration of an appropriate agent

Specific BP levels do not determine the severity and the emergency of the situation .

Autoregulatory structural and functional changes may vary between individuals, such that some individuals may develop target organ damage at lower BP.

Understanding of autoregulation is crucial for therapeutic decisions; sudden lowering of BP into a “normal” range could lead to inadequate tissue perfusion.

There is evidence that abrupt lowering of BP is harmful.

The use of sublingual nifedipine may precipitate stroke or shunt blood away from the penumbra of the brain, resulting in cognitive dysfunction.

The goal of antihypertensive therapy is not to rapidly normalize BP .

To prevent target organ damage by gradually reducing BP while minimizing the risk of hypoperfusion.

The mean BP should be reduced by no more than 20% to 25% within the first few minutes to an hour.

A diastolic BP target between 100 and 110 mm Hg or a reduction of 25% compared with the initial baseline, whichever is higher, is appropriate to be achieved within the next 2 to 6 hours.

Reduction of BP diastolic pressure to less than 90 mm Hg or by 35% or more of the initial mean BP has been associated with major organ dysfunction, coma, and death.

If the level of BP reduction is well tolerated and the patient clinically stable, further gradual reductions toward levels below 140/90 mm Hg should be implemented within the next 24 to 48 hours.

Typically, a long-acting oral calcium channel blocker (CCB) is given along with either an α- and β-blocker like carvedilol or nebivolol or RAS blocker, and the intravenous medication is gradually reduced during 1 to 2 hours

An important consideration before initiation of intravenous therapy is assessment of the patient’s volume status.

Because of pressure natriuresis, patients with hypertensive emergencies may be volume depleted, and restoration of intravascular volume may help restore organ perfusion and prevent a precipitous fall in BP.

Major exceptions to these treatment recommendations

patients with acute stroke, in whom there is no clear evidence to support immediate BP lowering and a more cautious approach is needed.

patients with aortic dissection, who should have their systolic BP lowered to below 100 mm Hg if tolerated

patients in whom BP should be lowered to enable the use of thrombolytic agents

IDEAL IV ANTI- HYPERTENSIVE

IDEAL IV ANTI- HYPERTENSIVE” Lower the BP without compromising blood flow to critical organs

Vasodilators generally considered first because they preserve organ blood flow in the face of reduced perfusion and also tend to increase CO.

Profile of an ideal IV antihypertensive

Preserves GFR and renal blood flow Few or no drug reactions Little or no potential for exacerbation of co-morbid conditions Rapid onset and offset of action Minimal hypotension Minimal need for continuous BP monitoring and frequent dose

titration No acute tolerance Ease of use and convenience Safe and no toxic metabolites Multiple formulations for short and long term use Minimal symphathetic activation

Sodium Nitroprusside MoA: Direct smooth muscle dilator (art + ven) Nitric oxide

compound Potent preload and afterload reducer Causes cerebral vasodilation Ultra short acting Immediate onset – DoA : 10min Dose: 0.1-0.5mcg/kg/min IV infusion titrate to desired effect rates >10mcg/kg/min – cyanide toxicity

Adverse affects/Precautions: Cyanide and thiocyanate toxicity (pts with liver/renal dysfunction)

Can cause precipitous drop in BP (hypotensive effects unpredictable)

Ideally Art.line with continuous BP monitoring Causes significant reflex tachycardia ( incr Oxygen demand)

(angina/aortic dissection/cerebral oedema) Nausea and vomiting Increased ICP Drug of choice: Perioperative HPT Cocaine toxicity Aortic

dissection(combination) Neurologic syndromes

Nitroglycerin MoA: Potent vasodilator (nitric oxide compound) Primary affects the venous system, decrease preload Decreases

coronary vasospasm Dose: cont infusion start 5mcg/min, incr by 5mcg/min every 3-

5min to 20mcg/min If NO Response increase by 10mcg/min every 3-5min,up

200mcg/min Onset : 2-5min/ DoA : 5-10min

Adverse effects/precautions: Constant monitoring is essential Tolerance from uninterrupted use (12hr withdrawal)

Headache, tachycardia, flushing Contra ind: Concurrent use with PDE-5 inhibitors - causes

significant hypotension Head trauma/cerebral haemorrhage Severe anaemia Drug of choice: Acute HF ACS

Nicardipine

Ca channel blocker – selective arterial vasodilator Onset: 1-5min DoA: 15-30min Dose: start 5mg/hr IV infusion, titrate every 15min to max

15mg/hr. Advantages: Cause cerebral and coronary vasodilatation Precautions: can worsen/cause HF liver failure can exacerbate

renal insuff. Ideal for CNS emergencies

Fenoldopam MoA: Peripheral dopamine agonist (high vs low doses) causes

selective neuro vasodilatation mesenteric vasodilatation increases renal blood flow and sodium excretion

Onset – <5min, but more gentle, lasts for 30min (titratable, predictable and stable) Standard BP monitoring is sufficient, no toxic metabolites

Dosing: Start at 0.1-0.3mcg/kg/min IV infusion May be increased in increments of 0.05- 0.1mcg/kg/min every 15min, until target BP reached

Precautions: Pts with glaucoma or intraocular hypertension Dose related tachycardia can occur – angina Close BP monitoring Close K monitoring Caution with raised ICP

Drug of choice Renal insuffiency Strokes ( combination with nicardipine)

Hydralazine MoA: Decreases systemic resistance by direct vasodilation of

arterioles Dose: 5-20mg IV bolus or 10-40mg IV repeat every 4-6hrs Adverse effects/Precautions tachycardia, flushing, headache

sodium and water retention increased ICP adjust dose in severe renal dysfunction response may be delayed and unpredictable

drug of choice in pregnancy(Eclampsia), but B-blocker/Labetalol

Enalapril

The active component of Enalapril (hydrolyzed in liver and kidney) MoA: ACE inhibitor

Dose: 0.625-2.5mg every 6hr IV Not titratable Onset – within 30 min + long half life

Adverse effects/Precautions Contra-indicated – volume depletion, renal vascular disease Prolonged ½ life

Labetolol

MoA: selective alpha blocker – will reduce vascular smooth m. resistance non-selective Beta blocker – decrease cardiac inotropic and myocardial O2 consumption, will prevent reflex tachycardia

Dose: Bolus: effect in 5-10min,max effect at 20min. (DoA: 2-6hrs) 1st dose 20mg then every 10-20min 2nd dose 40mg, 3rd dose 80mg. Cont. infusion: 0.5 – 2mg/min – titrate to response,max 300mg total dose Difficult to titrate due to very wide dose range

Advantages: smooth onset Transition to oral Rx easy (dose equivalent) Improve cerebral blood flow – stroke pt No need for ICU/Arterial line

Adverse effects/precautions Relative CI – Heart failure, heart block, Asthma (bronchoconstriction) Vomiting, scalp tingling Impaired hepatic function Elderly patients

Contraindicated in HPT secondary to Cocaine use/Phaeochromocytoma (B-blocker effect outway the alpha effect, thus unapposed alpha constriction)

Drug of choice: Aortic dissection Hypertensive emergencies

Esmolol

MoA: highly selective beta blocker Dose: (titratable) bolus: 250-500mcg/kg IV over 1-3min infusion:

50- 100mcg/kg/min may repeat bolus after 5min or increase infusion rate to 300mcg/kg/min Onset 1-2min / short acting

Adverse effect/Precautions Hypotension common nausea Asthma 1st degree AV block heart failure

Contraindications Sinus bradycardia Heart block Cardiogenic shock Bronchial asthma Uncompensated CF Pregnancy

Drug of choice: Aortic dissection ( with nitrate)

Phentolamine

MoA: alpha adrenergic receptor blocker Dose: load 5-20mg IV every 5min or infusion 0.2-0.5mg/min

Onset 1-2min Adverse effect/precautions tachycardia flushing/headache MI

cerebrovascular spasm Contra-indications renal impairment Concurrent use with PDE-5

inhibito coronary or cerebral arterioscleros Drug of choice Cocaine associated HPT crisis Pheochromocytoma

HPT crisis

Special situations

Neurological emergencies Acute ICH/SAH Treatment based on clinical/radiographic evidence of raised ICP Raised ICP – MAP<130 (1st 24hrs) No raised ICP – MAP<110

Drug of choice: Sodium Nitroprusside Labetalol Nicardipine

Cardiovascular emergencies ACS treat if SBP>160 and/or DBP>100 Reduce MAP by 20 -30% of baseline nitrates should be given till symptoms subside or until DBP<100

Drug of choice: Nitroglycerine Labetalol Nicardipine

Acute HF (pulmonary edema) treat with vasodilator (additional to diuretics) Sodium Nitroprusside in conjunction with morphine, oxygen and loop diuretic Enalaprilat also an option

CVS emergencies Aortic dissection anti-hypertensive Rx is aimed at reducing the shear stress on aortic wall (BP and Pulse) immediate lowering of BP – lifesaving maintain SBP<110, unless signs of end organ hypoperfusion

preferred Rx is combination of Morphine, B-blocker and vasodilator Nitroprusside + Labetalol

Cocaine toxicity/pheochromocytoma Hpt and tachycardia rarely require

specific Rx Alpha adrenergic blockers – preferred B – blockers can be added, but only after alpha blockade.

Drug of choice Phentolamine Labetalol Diazepam

Pre-eclampsia/Eclampsia Goal SBP<160 and DBP<110 in pre-and- intrapartum periods. Platelets < 100 000, BP should be maintained < 150/100

IV Magnesium to prevent seizures Drug of choice: Methyldopa Hydralazine

Perioperative hypertension target BP to within 20% of baseline, except if potential for life threatening arterial bleeding typically related to catecholamine surge post-op. Drug of choice : B-blocker Labetalol

Treatment of Hypertensive Urgencies

There is no proven benefit from rapid BP reduction in asymptomaticpatients without evidence of acute target organ damage;

BP lowering should occur during a longer time than for a hypertensive emergency.

BP reduction to levels within the range below 160/100 mm Hg may be accomplished within 2 to 4 hours in the emergency department with orally administered drugs.

the most important aspect of treatment of a hypertensive urgency is not achievement of BP goal but ensuring adequate follow-up, within a week generally.

The choice of drugs for treatment of hypertensive urgency is much broader than for emergencies

Almost all antihypertensive drugs lower BP effectively in a reasonable time.

Captopril, clonidine, labetalol, and other shortacting antihypertensive drugs have been mostly used for this .

Short-acting nifedipine once commonly used, is now contraindicated secondary to a higher incidence of stroke, myocardial infarctions, and deaths related to precipitous hypotensive episodes

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