Hypertensive Emergencies

Dr. Herb RussellPrepared by

Anthony G. Hillier, D.O.

September 2005

Why this is a difficult topic

Hypertension is common (up to 25%) but emergencies are rare

Failing to treat an emergency AND treating a non-emergency can have serious consequences for the patient

Blood pressure alone is a poor indicator of an emergency

Why this is a difficult topic

The physical exam is often not helpful Different emergencies have vastly

different goals in BP reduction The first line agent for one emergency

may be contraindicated for another emergency

Lack of consensus regarding definitions, therapeutic goals, and 1st line medications

Definitions

Hypertensive Emergency: A relatively high blood pressure with evidence of target organ damage.

Hypertensive Urgency: Elevated BP with imminent risk of target organ damage

Definitions

Acute Hypertensive Episode: SBP >180 or DBP >110 and no target organ damage

Transient Hypertension: Hypertension that occurs in association with •Pain

•Withdrawal syndromes

•Some toxic substances

•Anxiety

•Cessation of medications

ED Evaluation

History•History of HTN

•Blood pressure trends

•Prescribed medications

•OTC medications Review of systems directed at:

•CNS (HA, hemiparesis)

•Cardiac (CP, dyspnea)

•Compliance

•Past medical history

•Family history

• Illicit drug use

•Renal (hematuria)

ED Evaluation

Physical Exam•Appropriate sized cuff

•Measure arms and legs

•Brachial difference <20mm Hg

•Focus on areas of potential target-organ damage-CNS -Heart -Retina-Pulmonary -Pulses -Renal

Cotton wool spot (soft exudates)

Cotton wool spots

Hard exudates

Retinal Hemorrhage

Disk Edema

Diagnostic Studies

CBC-hemolytic anemia Glucose-hypoglycemia Electrolytes-hyperkalemia BUN/Cr-azotemia, ARF Urine-proteinuria, RBC cast CXR-Pulmonary edema, aortic dissection ECG-ischemia, infarction pattern Head CT-hemorrhage, infarction

Schistocytes

What precipitates an emergency?

1. Non-compliance with medications in a chronic hypertensive patient

2. Those with secondary hypertension (e.g. pheochromocytoma, reno-vascular hypertension, Cushing’s)

3. Hypertension during pregnancy is a major risk factor for women

General Management Goals

Reduce BP so autoregulation can be re-established

Typically, this is a ~25% reduction in MAP

Or, reduce MAP to 110-115 Avoid

•Lowering the BP too much or too fast.

•Treating non-emergent hypertension

General Management Goals

Exceptions: aortic dissection and eclampsia

In aortic dissection and eclampsia, BP should be lowered to normal levels

Search for secondary causes

Pharmacology-Nitroprusside

Dose: 0.3-10 mcg/kg/min Actions: Equally rapid decrease of

both preload and afterload Indications: All hypertensive

emergencies including post-partum eclamplsia

Half-life: 3-4 minutes Metabolism: Liver

Pharmacology-Nitroprusside

Excretion: Kidney Adverse Effects:

•Cyanide toxicity with prolonged use (rare)

•Inhibits hypoxia induced pulmonary vasoconstriction

•Coronary steal syndrome

•Increased ICP Contraindications:

•Other cyclic GMP inhibitors (i.e. sildenafil)

Pharmacology-Labetalol

Dose: Bolus of 20mg IV, double bolus up to 80 mg, or infusion of 2mg/min to maximum total of 300mg

Actions: Selective α1 and nonselective β–blocker 4-8 times that of α-blockade.

Indications: Hypertensive emergencies, including those from catecholamine stimulation and PIH. Does not decrease cerebral or coronary blood flow.

Pharmacology-Labetalol

Onset: 5-10 min Half-life: 5.5 hrs Metabolism: Hepatic Adverse Effects:

•May exacerbate CHF and induce bronchospasm

•In low doses, may have a paradoxical increase in BP when used in catecholamine excess

Pharmacology-Esmolol

Dose: Loading dose of 500mcg/kg over 1 min, the infusion of 50-300mcg/kg/min

Actions: Ultra-short acting β1-selective adrenergic blocker

Indications: Used in conjunction with nitroprusside or phentolamine for hypertensive emergencies

Pharmacology-Esmolol

Onset: Less than 5 mins Half-life: 9mins Metabolism: Erythrocytes Adverse Effects:

•May induce bronchospasm

•Avoid as sole agent in catecholamine excess

Pharmacology-Nitroglycerin

Dose: Infusion rate 5-10mcg/min, titrate up 10mcg every 5 mins

Actions: Greater preload reduction than afterload, until high rates, then equal

Indications: Agent of choice for moderate hypertension complicating unstable angina, MI or pulmonary edema

Pharmacology-Nitroglycerin

Onset: Immediate Half-life: 4 mins Metabolism: Hepatic Adverse Effects: HA, tachycardia,

hypotension Contraindications:

•Other cyclic GMP inhibitors (i.e. sildenafil)

Pharmacology-Hydralazine

Dose: 10-20 mg, repeated in 30 mins Actions: Direct arteriolar dilator Indications: PIH, pre-eclampsia Onset: 10 mins Half-life: 2-4 hrs Metabolism: Liver acetylation Excreted: Urine

Pharmacology-Hydralazine

Adverse Effects:•Decrease dose in renal insufficiency

•High incidence of hypotension in “slow acetylators”

•Reflex tachycardia

•Should not be used in aortic dissection and Coronary artery disease

•Lethargy

Pharmacology-Enalaprilat

Dose: 0.625-1.25mg IV bolus Actions: Afterload reduction with

lowered MAP, PCWP and increased coronary vasodilatation

Indications: Hypertensive emergencies

Onset: Within minutes Metabolism: None

Pharmacology-Enalaprilat

Excreted: Urine Adverse Effects:

•Angioedema

•Cough

•Worsening renal function

•Hyperkalemia

Pharmacology-Others

Trimethaphan-ganglionic blocking agent Fenoldopam-dopaminergic receptor

agonist Nicardipine-dihydropyridine calcium

channel blocker Urapidil-peripheral a1-receptor blocker

and a central 5-HT1A-receptor agonist

Categories of Hypertensive Emergencies

Hypertensive encephalopathy

Stroke syndromes•Embolic

•Hemorrhagic

•Subarachnoid hemorrhage

Categories of Hypertensive Emergencies

Cardiovascular•Acute LV failure (“Flash” pulmonary

edema)

•Acute coronary syndrome

•Aortic dissection Pregnancy related hypertension

•Pre-eclampsia

•Eclampsia

•HELLP syndrome

Categories Catecholamine excess

•Pheochromocytoma

•MAOI + tyramine

•Cocaine/amphetamines/OTCs

•Clonidine withdrawal Other

•Renal failure

•Epistaxis

•Childhood hypertension

Hypertensive Encephalopathy

Symptoms:•Mental status change – somnolence,

confusion, lethargy, stupor, coma, seizure

•Focal neurologic deficit

•Headache – alone not sufficient to diagnose a hypertensive encephalopathy

•Nausea and vomiting Signs:

•Papilledema, cotton wool exudates

Diagnostics

Hypertensive encephalopathy is a diagnosis of exclusion – thus, exclude the other possibilities!

Only definitive criteria is a favorable response to BP reduction. However clinical improvement may lag behind BP improvement by hours to days

Pathophysiology

A loss of cerebral autoregulation. Autoregulation is best studied in the

brain but present in heart and kidneys as well

Represents the body’s attempt to maintain constant FLOW of blood to perfuse the cells

Autoregulation

In the uninjured, normotensive brain, autoregulation is effective over MAP ranging from about 50 – 150

In the chronic hypertensive, this range is increased (e.g. 80 – 180)

Autoregulation

Pathophysiology

Loss of autoregulation leads to:•Cerebral hyper-perfusion

•Vascular permeability

•Cerebral edema

•Vasospasm

•Ischemia

•Punctuate hemorrhages

Therapy

Untreated, hypertensive encephalopathy leads to coma and death

Goal is to reduce MAP by 20-25% in the first hour

This will get MAP back into range where autoregulation is re-instituted

Therapy

Nitroprusside•1st line, 0.3 – 10 mcg/kg/minute

Labetalol Enalaprilat Fenoldopam

Stroke Syndromes

Thrombo-Embolic CVA

Represent 85% of all strokes BP elevations are generally mild-

moderate and represent a physiologic response to maintain cerebral perfusion pressure to the penumbra, which has lost its ability to autoregulate

Embolic CVA - Dilemma

Inappropriate lowering of the BP may convert the potentially salvageable ischemic penumbra to true infarction.

However, persistent BP >185/110 is a contraindication to thrombolytic therapy (it significantly increases risk of intra-cranial bleeding)

Embolic CVA –When to Rx HTN

For thrombolytic candidates, 1-2 doses of labetalol (5mg) or nitroglycerin paste may be used in attempt to get BP <185/110

If thrombolytics are given, then the BP MUST be aggressively kept below 185/110!

Embolic CVA – When to Rx HTN

According to National Institutes of Neurologic Disorders and Stroke:•SBP <220, no treatment

•DBP <120, no treatment Tintinalli suggests not treating DBP

<140 Others use MAP <130

Embolic CVA – When to RX

If complicated by:•Aortic dissection

•Hypertensive encephalopathy

•AMI

•Renal failure

Embolic CVA –How to Rx HTN

Goal is to reduce MAP 10-20% in uncomplicated embolic CVA with markedly elevated pressures

Labetalol: 5mg doses Nitroglycerin paste

Why not treat everybody?

Danger of being too aggressive in acute CVA is well documented.

Many studies show a worsening of neurologic outcome when the above guidelines are not followed.

Hemorrhagic CVA

Unlike embolic CVA, BP elevations in hemorrhagic CVA are profound

However, this again represents a physiologic response to increased intracranial pressure (and free blood irritating the autonomic nervous system)

Typically is transient

Hemorrhagic CVA – When to Rx

Evidence to support anti-hypertensive therapy in acute intracranial hemorrhage is lacking

However, modest reductions of ~20% MAP have not been show to adversely affect outcome

Hemorrhagic CVA - Rx

Labetalol is agent of choice ACE inhibitor can be used but not as

well studied. Vasodilators such as nitroprusside

and nitroglycerin are contraindicated because they may raise the ICP

Subarachnoid Hemorrhage

A special subset of hemorrhagic CVA. Evidence suggests that there may be

less vasospasm and less re-bleeding if SBP <160 or MAP <110

Agents:•Oral nimodipine 60mg q 4hr x 21 days

•IV nicardipine 2mg bolus, then 4-15mg/hr

Acute Left Ventricle Failure

Pathophysiology

Abrupt, severe increase in afterload leads to systolic and diastolic dysfunction.

Vicious cycle ensues:•Heart failure causes poor coronary perfusion,

LV ischemia and worsening failure

•CHF leads to hypoxia and worsens LV ischemia

•Renal hypoperfusion leads to renin release and this increases afterload

Signs and Symptoms

Abrupt and severe dyspnea, tachypnea, and diaphoresis

Rales, wheezes, distant breath sounds, frothy sputum, and gallop rhythm

Goals of therapy

1. Reduce preload and afterload! 2. Minimize coronary ischemia by

increasing supply (blood to coronary arteries) and decrease demand (wall tension, tachycardia)

3. Oxygenate, ventilate, clear pulmonary edema.

Therapy

Nitroglycerin•Arterial (especially coronaries) and veno-dilator,

reducing preload and afterload

Lasix• Initially a vasodilator, then diuretic

Morphine•Vasodilator and sympatholytic

ACE inhibitor• Interrupts the renin-angiotensin-aldosterone axis

Acute Coronary Syndrome

Elevated BP significantly increases LV wall tension

Wall tension is one of main determinants of myocardial oxygen demand.

ACS therapy goals

Goal is to decrease wall tension by decreasing preload and afterload.

Typical agents do this well: Nitroglycerin, beta-blockers, morphine

Avoid hydralazine and minoxidil, as they increase myocardial oxygen demand.

Aortic Dissection

Classification

Stanford A•Involves ASCENDING aorta

•More common

•More often fatal

•REQUIRES surgery for survival Stanford B

•Involves DESCENDING aorta

•May be managed medically

Pathophysiology

Degeneration of the media•Normal aging

•Pregnancy

•Marfans and Erhlers-Danlos syndromes Hypertension Bicuspid aortic valve Flexion of aorta with each heartbeat Atherosclerosis – minor factor

Pathophysiology

Hydrodynamic force of blood column tears the intima and dissects into the media, creating a false lumen.

Can extend proximal or distal, re-enter the aorta through the intima (rare), or dissect through the adventitia (fatal)

Pathophysiology

Worsening of the dissection dependent on:•1. Level of elevated BP

•2. Slope of the pulse wave – dP/dt. This increases the “shear force” on the dissection. Increased shear force leads to propagation of the dissection

Complications

Retrograde Dissection•Into AV – acute regurgitation and CHF

•Into pericardium – tamponade

•Into coronary arteries - AMI Anterograde Dissection

•Into carotid artery - CVA

•Into renal arteries – ARF

•Into anterior spinal artery - paraplegia

Signs and Symptoms

Severe tearing chest pain, maximal at onset, radiates to back, may migrate as the dissection propagates

Diaphoresis N/V Feeling of doom (angor animi) and

anxiety

Diagnostics

CXR •may be normal in up to 12% !!

•Wide mediastinum

•Calcium sign

•Deviation of trachea or NG tube

Diagnostics - CXR

Therapy

Goal is to reduce both the BP and the slope of the pulse wave!

BP goal is SBP of 100-120 If patient presents with normal BP,

still need to decrease the shear forces!!

Therapy

Beta-blocker for decreasing the slope of the pulse wave (e.g. esmolol)

Nitroprusside for BP reduction (started after or with the beta-blocker to avoid reflex tachycardia)

Labetalol as monotherapy Trimethaphan if beta-blocker

contraindicated

Doses

Esmolol: 500mcg/kg bolus, then 50-300 mcg/kg/min

Nitroprusside: 0.3 – 10 mcg/kg/min Labetalol: 20mg IV q5-10 minutes,

increasing by 20mg up to 80mg per dose, total not to exceed 300mg.

Trimethaphan: 1 – 2mg/minute

Pregnancy and Hypertension

Complicates 5% of pregnancies Risk factors:

•Nulliparity

•Age >40

•African American

•Chronic renal failure

•Diabetes mellitus

•Multiple gestations

Pregnancy and Hypertension

Accounts for 18% of maternal deaths Most common risk factor for

placental abruption Defined as:

•Greater than 140/90

•SBP increased >20 from baseline

•DBP increased >10 from baseline

Pregnancy and Hypertension

Pre-eclampsia•Hypertension

•Proteinuria >300mg per 24 hr.

•Peripheral edema or weight gain >5 lbs in 1 week

•Presents >20 weeks except in gestational trophoblastic disease

Eclampsia•Pre-eclampsia +

seizures – This is an emergency !!!!

HELLP syndrome•Variant of pre-

eclampsia

•Blood pressure lower

•Predilection for multigravid

Pathophysiology

Pre-eclampsia and eclampsia may occur up to 6 weeks post partum

Not well understood, but thought to be loss of normal vasodilatation:•Increased thromboxane

•Increased endothelin

•Increased sympathetic nerve activity

•Decreased nitric oxide formation

•Oxidative stress

Signs and symptoms

Restlessness and hyper-reflexia early Headache Visual disturbance Peripheral edema Abdominal pain

Therapy

Any pregnant patient with BP >140/90 and any symptoms should be hospitalized

Eclampsia and patients with pre-eclampsia + severe symptoms (HA, abdominal pain) but no seizures should be treated very aggressively!

Therapy

Definitive therapy is delivery of the fetus and placenta

Magnesium: 4-6gm over 15 minutes, drip 1-2gm per hour

Hydralazine: 5-10mg IV, drip 5-10mg per hour

Labetalol: 20mg IV, repeat prn q 10 minutes, drip 1-2mg per minute

Catecholamine excess

Pheochromocytoma Monoamine oxidase inhibitor +

tyramine Cocaine/amphetamines/OTC herbals

(PPA, ephedra, trytophan) Clonidine withdrawal

Pheochromocytoma

Is a tumor of adrenergic cells Most common site is adrenal medulla Increased risk in patients with von

Recklinhausen’s disease (aka neurofibromatosis)

Neurofibromas and café au lait spots

Signs and symptoms

Chronically elevated BP with paroxysms of palpitations, diaphoresis, tachycardia, malaise, apprehension, HA, abdominal pain, and angina

Episodes precipitated by physical or emotion stress, eating, position, or micturation

Diagnosis

Commonly mislabeled as panic attacks or anxiety disorder

Diagnosed by detecting elevated levels of catecholamines and their by-products in the urine

Clonidine withdrawal

Occurs in patients on clonidine who abruptly discontinue therapy

Symptoms very similar to pheochromocytoma

Occur 16-48 hours after last dose Treatment is to re-start clonidine

MAOI + tyramine

Tyramine is found in many foods, is a sympathomimetic like amphetamine, and causes a transient release of norepinephrine (NE) in all people when ingested

Patients on MAOIs (Nardil, Parnate, Marplan) experience an exaggerated response to tyramine, resulting in prolonged and severe hypertension

Foods containing tyramine

Beer Wine Aged cheeses Chocolate Coffee Cream

Chicken liver Pickled herring Broad beans

(dopamine) Yeast Citrus fruits Snails

MAOIs and medications

Some pharmaceuticals can also cause severe hypertension when taken with MAOIs

Meperidine Ephedrine TCAs Reserpine Dopamine Methyldopa Guanethidine

Ingestions

Cocaine •blocks re-uptake of NE, dopamine, and

serotonin Amphetamines

•Stimulate release of and block re-uptake of catecholamines

•Also may directly stimulate catecholamine receptors

Ingestions

Over-the counter medications•Ephedra – weight loss supplements

•PPA – (Phenylpropanolamine ) decongestants and weight loss supplements

•Tryptophan – supplement for depression, insomnia, migraines

Treatment goals

Typically the goal is to reduce MAP by ~25% over several hours

Treatment for catecholamine excess

Phentolamine•Alpha blocker; the mainstay of therapy

•Dose: 1-5mg IV bolus or drip 5-10mcg/kg per minute

Beta-blocker•May be added to control tachycardia

Benzodiazepines•May be helpful in cocaine/amphetamine

Treatment for catecholamine excess

Labetalol•Its use as monotherapy is controversial

•Recall that its alpha: beta is 1:3 to 1:8

•Some texts recommend it; other note the potential for worsening BP with it as monotherapy for the catecholamine excess conditions

•Probably best to use phentolamine 1st

Treatment of Hypertensive Urgencies

Goal: Gradual reduction of blood pressure over 24 hours

Treatment: •Restart prescribed anti-hypertensive

medications for the non-compliant patient

•Clonidine

•Captopril

•Losartan Follow up within 24 hours

•Sublingual nitroglycerine

•Nifedipine (don’t use)

Treatment of Hypertensive Episode

Treat cause of hypertensive episode (i.e. pain, anxiety)

Refer to a primary care physician and start anti-hypertensive medications only upon advice of referring physician

Why not treat all elevated BP in the ED?

Association of overly aggressive BP reduction in setting of stroke with worse neurologic outcome widely shown

What about the person incidentally found to have elevated BP?

From Journal of Emergency Medicine, 2000, pp 339-45.

“Stroke Precipitated by Moderate Blood Pressure Reduction”

6 cases total; All presented to an ED. 2 with completely resolved TIAs and 4 with no neurological complaints at all.

All suffered CVAs and had permanent dysfunction or death.

Case

60 year male with “malaise” Initial BP 170/100, remainder of

exam normal Treated with 10mg nifedipine

sublingual Returned 3 hours later with BP

120/88 and left hemiparesis. MRI showed infarct.

Case

30 year female with “abdominal pain”

Known hypertensive, off meds for 2 weeks

BP 280/120 initially All HTN meds restarted in ED:

captopril, triamterene/HCTZ, nifedipine, and hydralazine

Case

2 hours later in the ED, complained of severe vision loss

BP 160/85 Ophthalmology consult confirmed

retinal ischemia Only partial recovery of vision

Starting anti-HTN therapy in the ED

May mislead the patient to believe that they are cured

May interfere with office assessment of the true nature of the HTN

Best treatment in the ED is likely education regarding the chronic nature of hypertension and need for follow up!

Summary – Neurologic emergencies

Hypertensive encephalopathy

Embolic CVA

Hemorrhagic CVA

SAH

Nitroprusside, goal ~25 reduction

Only if >220/120 or>185/110 for t-PA

Labetalol for ~10-20% reduction

Nimodipine 60 mg Q4hrs x 21 days

Summary – Cardiovascular emergency

Aortic dissection

Acute LV failure

Acute coronary syndrome

Nitroprusside + Esmolol or Labetalol – SBP ~100

NTG, Lasix, MS04 for symptoms and ~10-15% reduction

NTG, MS04, beta-blocker to symptom improvement

Summary – Other emergencies

Eclampsia and HELLP

Catecholamine excess

Goal DBP ~90; magnesium, hydralazine, labetalol, delivery!

Phentolamine +/-beta blocker for ~25% reduction over several hours

Pre-Test Questions

1. In which of the following would a SBP of 100-120 be appropriate?

A. Aortic dissection B. Thrombo-embolic CVA C. Hemorrhagic CVA D. Subarachnoid hemorrhage E. Hypertensive encephalopathy

A. Aortic dissection

In all the other scenarios, such a precipitous drop in BP is likely to worsen outcome

2. Which emergency – medication is LEAST appropriate?

A. Aortic dissection – esmolol + nipride

B. Aortic dissection – labetalol C. Eclampsia – magnesium +/-

hydralazine D. Pheochromocytoma – esmolol E. Acute LV failure - NTG

D. Pheochromocytoma - esmolol

Although use of Labetalol is controversial and possibly indicated, a pure beta-blocker like esmolol is grossly inappropriate in emergencies caused by catecholamine excess.

3. All the following regarding CVAs are true EXCEPT:

A. Persistent BP >185/110 is a contraindication to thrombolytics

B. Hemorrhagic CVAs tend to have higher BP than embolic

C. Lowering the BP in the acute setting may worsen outcome

D. If BP needs lowering in hemorrhagic CVA, Nipride is the agent of choice

D. If BP needs lowering in hemorrhagic CVA, Nipride is the agent of choice

Nipride and other vasodilators are relatively contraindicated in hemorrhagic CVA as they may worsen ICP.

Labetalol is the agent of choice IF BP needs to be lowered

4. In HTN with pregnancy, all the following are true EXCEPT:

A. At a BP of 130/85, a patient may experience a HTN emergency

B. Definitive therapy for eclampsia is magnesium

C. HELLP is a variant of pre-eclampsia, is treated as aggressively as eclampsia

D. HTN is the most common risk factor for placental abruption

B. Definitive therapy for eclampsia is magnesium

Definitive therapy for eclampsia is delivery of the fetus and placenta – involve your consultant early!!

Questions and Comments