Hypertensive Emergencies

Dr. Herb Russell

Prepared 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 1 st 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 • • Compliance Past medical history Family history Illicit drug use Review of systems directed at: • CNS (HA, hemiparesis) Cardiac (CP, dyspnea) • 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.

2.

3.

Non-compliance with medications in a chronic hypertensive patient Those with secondary hypertension (e.g. pheochromocytoma, reno-vascular hypertension, Cushing’s) 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: • Contraindications: • Cyanide toxicity with prolonged use (rare) Inhibits hypoxia induced pulmonary vasoconstriction Coronary steal syndrome Increased ICP 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 α 1 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 β 1 -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 a 1 -receptor blocker and a central 5-HT 1A -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 • 1 st 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 1 st

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 • Sublingual nitroglycerine Captopril Losartan • Follow up within 24 hours 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, MS0 4 for symptoms and ~10-15% reduction NTG, MS04, beta blocker to symptom improvement

Summary – Other emergencies  Eclampsia and HELLP  Goal DBP ~90; magnesium, hydralazine, labetalol, delivery!

 Catecholamine excess  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