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Hypertensive Emergencies
Herb Russell D.O.
September 28, 2006
Why this is a difficult topic
Hypertension is common (up to 25%, 50 million) 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
JNC - 7
New classification scheme:•PreHTN SBP 120-139 DBP 80-89
•Stage I SBP 140-159 DBP 90-99
•Stage II SBP 160 DBP 100
Definitions
Hypertensive Emergency: A relatively high blood pressure with evidence of target organ damage (CNS, CV, renal).•Urgent lowering in minutes to hours.
Hypertensive Urgency: Severely elevated BP without target organ damage.•Lower in days to weeks.
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 both 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)
Hard exudates
Disk Edema
Diagnostic Studies
CBC-hemolytic anemia 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 Reflex)
3. Hypertension during pregnancy is a major risk factor for women
Our Job
ED physician must:•1. Appropriately evaluate patients with
elevated BP.
•2. Correctly classify the HTN.
•3. Determine aggressiveness and timing of the therapeutic interventions.
•4. Make the correct disposition.
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 (arterialor and venous smooth muscle).
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)
•Prolonged use and >10g/min• Inhibits hypoxia induced pulmonary
vasoconstriction
•Coronary steal syndrome
• Increased ICP
Contraindications:•Other cyclic GMP inhibitors (i.e. sildenafil, etc.)
Pharmacology-Labetalol
Dose: Bolus of 20mg IV, double bolus up to 80 mg, or infusion of 2mg/min to maximum total of 300mg•Peds: 0.4-1 mg/kg/hr
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, then 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 (rare)
•Bradycardia and heart block
•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, etc.)
Pharmacology-Hydralazine
Dose: 10-20 mg, repeated in 30 mins•Peds: 0.1 mg/kg
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
•Drug-induced Lupus
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 causing edema and microhemorrhages.
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 despite change in BP.
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 treat 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 treat 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 treat
If complicated by:•Aortic dissection
•Hypertensive encephalopathy
•AMI
•Renal failure
Embolic CVA – How to treat HTN
Goal is to reduce MAP 10-20% in uncomplicated embolic CVA with markedly elevated pressures
Labetalol: 5mg doses Nitroglycerin IV or nitroprusside
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.•There is no evidence to suggest that HTN
provokes further bleeding in ICH. 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•First Line in combination with ACE-I
•Arterial (especially coronaries) and veno-dilator, reducing preload and afterload
ACE inhibitor• Interrupts the renin-angiotensin-aldosterone axis
Lasix• Initially a vasodilator, then diuretic
Morphine•Vasodilator and sympatholytic
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
DeBakey (old)•1 – Ascending and
Descending
•2 – Ascending Only
•3 – Descending Only•A – above
diaphragm
•B – below diaphragm
Risk Factors
Male HTN Pregnancy Chest Trauma Cocaine CV Surgery
Marfan’s Ehrler-Danlos MDMA (ecstasy) -1 antitrypsin def. Age >60
Pathophysiology
Degeneration of the media•Normal aging
•Pregnancy
•Marfan’s 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 subclavian artery – Ischemic limb
•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 impending doom (angor
animi) and anxiety
Diagnostics
CXR •may be normal in up to 12% !!
•Wide mediastinum
•Calcium sign
•Deviation of trachea or NG tube to right
•Left pleural effusion
•Apical cap
•Left Mainstem Bronchus shift
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 multigravids
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; others 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 1
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 2
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
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 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, ACEI, Lasix for symptoms and ~10-15% reduction
NTG, MS04, beta-blocker for 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
Summary – Hypertensive Urgency
Unnecessary to lower BP in the ED•May be harmful-First do no harm
No history of renal dysfunction?•Normal UA obviates need for lab tests
History of renal dysfunction?•UA and BMP
Symptoms of cardiac dysfunction or chest pain•CXR and ECG
Disposition• If above negative, refer for outpatient evaluation
within 7 days
Questions and Comments