Transcript Hypertensive Emergencies

Hypertensive Emergencies
Herb Russell D.O.
September 28, 2006
Why this is a difficult topic
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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
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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
• Stage I
• Stage II
SBP 120-139
SBP 140-159
SBP 160
DBP 80-89
DBP 90-99
DBP 100
Definitions
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Hypertensive Emergency: A relatively
high blood pressure with evidence of
target organ damage (CNS, CV, renal).
• Urgent lowering in minutes to hours.
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Hypertensive Urgency: Severely
elevated BP without target organ
damage.
• Lower in days to weeks.
Definitions
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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
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History
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Review of systems directed at:
• History of HTN
• Blood pressure trends
• Prescribed medications
• OTC medications
• Compliance
• Past medical history
• Family history
• Illicit drug use
• CNS (HA, hemiparesis)
• Cardiac (CP, dyspnea)
• Renal (hematuria)
ED Evaluation
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Physical Exam
• Appropriate sized cuff
• Measure both arms and legs
• Brachial difference <20mm Hg
• Focus on areas of potential target-organ
damage
-CNS
-Pulmonary
-Heart
-Pulses
-Retina
-Renal
Cotton wool spot (soft exudates)
Hard exudates
Disk Edema
Diagnostic Studies
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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.
2.
3.
Non-compliance with medications in a
chronic hypertensive patient
Those with secondary hypertension
(e.g. pheochromocytoma, reno-vascular
hypertension, Cushing’s Reflex)
Hypertension during pregnancy is a
major risk factor for women
Our Job
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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
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Reduce BP so autoregulation can be reestablished
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
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Exceptions: aortic dissection and
eclampsia
In aortic dissection and eclampsia, BP
should be lowered to normal levels
Search for secondary causes
Pharmacology-Nitroprusside
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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
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Excretion: Kidney
Adverse Effects:
• Cyanide toxicity with prolonged use (rare)
• Prolonged use and >10g/min
• Inhibits hypoxia induced pulmonary vasoconstriction
• Coronary steal syndrome
• Increased ICP
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Contraindications:
• Other cyclic GMP inhibitors (i.e. sildenafil, etc.)
Pharmacology-Labetalol
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Dose: Bolus of 20mg IV, double bolus up to
80 mg, or infusion of 2mg/min to maximum
total of 300mg
• Peds:
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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
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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
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Dose: Loading dose of 500mcg/kg over
1 min, then infusion of 50300mcg/kg/min
Actions: Ultra-short acting β1selective adrenergic blocker
Indications: Used in conjunction with
nitroprusside or phentolamine for
hypertensive emergencies
Pharmacology-Esmolol
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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
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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
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Onset: Immediate
Half-life: 4 mins
Metabolism: Hepatic
Adverse Effects: HA, tachycardia,
hypotension
Contraindications:
• Other cyclic GMP inhibitors (i.e. sildenafil, etc.)
Pharmacology-Hydralazine
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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
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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
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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
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Excreted: Urine
Adverse Effects:
• Angioedema
• Cough
• Worsening renal function
• Hyperkalemia
Pharmacology-Others
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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
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Hypertensive encephalopathy
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Stroke syndromes
• Embolic
• Hemorrhagic
• Subarachnoid hemorrhage
Categories of Hypertensive
Emergencies
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Cardiovascular
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Pregnancy related hypertension
• Acute LV failure (“Flash” pulmonary edema)
• Acute coronary syndrome
• Aortic dissection
• Pre-eclampsia
• Eclampsia
• HELLP syndrome
Categories
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Catecholamine excess
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Other
• Pheochromocytoma
• MAOI + tyramine
• Cocaine/amphetamines/OTCs
• Clonidine withdrawal
• Renal failure
• Epistaxis
• Childhood hypertension
Hypertensive Encephalopathy
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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
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Signs:
• Papilledema, cotton wool exudates
Diagnostics
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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
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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
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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
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Loss of autoregulation leads to:
• Cerebral hyper-perfusion
• Vascular permeability
• Cerebral edema
• Vasospasm
• Ischemia
• Punctuate hemorrhages
Therapy
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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
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Nitroprusside
• 1st line, 0.3 – 10 mcg/kg/minute
Labetalol
Enalaprilat
Fenoldopam
Stroke Syndromes
Thrombo-Embolic CVA
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Represent 85% of all strokes
BP elevations are generally mildmoderate and represent a physiologic
response to maintain cerebral perfusion
pressure to the penumbra, which has
lost its ability to autoregulate
Embolic CVA - Dilemma
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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
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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
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According to National Institutes of
Neurologic Disorders and Stroke:
• SBP <220, no treatment
• DBP <120, no treatment
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Tintinalli suggests not treating DBP <140
Others use MAP <130
Embolic CVA – When to treat
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If complicated by:
• Aortic dissection
• Hypertensive encephalopathy
• AMI
• Renal failure
Embolic CVA – How to treat HTN
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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?
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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
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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
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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.
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However, modest reductions of ~20%
MAP have not been show to adversely
affect outcome.
Hemorrhagic CVA - Rx
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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
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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
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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
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Abrupt and severe dyspnea, tachypnea,
and diaphoresis
Rales, wheezes, distant breath sounds,
frothy sputum, and gallop rhythm
Goals of therapy
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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
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Nitroglycerin
• First Line in combination with ACE-I
• Arterial (especially coronaries) and veno-dilator,
reducing preload and afterload
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ACE inhibitor
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Lasix
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Morphine
• Interrupts the renin-angiotensin-aldosterone axis
• Initially a vasodilator, then diuretic
• Vasodilator and sympatholytic
Acute Coronary Syndrome
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Elevated BP significantly increases LV
wall tension
Wall tension is one of main determinants
of myocardial oxygen demand.
ACS therapy goals
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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
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Stanford A
• Involves ASCENDING
•
•
•
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aorta
More common
More often fatal
REQUIRES surgery
for survival
Stanford B
• Involves
DESCENDING aorta
• May be managed
medically
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DeBakey (old)
• 1 – Ascending and
•
•
Descending
2 – Ascending Only
3 – Descending Only
• A – above diaphragm
• B – below diaphragm
Risk Factors
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Male
HTN
Pregnancy
Chest Trauma
Cocaine
CV Surgery
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Marfan’s
Ehrler-Danlos
MDMA (ecstasy)
-1 antitrypsin def.
Age >60
Pathophysiology
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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
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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
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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
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Retrograde Dissection
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Anterograde Dissection
• Into AV – acute regurgitation and CHF
• Into pericardium – tamponade
• Into coronary arteries - AMI
• Into carotid artery – CVA
• Into subclavian artery – Ischemic limb
• Into renal arteries – ARF
• Into anterior spinal artery - paraplegia
Signs and Symptoms
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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
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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
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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
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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
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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
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Complicates 5% of pregnancies
Risk factors:
• Nulliparity
• Age >40
• African American
• Chronic renal failure
• Diabetes mellitus
• Multiple gestations
Pregnancy and Hypertension
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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
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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
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Eclampsia
• Pre-eclampsia +
seizures – This is an
emergency !!!!
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HELLP syndrome
• Variant of pre•
•
eclampsia
Blood pressure lower
Predilection for
multigravids
Pathophysiology
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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
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Restlessness and hyper-reflexia early
Headache
Visual disturbance
Peripheral edema
Abdominal pain
Therapy
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Any pregnant patient with BP >140/90
and any symptoms should be
hospitalized
Eclampsia and patients with preeclampsia + severe symptoms (HA,
abdominal pain) but no seizures should
be treated very aggressively!
Therapy
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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
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Pheochromocytoma
Monoamine oxidase inhibitor + tyramine
Cocaine/amphetamines/OTC herbals
(PPA, ephedra, trytophan)
Clonidine withdrawal
Pheochromocytoma
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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
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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
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Commonly mislabeled as panic attacks or
anxiety disorder
Diagnosed by detecting elevated levels
of catecholamines and their by-products
in the urine
Clonidine withdrawal
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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
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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
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Beer
Wine
Aged cheeses
Chocolate
Coffee
Cream
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Chicken liver
Pickled herring
Broad beans
(dopamine)
Yeast
Citrus fruits
Snails
MAOIs and medications
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Some
pharmaceuticals can
also cause severe
hypertension when
taken with MAOIs
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Meperidine
Ephedrine
TCAs
Reserpine
Dopamine
Methyldopa
Guanethidine
Ingestions
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Cocaine
• blocks re-uptake of NE, dopamine, and
serotonin
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Amphetamines
• Stimulate release of and block re-uptake of
catecholamines
• Also may directly stimulate catecholamine
receptors
Ingestions
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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

Benzodiazepines
• May be added to control tachycardia
• 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
• Sublingual nitroglycerine
Captopril
• Nifedipine (don’t use)
Losartan
Follow up within 24 hours
Treatment of Hypertensive Episode

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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.
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“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
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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
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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
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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

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Hemorrhagic CVA


SAH


Nitroprusside, goal
~25 reduction
Only if >220/120
or>185/110 for t-PA
Labetalol for ~1020% 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, betablocker 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

No history of renal dysfunction?

History of renal dysfunction?

Symptoms of cardiac dysfunction or chest
pain
• May be harmful-First do no harm
• Normal UA obviates need for lab tests
• UA and BMP
• CXR and ECG

Disposition
• If above negative, refer for outpatient evaluation
within 7 days
Questions and Comments