Transcript Hypertensive Crisis

Evaluation and
Management of
Hypertensive Emergencies
Kimberly Zammit, Pharm.D., BCPS, FASHP
Clinical Coordinator: Buffalo General Hospital
[email protected]
Define the JNC-7 classification of blood pressure
Differentiate the presentation and management
strategies for hypertensive urgencies and
emergencies.
 Compare and contrast pharmacotherapeutic agents
available for the management for acute blood
pressure control.
 Identify treatment goals for patients requiring acute
blood pressure management
 Recommend antihypertensive therapeutic regimens
tailored for specific patient characteristics.


Epidemiology

American Heart Association estimates 73 million
Americans have high blood pressure

~1 – 2% of hypertensive patients will have a
hypertensive emergency in their lifetime

Represents 3% of all ED visits and 25% of all
medical urgencies/emergences in the ED
 113 million ED visits in 2003
American Heart Association. Heart Disease and Stroke Statistics 2008.
Zampaglione B, et al. Hypertension 1996;27:144-147.
Epidemiology
51 yo WM is admitted to your emergency department
with a CC of 2 day history of a “dull” headache and
blurry vision. He decided to come to ED today because
he developed SOB and dizziness while exercising.
PMH:
 HTN and Hyperlidemia
Vital Signs:
 HR 105 BP 240/ 138 RR 24, T 37.6,
 Ht 70”, Wt 95 kg
Pertinent physical findings reveal:
 Papilledema and a grade II/IV SEM
Laboratory Results:
 Na 135, K 3.5, Cl 108, CO2 22, BUN 50, Cr 2.4
 Troponin negative (thus far)
Diagnostics:
 CXR: Enlarged heart
 CT Head: No bleeding is evident
 ECG: No ischemic changes, evidence of LVH
 Medications:
 Metoprolol 100 mg BID (stopped one week ago)
 HCTZ 25 mg Daily
 Simvastatin 20 mg Daily
 Aspirin 81 mg Daily
 Social:
 Former smoker, “Social” EtOH, Denies illcit drugs
 Allergies:
 NKDA

 True
 False
Hypertension Nomenclature:
JNC7
Category
Normal
Pre-hypertensive
Hypertension
Hypertensive
Crisis*
SBP (mmHg)
<120
120 - 139
140 – 179
≥ 180
DBP (mmHg)
<80
80 – 89
90 – 109
≥ 110
* Hypertensive emergency is NOT defined by any absolute blood pressure
measurement
Hypertensive Crisis
Hypertensive Urgency
Hypertensive Emergency
Elevated BP WITHOUT
Elevated BP WITH evidence
evidence of ACUTE end organ of ACUTE end organ damage
damage
Malignant Hypertension
Retinal hemorrhages,
exudates, and papilledema
Renal involvement in the form
of malignant nephrosclerosis
Usually associated with a DBP
greater than 130 mm Hg
Accelerated Hypertension
Similar to malignant
hypertension but
papilledema is absent
Better prognosis than
malignant hypertension
Etiology


Essential Hypertension





Renal Disease
 Parenchymal disease
 Renal artery stenosis
 Renal crisis from:
▪ Systemic sclerosis
▪ Systemic lupus
Endocrine Disease

 Post-renal transplant
 Tubulointerstitial
nephritis
Vaidya et al. Hospital Physician March 2007.
Chobanian A, et al. Hypertension 2003;42(6):1206-1252.
Pheochromocytoma
Glucocorticoid excess
Primary aldosteronism
Renin-secreting tumor
Cerebrovascular
Disease
 Ischemic stroke
 Intracranial hemorrhage
 Head injury/CNS trauma
Etiology

Other

 Eclampsia/severe pre




eclampsia
Burns
Vasculitis
Autonomic hyperactivity
Pregnancy
Sleep apnea
Vaidya et al. Hospital Physician March 2007.
Chobanian A, et al. Hypertension 2003;42(6):1206-1252.
Medications
 Non-compliance
 Illicit drug use
 Drug interactions
 Adverse effect
Organs at Risk


Neurovascular

Cardiopulmonary
 Subarachnoid
 Decompensated HF
hemorrhage
 Intracranial hemorrhage
 Cerebral infarction
 Hypertensive
encephalopathy
 Pulmonary edema
Ocular
 Papilledema
 Retinopathy
 Aortic dissection
 ACS
 LV dysfunction

Renal
 Renal failure
 Proteinuria
Pathophysiology of
End-Organ Damage
Abrupt increase in SVR
mediated by humoral vasoconstrictors
Mechanical Stress
Endothelial injury
Increased permeability, activation
of coagulation and platelets,
deposition of fibrin
Endothelial Injury
Arteriole Necrosis
Ischemia and release of
vasoactive mediators
Marik PE, Varon J Chest 2007;131:1949-62
Pressure
Natriuresis
Renal
Vasoconstriction
RAA
activation
Vasoconstriction
Cytokine
activation
End organ
hypoperfusion,
ischemia and
dysfunction
End Organ Damage:
Hypertensive Emergency
End-Organ Damage
Cardiovascular
Frequency (%)
55.3
Acute Pulmonary Edema
22.5
Acute Congestive Heart Failure
14.3
Acute Coronary Syndrome
12
Eclampsia
4.5
Aortic Dissection
2.0
CNS Complications
45.3
Cerebral Infarction
24.5
Hypertensive Encephalopathy
16.3
Intracerebral or subarachnoid hemorrhage
4.5
Zampaglione B, et al. Hypertension 1996;27:144-147.
Signs & Symptoms
Headache
Epistaxis
HTN Urgency (%)
Chest Pain
Dyspnea
Faintness
Agitation
N. Deficit
Vertigo
Paresthesia
Vomiting
Arrhythmia
Zampaglione B, et al. Hypertension 1996;27:144-147.
22
17
9
9
10
10
3
7
6
2
6
HTN Emergency (%)
3
0
27
22
10
2
21
3
8
3
0
1.
2.
3.
4.
5.
Acute Condition
Death Rehospitalization
ACS1,2,3
5-7%
30%
CHF4
8.5%
26%
Severe Hypertension5 11%
37%
OASIS-5 NEJM 2006
GUSTO IIb NEJM 1996
GRACE JAMA 2007
IMPACT-HF J Cardiac Failure 2004
STAT Registry results
Initial Evaluation

Early Triage
 Obtain BP at least twice

Medications




Current meds/OTCs
Compliance
Drug Interactions
Recreational drugs
▪ Cocaine
▪ Amphetamines
▪ Phencyclidine

Patient History





PMH
Family History
Baseline BP recordings
Recent activities
Symptoms
▪ CV
▪ Renal
▪ Neurologic
Physical Exam and Diagnostics
Focus on detection of end organ damage

Physical Examination
 Neuro exam
▪ Focal findings
▪ Mental status changes
 Fundoscopic exam
▪ Cotton wool exudates
▪ Hemorrhages
▪ Papilledema
 Cardiac exam
▪ Heart sounds
▪ Pulses

Diagnostic Studies
 Urinalysis
 Electrolytes
 BUN and SCr
 CBC/platelets
 Chest X-Ray
 EKG
 Serum glucose
 Brain CT/MRI
Hypertensive Emergency
Initial Treatment Goals

Prompt, but controlled reduction in BP
 Reduce MAP by < 25% during the first minute to 1 hr
 If stable, reduce to 160/110 mmHg within the next 2 –
6 hours
 Gradual reduction to goal over next 24 – 48 hours
 Exceptions: Ischemic stroke, stroke eligible for t-PA,
acute aortic dissection, SAH, ICH

Choice of agent should be tailored to clinical
situation
 Type of end-organ damage / presentation
Chobanian A, et al. Hypertension 2003;42:1206-1252.
Hypertensive Emergency
Initial Treatment Goal Exceptions
Ischemic Stroke
(not a tPA candidate)
Ischemic Stroke
(tPA candidate)
Treat SBP > 220 mmHg
and/or DBP >120 mmHg only
Treat SBP > 185 mmHg and/or
DBP >110 mmHg
Acute Aortic
Dissection
Subarachnoid or
Intracranial Hemorrhage
Rapid reduction (5 – 10
Balance risk of re-bleeding with
risk of reducing cerebral
perfusion pressure
minutes) to a SBP between 100
– 120 mmHg (if tolerated)
Cerebral Blood Flow (ml/min/100 g)
Cerebral Auto-regulation
100
Normal Regulatory
Range
50
Normotensive
50
Chronically Hypertensive
100
150
Mean Arterial Pressure (mmHg)
200
Leonardi-Bee Stroke 2002:33;1351-1357
Death ordependency at
6months
Mortality 14 days
Blood Pressure vs Outcomes in
Acute Ischemic Stroke
a) Labetalol
b) Esmolol
c) Fenoldopam
d) Nitroglycerin


Beta-Blockers
 Labetalol
Calcium Channel
Blockers
 Esmolol
 Nicardipine
 Metoprolol
 Clevidipine

 Verapamil
Vasodilators
 Diltiazem
 Nitroprusside
 Nitroglycerin
 Hydralazine

Miscellaneous
 Enalaprilat
 Fenoldopam
Labetolol
32%
Metoprolol
17%
Nitroglycerin
15%
Hydralazine
15%
Nicardapine
8%
Sodium nitroprusside
5%
Other
8%
0%
www.outcome.org/stat
10%
20%
30%
40%
One
First IV Antihypertensive
Labetolol (n=501)
32%
40%
Nitroglycerin (n=241)
41%
Hydralazine (n=235)
41%
Nicardapine (n=121)
25%
37%
27%
32%
14%
28%
32%
Percent of Patients
www.outcomes.org/stat
23%
45%
51%
22%
Three or more
42%
Metoprolol (n=277)
Sodium nitroprusside (n=82)
Two
21%
46%
Hypertensive Emergency Treatment
Disease-specific Recommendations
Conditions
Preferred
Agent
Goal
Risks
Pre-eclampsia
Eclampsia
Labetalol
Nicardipine
Hydralazine
Magnesium
sulfate (Seizures)
160 / 110
150 / 100 if
platelets are
<100K
Hypotension
Reduce BP 20%
Hypotension
and
worsening
renal failure
Acute renal
Nicardipine
failure
Labetalol
Microangiopathic Nitroglycerin
anemia
Hypertensive Emergency Treatment
Disease-specific Recommendations
Conditions
Preferred Agent Goal
Risks
Sympathetic crisis
Cocaine or other
sympathomimetic;
Pheochromocytoma
MAOIs/tyramine
Abrupt clonidine or
beta-blocker d/c
Fenoldopam
Nicardipine,
verapamil or
diltiazem in
combination with
benzodiazepine
Phentolamine
(NO beta-blocker)
Reduce
excessive
sympathetic
tone.
Relieve
symptoms
alpha
storm
Cardiac Surgery
140/90
Otherwise no
specifc goals
Excess
reduction
Acute postoperative Esmolol,
hypertension
nicardipine, or
labetalol
Hypertensive Emergency Treatment
Disease-specific Recommendations
Conditions
Preferred
Agent
Goal
Acute ischemic
stroke
Nicardipine,
labetalol
Treat when >
Excessive BP
220/ 120 except decrease may
w/thrombolytics worsen ischemia
> 185/ 110
Intracranial
Hemorrahge
Nicardipine,
Treat to target
labetalol, esmolol MAP 130
Precipitous BP
fall may increase
mortality
SAH
Nicardipine,
SBP < 160
labetalol, esmolol
Keep SBP > 120
to maintain CPP
Hypertensive
Nicardipine,
Decrease MAP
Encephalopathy labetalol, esmolol 15 - 20%
Risks
Aggressive BP
fall may produce
ischemia
Hypertensive Emergency Treatment
Disease-specific Recommendations
Conditions Preferred Agents
Goal
Risks
Acute
myocardial
ischemia
Reduce SBP
20 – 30%
Beta-blockade
could worsen
LV function
Acute aortic Labetalol
dissection
Nicardipine and
esmolol
Nitroprusside with
esmolol
Reduce shear
forces
SBP 120 – 140
HR 60
Need
continuous BP
monitoring
Acute
pulmonary
edema or
heart failure
Reduce BP by
vasodilatation
Promote diuresis
Symptom relief
Worsening
renal failure
Labetalol
Esmolol and NTG
Nicardipine or
nitroprusside w/ NTG
and loop diuretic;
May cautiously use
enalaprilat
a) Decrease MAP 25-30 %
b) Decrease MAP 15 -20 %
c) SBP no lower than 185
d) SBP no lower than 160

Alpha1 and beta blocking properties (ratio 1:7)
 Onset: 3 – 5 minutes, peak 5 – 15 minutes
 Duration: 3 – 6 hours


Safe in pregnancy
AE: Bradycardia, bronchospasms, hepatotoxicity

Dosing Strategies (IV – Max 300 mg/day)
 20 mg IV bolus, repeat 20 – 80 mg increments Q10min
 Infusion: 1 – 2 mg/min initial, titrate to effect
▪ CAUTION: Accumulation WILL occur


Ultra-short acting cardioselective betablocker
Metabolism: RBC esterases
 Onset: within 60 sec
 Duration: 10 – 20 minutes
 Elimination ½ life: 9 min

Dose (max - 300 mcg/kg/min)
 0.5 – 1 mg/kg bolus over 1 min, infusion at 50
mcg/kg/min – can increase every 5 minutes
Esmolol
Labetalol
Bolus +
Continuous infusion
Bolus
Continuous infusion
Onset
Rapid
(60 seconds)
Intermediate
(peak 5-15 min)
Offset
(Duration of action)
Rapid
(10-20 min)
Slower
(2-4 h)
Heart Rate
Decreased
+/-
0
Decreased
Decreased
+/-
Positive
Positive
Sinus bradycardia
Heart block >1°
Overt heart failure
Cardiogenic shock
Cocaine Intoxication
Severe bradycardia
Heart block >1°
Overt heart failure
Cardiogenic shock
Cocaine Intoxication
Administration
SVR
Cardiac output
Myocardial O2 balance
Contraindications

Peripheral Dopamine-1 Agonist
 Improves creatinine clearance, urine flow rates, and
sodium excretion in severely hypertensive patients
with both normal and impaired renal function.


Rapid, extensive hepatic conjugation
The onset of action is within 5 min, with the
maximal response being achieved by 15 min.
 Duration of action is 30 to 60 min

An initial starting dose of 0.1 mcg/kg/min
 Increase 0.05 to 0.1 mcg/kg/min to max of 1.6
mcg/kg/min

Nausea, headache, flushing

Potent venodilator, higher doses affect
arterial tone
 Onset: 2 – 5 minutes
 Duration: 5 – 10 minutes

Tolerance with prolonged infusions (> 24 hrs)
Second agent often required
Primary role in AMI ,Pulmonary edema

AE: HA, vomiting, methemoglobinemia


 ICP may increase, CO may decrease in volume-depleted

Potent arterial and venous vasodilator
 Onset: seconds
 Duration: 2 – 5 minutes


Reduces preload and afterload
Arterial line required to monitor BP
 Due to potency, rapidity of action, and
tachyphylaxis

Disadvantages
 Cyanide toxicity, increased ICP, coronary steal
 May increase mortality after AMI
CN

Cyanide Toxicity
 Metabolized in liver to


thiocyanate via thiosulfate
 Start 0.3 mcg/kg/min
 Titrate every 5 minutes
 Thiocyanate eliminated via
kidney

in “healthy” patients
thiocyanate cause toxicity
thiosulfate per 100 mg SNP
to IV bag to reduce toxicity
Doses < 2 mcg/kg/min
 low risk of cyanide toxicity
 Both cyanide and
 Add 1 gm sodium
Protect from light
Dosing

Max 10 mcg/kg/min
 Short durations only due to
risk of toxicity

Dihydropyridine CCB,
exhibiting selective
vasodilatation
 Onset: 5 – 15 minutes
 Duration: 2 – 6 hours

Strong cerebral and
coronary vasodilatory
activity
 Reduces BP but increases
cerebral perfusion pressure

Dose
 Initiate at 5mg/hr
 Titrate by 2.5 mg/hr
increments
 Rapid control titrate
every 5 minutes
▪ When desired result,
reduce dose to 3 mg/hr**
 Gradual control titrate
every 15 minutes
 Max 15 mg/hr
** Recommendation comes from post-operative hypertension patients. Experience suggest it often fails
to optimize blood pressure management in populations other than post-op hypertension.
Adverse Events
Nicardipine
Nitroprusside
Hypotension
Flushing
Nausea
Dizziness
Headache
Thiocyanate
Injection site pain
5.6%
NA
4.9%
1.4%
14.6%
NA
1.4%
36.9%
9.8%
11.0%
6.8%
27.6%
14.0%
NA

Ultra-rapid acting,L-type
calcium channel blocker





 Short half-life (< 2 min)
 Eliminated via plasma
esterases
 No renal/hepatic dosage
adjustments

Initiate at 1 – 2 mg/hr
 Most patient achieve
response with 4 – 6 mg/hour
 Limited experience up to 32
mg/hour
▪ Maximum 1000 ml daily
Most common

Headache (6.3%)
Nausea (4.8%)
Chest discomfort (3.2%)
Vomiting (3.2%)
Disadvantages:
 Lipid based
▪ Contraindicated in patients
with allergies to soybeans,
soy products, eggs, or egg
products
▪ Must be discarded in 4
hours
 $$$$$ (~ $145 per 25 mg vial)


Prodrug of enalapril
Pharmacodynamics make it difficult to use in
hypertensive crisis:
 Onset 15 minutes, peak~1 hr, duration 6 hours

Dose
 1.25 mg over 5 min every 4 to 6 h, titrate by 1.25-mg
increments at 12- to 24-h intervals to max of 5 mg q6h


May further compromise renal function
Most utility for CHF

Direct relaxation of vascular smooth muscle
 Reflex tachycardia, increased stroke volume

Time and degree of hypotensive effects are
variable
 Onset: 10 – 30 minutes
 Duration: 3 – 9 hours

Hepatic acetylation and renal elimination

Use: Eclampsia - 10 – 20 mg IV bolus, repeat in
30 min as needed

The most appropriate therapeutic option
for hypertensive emergencies requires
meticulous attention must be paid to:
 Distinction between urgency and emergency
 Precipitating factors
 Concomitant illnesses
 Blood pressure goals
 Pharmacokinetics





Marik PE et al. Chest 2007;131:1949-1962.
Amin et al. Annals of Emergency Medicine
2008;51(30):S10-S15.
Chobanian A et al. JAMA 2003;289(19):2560-72.
Haas CE et al AJHP2004; 61:1661–1673
Pollack C et al. Ann Emerg Med 2008