EMERGENCY TREATMENT
OF HYPERTENSIVE CRISIS
Antihypertensive Agents That Are Useful in Hypertensive Crises
-
Nitroprusside (Nipride) IV
Initial dose 0.3 µg/kg/min (Max dose 10µg/kg/min) Onset of action
<1 minute, duration <2 minutes
Best use for Encephalopathy, left ventricular failure, aortic dissection
(with ?-blocker)
Major side effects: Cyanide/thiocyanate toxicity (thiocyanate level>10
mg/dl is toxic; >20 mg/dl may be fatal) ; hypotension, N&V, apprehension,
convulsion, twitching, psychosis, dizziness, etc. It
has decreased efficacy in renal failure
-
Nitroglycerin IV
Initial dose 5 µg/min (Max dose 100 µg/min) Onset of action <5
minutes, duration <5 minutes
For use for Unstable angina, MI. Excellent for titrating blood pressure
in setting of coronary ischemia
Major side effect: headache, tachycardia, vomiting, methemoglobinemia
-
Labetalol (Trandate) IV
Mixed alpha/beta blocker, excellent for most
hypertensive emergencies.
First or second line for eclampsia; excellent
in catecholamine surges
Initial dose :20 mg IV bolus over 2 minutes, then 20- 80 mg q10 min
prn, or Continuous infusion at 0.5-2.0 mg/min (Max dose 300 mg),
Onset of action <5 minutes, duration 1-4 hours, but variable
Best use for Stroke, intracranial hemorrhage
Side effects: Nausea Fatigue, dizziness, scalp tingling
Contraindication: Asthma or bronchospasm, overt cardiac failure,
>first-degree heart block, severe bradycardia
-
Diazoxide (Hyperstat) IV
Initial dose: 1-3 mg/kg (up to 150 mg) IV bolus q5-15 min over 5 minutes
until BP is controlled (Max dose 600 mg),
Onset of action <2 minutes, duration 6-12 hours
Side effects: — Profound hypotension Elevated heart rate, elevated glucose,
sodium retention
Contraindication: Thiazide allergy
-
Nicardipine (Cardene) IV
Initial dose: 5 mg/h (Max dose 15 mg/h), Onset of action <1 hour, duration
<1 hour
Best use for Vascular surgery, subarachnoid hemorrhage
Side effects: Headache ,Elevated heart rate
Contraindication: Severe aortic stenosis
-
Enalapril (Vasotec) IV
Highly variable response; precipitous BP drop in high-renin states, rarely
angioedema, hyperkalemia, or acute renal failure.
Initial dose: 1.25 -5mg IV over 5 min q6h if needed, duration 6 hours
Best use for Left ventricular failure
Contraindication: Angioedema
-
Diltiazem (Cardizem) IV
Initial dose 0.25 mg/kg over 2 min, followed by infusion of 0.35 mg/kg at
an initial rate of 10 mg/hour
Onset: 3-30 min
Adverse effects: excessive hypotension, flushing
-
Trimethaphan
Initial dose: 1 mg/min (Max dose 4 mg/min), Onset of action <5 minutes,
duration <10 minutes
Best use for Aortic dissection (with ?-blocker)
Side effect: Orthostatic hypotension
Contraindication: Severe volume depletion
-
Hydralazine (Apresoline) IV
Indicated primarily for eclampsia
Dose is 10-50 mg IV or IM titrate to effect (onset <20 minutes, duration
3-8 hours)
Can be given IM as well, 10-50mg (onset 20-30 minutes)
Onset: 10- 20 min ; Duration: 3 -8 h
Adverse effects: tachycardia, flushing, contraindicated in angina or aortic
dissection
-
Phentolamine
Mainly for catecholamine surges as in
pheochromocytoma hypertension (pure
alpha-adrenergic blockade)
Dose is 5-15mg IV; onset 1-2 minutes; duration 3-10 minutes
Side effects: Tachycardia, flushing and headache may occur
-
Esmololol (Breviblock®)
Mainly for acute aortic dissection, perioperatively, acute coronary
ischemia
May be used with caution in acute MI with depressed LV to modulate heart
rate
Very short half life (2-4 minutes) non-selective ß-blockade
Dose is 250-500µg/kg/min for 1 minute, then 50-100µg/kg for 4
minutes
Sequence may be repeated, and continuous drip may be maintained
Onset of action is 1-2 minutes; 10-20 minute duration
Very close monitoring is required, and fluid load is large with this agent
Oral Medications for Hypertensive
Urgency:
-
Clonidine (Catapres)
0.2 mg PO, followed by 0.1 mg/hr to total of 0.8 mg until the diastolic
BP is <110 mmHg, or reduction in diastolic BP of 20 mmHg or more.
Onset 30-120 min; Duration 8-12 h
Adverse effects: sedation, dry mouth, dizziness, orthostasis, bradycardia
Contraindicated in pts with sinus bradycardia, sick sinus synd., or heart
block.
-
Labetalol (Trandate)
200-300 mg PO, followed by 100-200 mg q8h
Onset 1-2h; Duration 12-24 h
Adverse effects: bradycardia
-
Furosemide (Lasix)
20-40 mg PO or IV
-
Nicardipine (Cardene)
20-40 mg PO tid (Max 120 mg/day) or IV 5 mg/h, increase by 2.5 mg/h q5-15
min to max 15 mg/h.
-
Captopril (Capoten)
12.5-25 mg PO ,may repeat at intervals of = or > 30-60 min (Typical dose
<150mg/d; Max 450 mg/d)
----------------------------------------------------------------------------------------------------------------------------
Distinguish between a hypertensive emergency and a pseudocrisis in patients
with markedly elevated BP.
-
Do not use parenteral or sublingual drugs to treat markedly elevated BP
(>180/110 mm Hg to 220/120 mm Hg) in the absence of symptoms or progressive
target organ damage.
-
Use the following treatment approaches:
-
Administer one or more rapid-onset oral antihypertensive
drugs (e.g., furosemide, propranolol, captopril, clonidine, or
nicardipine);
once BP is less than 180/110 mm Hg, administer a longer-acting
formulation and recheck the BP within 48 hours.
-
Administer a longer-acting oral formulation from the start and recheck BP
in 48 hours.
In less than hypertensive crises, but in
hypertension urgency:
one or more rapid-onset oral antihypertensive drugs, as:
-
Furosemide (Lasix) 20-40 mg PO or IV
-
Clonidine 01.-0.2 mg PO
-
Nicardipine (Cardene) 20-40 mg PO tid (Max 120 mg/day) or IV 5 mg/h, increase
by 2.5 mg/h q5-15 min to max 15 mg/h.
-
Captopril 12.5-25 mg PO ,may repeat at intervals of = or > 30-60 min (Typical
dose <150mg/d; Max 450 mg/d)
-
Top |
| Malignant Hypertension
(Accelerated hypertension
) REF:
DynaMed 2009
No evidence that antihypertensive drugs reduce mortality
or morbidity in patients with hypertensive emergencies (Cochrane
Library 2008 Issue 1) update
Description: rapidly rising blood pressure
- systolic blood pressure > 200 mmHg, diastolic blood pressure > 120-140
mmHg
Types:
-
hypertensive urgency if 180/100 - admit
to floor, administer PO medications
-
hypertensive emergency if end-organ
damage - admit to medical ICU, IV nitroprusside
Who is most affected: young males
Incidence/Prevalence: rare, < 5% hypertensive patients
Causes and Risk Factors
Causes: complication of essential or secondary hypertension
Pathogenesis:
-
produces malignant nephrosclerosis, arteriolar damage
-
renal biopsy would show fibrinoid necrosis of arterioles, necrotizing and/or
hyperplastic (onion-skinning) arteriosclerosis, necrotizing glomerulonephritis
Physical Exam:
-
HEENT: focal retinal hemorrhages and
papilledema
Grade III - flame hemorrhage, cotton-wool spot, < 1:2 A-V ratio
Grade IV - papilledema: no disc margin, may go blind
-
Cardiac: left ventricular (LV)
hypertrophy, LV failure
-
Neuro: mental status exam changes
Complications of Malignant Hypertension:
-
blindness (macular edema, retinal hemorrhage), encephalopathy, renal damage
-
cerebral hypoperfusion if blood pressure lowered > 40% in initial 24 hours
Prognosis:
-
fatal within 1-2 years from congestive heart failure, stroke or renal failure
-
onion-skinning correlates with renal failure
-
90% dead in 6 months without treatment
No evidence that antihypertensive drugs reduce mortality or morbidity
in patients with hypertensive emergencies (level 2 [mid-level] evidence)
-
based on Cochrane review limited by heterogeneity
-
systematic review of 15 randomized trials evaluating antihypertensive drugs
in 869 patients presenting with hypertensive emergency
-
2 trials were placebo-controlled, 14 of 15 trials were open-label
-
drug classes evaluated were nitrates (9 trials), ACE inhibitors (7 trials),
diuretics (3 trials), calcium channel blockers (6 trials), alpha-1 adrenergic
antagonists (4 trials), direct vasodilators (2 trials), and dopamine agonists
(1 trial)
-
among 7 trials that reported mortality, 6 deaths occurred but allocated treatment
group was not reported for 5 of the deaths
-
insufficient data on clinical outcomes for meta-analysis
-
Reference - systematic review last updated 2007 Oct 19 (Cochrane Library
2008 Issue 1:CD003653)
Top
Treatment overview:
-
hypertensive urgency if 180/100 - admit
to floor, administer PO medications
-
hypertensive emergency if end-organ damage (e.g. aortic dissection or pulmonary
edema)
-
admit to medical ICU
-
immediate lowering of blood pressure with IV medication
-
monitor blood pressure with arterial line in ICU
drug of choice based on underlying disease
-
sodium nitroprusside drug of choice in most cases
-
nicardipine and fenoldopam are reasonable alternatives
-
labetalol acceptable in patients without second- or third-degree heart block,
bronchospastic disease or bradycardia
-
nitroglycerin drug of choice if cardiac ischemia, angina, or following cardiac
bypass surgery
-
phentolamine drug of choice if catecholamine-related hypertensive emergency
-
esmolol drug of choice for aortic dissection or postoperative hypertension
-
hydralazine drug of choice in pregnancy if related to eclampsia
target blood pressure
-
reduce mean arterial blood pressure by 25% within 2 hours
-
reduce minimum diastolic pressure to 100 mmHg within 2-6 hours
-
avoid abrupt decreases in blood pressure
-
in aortic dissection, start with beta blockers and lower systolic blood pressure
as much as possible without compromising cerebral, cardiac or renal blood
flow
some IV drugs used for severe hypertension
-
esmolol 1 mg/kg over 30 seconds then 150-300 mcg/kg/minute, beta blocker,
onset of action 2 minutes, duration 18-30 minutes
-
nicardipine 5-15 mg/hour until target blood pressure then 3-5 mg/hour, calcium
channel blocker, onset of action 45 minutes for 50% of maximal effect, duration
30 minutes for 50% decrease in effect
-
nitroprusside 0.5-8 mcg/kg/minute, nitric oxide releaser, onset of action
seconds, duration 3-4 minutes
-
fenoldopam 0.1-1.6 mcg/kg/minute, selective dopamine DA1 agonist, onset of
action 15 minutes for 50% maximal effect, duration 15 minute for 50% decrease
in effect
Top
Parenteral (IV) vasodilators
sodium nitroprusside (Nipride) 0.25-10 mcg/kg/minute
-
immediate onset, duration 3-5 minutes
-
IV infusion 50 mg/500 ml D5W at 0.3-0.8 mcg/kg/min, titrate to BP, maximum
dose 10 mcg/kg/min, maximal dose for 10 min only
-
arteriolar and venous vasodilator
-
drug of choice in hypertensive encephalopathy, hypertension and intracranial
bleed, malignant hypertension, hypertension and heart failure, dissecting
aortic aneurysm (with propranolol)
-
side effects - hypotension, nausea, vomiting, apprehension, cyanide/thiocyanate
toxicity, muscle twitching, methemoglobinemia acidosis, carbon dioxide retention,
cutis anserina (goose flesh), abdominal cramping, headache
-
cyanide/thiocyanate toxicity
-
may occur with prolonged (> 48 hours) or too rapid (> 2 mcg/kg/minute)
infusion
-
discontinue nitroprusside if serum thiocyanate > 12 mg/dL (206.4 µmol/L)
or signs of intoxication (acute psychosis, disorientation, muscle spasms,
hyperreflexia)
-
may cause hypoxemia in patients with chronic pulmonary disease by reversing
pulmonary vasoconstriction
-
delivery system must be light resistant (e.g tubing wrapped in aluminum foil)
nicardipine (Cardene IV)
-
IV 5 mg/hour, increase by 2.5 mg/hour every 15 minutes up to 15 mg/hour
-
onset 1-5 minutes, duration 3-6 hours, takes 48 hours to reach steady state
-
dihydropyridine calcium channel blocker
-
may cause reflex tachycardia, headache, flushing
clevidipine (Cleviprex) FDA approved
for intravenous use in lowering high blood pressure
-
onset 2-4 minutes, druation 5-15 minutes
-
1-2 mg/hour ingtravenously, up to 4-6 mg/hour (or maximum 16 mg/hour)
-
may cause reflex tachycardia
-
calcium channel blocker
-
costs about $180 per 25 mg vial, more than esmolol, slightly less than
nicardipine
-
lipid emulsion containing 2 kcal/mL
-
Reference - Med Lett Drugs Ther 2008 Sep 22;50(1295):73 TOC, Prescriber's
Letter 2008 Oct;15(10):56
fenoldopam mesylate (Corlopam)
-
onset 4-5 minutes, duration 10-15 minutes
-
0.1-1.6 mcg/kg/minute, no bolus, titrate by 0.05-0.1 mcg/kg/min every 15
minutes
-
dopamine D1-like receptor agonist, arteriolar vasodilator, natriuretic and
diuretic effects
-
unlike other parenteral antihypertensive agents, fenoldopam maintains or
improves renal function
-
available for in-hospital, short-term (up to 48 hours) management of severe
hypertension, from Neurex (Monthly Prescribing Reference 1998 Jan;A-23)
-
fenoldopam as effective as sodium nitroprusside in open randomized trial
of 153 patients with diastolic BP at least 120 mmHg (Acad Emerg Med 1995;2:959)
-
side effects - hypotension, flushing, dizziness, headache, reflex tachycardia,
nausea, hypokalemia, increased intraocular pressure
-
safety with beta blocker not established, may cause unanticipated degree
of hypotension
-
contraindicated if allergy to sulfites
-
review of fenoldopam can be found in N Engl J Med 2001 Nov 22;345(21):1548
nitroglycerin (Nitro-bid IV)
-
onset 2-5 minutes, duration 5-10 minutes
-
5-100 mcg/min as IV infusion
-
venous >> arteriolar vasodilator
-
side effects - headache, tachycardia, vomiting, flushing, methemoglobinemia,
tolerance with prolonged use
-
requires special delivery system due to drug binding to PVC tubing
diazoxide (Hyperstat)
-
onset 1-5 minutes, duration 6-12 hours
-
1-3 mg/kg (maximum 150 mg) IV every 5-15 minutes or IV infusion at 15-30
mg/min until desired effect
-
arteriolar vasodilation
-
second drug of choice in hypertensive encephalopathy, malignant hypertension
-
contraindications - ischemic heart disease, intracranial hemorrhage, dissecting
aneurysm, pulmonary edema
-
side effects - hypotension, tachycardia, aggravation of angina pectoris,
nausea, vomiting, hyperglycemia with repeated injections, sodium retention,
cardiac ischemia
hydralazine (Apresoline) 5-10 mg IV every 20-30
minutes
-
onset 10-30 minutes with 10-20 mg IV bolus, onset 20-30 minutes with 10-40
mg IM
-
duration 2-6 hours
-
10-40 mg IM/IV every 4-6 hours prn
-
mechanism of action - vasodilation of arterioles
-
drug of choice in eclampsia
-
contraindication - hypertension with heart failure, cardiac ischemia, angina,
aortic dissection
-
side effects - tachycardia, cardiac ischemia, headache, vomiting, aggravation
of angina pectoris, flushing
enalaprilat (Vasotec IV)
-
onset 15-30 minutes, peak effect 4 hours, duration 6-12 hours
-
0.625 mg IV every 6 hours, response variable and sometimes excessive
-
doses of enalaprilat higher than 0.625 mg are no more effective for initial
therapy; 65 patients with hypertensive urgencies (systolic blood pressure
> 210 mmHg and/or diastolic blood pressure > 110 mmHg) or emergencies
(diastolic blood pressure > 100 mmHg and angina pectoris, hypertensive
encephalopathy, or congestive heart failure) were randomized to enalaprilat
0.625 mg vs. 1.25 mg vs. 2.5 mg vs. 5 mg; 67% vs. 65% vs. 59% vs. 62% achieved
response within 45 minutes defined as stable reduction of systolic blood
pressure < 180 mmHg, diastolic blood pressure < 95 mmHg and relief
of symptoms in patients with hypertensive emergencies; no severe side effects
(Arch Intern Med 1995 Nov 13;155(20):2217)
-
mechanism of action - ACE inhibitor
-
risks - renal failure in patients with bilateral renal artery stenosis,
hypotension (precipitous drop in blood pressure if volume-depleted)
Parenteral adrenergic inhibitors
labetalol (Trandate, Normodyne)
-
onset 5-10 minutes, duration 3-6 hours
-
20 mg slow IV injection over 2 minutes, may repeat 20-80 mg every 10 minutes,
do not exceed 300 mg total, alternatively 2 mg/minutes IV infusion
-
beta and alpha-1 blocker
-
use in severe hypertension
-
contraindications - bronchial asthma, bronchospasm, acute left ventricular
failure, bradycardia, second or third-degree heart block, cardiogenic shock,
hypoperfusion
-
side effects - postural hypotension, dizziness, fatigue, nausea,
bronchoconstriction, heart block
esmolol (Brevibloc)
-
250-500 mcg/kg/minute for 1 minute, then 50-300 mcg/kg/minute (for 4 minutes)
-
beta-1-selective adrenergic receptor blocker
-
very short duration of action (half-life 9 minutes)
-
onset < 5 minutes, duration 10-20 minutes
phentolamine
-
alpha blocker
-
used primarily for catecholamine-related hypertensive emergencies, such as
cocaine intoxication, amphetamine toxicity, clonidine withdrawal, monoamine
oxidase inhibitor drug interactions, pheochromocytoma
-
onset 1-2 minutes, duration 3-10 minutes
-
5-15 mg IV bolus
-
side effects - tachycardia, orthostatic hypotension, headache, flushing
trimethaphan camsylate (Arfonad)
-
immediate onset or 1-5 minutes, duration 10-15 minutes
-
IV infusion 500 mg/500 ml D5W at 1 mg/ml (1-4 mg/min), titrate to blood pressure
-
mechanism of action - ganglionic blockade
-
drug of choice in dissecting aortic aneurysm (if propranolol cannot be used
with nitroprusside)
-
contraindicated if hypertension and renal failure
-
side effects - urinary retention, paralytic ileus, tachyphylaxis, orthostatic
hypotension, blurred vision, dry mouth
methyldopate - onset 30-60 minutes; 250-500
mg IV every 6 hours; drowsiness
Top
_______________________________________________________________________________________________
oral agents
-
nifedipine (Procardia, not extended release)
-
onset 15-30 minutes with 10-20 mg PO, duration 3-5 hours
-
10 mg capsule SL, perforate 5-10 holes with small needle, have patient chew
capsule; repeat after 30 minutes
-
mechanism of action - vasodilation
-
side effects - headache, palpitations, fluid retention, rapid uncontrolled
reduction in BP may precipitate circulatory collapse if aortic stenosis
-
sublingual nifedipine should not be used for hypertensive emergencies, given
unproven effectiveness and serious reported adverse effects [9 reports of
transient cerebral or cardiac ischemia, 5 reports of myocardial infarction,
1 sinus arrest, 1 fetal distress after cesarean section] consistent with
abrupt lowering of blood pressure (JAMA 1996 Oct 23/30;276(16):1328)
-
nicardipine (pending FDA approval) -
onset 1-5 minutes, duration 3-6 hours; 5 mg/hr, increase by 2 mg/hr every
15 minutes, maximum dose 15 mg/hour; mechanism of action - vasodilation;
for treatment of hypertension crisis; side effects - headache, nausea, vomiting,
hypotension
-
captopril - onset 15-30 minutes; 25 mg
PO repeat prn; hypotension, renal failure in bilateral renal artery stenosis
-
clonidine - onset 30-60 minutes; 0.1-0.2
mg PO, repeat every hour as required to total dose of 0.6 mg; hypotension,
drowsiness, dry mouth
-
labetalol - onset 30 minutes to 2 hours;
200-400 mg PO, repeat every 2-3 hours
-
consider addition of diuretic
 |
