eMedicine Specialties > Nephrology > Hypertension and the Kidney
Hypertension, Malignant: Treatment & Medication
Updated: Sep 15, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Patients with malignant hypertension usually are admitted to an intensive care unit for continuous cardiac monitoring and frequent assessment of neurologic status and urine output. An intravenous line is started for fluids and medications. Patients typically have altered blood pressure autoregulation, and overzealous reduction of blood pressure to reference range levels may result in organ hypoperfusion. The initial goal of therapy is to reduce the mean arterial pressure by approximately 25% over the first 24-48 hours. An intra-arterial line is helpful for continuous titration of blood pressure. Sodium and volume depletion may be severe, and volume expansion with isotonic sodium chloride solution must be considered.1
Hypertensive urgencies do not mandate admission to a hospital. The goal of therapy is to reduce blood pressure within 24 hours, which can be achieved as an outpatient.
Surgical Care
A therapy under clinical trial involving implantation of a carotid baroreflex stimulator has shown some promising results.6
Consultations
- In patients with stroke, cardiac compromise, or renal failure, appropriate consultation should be considered.
- In institutions with specialists in hypertension, prompt consultation may improve the overall control of blood pressure.
Diet
Initially, patients treated for malignant hypertension are instructed to fast until stable. Once stable, all patients should obtain good long-term care of their hypertension, including a diet that is low in salt. If indicated, the patient should follow a diet that can induce weight loss.
Activity
Activity is limited to bedrest until the patient is stable. Patients should be able to resume normal activity as outpatients once their blood pressure has been controlled.
Medication
No trials exist comparing the efficacy of various agents in the treatment of malignant hypertension. Drugs are chosen based on their rapidity of action, ease of use, special situations, and convention.
Once the diagnosis of hypertensive emergency is made, the most commonly used intravenous (IV) drug is nitroprusside. An alternative for patients with renal insufficiency is IV fenoldopam. Labetalol is another common alternative, providing easy transition from IV to oral (PO) dosing. Beta-blockade can be accomplished intravenously with esmolol or metoprolol. Also available parenterally are diltiazem, verapamil, and enalapril. Hydralazine is reserved for use in pregnant patients, while phentolamine is the drug of choice for a pheochromocytoma crisis.
Vasodilators
Reduce systemic vascular resistance (SVR), decreasing afterload and improving cardiac output.
Nitroprusside (Nipride)
Nearly immediate onset of action and short half-life. Acts by causing relaxation of vascular smooth muscle, resulting in vasodilation and inotropy. Blood pressure can be titrated to the desired level.
Administration requires an IV infusion pump and an arterial line for continuous measurement of blood pressure.
Adult
0.25-10 mcg/kg/min IV
Pediatric
Not established
None reported
Documented hypersensitivity; subaortic stenosis; idiopathic, hypertrophic, and atrial fibrillation or flutter; head trauma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Carries risk of cyanide toxicity that can result in venous hypoxemia, acidosis, mental status changes, and death, especially in renal and hepatic impairment; thiocyanate levels >60 mg/L are mildly neurotoxic and can become life-threatening at approximately 200 mg/L; methemoglobinemia, headache, nausea, and vomiting also are possible; caution in increased intracranial pressure, hepatic failure, severe renal impairment, and hypothyroidism; sodium nitroprusside has the ability to lower blood pressure and should be used only in those patients with mean arterial pressures >70 mm Hg
Fenoldopam (Corlopam)
In patients with renal insufficiency, fenoldopam provides an alternative to nitroprusside without the threat of cyanide and thiocyanate toxicity. Permits precise titration to the desired blood pressure level. Studies demonstrate safety of administration without invasive monitoring; however, clinician may choose invasive monitoring because fenoldopam causes rapid blood pressure changes.
Adult
0.03-1.6 mcg/kg/min IV
Pediatric
Not established
Concurrent use with acetaminophen may decrease levels
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause headache, nausea, vomiting, and hypotension; monitor blood pressure and heart rate q15min; caution in cirrhosis, portal hypertension, unstable angina, and glaucoma
Enalaprilat (Vasotec IV)
Competitive ACE inhibitor. Reduces angiotensin II levels, decreasing aldosterone secretion. Typically not DOC but an appropriate alternative to nitroprusside in patients with congestive heart failure and stroke. May have beneficial effect on cerebral vascular autoregulation during hypertension.
Adult
1.25-5 mg/dose IV over 5 min q6h
Pediatric
Not established
NSAIDs may reduce hypotensive effects; may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; hypotensive effects may be enhanced when administered concurrently with diuretics
Documented hypersensitivity; pregnancy, especially second and third trimesters
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category D in second and third trimesters; caution in renal impairment, angioedema, renal artery stenosis (bilateral or with solitary kidney), or severe congestive heart failure; may cause neutropenia, rash, cough, and hyperkalemia; if the patient is hypovolemic, enalapril can induce dramatic drops in blood pressure
Hydralazine (Apresoline)
Decreases systemic resistance through direct vasodilation of arterioles. Only indicated in pregnancy because it improves uterine blood flow. Increases intracranial pressure.
Adult
10-40 mg IV; may repeat q15-30min; infuse at 1.5-5 mcg/kg/min
Pediatric
Not established
MAOIs and beta-blockers may increase toxicity; pharmacologic effects may be decreased by indomethacin
Documented hypersensitivity; mitral valve rheumatic heart disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in suspected coronary artery disease and cerebrovascular disease
Calcium channel blockers
These agents cause vascular smooth muscle to relax, which in turn leads to vasodilation and a corresponding drop in blood pressure.
Verapamil (Calan, Isoptin)
Nondihydropyridine calcium channel blocker. During depolarization, inhibits calcium ions from entering slow channels or voltage-sensitive areas of the vascular smooth muscle and myocardium.
Adult
5-10 mg IV infused over 2 min; repeat dose 15-30 min later if patient does not respond satisfactorily to initial dose; followed by 0.005-0.375 mg/kg/min
Pediatric
Not established
May increase carbamazepine, digoxin, and cyclosporine levels; coadministration with amiodarone can cause bradycardia and a decrease in cardiac output; when administered concurrently with beta-blockers, may increase cardiac depression; cimetidine may increase levels; may increase theophylline levels
Documented hypersensitivity; hypotension (<90 mm Hg systolic); wide complex tachycardia, Mobitz type 2 or third-degree heart block, acute MI with pulmonary edema, atrial fibrillation or flutter in the presence of accessory bypass tract
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hepatocellular injury may occur; transient elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have occurred (elevations have been transient and may disappear with continued verapamil treatment); monitor liver function periodically; caution with concomitant use of beta-blockers, left ventricular failure, first- or second-degree heart block (Mobitz 1), and bradycardia
Diltiazem (Cardizem, Dilacor, Tiamate)
Nondihydropyridine calcium channel blocker. During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium.
Adult
0.25 mg/kg IV bolus (20 mg); may repeat 0.35-mg/kg bolus (25 mg) in 15 min; followed by 5-20 mg/h IV infusion
Pediatric
Not established
May increase carbamazepine, digoxin, cyclosporine, and theophylline levels; when administered with amiodarone, may cause bradycardia and a decrease in cardiac output; when administered with beta-blockers, may increase cardiac depression; cimetidine may increase diltiazem levels
Documented hypersensitivity; wide complex tachycardia, Mobitz 2 second- or third-degree AV block, acute MI with pulmonary edema and hypotension (<90 mm Hg systolic)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur; concomitant use of beta-blockers; left ventricular failure; first- or second-degree heart block (Mobitz 1); bradycardia; atrial fibrillation or flutter in presence of accessory bypass tract
Beta-adrenergic blockers
Inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation.
Labetalol (Normodyne, Trandate)
Blocks beta1-adrenergic receptor sites, alpha1-adrenergic receptor sites, and beta2-adrenergic receptor sites, thereby decreasing blood pressure. Provides effective approach in treating patients with hypertensive emergency. Close patient monitoring is necessary (hypotension and heart block can occur). Start PO antihypertensive therapy as soon as possible.
Available in a vial that can be stored at room temperature and is available for immediate administration. Therapy with IV labetalol can be started immediately following the diagnosis of hypertensive emergency.
Adult
20 mg IV over 2 min, followed by 40-80 mg at 10-min intervals; not to exceed 300 mg per dose; alternatively, a continuous IV infusion at 2 mg/min can be started, with subsequent adjustment
Pediatric
Not established
Decreases effect of diuretics and increases toxicity of methotrexate, lithium, and salicylates; may diminish reflex tachycardia resulting from nitroglycerin use without interfering with hypotensive effects; cimetidine may increase blood levels; glutethimide may decrease effects by inducing microsomal enzymes
Documented hypersensitivity; cardiogenic shock, bradycardia, AV block, uncompensated congestive heart failure; pulmonary edema, reactive airway disease
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in impaired hepatic function; discontinue therapy if signs of liver dysfunction develop; lower response rate and higher incidence of toxicity may be observed in elderly patients
Esmolol (Brevibloc)
Excellent drug for use in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.
Adult
Initial: 500 mcg/kg/min IV loading dose for 1 min
Maintenance: 50-300 mcg/kg/min IV
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effect; cardiotoxicity may increase when administered concurrently with sparfloxacin, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents
Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, AV conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm, may worsen when medication is abruptly withdrawn; withdraw drug slowly and monitor patient closely; caution in CHF, bronchospasm, and peripheral vascular disease; requires large volume of IV fluid to administer, which may be inappropriate for some patients
Metoprolol (Lopressor, Toprol XL)
Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor blood pressure, heart rate, and ECG.
Adult
5 mg IV q2min for 3 doses; may repeat sequence q30min prn
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; toxicity may increase with coadministration of sparfloxacin, phenothiazines, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and oral contraceptives; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Documented hypersensitivity; uncompensated congestive heart failure, bradycardia, cardiogenic shock, AV conduction abnormalities; asthma
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG
Alpha-adrenergic blockers
At low doses, alpha-adrenergic receptor blockers may be used as monotherapy in the treatment of hypertension. At higher doses, they may cause sodium and fluid to accumulate. As a result, concurrent diuretic therapy may be required to maintain the hypotensive effects of the alpha-receptor blockers.
Phentolamine (Regitine)
Alpha1- and alpha2-adrenergic blocking agent that blocks circulating epinephrine and norepinephrine action, reducing hypertension that results from catecholamine effects on the alpha-receptors. DOC in pheochromocytoma crisis. May be useful in withdrawal from alpha agonists or the interaction of MAOIs with tyramine-containing foods, but it is less titratable than nitroprusside.
Adult
5-20 mg IV q5-10min
Pediatric
Not established
Concurrent administration of epinephrine or ephedrine may decrease effects; ethanol increases toxicity
Documented hypersensitivity; coronary or cerebral arteriosclerosis; renal impairment
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in tachycardia, peptic ulcer, and gastritis; cerebrovascular occlusions and MIs can occur following administration
More on Hypertension, Malignant |
| Overview: Hypertension, Malignant |
| Differential Diagnoses & Workup: Hypertension, Malignant |
 Treatment & Medication: Hypertension, Malignant |
| Follow-up: Hypertension, Malignant |
| Multimedia: Hypertension, Malignant |
| References |
| Further Reading |
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References
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Further Reading
Related eMedicine topics:
Encephalopathy, Hypertensive
Hypertension [Nephrology]
Hypertension [Ophthalmology]
Hypertension [Pediatrics: Cardiac Disease and Critical Care Medicine]
Hypertensive Emergencies
Ocular Hypertension
Papilledema
Pseudopapilledema
Clinical guidelines:
ACR Appropriateness Criteria® renovascular hypertension. American College of Radiology - Medical Specialty Society. 1995 (revised 2007). 9 pages. NGC:006003
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of hypertension. American Association of Clinical Endocrinologists - Medical Specialty Society. 2006 Mar-Apr. 30 pages. NGC:005007
Clinical trials:
Single Incision Laparoscopy (SIL)
Keywords
malignant hypertension, hypertensive emergency, hypertension, high blood pressure, metoprolol, verapamil, diltiazem, labetalol, papilledema, hydralazine, nitroprusside, hypertensive, hypertensive urgency, phentolamine, hypertensive encephalopathy, accelerated hypertension, fibrinoid necrosis of arterioles and small arteries, microangiopathic hemolytic anemia, elevated blood pressure
