How Should We Treat a Hypertensive Emergency?

Karl Heinz Rahn, MD, PhD

Hypertensive emergencies are life-threatening situ- ations caused by acute blood pressure elevation. They require immediate treatment with antihyper- tensive drugs. Such emergencies include hyperten- sive crisis, acute left ventricular heart failure or intracranial bleeding in patients with hypertension, malignant hypertension resistant to treatment, and serious blood pressure elevations after vascular surgery. A hypertensive crisis may be defined as a sudden increase in systolic and diastolic blood pres- sure that causes functional disturbances of the cen- tral nervous system, the heart or the kidneys. In patients with hypertensive crisis, treatment should be started with an 4 receptor-blocking agent if pheochromocytoma has not been excluded by pre- vious workup. Antihypertensive agents with a rapid onset of action-nifedipine, clonidine, dihydrala- zine, diazoxide and sodium nitroprusside-are be- ing used.

(Am J Cardiol 1989;63:48C-SOC)

From the Department of Medicine D, University of Miinster, Miinster, Germany.

Address for reprints: K. H. Rahn. MD, WD, Department of Medi- cine D, University of Miinster, Albert-Schweitzer-Str. 33, D-4400 Miinster. Germany.

H ypertensive emergencies are life-threatening situations caused by acute blood pressure eleva- tion. They require immediate treatment with anti-

hypertensive drugs. Such emergencies include hyperten- sive crisis, acute left ventricular heart failure or intracra- nial bleeding in patients with hypertension, malignant hypertension resistant to drug treatment and serious blood pressure elevations after vascular surgery.

A hypertensive crisis is defined as a sudden increase in systolic and diastolic blood pressure, causing functional disturbances of the central nervous system, the heart or the kidneys. In adults, diastolic blood pressure usually is greater than 120 mm Hg. Severe headache localized in the occipital region often is an early symptom of a hyper- tensive crisis. Another symptom is hypertensive encepha- lopathy, characterized by disorientation, vomiting, and eventually coma with respiratory disturbances and con- vulsions. A further symptom of a hypertensive crisis is disturbance in kidney function.

The diagnosis of a hypertensive crisis may not be based exclusively on blood pressure values. An increase in blood pressure to 280/150 mm Hg within several weeks often does not cause significant symptoms in a patient. In such a situation this diagnosis would not be justified. Thus, a hypertensive crisis is characterized by a sudden increase in blood pressure-within minutes or hours-in conjunction with signs of a functional impairment of tar- get organs of hypertension. The duration of a hyperten- sive crisis may be minutes, hours or days.

In most patients, such crises develop on the basis of a preexisting hypertension, Rarely does such a crisis begin at normal blood pressure levels. Diseases predisposing to a hypertensive crisis are chronic renal disease, toxemia of pregnancy, essential hypertension, renovascular hyper- tension, pheochromocytoma and acute glomerulonephri- tis, as well as drugs.

TREATMENT In all patients with a hypertensive crisis in whom a

pheochromocytoma has not been excluded by previous workup, treatment should be started with intravenous injections of an a receptor-blocking agent. It is advisable to begin therapy with a dose of 5 mg of phentolamine, a drug used often in such situations. If blood pressure does not decrease sufficiently, additional 5-mg doses may be given up to a total of 20 mg. Pheochromocytoma as cause of the hypertensive crisis is highly improbable if this dose also does not have a significant hypotensive effect (i.e., decrease in blood pressure by more than 25 mm Hg systolic).

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TABLE I Drugs Used for Hypertensive Emergencies

Drug Dose (mg) Onset of Actlon

(ml%

Duration of Actlon (hours) Adverse Effects

Nlfedlplne

Clonldlne

Dlhydralazine

Dlazoxlde

Sodium

nltroprusslde

5-20 (orally)

0.0754.3

0.v ) 6.25-25

(1 v ) 7 5-300

(iv) 0.02-l/mln

(1 v )

3--6 Flush

5-10 6-8 Sedation

5-10 4-6 Tachycardla

l-5

BegInnIng of InfusIon

1-12

End of infuslon

Tachycardla. hyperglycemia

Cyanide, thlocyanate lntoxicatlon

IV = Intravenously

A substantial decrease in blood pressure after the injection of phentolamine must not be considered as proof of pheochromocytoma. This drug, as well as other (Y re- ceptor-blocking agents, sometimes has an acute antihy- pertensive effect in other hypertensive diseases. Recently, labetalol is sometimes used in place of phentolamine. The available formulation of labetalol combines 01 and /? re- ceptor-blocking properties.

There are now several drugs available for the treat- ment of a hypertensive crisis not due to pheochromocyto- ma and for the treatment of other hypertensive emergen- cies. A drug administered during such emergendies should have a rapid onset of action. Intravenous applica- tion should be possible because many patients with a hypertensive crisis are unable to swallow. Such a drug should have a reliable antihypertensive effect and should be devoid of serious adverse effects.

The treatment of patients with hypertensive emergen- cies has become much easier with the introduction of calcium antagonists into therapy. The antihypertensive effect of nifedipine given orally begins 15 to 20 minutes after the application (Table I) .’ The maximal effect usu- ally is reached after 30 minutes. It is advisable to give, as an initial dose, 5 mg of nifedipine in order to avoid hypo- tension. The onset of the antihypertensive action of nifed- ipine may even be more rapid when the drug is given sublingually. Flush may be an adverse effect of nifedipine given to patients in a hypertensive crisis.

It is our experience that in about 60% of the patients with hypertensive crisis, monotherapy with nifedipine sufficiently reduced blood pressure. Because of the few adverse effects to be expected with appropriate dosage, nifedipine now is often used as the first drug for treatment of hypertensive emergencies, particularly when therapy has to be started outside the hospital. Nifedipine is now also available for intravenous application. Nitrendipine, a

nifedipine-like calcium antagonist, also has a rapid and reliable blood pressure-reducing effect when adminis- tered intravenously. Verapamil and verapamil-like calci- um antagonists may prolong atrioventricular conduction when given intravenou?ly. These drugs, therefore, are no

longer being given to patients with hypertensive emergen- cies.

Clonidine (Table I), initial dose 0.075 mg, often re- duces blood pressure in patients with hypertensive emer- gencies within approximately 5 minutes. Sometimes, there is a short-lasting increase in blood pressure after intravenous application of clonidine. In our experience, this increase never exceeds 20 mm Hg and is of no’ clinical significance. Frequently, clonidine causes sedation in the patient. Generally, this is an unwanted effect in a hyper- tensive crisis and in other hypertensive emergencies be- cause it makes the judgment of cerebral function of the patient difficult.

Dihydralazine (Table 1) has a hypotensive effect that begins approximately 5 minutes after intravenous injec- tion and lasts about 6 hours. With higher doses of this drug, there is usually a substantial increase in heart rate. Concomitantly, there is an increase in cardiac output. Increase in both heart rate and cardiac output is due to activation of the baroreflex with subsequent increase of sympathetic activity. The blood pressure-reducing effect of dihydralazine is, therefore, more pronounced when the drug is combined with an agent inhibiting the sympathet- ic nervous system. For this reason, dihydralazine is often combined with clonidine for the treatment of hyperten- sive emergencies. Both drugs have similar onset and dura- tion of antihypertensive action.

Urapidil, which combines CXI and CY~ receptor-blocking activity, can be administered alone or in combination with dihydralazine for the treatment of patients with hypertensive emergencies.2

Diazoxide is more potent than dihydralazine as a va- sodilating agent and, therefore, can be used in the form of monotherapy in hypertensive emergencies. The antihy- pertensive effect begins 1 to 5 minutes after intravenous injection of the drug and has a duration ranging from 1 to 12 hours. As with dihydralazine, diazoxide increases heart rate. Furthermore, the drug causes hyperglycemia. This adverse effect usually does not require additional treatment because diazoxide usually is given for only a few days. Nevertheless, blood glucose levels should be

THE AMERICAN JOURNAL OF CARDIOLOGY FEBRUARY 2, 1989 e

A SYMPOSIUM: ACUTE BLOOD PRESSURE ELEVATION AND THE BRAIN

TABLE II Steps In the Treatment of Hypertensive Emergencies

1. Nlfedtpine 5 mg orally 2 Nif&plne 10 mg orally 3 Clonldlne 0.15 mg + dlhydralazlne 12.5 mg 1.v 4, Repeat of above 5. Dlazoxlde 150 mg i.v. 6 Repeat of above 7. Sodium nltroprusslde 0.02-l mg/min I.V.

controlled in all patients treated with diazoxide for more than 1 day, especially in patients with impaired glucose tolerance before application of the drug.3

Of all drugs thus far mentioned, sodium nitroprusside has the most reliable antihypertensive effect. Because of poor bioavailability of oral doses, the drug has to be infused intravenously. The initial dose should be about 0.02 mg/min. A dose of 1 mg/min should not be exceed- ed. The antihypertensive action begins immediately when the infusion is begun and ends when the intravenous application is stopped. The most important adverse ef- fects of sodium nitroprusside are cyanide and thiocyanate intoxication. To prevent cyanide toxicity, it is advisable to infuse sodium nitroprusside together with hydroxoco- balamin4 or with sodium thiosulphate.5

Nifedipine, clonidine, dihydralaiine, diazoxide and sodium nitroprusside have substantially improved the therapy of hypertensive emergencies. These agents repre- sent an armament that can be used effectively in different clinical situations. In general, the use of nifedipine re-

quires less supervision of the patient than the application of the other drugs. The most careful observation of the patient is mandatory when sodium nitroprusside is used. In this case, blood pressure has to be measured every 30 to 60 seconds until the desired level is obtained. Thereafter, blood pressure should be controlled every 10 minutes during constant infusion of the drug. Because of the re- quired careful observation of the patients, sodium nitro- prusside is predominantly used in hypertensive emergen- cies when other drugs have been ineffective.

On the basis of these considerations, the following procedure may be recommended in hypertensive emer- gencies (Table II): Therapy should commence with nifed- ipine orally. If this proves-to be ineffective, repeated doses of clonidine combined with dihydralazine should be ad- ministered intravenously. In case of insufficient efficacy, diazoxide should be given. If with all these measures blood pressure does not decrease to adequate levels, an intravenous infusion with increasing doses of sodium ni- troprusside should be given.

REFERENCES 1. Magometschnigg D. Zur Therapie be1 hypertonen Krisen. Dtsch Med Wo- chenschr 1982;107:1423-1428. 2. Zahringer J, Klepzig M, Greif J, Ludwig B, Strauer B. Antihypertensive Therapie mit Urapidil beI Hochdruckkrisen. Herz/Kreislauf 1983,15:546-549, 3. Rahn KH. The use of vasodilating agents in the treatment of a hypertensive crisis. Prog Pharmacol 1980;3/4:1 IS-1 19. 4. Cottrell JE, Casthely P, Brodie JD, Pate1 K, Klein A, Turndorf H. Prevention of nitroprusside-induced cyanide toxicity with hydroxocobalamm. N EnglJ Med 1978;298:809-811. 5. Schulz V, Bonn R, KImmerer H, Kriegel R, Ecker N. Counteraction of cyanide poisonmg by thiosulphate when administering sodmm nitroprusside as a hypotensive treatment. Klin Wochenschr 1979:57:905-908.

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