M.R. was experiencing chest pain, and had tachycardia on admission; these signs
and symptoms are most likely caused by his severely elevated BP and the presence of
acute left ventricular failure. Even though labetalol may have alleviated M.R.’s
angina, the negative inotropic action could acutely compromise his left ventricular
dysfunction, an effect that outweighs the potential benefit of afterload reduction. In
addition, even though labetalol is one of the safest β-blocking drugs when used in
100 β-blocker therapy should be avoided as initial treatment in
patients with asthma. Labetalol should be used only if alternative methods of
reducing M.R.’s pressure fail.
QUESTION 1: C.M., a 52-year-old Caucasian man, is admitted to the hospital with a 3-day history of
abdomen is unremarkable, and there is no peripheral edema. The neurologic examination is normal.
Significant laboratory values include the following:
nonspecific ST-T wave changes. The chest radiograph reveals mild cardiomegaly.
The presence of chest pain, retinopathy, and new-onset renal disease, as well as
the magnitude of the BP elevation in C.M., classifies his presentation as a
hypertensive emergency that warrants a prompt reduction in BP. Sublingual and
topical nitroglycerin may help in acutely and temporarily lower his BP and relieve
his chest pain while waiting for more definitive treatment to be implemented.
IV labetalol has been used successfully in hypertensive emergencies.
blocks both β- and α-adrenergic receptors and also may exert a direct vasodilator
effect. The β-blockade is nonselective with β- to α-potency of 3:1 for oral and 7:1
for IV. Labetalol is advantageous in C.M. because the immediate onset of action will
reduce peripheral vascular resistance without causing reflex tachycardia. Myocardial
oxygen demand will be reduced and coronary hemodynamics will be improved,
making this agent an excellent choice for patients such as C.M., with anginal
symptoms or MI. In addition, IV labetalol does not significantly reduce cerebral
blood flow; therefore, it may be useful in patients with cerebrovascular disease.
Fenoldopam or nitroprusside could also be used to treat C.M. Fenoldopam could
be considered, but C.M.’s history of glaucoma would preclude its use. Additionally,
fenoldopam would not be preferred due to the potential for reflex tachycardia and
risk of worsening ischemia. Treatment with nitroprusside would expose C.M. to the
potential risk of cyanide and thiocyanate toxicity with his new-onset acute kidney
injury. In contrast, labetalol has been used successfully in patients with renal disease
without deleterious side effects.
101,102 Labetalol is eliminated by glucuronidation in
the liver, with less than 5% of the dose being excreted unchanged in the urine.
Contraindications and Precautions
CASE 16-3, QUESTION 2: What cautions should be exercised when using labetalol in C.M.?
Labetalol’s disadvantages are primarily related to its β-blocking effects.
Therefore, it should not be used in patients with asthma, heart block greater than first
degree, or sinus bradycardia, and it should be used with caution in patients with
(see Case 16-2, Question 10). None of these are present in
C.M. Like other β-blockers, labetalol should also be used with caution in patients
104 Labetalol has been effective in the treatment of hypertension associated
with pheochromocytoma and excess catecholamine states as well as those with
rebound hypertension from β-blocker withdrawal.
105 However, because labetalol is
primarily a β-blocker, paradoxic hypertension may occur in patients with
pheochromocytoma. These individuals have adrenal tumors that excrete high amounts
of norepinephrine, which results in relatively unopposed α-receptor stimulation.
More clinical experience is required before labetalol can be recommended in
patients with pheochromocytoma.
CASE 16-3, QUESTION 3: How should parenteral labetalol be given to C.M.?
IV labetalol can be given by pulse administration or continuous infusion.
injections are administered, beginning with 20 mg given over 2 minutes, followed by
40 to 80 mg every 10 to 15 minutes until the desired response is achieved or a
cumulative dose of 300 mg is reached. The desired response is usually achieved with
a mean dose of 200 mg in 90% of patients.
93 The maximal effect occurs within 10
95 and the antihypertensive response may persist for more than 6 hours.
Because the rate of BP reduction is accelerated with an increase in infusion rate,
controlled continuous infusion may provide a more gradual reduction in arterial
pressure with less frequent adverse effects.
97,108 The infusion can then be started at a
rate of 2 mg/minute and titrated until a satisfactory response is achieved or until a
cumulative dose of 300 mg is reached.
infusion, C.M. became faint and dizzy while ambulating. Should oral labetalol be withheld in C.M.?
Postural hypotension and dizziness are dose related and more commonly
associated with the IV route of administration.
99,103 C.M. should remain in a supine
position after the IV administration of labetalol, and his ability to tolerate an upright
position should be established before permitting ambulation. Oral labetalol can be
given to C.M. when his symptoms resolve. There is no correlation between the oral
maintenance dose and the total initial IV dose. C.M. should be started on an empiric
dose of 100 to 200 mg of oral labetalol 2 to 3 times per daily, and this should be
CASE 16-3, QUESTION 5: What other side effects can occur with labetalol therapy?
Other side effects commonly associated with labetalol include nausea, vomiting,
abdominal pain, and diarrhea in up to 15% of the patients.
unusual side effect that has been reported in a few patients after IV administration; it
tends to disappear with continued treatment. Other side effects include tiredness,
weakness, muscle cramps, headache, and skin rashes.
CASE 16-3, QUESTION 6: Would parenteral nitroglycerin be an acceptable alternative to labetalol for
Hypertensive emergencies in the setting of unstable angina or MI requires an
immediate reduction in BP. Nitroprusside has been used successfully, but IV
nitroglycerin can have more favorable effects on collateral coronary flow in patients
109 By diminishing preload, nitroglycerin decreases left
ventricular diastolic volume, diastolic pressure, and myocardial wall tension, thus
reducing myocardial oxygen consumption.
110 These changes favor redistribution of
coronary blood flow to the subendocardium, which is more vulnerable to ischemia.
At high dosages, nitroglycerin dilates arteriolar smooth muscles, and this reduction in
afterload also decreases myocardial wall tension and oxygen consumption.
IV nitroglycerin has a rapid onset of action and a short duration, and is easily
titratable. It is generally appropriate to begin IV nitroglycerin in the dose range of 5
to 10 mcg/minute, increased as needed to control pressure and symptoms. The usual
dose is in the range of 40 to 100 mcg/minute. The major limiting side effects are
headache and the development of tolerance. In general, IV nitroglycerin is well suited
for use in patients such as C.M. who have angina or in patients who have
hypertensive emergency associated with MI or coronary artery bypass surgery.
or papilledema. The lungs were clear. Cardiac examination was pertinent for cardiomegaly and an S4
The remainder of the physical workup was normal.
Laboratory results include the following values:
Serum creatinine, 2.5 mg/dL (baseline serum creatinine 1.9 mg/dL)
Urinalysis reveals 2+ protein, 2+ hemoglobin with 4 to 10 red blood cells per high-power field. The
IV, and a repeat BP after 1 hour was 150/100 mm Hg. What are the advantages and disadvantages of
parenteral hydralazine, and when should it be used to acutely lower BP?
Hydralazine is a direct vasodilator that reduces total peripheral resistance through
relaxation of the arterial smooth muscle. It is rarely used to treat hypertensive
emergencies because its antihypertensive response is less predictable than that of
other parenteral agents. Additionally, hydralazine has a prolonged half-life, which
can be problematic if too fast correction or hypotension occurs.
effective in controlling crises associated with essential hypertension.
Hydralazine should not be used in patients with coronary heart disease because the
reflex tachycardia causes an increase in myocardial oxygen demand, which may
result in the development or worsening of ischemic symptoms. In addition,
hydralazine should be avoided in patients with aortic dissection because of its reflex
cardiostimulating effect. In contrast, hydralazine can be useful in patients such as
T.M., who have chronic renal failure because the reflex increase in cardiac output is
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