Indications for β-adrenergic receptor blockade

Because β-adrenergic receptor blocking agents have negative inotropy and chronotropy—decreasing myocardial oxygen demand and improving myocardial perfusion—they are used in the treatment of a number of conditions. β-Adrenergic receptor blocking agents reduce the exercise-induced increase in contractility and blood pressure; therefore, they are used to treat all classes of angina except variant or Prinzmetal angina. When β adrenergic receptor blocking agents are administered correctly, patients will ideally have heart rates between 50 and 60 beats/min at rest and no more than 100 beats/min with exercise.

For similar reasons, β-adrenergic receptor blocking agents are very effective in reducing the frequency and number of ischemic episodes in patients with myocardial ischemia or acute coronary syndromes. By decreasing inotropy and chronotropy, heart rate, contractility, afterload, and myocardial wall stress are all decreased, which optimizes myocardial O₂ supply/demand. Current recommendations for patients with acute coronary syndromes are for β-adrenergic receptor blocking agents to be started early, along with statins, antiplatelet drugs, and angiotensin-converting enzyme inhibitors. This quadruple therapy has been associated with a 90% reduction in mortality rates at 6 months following the diagnosis of acute coronary syndrome. In patients who have had an acute myocardial infarction, β-adrenergic receptor blocking agents are specifically indicated to treat ongoing pain, tachycardia, hypertension, or ventricular rhythm instability. The initiation of β-adrenergic receptor blocking agents early after infarction and continued long-term has been associated with a reduction in mortality rate by as much as 25%.

β-Adrenergic receptor blocking agents lower blood pressure by decreasing cardiac output and peripheral vascular resistance and are specifically indicated to treat hypertension in patients with congestive heart failure, with coronary artery disease, and after myocardial infarction. Patients with congestive heart failure, even if they are not hypertensive, can benefit from β-blockade; the administration of carvedilol and of metoprolol have been reported to improve cardiac ejection fraction, reverse abnormal patterns of gene expression toward normal, and decrease mortality rate.

Because of their negative dromotropy, inhibitory effects in the sinus and atrioventricular nodes, and other antiarrhythmic properties (Table 91-1), β-adrenergic receptor blocking agents are recommended to acutely and chronically treat a number of tachyarrhythmias. They are indicated to treat supraventricular tachycardias, to control the rate in patients with atrial fibrillation, and to treat ventricular tachyarrhythmias (specifically metoprolol and sotalol [class III antiarrhythmic]). β-Adrenergic receptor blocking agents also counteract the arrhythmogenic effects of excess catecholamine stimulation, as seen, for example, in patients after myocardial infarction.

β-Adrenergic receptor blocking agents are recommended to treat hypertrophic obstructive cardiomyopathy to decrease systolic anterior motion of the anterior mitral valve leaflet. In patients with mitral stenosis, by decreasing the heart rate both at rest and during exercise, β-blockade prolongs diastolic filling time and, therefore, improves cardiac output. In patients with mitral valve prolapse, β-adrenergic receptor blocking agents are recommended to treat any associated arrhythmias. β-Blockade is indicated in patients with dissecting aortic aneurysms to decrease pulse pressure and sheer stress on the aortic wall.

The cyanotic spells associated with the tetralogy of Fallot are decreased in frequency and severity by the administration of β-adrenergic receptor blocking agents. In patients with congenital long QT syndrome, β-blockade restores the imbalance between the left and right stellate ganglia.

In patients with thyrotoxicosis, β-adrenergic receptor blocking agents control the associated tachycardia, palpitations, and anxiety. The use of β-adrenergic receptor blocking agents is strongly recommended to treat hypertension and tachycardia in patients with thyroid storm, if left ventricular function is normal.

Patients coming to the operating room may be on β-adrenergic receptor blocking agents for other reasons, such as to treat anxiety, essential tremor, neurocardiogenic syncope, and open-angle glaucoma and for prophylaxis of migraine headaches.

Of particular importance for anesthesia providers, β-adrenergic receptor blocking agents should be used in patients at high risk for experiencing a coronary event and who are undergoing noncardiac and vascular operations, but this recommendation is not without risk if the patient has not been on β-adrenergic receptor blocking agents before the operation. The POISE study demonstrated that extended-release metoprolol decreased the rate of myocardial events but was associated with an increased risk of stroke and a higher mortality rate at 30 days. However, patients who are on β-adrenergic receptor blocking agents preoperatively but have not taken their usual daily dose should receive a β-adrenergic receptor blocking agent preoperatively.

Pharmacology of β-adrenergic receptor blocking agents

Multiple β-adrenergic receptor blocking agents are available, differing in β₁ cardioselectivity, lipid solubility, and whether or not they have intrinsic sympathomimetic activity (see Table 91-1).

Side effects

Because of their mechanism of action, β-adrenergic receptor blocking agents are associated with a number of symptoms and signs that are not truly side effects but, rather, sequelae of their mechanism of action. These sequelae include bradycardia, hypotension, and central nervous system effects, which include sedation, fatigue, (combination of peripheral and central effects), sleep disturbances, depression, and hallucinations. In men, β-adrenergic receptor blocking agents increase the incidence of impotence. As mentioned, the use of even the most cardioselective β-adrenergic receptor blocking agents is associated with bronchospasm in patients with a history of asthma. They may mask hypoglycemic symptoms in patients with diabetes and increase triglyceride and reduce high-density lipoprotein levels.

Abrupt discontinuation of β-adrenergic receptor blocking agents is associated with rebound hypertension and tachycardia, which can result in myocardial ischemia or infarction. With respect to specific side effects, labetalol has been associated with an increase in concentration of liver enzymes, an increased concentration of antinuclear and antimitochondrial antibodies, pruritus of the scalp, and positive tests for pheochromocytoma because it interferes with assays of metanephrine and catecholamines. Contraindications to the use of β-adrenergic receptor blocking agents are listed in Box 91-1.

Anesthesia providers should use β-adrenergic receptor blocking agents sparingly and with caution in patients taking digitalis, calcium channel blockers, or disopyramide. Levels of β-adrenergic receptor blocking agents metabolized by the liver (propranolol, metoprolol, carvedilol, labetalol) are increased by cimetidine, which decreases hepatic blood flow. In patients who have taken an accidental or intentional overdose of β-adrenergic receptor blocking agents, the side effects can be mitigated by glucagon, 100 mg/kg, administered intravenously over 1 min, then 1 to 5 mg/h; isoproterenol, up to 0.1 g·kg⁻¹·min⁻¹; or dobutamine, 15 μg·kg⁻¹·min⁻¹.