The cardiovascular system can be influenced by a variety of medications used in the operating room and intensive care units. Pharmacologic agents may change the contractility of the heart (inotropy), heart rate (chronotropy), conduction of electricity through the atrioventricular (AV) node (dromotropy), or relaxation of the heart in diastole (lusitropy). Vasoactive drugs may constrict (vasopressors) or widen (vasodilators) blood vessels either by influencing receptors of the autonomic nervous system (alpha₁, beta₁, and beta₂ receptors) or by direct actions on the smooth muscle of the vascular wall.

Maintaining a normal heart rate and rhythm is essential for optimal cardiac function. Antiarrhythmic agents are commonly used in the perioperative period to accomplish this. Drugs impacting the cardiovascular system are used to overcome the sequelae of cardiovascular disease, the effects of cardiovascular-depressant drugs (e.g., anesthetic agents), physiologic reflexes, and/or any combination of these. This chapter introduces the anesthesia technician to the mechanism of action and uses of positive inotropic agents, vasoactive drugs, and antiarrhythmic agents. The cardiovascular actions of anesthetic drugs are described elsewhere.

Drugs that increase the force of myocardial contraction are called positive inotropic agents and include catecholamines, phosphodiesterase (PDE) inhibitors, and myofilament calcium sensitizers. Catecholamines and PDE inhibitors increase calcium concentration in the cytoplasm of cardiac muscle cells by different mechanisms to help generate a greater force of contraction. Myofilament calcium sensitizers enhance the interaction between the contractile proteins within myocardial cells without increasing intracellular calcium.

Stimulation of beta₁-adrenergic receptors that are coupled to G proteins activates the enzyme adenylyl cyclase, which, in turn, forms cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (see Fig. 8.1). cAMP increases contractility (via increased intracellular calcium concentration) of cardiac muscle while also causing relaxation in smooth muscle (e.g., in blood vessels). It is metabolized by the enzyme PDE. PDE is targeted by a variety of drugs called PDE inhibitors that increase cAMP levels by inhibiting PDE and preventing breakdown of cAMP.

The naturally occurring catecholamines epinephrine, norepinephrine, and dopamine are produced in the medulla of the adrenal gland. Norepinephrine is also synthesized in adrenergic nerves and functions as a neurotransmitter in the sympathetic division of the autonomic nervous system (see Chapter 14). Epinephrine and norepinephrine are considered stress hormones when released into the bloodstream from the adrenal gland. The half-lives of endogenous as well as synthetic catecholamines, such as dobutamine and isoproterenol, are short (minutes), and these drugs are quickly deactivated primarily by reuptake into presynaptic neurons or metabolism by enzymes. The metabolites can be detected in the urine and are elevated in patients with catecholamine-producing tumors such as pheochromocytoma. The drugs stimulating alpha and beta adrenoceptors to produce their actions have proportionally different effects on heart, vasculature, and other smooth muscles dependent on their affinity for receptor types (see Table 8.1).

Epinephrine is a naturally occurring catecholamine that is produced from its precursor, norepinephrine, exclusively in the adrenal medulla.

It has a wide range of physiologic effects including increasing heart rate, myocardial contractility, and conduction in the heart by stimulating primarily beta₁-adrenergic receptors. Increased peripheral vascular tone (afterload) is mediated by the activation of alpha₁-adrenergic receptors, while relaxing bronchial smooth muscle (bronchiodilation) is caused by the activation of beta₂ receptors. Beta₂ receptors are also located on vascular smooth muscle cell membranes, and stimulation of these receptors by low doses of epinephrine produces vasodilation. Epinephrine also influences metabolism by increasing glycogenolysis in the liver and lipolysis in adipose tissue.

In anesthetic practice, epinephrine may be used intravenously in life-threatening situations including cardiac arrest, low cardiac output syndromes, anaphylaxis, or bronchospasm. Added to solutions of local anesthetics in a concentration of 1:200,000, it prolongs the action of the anesthetic by constricting surrounding blood vessels and decreasing systemic reabsorption.

In cardiopulmonary resuscitation, epinephrine is administered intravenously in 1-mg (0.02 mg/kg) increments every 3 minutes per advanced cardiac life support (ACLS) guidelines in a dilution of 1:10,000 (0.1 mg/mL) (see Chapter 61). At this high dose, the arterial vasoconstrictor properties predominate causing increased diastolic pressures, which improve coronary artery perfusion. As a continuous infusion, epinephrine is usually administered between 0.03 µg/kg/min and 0.15 µg/kg/min. At lower doses, the effects on beta₁ and beta₂ adrenoceptors (bronchodilation, inotropy, and chronotropy) usually predominate, while at high doses epinephrine can cause profound vasoconstriction through alpha₁ activation. Epinephrine can produce cardiac arrhythmias, especially in the presence of the anesthetic halothane. Increases in heart rate in patients with coronary artery disease may cause myocardial ischemia. In general, the beta-adrenergic stimulant properties of epinephrine
and other catecholamines will be diminished in patients taking beta-blocking drugs. There is a very high variability in the response between patients, and thus this drug should always be titrated carefully to the desired effect. Infusion through a central venous line is recommended for higher concentrations as extravasation can cause tissue necrosis. In general, solutions containing catecholamines for infusion should be prepared in 5% glucose to avoid deactivation in alkaline solutions.