15: Inotropes and Vasodilator Drugs

Published on 06/02/2015 by admin

Filed under Anesthesiology

Last modified 06/02/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 0 (0 votes)

This article have been viewed 1496 times

CHAPTER 15 Inotropes and Vasodilator Drugs

Nathaen Weitzel, MD

Editors note: chapter 1 complements this discussion.

1 What are the benefits of cardiovascular drugs?

All of the components of organ perfusion, including preload (end-diastolic volume), afterload, inotropy, heart rate, and myocardial oxygen supply and demand can be pharmacologically modified. An underlying concept is the Frank-Starling principle, which states that increased myocardial fiber length (i.e., end-diastolic volume) improves contractility up to a point of optimal contractile state, further stretching results in declining performance.

2 Discuss the limitations of drugs that alter vascular tone

Preload can be altered with intravascular volume shifts and with drugs that change vascular tone, most notably the venous capacitance vessels. In addition, arterial vasodilators may shift failing myocardium to a more effective contractile state as a result of afterload reduction and decreased impedance to ventricular ejection. However, the intrinsic contractile state is not improved by vasodilators, in contrast to the effect of positive inotropic agents.

3 What are the general goals of inotropic support and the characteristics of the ideal inotrope?

The goal is increasing cardiac output by improving myocardial contractility to optimize end-organ perfusion. In addition, for enlarged hearts a decrease in ventricular diameter, wall tension, and myocardial oxygen demand is also desirable and should enhance the contractile state and myocardial perfusion. Some inotropic agents also decrease pulmonary vascular resistance, improving right heart output and forward flow.

4 Discuss the hemodynamic profile of the phosphodiesterase III inhibitors amrinone and milrinone

Amrinone and milrinone are approximately equipotent to dopamine and dobutamine in increasing cardiac output through increased inotropy and improved lusitropy (myocardial relaxation). In addition to direct myocardial effects, vasodilation typically occurs, making it difficult to separate the relative contributions of these effects on enhanced cardiac output. Right ventricular function can be favorably impacted as these agents decrease pulmonary vascular resistance (comparable to 20 ppm of nitric oxide in cardiac surgery patients), thus improving forward flow. Coronary vessels and arterial bypass grafts (internal mammary and gastroepiploic arteries and radial artery grafts) become dilated; furthermore, in the presence of these drugs they are less subject to the vasoconstrictive effects of concomitantly administered α-adrenergic agonists.

5 What untoward effects can result from use of phosphodiesterase inhibitors? How are these minimized?

Because the vasodilator effects may be profound, concurrent use of vasoconstrictors (e.g., epinephrine, norepinephrine, and phenylephrine) is often necessary, particularly after cardiopulmonary bypass. Prolonged infusion of amrinone, but not milrinone, may cause significant thrombocytopenia through nonimmune-mediated peripheral platelet destruction.

6 What are other advantages of the phosphodiesterase inhibitors?

In addition to positive inotropy, lusitropy, vasodilation, and a relative lack of significant tachyarrhythmias, these inhibitors may transiently restore β-adrenergic function by decreasing cyclic adenosine monophosphate (cAMP) breakdown and potentiating the action of administered β-adrenergic agonists. These drugs dilate coronary arteries and grafts, improving collateral coronary circulation and attenuating thromboxane activity; in certain clinical situations they may help decrease myocardial oxygen consumption.

7 What intracellular intermediary is involved in the actions of phosphodiesterase III inhibitors and sympathomimetic amines?

Both drug classes increase intracellular cAMP concentrations. Sympathomimetic β-adrenergic stimulation activates sarcolemmal adenyl cyclase, resulting in the generation of increased cAMP from adenosine triphosphate (ATP). Phosphodiesterase (PDE) III inhibitors decrease the breakdown of cAMP. A synergistic effect is noted when β-adrenergic agonists are infused along with PDE III inhibitors.

8 How does increased intracellular cAMP affect the cardiac myocyte? What are the corresponding effects on myocardial function?

Increased intracellular cAMP activates protein kinases, which phosphorylate proteins in the sarcolemma, sarcoplasmic reticulum (SR), and tropomyosin complex. This causes elevated calcium (Ca2+) influx via Ca2+ channels, amplifying the effects of Ca2+ on contractile elements. In addition, increased protein phosphorylation in the SR and tropomyosin complex improves lusitropy by stimulating reuptake of Ca2+ into the SR. The end result is a restoration of the myofilaments to their resting state.

9 Describe the hemodynamic profiles of epinephrine, norepinephrine, and dopamine

The effects of a low-dose infusion of epinephrine (<0.04 mcg/kg/min) are primarily limited to stimulation of β1– and α2-adrenergic receptors in the heart and peripheral vasculature, resulting in positive chronotropy, dromotropy (conduction velocity), inotropy, increased automaticity, and vasodilation. Moderate-dose infusion (0.04 to 0.12 mcg/kg/min) generates greater α-adrenergic effects and vasoconstriction, and high-dose infusion results in such prominent vasoconstriction that many of the β-adrenergic effects are blocked.

Hemodynamic dose-response relationship of epinephrine:

image <0.04 mcg/kg/min Primarily β-stimulation
image 0.04 to 0.12 mcg/kg/min Mixed alpha and β-stimulation
image >0.12 mcg/kg/min Primarily α-stimulation

The potency of norepinephrine in stimulating β-adrenergic receptors is similar to that of epinephrine, but it results in significant α-adrenergic stimulation at much lower doses. Typical dosage ranges are 0.02 to 0.25 mcg/kg/min.

Dopamine stimulates specific postjunctional dopaminergic receptors in renal, mesenteric, and coronary arterial beds to produce vasodilation. These dopaminergic effects occur at lower doses (0.5 to 1.0 mcg/kg/min), becoming maximal at 2 to 3 mcg/kg/min. At intermediate doses (2 to 6 mcg/kg/min) β1-adrenergic stimulation is evident. Beginning at doses of about 10 mcg/kg/min (but as low as 5 mcg/kg/min), α-adrenergic stimulation is seen, which at higher doses overcomes dopaminergic effects, producing vasoconstriction.

10 Describe the hemodynamic profiles of isoproterenol and dobutamine

Isoproterenol is an extremely potent β1– and β2– agonist that possesses no α-stimulating properties. Therefore isoproterenol increases heart rate, automaticity, and contractility and dilates both venous capacitance and arterial vessels. It may be a good choice for heart-rate maintenance in a denervated nonpaced transplanted heart. Dobutamine acts principally on β-adrenergic receptors, impacting β1-receptors in a relatively selective fashion. In addition, it has a mild indirect β1

Related posts:

58: Congenital Heart Disease 59: Fundamentals of Obstetric Anesthesia 34: Heart Failure 66: Epidural Analgesia and Anesthesia 76: Electroconvulsive Therapy 41: Acute Respiratory Distress Syndrome (ARDS)