Neonatology

Inotropes (b -adrenergic) and Pressors (a -adrenergic)

Jon Palmer, VMD, Associate Professor, New Bolton Center, University of Pennsylvania

a 1-adrenergic effects:

Increased systemic vascular resistance (construction of smooth muscles)

Elevated systolic and diastolic blood pressure

Decreased perfusion of splanchnic, mucosal, renal, and dermal circulation

Inhibit insulin secretion

a 2-adrenergic effects:

Inhibit norepinephrine release

Negative chronotrophy

Release of growth hormone

b 1-adrenergic effects:

Increased myocardial contractility (inotropic)

Increased heart rate (chronotropic)

Increased conduction velocity through the atrioventricular node

Myocardial irritability

Enhance renin secretion

Lipolysis

 

b 2-adrenergic effects:

Relaxation of smooth muscle - vasodilation

Relaxation of skeletal muscle vasculature

Relaxation of smooth muscle in bronchi - bronchodilation

Enhance glucagon secretion - glycogenolysis

Hypokalemia

D1 Dopaminergic receptors

Post synaptic active relaxation of smooth muscles in vascular beds

Stimulate increased renal, splanchnic, cerebral and corinary blood flow through active vasodilation.

D2 Dopaminergic receptors

Inhibits release of prolactin

Inhibit release of b -endorphin

Inhibits release of thyrotropin, aldosterone

Direct renal tubular affect causing naturesis

 

Sympathetic control of vascular resistance is maintained by the vasomotor center of the lower pons and medulla. Constant sympathetic tone maintains vascular tone at approximately 50% construction allowing for both increase and decrease in vasomotor activity in response to physiologic changes in cardiovascular status. Exogenous catecholamines override this control with direct stimulation of adrenergic receptors increasing sympathetc tone.

 

Inotropes (b -adrenergic)

Dobutamine

Epinephrine

Isoproterenol (mild vasodilation - b 2)

Norepinephrine + phentolamine

Nitroprusside + (norepinephrine or epinephrine or dopamine)

 

Pressors (a -adrenergic)

Phenylephrine

Norepinephrine

 

Mixed agents (a -adrenergic, b -adrenergic)

Dopamine

Epinephrine

 

Vasodilators (afterload reducers)

Nitroprusside (primarily systemic vasodilator)

Nitroglycerin (primarily pulmonary vasodilator)

Phentolamine

 

Dobutamine has primarily b 1 at low to moderate doses and thus is a good inotrope. In man some a 2 activity may result in mild vasodilation but in general a 1and a 2 stimulus is well balanced so that clinically they are not important. In adult horses a 1 activity appears as the dose increases causing significant vasoconstriction.

 

Dopamine has dopaminergic activity at low doses, b 1 & b 2 activity at moderate doses, and a 1 activity at high doses. It causes norepinephrine release from nerve terminals which has lead to the suggestion that this is its major mode of action at high doses and the suggested limitation in critical patients who become depleted. At doses over 20 g/kg/min intrapulmonary shunting may occur and so limits its dosage (dobutamine dose not have this limit and is sometime given in doses as high as 40-50 g/kg/min).

 

Epinephrine has a 1, a 2, b 1, b 2 activity; Beta activity is predominant resulting in increased cardiac output and decreased peripheral resistance at low doses. It has been associated with hyperglycemia, hypokalemia, lipolysis, and increased platelet aggregation. It's affect on renal function is controversial.

 

Norepinephrine has a 1 and b 1 activity but variable b 2 activity resulting in potent vasopressor activity; it as both inotropic and chronotropic activities but its chronotropic affect is usually blunted by vagal reflex slowing the heart rate induced by the rise in blood pressure. There is an increase in myocardial oxygen consumption due to cardiostimulation and increased afterload.

 

 

Relative Potency of Inotropes and Pressors

 

Drug

Infusion Rate*

a Effect

(Pressor)

b Effect (Inotropic)

Use

Dopamine 1 - 5 g/kg/min

(dopaminergic effect)

5 - 15 g/kg/min

10 - 20 g/kg/min

+

++

+++

+

++

++

1st line choice, good mixed a and b response

Dobutamine

2 - 20 g/kg/min

(high doses)

+

(++)

+++

good b effects;
add to dopamine for additional inotropic effect
(limiting tachycardia )

Epinephrine

0.1-1g/kg/min

(max 3 g/kg/min)

++

+++

use if not responding to dopamine; good mixed a and b response

Norepinephrine

0.05 - 1 g/kg/min

(max 2 g/kg/min)

+++

+

primarily a effect; should be combined with a b drug

Phenylephrine

0.1 - 1 g/kg/min

+++

0

primarily a effect; should be combined with a b drug

* These rate serve as guidelines for therapy. The pharmacokinetics of these drugs are not consistent between individuals and within the same foal overtime. For this reason, the dose must be titrated for the individual and may need to be adjusted over time.

Copyright 1997 Dr. Jon Palmer, Neonatal Intensive Care Unit